bluuebunny/crossref_metadata_2025 huggingface dataset:
A Proteção de Marcas do Segmento de Fitoterápicos
Authors: Marques de Albuquerque Daniel , Aquino Pereira Sammy
Published: March 2022

Fitoterápicos são remédios reproduzidos a partir de partes vegetais ou plantas consideradas medicinais e que podem ser representadas pelas marcas, por meio de um ativo intangível. O objetivo deste trabalho é identificar o registro de marcas associadas a produtos fitoterápicos, com o intuito de avaliar se as empresas utilizam a estratégia de proteção da marca para validar seus produtos. A metodologia utilizada baseou-se na identificação da Classificação de Nice para fitoterápicos, o levantamento das marcas e empresas detentoras do registro, assim como a busca de informações na internet aberta sobre a comercialização das marcas identificadas. Como resultado, identificou-se que apenas cinco empresas estavam com suas marcas em vigor, mas apenas uma empresa utilizava a marca do produto fitoterápico. Portanto, pode-se demonstrar a baixa demanda pelo uso de ativo intangível no que se refere à comercialização de produtos fitoterápicos.
Proposta de Fortalecimento do Núcleo de Inovação Tecnológica a partir da Relação Universidade Pública e Fundação de Apoio em Alagoas
Authors: FERREIRA EDJANNE , Escodro Pierre , Santos Taciana
Published: March 2022

O estudo objetiva analisar como a relação entre Universidade Federal de Alagoas (UFAL) e a Fundação Universitária de Desenvolvimento de Extensão e Pesquisa (FUNDEPES), entidade registrada e credenciada para dar suporte a projetos de pesquisa, ensino, extensão e de desenvolvimento institucional, científico e tecnológico em Alagoas, pode fortalecer o Núcleo de Inovação Tecnológica (NIT/UFAL). A pesquisa foi realizada por meio de informações extraídas de sites oficiais da Ufal, Fundepes e outros órgãos. Os resultados mostram lacunas existentes na norma que disciplina o relacionamento entre a Ufal e a Fundepes, com necessidades de atualização às diretrizes nacionais constantes na nova Lei de Inovação promulgada em 2016. Assim, a proposição de atualização dessa norma para aperfeiçoar a relação entre a Ufal e Fundepes impulsiona o fortalecimento do NIT, buscando obter um melhor desempenho quanto à desburocratização de processos e gestão da propriedade intelectual, estimulando a inovação no Estado.
Editorial
Authors: Frey Irineu Afonso , Quintella Cristina M. , Uchôa Sílvia Beatriz Beger
Published: March 2022

O ano de 2021 foi mais um ano difícil para todos, convivendo com o assombro da pandemia de Covid-19 que nos assola desde 2020. A revista Cadernos de Prospecção, no seu compromisso assumido com a comunidade científica, especialmente com o Mestrado Profissional em Propriedade Intelectual e Transferência de Tecnologia para Inovação (ProfNIT), continuou com as suas atividades de maneira comprometida e focada, na socialização do conhecimento produzido, nas mais diversas frentes, relacionado ao tema de inovação.
Esse mais recente número da revista do ano de 2021 traz 21 artigos de 58 autores afiliados a 24 instituições de 13 Unidades da Federação localizadas nas cinco regiões do Brasil, mostrando a abrangência em todo o território nacional.
Os temas abordados nos artigos selecionados abarcam desde a pandemia do coronavírus, prospecções tecnológicas em áreas relevantes, como as da saúde e educação, até discussões sobre aspectos diversos sobre propriedade intelectual e transferência de tecnologia (PI e TT). São apresentados artigos versando sobre cultivares, marcas, transferência de tecnologia, entre outros.
Muito mais do que um canal de publicização de trabalhos desenvolvidos no âmbito do referido mestrado, a revista se consolida como importante disseminador da cultura de PI e TT, aberto para toda a sociedade.
A revista Cadernos de Prospecção, atenta às novas demandas, anuncia ampliação do escopo de suas publicações a partir de dezembro de 2021 com a criação de uma secção de Indicações Geográficas, visando atender às demandas de uma área que apresenta um crescimento de produção científica dentro do Profnit e da comunidade acadêmica.
Convidamos os leitores a navegarem nesse vasto oceano de PI e TT, desejando a todos uma boa e proveitosa leitura.
Differences in cardiovascular risk levels between cleaning staff and hotel housekeepers
Authors: López-González Ángel Arturo , Manzanero Zoe , González San Miguel Hilda María , Arroyo Bote Sebastiana , Riutord Sbert Pere , Rigo Vives María del Mar , Ramírez Manent José Ignacio
Published: March 2022

Background and objective

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, with a greater incidence in the most disadvantaged social classes. In this study, we aimed to evaluate the level of cardiovascular risk in cleaning workers.

Methods

This was a descriptive, cross-sectional study in 46.632 cleaning workers (40.169 women and 6.463 men). Thirty-one different scales related to cardiovascular risk were studied (14 assessing overweight and obesity, 5 determining the risk of nonalcoholic fatty liver disease, 5 scales of cardiovascular risk, 4 atherogenic indices, and 3 scales of metabolic syndrome, among others). The results obtained were divided between personnel who perform their cleaning tasks in the hotel and catering industry and those in other sectors.

Results

The prevalence of obesity and arterial hypertension in cleaning workers was over 20% in both sexes. A similar amount was observed in moderate or high values on the REGICOR (Registre GIroní del COR) scale. More than 15% presented metabolic syndrome according to the NCEP ATPIII (National Cholesterol Education Program-Adult Treatment Program III) criteria, while over 10% of women and 20% of men had a high risk of nonalcoholic fatty liver disease assessed with the fatty liver index.

Conclusion

Cardiovascular risk is higher, in both sexes, in the group of cleaning workers who work in companies other than hotels.
Marginal Odds Ratio Estimators
Authors: Drake Christiana
Published: March 2022

The odds ratio is a common measure to assess the association between a binary predictor variable and a binary outcome. In epidemiology, the outcome is often the disease status, and the predictor of interest is a suspected risk factor for the disease. The purpose of the study is an attempt to establish a causal association between exposure and disease. If the object of a study is the estimation of a marginal odds ratio, defined as the ratio of the odds that would be observed in a population if everyone were exposed versus the odds in the same population if no one were exposed, methods such as the Mantel–Haenszel estimator are commonly used. When it is necessary to adjust for many confounders and/or continuous confounders, this approach results in a biased and inconsistent estimator, including matching and stratification by the propensity score. An alternative to matching is inverse probability weighting by the propensity score. The resulting estimator is consistent, provided the propensity score model is correct and adjusts for all confounders.
Presence and Implications of Anti‐Angiotensin Converting Enzyme‐2 Immunoglobulin M Antibodies in Anti‐Melanoma‐Differentiation‐Associated 5 Dermatomyositis
Authors: Mecoli Christopher A. , Yoshida Akira , Paik Julie J. , Lin Cheng Ting , Danoff Sonye , Hanaoka Hironari , Rosen Antony , Christopher‐Stine Lisa , Kuwana Masataka , Casciola‐Rosen Livia
Published: March 2022

Objective

Patients with anti‐melanoma‐differentiation‐associated 5 (anti‐MDA5)‐positive dermatomyositis (DM) share several striking similarities to patients with SARS‐CoV‐2. Our objective was to assess the prevalence of anti‐angiotensin converting enzyme‐2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS‐CoV‐2, in two independent anti‐MDA5‐positive DM cohorts.

Methods

Anti‐ACE2 IgM antibodies were assayed by enzyme‐linked immunosorbent assay (ELISA) in two anti‐MDA5‐positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new‐onset disease (n = 32). Additionally, 118 patients with SARS‐CoV‐2 with a spectrum of clinical severity were tested for anti‐MDA5 antibodies by ELISA.

Results

Five of fifty‐two (9.6%) North American patients and five of thirty‐two (15%) Japanese patients were positive for anti‐ACE2 IgM. In the North American cohort, all five patients with anti‐ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti‐ACE2‐IgM‐negative group. In the Japanese cohort, all five anti‐ACE2‐IgM‐positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti‐ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar‐arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM‐negative group.

Conclusion

We describe anti‐ACE2 IgM autoantibodies in two independent cohorts with anti‐MDA5‐positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.
Microfluidic Particle Reactors: From Interface Characteristics to Cells and Drugs Related Biomedical Applications
Authors: Hao Xin , Du Ting , He Huatao , Yang Feng , Wang Yilan , Liu Gang , Wang Yaolei
Published: March 2022

Functional microfluidic particle reactors (MPRs), prepared with microfluidic emulsions with biomaterials as the templates, can directly encapsulate bioactive substances to achieve different biomedical applications. Different types of MPRs (such as single structure MPRs, mixed structure MPRs, and all‐aqueous structure MPRs) have multifarious functions owing to the prominent interface characteristics endowed by emulsion templates with exquisite controlled fluid components and interface structures, as well as functional biomaterials with attractive properties. Notably, the constructed MPRs are endowed with better controllability, biocompatibility, and injectability with the significant advances in the burgeoning droplet microfluidic technology and material science. This contributes to the improvement of the flexibility and degree of freedom of the MPRs supporting cell and drug‐related biomedical applications (such as 3D cell culture, cell/drug delivery, and controlled drug release), leading to more effective diagnosis and treatment. In this paper, the correlation between the particle structure, determined by optimizing emulsion template fluid components and interfacial complexity, and the interface characteristics of the MPRs are primarily investigated. Next, the interface characteristics of the MPRs expanded by functional biomaterials are reviewed, as well as the distinct properties of MPRs in the biomedical applications related to cells and drugs. Finally, the existing challenges and future perspectives are discussed to improve the unique interface characteristics of MPRs in broader biomedical applications.
Photon Walk in Transparent Wood: Scattering and Absorption in Hierarchically Structured Materials
Authors: Chen Hui , Montanari Céline , Shanker Ravi , Marcinkevicius Saulius , Berglund Lars A. , Sychugov Ilya
Published: March 2022

The optical response of hierarchical materials is convoluted, which hinders their direct study and property control. Transparent wood (TW) is an emerging biocomposite in this category, which adds optical function to the structural properties of wood. Nano‐ and microscale inhomogeneities in composition, structure, and at interfaces strongly affect light transmission and haze. While interface manipulation can tailor TW properties, the realization of optically clear wood requires detailed understanding of light–TW interaction mechanisms. Herein is shown how material scattering and absorption coefficients can be extracted from a combination of experimental spectroscopic measurements and a photon diffusion model. Contributions from different length scales can thus be deciphered and quantified. It is shown that forward scattering dominates haze in TW, primarily caused by refractive index (RI) mismatch between the wood substrate and the polymer phase. Rayleigh scattering from the wood cell wall and absorption from residual lignin have minor effects on transmittance, but the former affects haze. Results provide guidance for material design of transparent hierarchical composites toward desired optical functionality; it is demonstrated experimentally how transmittance and haze of TW can be controlled over a broad range.
A Multiple‐State Ion Synaptic Transistor Applicable to Abnormal Car Detection with Transfer Learning
Authors: Yu Ji-Man , Ham Gyeongdo , Lee Chungryeol , Lee Jae-Hyeok , Han Joon-Kyu , Kim Jin-Ki , Jang Donggon , Kim Nahyun , Kim Moon-Seok , Im Sung Gap , Kim Dae-Shik , Choi Yang-Kyu
Published: March 2022

An artificial synapse is an essential element to construct a hardware‐based artificial neural network (ANN). While various synaptic devices have been proposed along with studies on electrical characteristics and proper applications, a small number of conductance states with nonlinear and asymmetric conductance changes have been problematic and imposed limits on computational performance. Their applications are thus still limited to the classification of simple images or acoustic datasets. Herein, a polymer electrolyte‐gated synaptic transistor (pEGST) is demonstrated for video‐based learning and inference using transfer learning. In particular, abnormal car detection (ACD) is attempted with video‐based learning and inference to avoid traffic accidents. The pEGST showed multiple states of 8,192 (=13 bits) for weight modulation with linear and symmetric conductance changes and helped reduce the error rate to 3% to judge whether a car in a video is abnormal.
Atypical tooth wear found in fossil hominins also present in a Japanese macaque population
Authors: Towle Ian , MacIntosh Andrew J. J. , Hirata Kazuha , Kubo Mugino O. , Loch Carolina
Published: March 2022

Objectives

Atypical tooth wear, including macroscopically visible striations on anterior teeth and within root grooves on posterior teeth, are often regarded as evidence of non‐masticatory, tool use behavior in fossil hominins. Both these types of dental tissue loss are often considered unique to the genus Homo and suggested to be the earliest evidence of human cultural habits. The aim of this study was to describe similar tooth wear found in a wild primate population and to conduct a differential diagnosis of this atypical tissue loss.

Materials and Methods

The focus of this study was a sample of wild Japanese macaques from Koshima Island, Japan. Individuals were provisioned regularly on the beach as part of one of the longest running primate field sites. Tooth wear and fractures in this group were compared to two other non‐provisioned populations. Information on diet and behavior were obtained from extensive literature and on‐going field observations.

Results

All Koshima Island individuals analyzed showed atypical tooth wear. Large macroscopic striations were visible on many teeth, with sub‐vertical striations prominent on the labial surfaces of incisors. Root grooves on posterior teeth were observed in half of the individuals, some showing clear directional striations similar to those reported in “toothpick” grooves in fossil hominins. Tool use and the habitual insertion of non‐masticatory items in the mouth has not been observed in this population.

Discussion

Accidental ingestion of sand and oral processing of marine mollusks likely creates these atypical wear patterns. Implications for similar wear that has been associated with tool‐use in fossil hominin samples were discussed.
RETRACTED: Evaluation of psychometric characteristics of light triad personality questionnaire in nurses
Authors: Farah Bijari Azam , Hefazi Torghabeh Leila , Dehshiri Gholamreza
Published: March 2022

Introduction

Personality is one of the important etiological factors of psychological factors. In this regard, one of the important factors in the success of people's social and psychological life is the light triad personality. They are a combination of sympathy, compassion, and humanity. On the basis of results of the research, it is not possible to trust the psychometrics characteristics of tools; it is necessary to evaluate the psychometric characteristics of these tools. Meanwhile, the aim of the present study is the evaluation of psychometrics characteristics of light triad personality in nurses.

Methods

The statistical population includes all nurses who were employed in the summer and autumn of 2020 in private centers and hospitals affiliated with Mashhad University of Medical Sciences. The sample of this study was 245 nurses who were selected by convenience sampling. To analyze the data, exploratory and confirmatory factor analysis, Pearson correlation, total question‐score correlation, and reliability analysis were used by using SPSSV22 and LISRELV8.80 software.

Results

The results of exploratory and confirmatory factor analysis confirmed the three‐factor structure of the light triad personality questionnaire. The findings of the convergent validity of the light triad personality questionnaire were evaluated and confirmed via its simultaneous implementation by the Social Health and Emotional Sympathy Questionnaires and its divergent reliability was confirmed by the Machiavellian Questionnaire. The reliability coefficient of the questionnaire was obtained for the factors of sympathy, compassion, philanthropy, and totality by using Cronbach's alpha coefficient, 0.83, 0.75, 0.70, and 0.92, respectively.

Conclusion

Finally, with regard to the desired validity and reliability coefficients, ease of implementation, scoring, interpretation, and explanation, as well as a short time to answer, it can be said that light triad personality questionnaires were qualified for use in psychological research to measure the rate of light triad personality.
Organizational change in response to environmental complexity: Insights from the business model innovation literature
Authors: Martinez Fabien
Published: March 2022

Organizational change research to date has tended to proliferate on a conceptualization of change as a deliberate process driven by rational and formal strategic planning and fuelled by the expansion of exploitative resources. This conceptualization entails that change is essentially a process of reproduction in that it occurs along existing (incremental and cumulative) trajectories. Prompted by the need to manage increasingly complex and uncertain environments and foster progress towards sustainable development, the question of what are the exploratory forces that stimulate the capacity of business organizations to engage in discontinuous shifts towards new (flexible and creative) trajectories, without excessively disrupting existing ones, has comparatively been neglected. This paper contributes to address gaps in existing research by exploring how organizational change in response to complexity is framed in the literature on business model innovation. Three core categories of constraints to change are identified: relational flaws, functional flaws and the lack of moral motives; and three interacting forces that can be harnessed to overcome these constraints are suggested: sociability, agility and moral inclusivity. The resulting framework has broad implications for organizational change theory, practice, policy and research.
Prediction of tannin, protein, and total phenolic content of grain sorghum using image analysis and machine learning
Authors: Nazari Leyla , Khazaei Azim , Ropelewska Ewa
Published: March 2022

Background and Objectives

Sorghum is an alternative crop where poor soil is a limiting factor for the production of corn. Laboratory measurements of chemical compounds of grains are expensive, time‐consuming predominantly done on powdered samples. Therefore, a rapid and reliable method integrating image processing and machine learning was evaluated for the prediction of total phenolic compounds (TPCs), tannin, and protein.

Findings

The highest TPC (0.83%) was obtained for genotype KGS36 (the brown pericarp) followed by KGS23 (0.54%). The concentration of tannin ranged from 0.008% to 0.616%. Mean comparison revealed variation for the protein concentration (15.17%–11.53%); the highest content obtained by KGS25 and the lowest by KGS36 (p < .01). Multilayer perceptron (MLP) as one of the common artificial neural networks (ANNs) applied to simulate the chemical of the grains was evaluated through the textural features extracted from grain images. For the MLP network, the minimum number of hidden networks was set to 8 and the maximum number was set to 25. For learning and saving, the number of networks was set to 20 and the number of saved networks was set to 5. The best MLP models were selected based on performance (R) and error values for the train, test, and validation sets.

Conclusions

An ANN for the prediction of the chemical concentration was suggested. The correlations between predicted and observed data were higher than .915.

Significance and Novelty

These models are of great significance for the prediction of chemical concentrations of grain sorghum in plant breeding and food industry.
Epididymal leiomyosarcoma: Report of a rare case
Authors: Dehghani Mansoureh , Ariamanesh Mona , Khakbaz Ali
Published: March 2022

Epididymal leiomyosarcoma (LMS) is a rare malignancy. Because the risk of recurrence is high, proper approach is important. Here, we present a patient with scrotal swelling who underwent surgical excision via scrotal incision, and the histopathological diagnosis was epididymal LMS. The decision was then made to perform inguinal radical orchiectomy.
Familial essential thrombocythemia: 6 cases from a mono‐institutional series
Authors: Accurso Vincenzo , Santoro Marco , Mancuso Salvatrice , Vajana Giorgia , Tomasello Riccardo , Rotolo Cristina , Camarda Giulia , Mattana Marta , Siragusa Sergio
Published: March 2022

Rarely essential thrombocythemia (ET) is diagnosed in more than one person within a family. Familial myeloproliferative neoplasms are underdiagnosed. In this report, we describe 6 couples of familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.
Direct Conversion Syngas to Isobutanol over Ce/ZC Catalysts: Effect of Ce Promoter on the Catalytic Performance
Authors: Wang Liyan , Zhang Tao , Yang Jiaqian , Gong Nana , Ma Qingxiang , Wu Yingquan , Tan Yisheng
Published: March 2022

The fuel‐efficient production of isobutanol via CO hydrogenation is a meaningful path, but still remains large challenges. Here, varied contents Ce promoter were introduced to optimize the catalytic performance of ZnCr‐based catalysts. The evaluation results displayed that 2.5‐Ce/ZC catalyst obtained optimum total alcohols yield and isobutanol selectivity. A combination of XPS, TPD, and in‐situ FTIR measurements was performed to probe into the enhancing effect of Ce promoter. The XPS characterization results disclosed the evident changes in the oxygen vacancy concentration and electron structure derived from Ce doping. Furthermore, this unique structure promoted the formation of HCOO species, and modulated the HCOO binding with proper strength to enable further carbon chain growth. According to the acid‐base properties tests, the doping of Ce introduced meaningful medium strong acid and base sites. The facilitated C−C coupling activity was a forthright result that led to the production of C2+ products, especially isobutanol.
Performance and Mechanism of Gas‐Solid Adsorption in a Rotating Adsorption Bed
Authors: Guo Qiang , Zhao Yue , Qi Guisheng , Liu Youzhi
Published: March 2022

A rotating adsorption bed for adsorbing toluene by activated carbon was constructed. It was found that the adsorption capacity of the rotating bed was stronger than that of the fixed bed and showed a faster adsorption rate. The particle diffusion model showed that the adsorption process in a rotating adsorption bed was a combination of surface diffusion and particle diffusion. In the rotating adsorption bed, the contribution rate of intraparticle diffusion to the whole adsorption was the largest, and the adsorption rate of each stage of the rotary adsorption bed was higher than that of the fixed bed. The good external diffusion force of the rotating adsorption bed effectively realized the deep‐pore adsorption of the adsorbent and improved the utilization rate of the adsorbent.
Catalytic Oxidation of Veratryl Alcohol Derivatives Using RuCo/rGO Composites
Authors: Yu Daobo , Lei Puyi , Li Yanfang , Shen Wenzhuo , Zhong Min , Zhang Jiali , Guo Shouwu
Published: March 2022

Chemoselectively oxidizing Cα−OH to C=O has been considered as a key step for the oxidative depolymerization of lignin. In this work, we design and prepare a series of composites of RuCo alloy nanoparticles and reduced graphene oxide (RuCo/rGO) with different Ru to Co ratios and explore their catalytic activities in the oxidation of veratryl alcohol derivatives, which usually serve as the model compounds for studying lignin oxidation. It is illustrated that the Ru to Co ratio determines the morphology and average size of the RuCo alloy nanoparticles on rGO, and the overall catalytic activities of the composites. The RuCo alloy nanoparticles on rGO with Ru to Co ratios of 1 : 0 to 1.2 : 1 show a unique flower‐shaped morphology that increases the exposure of the active sites and thus promotes their contact with the substrates. The RuCo/rGO composites exhibit high catalytic activities for the oxidation of Cα−OH to aldehydes at 100 °C for 2 h. Additionally, the Co component affords the RuCo/rGO composites with magnetic properties that make the separation and recovery of the catalyst simple. Given the high catalytic performances and easy recovery, the RuCo/rGO composites would be potentially useful for the depolymerization of lignin.
A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors
Authors: Schueller Olivier , Willson Ashley , Singh Nand , Lohmer Lauren , Alabanza Anginelle , Patel Jeegar
Published: March 2022

Belumosudil is a selective Rho‐associated protein kinase 2 inhibitor. Inhibition of Rho‐associated protein kinase 2 has emerged as a promising treatment for chronic graft‐versus‐host disease by restoring immune homeostasis and reducing fibrosis. In vitro assessments have suggested that metabolism of belumosudil is primarily dependent on cytochrome P450 (CYP) 3A4 activity and that the solubility of belumosudil is pH dependent. As such, this 2‐part clinical drug‐drug interaction study was conducted to assess the effect of itraconazole (a strong CYP3A4 inhibitor), rifampicin (a strong CYP3A4 inducer), rabeprazole, and omeprazole (both proton pump inhibitors) on the pharmacokinetics of belumosudil. No clinically relevant change in belumosudil exposure was observed following a 200‐mg single oral dose of belumosudil with itraconazole; however, exposure of main metabolite, KD025m2, was decreased. Consistent with the proposed metabolic pathway of belumosudil, the strong CYP3A4 inducer rifampicin significantly decreased exposure of belumosudil and KD025m2 and increased KD025m1 exposure. When a 200‐mg single oral dose of belumosudil was coadministered with both rabeprazole and omeprazole, parent and metabolite exposures were largely reduced, suggesting that belumosudil dosage should be increased when given with PPIs. Administration of belumosudil with and without perpetrator drugs was safe, and no notable adverse events were reported.
Clinical Pharmacology of Insulin Aspart Biosimilar GP40071: Pharmacokinetic/Pharmacodynamic Comparability in Hyperinsulinemic Euglycemic Clamp Procedure
Authors: Drai Roman V. , Karonova Tatiana L. , Mayorov Alexander Y. , Makarenko Igor E. , Dorotenko Artem R. , Kulesh Viktoria S. , Kovalik Vladislav V. , Andreeva Alena T.
Published: March 2022

Insulin aspart is a short‐acting insulin analogue that is used to control postprandial glycemia levels in diabetic patients. The aim of this clinical trial was to compare the pharmacokinetics and pharmacodynamics of GP40071 (GP‐Asp) and NovoRapid Penfill (Novo‐Asp) in a hyperinsulinemic euglycemic clamp (HEC). This trial was conducted as a part of a GP40071 biosimilar clinical development program. This was a phase I randomized, double‐blind, two‐period crossover study. Twenty‐six healthy male volunteers aged 18 to 45 years who met the inclusion criteria underwent the procedure of an HEC following a single subcutaneous injection of 0.3 IU/kg of either GP‐Asp or Novo‐Asp into the abdomen. After doses, plasma glucose levels were monitored every 5 minutes for 8 hours. The adjustment of the glucose infusion rate (GIR) was based on the blood glucose measurements. The GIR values were used to evaluate the PD profiles of the studied drugs. Regular blood sampling was performed during the study to obtain sufficient pharmacokinetic data. The 90% confidence intervals for the geometric mean ratios of the pharmacokinetic (AUCins.0‐t, Cins.max) and pharmacodynamic (GIRmax, AUCGIR0‐t) parameters of GP‐Asp were within the 80%–125% comparability limits. The safety profiles of the drugs were also comparable. Bioequivalence, similar PD, and safety of GP‐Asp and Novo‐Asp were demonstrated.
Absolute Bioavailability, Mass Balance, and Metabolic Profiling Assessment of [14C]‐Belumosudil in Healthy Men: A Phase 1, Open‐Label, 2‐Part Study
Authors: Schueller Olivier , Skucas Ed , Regev Galit , Shaw Iain , Singh Nand , Sanghvi Mitesh , Croft Marie , Lohmer Lauren , Alabanza Anginelle , Patel Jeegar
Published: March 2022

Belumosudil is a selective Rho‐associated coiled‐coil containing protein kinase 2 (ROCK2) inhibitor. ROCK2 has been shown to drive proinflammatory response and fibrosis that occurs with chronic graft‐versus‐host disease; therefore, inhibition of ROCK2 has emerged as a therapeutic target for chronic graft‐versus‐host disease. In this phase 1 two‐part study, the pharmacokinetics, mass balance, and metabolic profile of belumosudil were evaluated after single doses of unlabeled belumosudil oral tablets (200 mg), radiolabeled belumosudil intravenous (IV) microtracer infusions (100 μg), and radiolabeled oral capsules (200 mg). Absolute bioavailability based on area under the plasma concentration–time curve from time 0 to infinity for the oral dose/area under the plasma concentration–time curve from time 0 to infinity for the IV dose was calculated as 63.7%. Radiolabeled IV microtracer dosing demonstrated a low extraction ratio and distribution of belumosudil into tissues. The majority of total radioactivity was recovered in feces, with minimal amounts recovered in urine, suggesting minimal renal elimination of belumosudil. In addition to parent and main metabolite KD025m2, metabolites identified in plasma included the phase 2 metabolites O‐dealkylated belumosudil sulfate and belumosudil glucuronide. These metabolites (with the exception of the glucuronide) in addition to monohydroxy‐belumosudil, and belumosudil diol were identified in feces. No metabolites in urine accounted for >10% of the radioactive dose.
User‐level parallel file system: Case studies and performance optimizations
Authors: Zou Yanliang , Chen Chen , Deng Tongliang , Zhang Jian , Zhu Xiaomin , Chen Si , Yin Shu
Published: March 2022

User‐level file systems are usually adopted to bridge the gap between efficacy and efficiency of file system developments for new applications' I/O demands. And the widely known user‐space file system framework, FUSE, is commonly utilized to deployed user‐level file systems. This article first uses a popular stack‐able file system as a case study to exam how FUSE affects I/O performance. Based on the testing and analytical results, this article then presents SHC, an implementation method to implement a user‐level file system without FUSE intervention. Experimental results indicate that SHC improves write bandwidth by up to 5.6x compared with that of FUSE and present leading superiority on read cases.
Molecular Engineering of CoII Porphyrins with Asymmetric Architecture for Improved Electrochemical CO2 Reduction
Authors: Bao Wenwen , Huang Senhe , Tranca Diana , Feng Boxu , Qiu Feng , Rodríguez‐Hernández Fermín , Ke Changchun , Han Sheng , Zhuang Xiaodong
Published: March 2022

The electrochemical reduction of carbon dioxide (CO2) based on molecular catalysts has attracted more attention, owing to their well‐defined active sites and rational structural design. Metal porphyrins (PorMs) have the extended π‐conjugated backbone with different transition metals, endowing them with unique CO2 reduction properties. However, few works focus on the investigation of symmetric architecture of PorMs as well as their aggregation behavior to CO2 reduction. In this work, a series of CoII porphyrins (PorCos) with symmetric and asymmetric substituents were used as model of molecular catalysts for CO2 reduction. Owing to the electron donating effect of 2,6‐dimethylbenzene (DMB), bandgaps of the complexes became narrower with the increasing number of DMB. As electrocatalysts, all PorCos exhibited promising electrocatalytic CO2 reduction performance. Among the three molecules, asymmetric CoII porphyrin (as‐PorCo) showed the lowest onset potential of −288 mV and faradaic efficiencies exceeding 93 % at −0.6 V vs. reversible hydrogen electrode, which is highly competitive among the reported state‐of‐art porphyrin‐based electrocatalysts. The CO2 reduction performance depended on π‐π stacking between PorCo with carbon nanotubes (CNTs) and adjacent PorCos, which could be readily controlled by atomically positioned DMB in PorCo. Density functional theory calculations also suggested that the charge density between PorCo and CNT was highest due to the weak steric hindrance in as‐PorCo, providing the new insight into molecular design of catalysts for efficient electrochemical CO2 reduction.
Shared reduced ordered binary decision diagram‐based thermal‐aware network synthesis
Authors: Das Apangshu , Kumar Singh Vivek , Nath Pradhan Sambhu
Published: March 2022

In this work, a multi‐objective algorithm based on nondominated sorting genetic algorithm‐II (NSGA‐II) for thermal‐aware realization of a combinational logic network has been implemented. Input variable ordering of shared reduced ordered binary decision diagram (SROBDD) is done using NSGA‐II such that resulting combinational circuit generates low hotspots by suitable power density distribution. Simultaneous co‐optimization among area, power, and temperature is important in the higher levels of electronic circuit design to reduce the cooling cost. Using a multi‐objective algorithm (NSGA‐II), an effort is made to decrease the temperature by co‐optimization between the power density, area, and power simultaneously. Microelectronics Center of North Carolina (MCNC) benchmark circuits are tested using the proposed approach and an improvement of 13.65% in the silicon area and up to 10% in power dissipation, and 2.72% peak temperature reduction is reported in comparison to existing literature. HotSpot tool and Cadence Innovus are used to determine the peak temperature, actual silicon chip area, and power dissipation of algorithmic optimized solutions.
Rhodium(III) Werner Complexes with 1,2‐Diphenylethylenediamine Ligands: Syntheses, Structures, and Applications as Chiral Hydrogen Bond Donor Catalysts and Agents for Enantiomer Purity Determinations
Authors: Wegener Aaron R. , Ghosh Subrata K. , Bhuvanesh Nattamai , Reibenspies Joseph , Gladysz John A.
Published: March 2022

Reactions of RhCl3 and (S,S)‐1,2‐diphenylethylenediamine (S,S‐dpen) in DMSO at 140 °C give Λ‐[Rh(S,S‐dpen)3]3+3Cl− (Λ‐(S,S)‐43+3Cl−) in 76 % yield. When CH2Cl2/water suspensions are treated with 1.0 equiv. of Na+ B(C6F5)4− or Na+ B(3,5‐C6H3(CF3)2)4−, the mixed salts Λ‐(S,S)‐43+2Cl−B(aryl)4− can be isolated from the organic layers (95–91 %). A wide variety of mixed and non‐mixed salts involving these and other anions (BF4−, ClO4−, I−) are also prepared. The lipophilic salts are highly enantioselective catalysts for the Michael addition of dimethylmalonate to trans‐ß‐nitrostyrene (acetone, 0 °C; 92–85 % ee). The crystal structures of seven solvated salts are determined, and hydrogen bonding between the trications and anions or solvate molecules analyzed. There is a notable affinity of chloride anions for the C3 face of Λ‐(S,S)‐43+, which features three synperiplanar NH groups. Λ‐(S,S)‐43+2I−B(C6F5)4− is an excellent chiral solvating agent for determining enantiomeric purities of chiral organic molecules with hydrogen bond accepting functional groups (11 mol% (average), CDCl3).
Shock capturing with the high‐order flux reconstruction method on adaptive meshes based on p4est
Authors: Fu Hao , Xia Jian , Ma Xiuqiang
Published: March 2022

High order schemes have been investigated for quite a long time, and the flux reconstruction (FR) scheme proposed by Huynh recently attracts the attention of researchers due to its simplicity and efficiency. Building the framework that bridges discontinuous Galerkin (DG) and spectral difference (SD) schemes, FR recovers DG and SD conveniently with a careful selection of parameters. In this article, FR scheme is realized based on the framework of p4est, an open source adaptive mesh refinement library. The shock capturing ability of localized Laplacian artificial viscosity and in‐cell piecewise integrated solution methods are compared. Curved boundary treatment for high order schemes is adopted. The performance of developed code is estimated in both one and two dimensions including curved boundary and shock cases, and some attractive results are obtained.
Directional selection and the evolution of breeding date in birds, revisited: Hard selection and the evolution of plasticity
Authors: Hadfield Jarrod D. , Reed Thomas E.
Published: March 2022

The mismatch between when individuals breed and when we think they should breed has been a long-standing problem in evolutionary ecology. Price et al. is a classic theory paper in this field and is mainly cited for its most obvious result: if individuals with high nutritional condition breed early, then the advantage of breeding early may be overestimated when information on nutritional condition is absent. Price at al.'s less obvious result is that individuals, on average, are expected to breed later than the optimum. Here, we provide an explanation of their non-intuitive result in terms of hard selection, and go on to show that neither of their results are expected to hold if the relationship between breeding date and nutrition is allowed to evolve. By introducing the assumption that the advantage of breeding early is greater for individuals in high nutritional condition, we show that their most cited result can be salvaged. However, individuals, on average, are expected to breed earlier than the optimum, not later. More generally, we also show that the hard selection mechanisms that underpin these results have major implications for the evolution of plasticity: when environmental heterogeneity becomes too great, plasticity is selected against, prohibiting the evolution of generalists.
Global factors and the transmission between United States and emerging stock markets
Authors: Naeem Muhammad Abubakr , Farid Saqib , Qureshi Fiza , Taghizadeh‐Hesary Farhad
Published: March 2022

In this study, we examine the influence of global factors in driving connectedness among Unite States and emerging stock markets. For this purpose, we employ widely recognized approaches of and Barunik and Krehlik to estimate connectedness among the underlying markets in time‐frequency domains. Also, we use the tests proposed by Péguin‐Feissolle and Teräsvirta to examine the impact of global factors on the transmission relationship between United States and emerging stock markets utilizing the non‐linear causality tests. The findings validate the influential role of global factors in channeling overall total spillovers between United States and emerging stock markets. However, the results for individual emerging markets show some degree of heterogeneous impact of global factors in driving connectedness across different emerging stock markets. Our robustness results also confirm the main findings. Important implications of findings are discussed for portfolio managers and policymakers.
Fenoldopam Sensitizes Primary Cilia-Mediated Mechanosensing to Promote Osteogenic Intercellular Signaling and Whole Bone Adaptation
Authors: Spasic Milos , Duffy Michael P. , Jacobs Christopher R.
Published: March 2022

Bone cells actively respond to mechanical stimuli to direct bone formation, yet there is no current treatment strategy for conditions of low bone mass and osteoporosis designed to target the inherent mechanosensitivity of bone. Our group has previously identified the primary cilium as a critical mechanosensor within bone, and that pharmacologically targeting the primary cilium with fenoldopam can enhance osteocyte mechanosensitivity. Here, we demonstrate that potentiating osteocyte mechanosensing with fenoldopam in vitro promotes pro-osteogenic paracrine signaling to osteoblasts. Conversely, impairing primary cilia formation and the function of key ciliary mechanotransduction proteins attenuates this intercellular signaling cascade. We then utilize an in vivo model of load-induced bone formation to demonstrate that fenoldopam treatment sensitizes bones of both healthy and osteoporotic mice to mechanical stimulation. Furthermore, we show minimal adverse effects of this treatment and demonstrate that prolonged treatment biases trabecular bone adaptation. This work is the first to examine the efficacy of targeting primary cilia-mediated mechanosensing to enhance bone formation in osteoporotic animals. © 2022 American Society for Bone and Mineral Research (ASBMR).
Necroptosis‐related lncRNA to establish novel prognostic signature and predict the immunotherapy response in breast cancer
Authors: Chen Fangyue , Yang Jun , Fang Min , Wu Yanmei , Su Dongwei , Sheng Yuan
Published: March 2022

Background

Necroptosis is a type of programmed cell death, and recent researches have showed that lncRNAs could regulate the process of necroptosis in multiple cancers. We tried to screen necroptosis‐related lncRNAs and investigate the immune landscape in breast cancer (BC).

Methods

The samples of breast normal and cancer tissue were acquired from TCGA and GTEx databases. A risk prognostic model was constructed based on the identified necroptosis‐related lncRNAs by Cox regression and least absolute shrinkage and selection operator (LASSO) method. Moreover, the forecast performance of this model was verified and accredited by synthetic approach. Subsequently, an accurate nomogram was constructed to predict the prognosis of BC patients. The biological differences were investigated through GO, GSEA, and immune analysis. The immunotherapy response was estimated through tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) score.

Results

A total of 251 necroptosis‐related lncRNAs were identified by differential coexpression analysis, and SH3BP5‐AS1, AC012073.1, AC120114.1, LINC00377, AL133467.1, AC036108.3, and AC020663.2 were involved in the risk model, which had an excellent concordance with the prediction. The pathway analyses showed that immune‐related pathways were relevant to the necroptosis‐related lncRNAs risk model. And the risk score was significantly correlated with immune cell infiltration, as well as the ESTIMATE score. Most notably, the patients of higher risk score were characterized with increased TMB and decreased TIDE score, indicating that these patients showed better immune checkpoint blockade response.

Conclusion

These findings were conducive to understand the function of necroptosis‐related lncRNAs in BC and provide a potential promising therapeutic strategy for BC.
Characterization of the significant decline in humoral immune response six months post‐SARS‐CoV‐2 mRNA vaccination: A systematic review
Authors: Notarte Kin Israel , Guerrero‐Arguero Israel , Velasco Jacqueline Veronica , Ver Abbygail Therese , Santos de Oliveira Maria Helena , Catahay Jesus Alfonso , Khan Md. Siddiqur Rahman , Pastrana Adriel , Juszczyk Grzegorz , Torrelles Jordi B. , Lippi Giuseppe , Martinez‐Sobrido Luis , Henry Brandon Michael
Published: March 2022

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID‐19) (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) messenger RNA (mRNA) vaccines such as Pfizer‐BioNTech (mRNA BNT161b2) and Moderna (mRNA‐1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti‐SARS‐CoV‐2 antibodies after the second dose of a primary cycle of COVID‐19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21–28 days after the second dose, after which serum levels progressively diminished at 4–6‐month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti‐receptor binding domain immunoglobulin G (IgG) and anti‐spike IgG, ranging from 94% to 95% at 90–180 days and 55%–85% at 140–160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient‐related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.
Reanalysis‐driven multi‐RCM high‐resolution simulation of precipitation within CORDEX East Asia Phase II
Authors: Tang Jianping , Xiao Yuxin , Hui Pinhong , Lu Yutong , Yu Ke
Published: March 2022

Under the Coordinated Regional Downscaling Experiment‐East Asia second phase (CORDEX‐EA‐II) framework, the performances of three regional climate models (RCMs), including Weather Research and Forecasting (WRF) model, RegCM4 and Consortium for Small‐Scale Modelling model in Climate Mode (CCLM), in simulating the climatic distribution, diurnal variation and extremes of precipitation during 1989–2009 are evaluated. The RCMs are driven by the ERA‐Interim reanalysis and the evaluation is based on both the gridded gauge‐based and the satellite‐derived precipitation data. In general, the RCMs can reproduce the spatial pattern of the mean daily precipitation, with the spatial correlations (SCORs) larger than 0.66, and CCLM has the lowest root‐mean‐square error over East Asia. For the diurnal cycle of precipitation, WRF outperforms the other two RCMs despite the peak time about 3 hr ahead in some areas. RegCM4 overestimates the amplitude of the diurnal curve, and CCLM has limited ability to simulate the diurnal variation over most areas. All the three RCMs can reproduce the spatial patterns of the extreme indices, with the SCORs larger than 0.57. WRF and CCLM perform the best for the frequency of wet days (R1mm) and moderate rain (R20mm), respectively. The intensity indices are overestimated over most land areas, with relatively higher SCORs in WRF and relatively lower biases in RegCM4. The consecutive wet days (CWD) can be well simulated by WRF and CCLM; however, RegCM4 overestimates it over most regions in East Asia. The overestimation of the extreme intensity and frequency indices may be related to the higher water vapour content and the weaker water vapour divergence in the lower layer, as well as the higher mid‐layer geopotential height, especially in CCLM.