bluuebunny/crossref_metadata_2025 huggingface dataset:
A biosocial return to race? A cautionary view for the postgenomic era
Authors: Meloni Maurizio , Moll Tessa , Issaka Ayuba , Kuzawa Christopher W.
Published: March 2022

Recent studies demonstrating epigenetic and developmental sensitivity to early environments, as exemplified by fields like the Developmental Origins of Health and Disease (DOHaD) and environmental epigenetics, are bringing new data and models to bear on debates about race, genetics, and society. Here, we first survey the historical prominence of models of environmental determinism in early formulations of racial thinking to illustrate how notions of direct environmental effects on bodies have been used to naturalize racial hierarchy and inequalities in the past. Next, we conduct a scoping review of postgenomic work in environmental epigenetics and DOHaD that looks at the role of race/ethnicity in human health (2000–2021). Although there is substantial heterogeneity in how race is conceptualized and interpreted across studies, we observe practices that may unwittingly encourage typological thinking, including: using DNA methylation as a novel marker of racial classification; neglect of variation and reversibility within supposedly homogenous racial groups; and a tendency to label and reify whole groups as pathologized or impaired. Even in the very different politico‐economic and epistemic context of contemporary postgenomic science, these trends echo deeply held beliefs in Western thinking which claimed that different environments shape different bodies and then used this logic to argue for essential differences between Europeans and non‐Europeans. We conclude with a series of suggestions on interpreting and reporting findings in these fields that we feel will help researchers harness this work to benefit disadvantaged groups while avoiding the inadvertent dissemination of new and old forms of stigma or prejudice.
Comparison of the arm‐lowering performance between Gorilla and Homo through musculoskeletal modeling
Authors: van Beesel Julia , Hutchinson John R. , Hublin Jean‐Jacques , Melillo Stephanie
Published: March 2022

Objectives

Contrary to earlier hypotheses, a previous biomechanical analysis indicated that long‐documented morphological differences between the shoulders of humans and apes do not enhance the arm‐raising mechanism. Here, we investigate a different interpretation: the oblique shoulder morphology that is shared by all hominoids but humans enhances the arm‐lowering mechanism.

Materials and methods

Musculoskeletal models allow us to predict performance capability to quantify the impact of muscle soft‐tissue properties and musculoskeletal morphology. In this study, we extend the previously published gorilla shoulder model by adding glenohumeral arm‐lowering muscles, then comparing the arm‐lowering performance to that of an existing human model. We further use the models to disentangle which morphological aspects of the shoulder affect arm‐lowering capacity and result in interspecific functional differences.

Results

Our results highlight that arm‐lowering capacity is greater in Gorilla than in Homo. The enhancement results from greater maximum isometric force capacities and moment arms of two important arm‐lowering muscles, teres major, and pectoralis major. More distal muscle insertions along the humerus together with a more oblique shoulder configuration cause these greater moment arms.

Discussion

The co‐occurrence of improved arm‐lowering capacity and high‐muscle activity at elevation angles used during vertical climbing highlight the importance of a strong arm‐lowering mechanism for arboreal locomotor behavior in nonhuman apes. Therefore, our findings reveal certain skeletal shoulder features that are advantageous in an arboreal context. These results advance our understanding of adaptation in living apes and can improve functional interpretations of the hominin fossil record.
Chemoselective and Diastereoselective Intramolecular (3+2) Cycloadditions of Epoxy and Aziridinyl Enolsilanes
Authors: Chen Yueyao , Ling Jesse , Keto Angus B. , He Yun , Low Kam‐Hung , Krenske Elizabeth H. , Chiu Pauline
Published: March 2022

Epoxy and aziridinyl enolsilanes react as oxyallylic cation equivalents in highly chemo‐ and diastereoselective intramolecular (3+2) cycloadditions with a range of dienes and olefins. With acyclic dienes, the (3+2) cycloaddition outcompetes the (4+3) pathway traditionally observed in this kind of system almost exclusively. With both conjugated dienes and isolated olefins, excellent diastereoselectivities are observed, and cycloadducts can be obtained in optically‐enriched forms. Computational studies indicate that the stepwise (3+2) cycloaddition involves an activated epoxy/aziridinyl intermediate and the conformational flexibility of the intermediate determines the preference for (3+2) cycloadduct formation. Further transformations of the (3+2) cycloadducts produce densely functionalized trans‐hydrindane scaffolds.
A Pyrene‐Triazacyclononane Anchor Affords High Operational Stability for CO2RR by a CNT‐Supported Histidine‐Tagged CODH
Authors: Contaldo Umberto , Curtil Mathieu , Pérard Julien , Cavazza Christine , Le Goff Alan
Published: March 2022

An original 1‐acetato‐4‐(1‐pyrenyl)‐1,4,7‐triazacyclononane (AcPyTACN) was synthesized for the immobilization of a His‐tagged recombinant CODH fromRhodospirillum rubrum(RrCODH) on carbon‐nanotube electrodes. The strong binding of the enzyme at the Ni‐AcPyTACN complex affords a high current density of 4.9 mA cm−2towards electroenzymatic CO2reduction and a high stability of more than 6×106 TON when integrated on a gas‐diffusion bioelectrode.
Effect of matrix deformability on the fracture properties of epoxy resins modified with core–shell and cross‐linked rubber particles
Authors: Imanaka Makoto , Narita Ichihito , Nakamura Yoshinobu , Hisaka Shigeki , Yoshida Shun , Hara Keisuke
Published: March 2022

The effect of matrix deformability on the mechanical and fracture properties of epoxies containing dispersed core–shell rubber (CSR) and cross‐linked rubber (CLR) particles was studied. The deformability of the matrix phase was varied using two types of curing agents, dicyandiamide (DICY) and piperidine, wherein the matrix phase cured with DICY has lower deformability than that cured with piperidine. Tensile and compression tests were conducted for the DICY‐ and piperidine‐cured epoxies. Under tensile load conditions, typical for CSR‐ and CLR‐modified epoxies, the DICY‐cured epoxies were brittle, whereas the piperidine‐cured epoxies failed under plastic deformation. Under compression loads, the 0.2% proof stresses of both rubber‐modified epoxies cured by DICY were higher than those cured by piperidine, wherein the proof stresses for both the DICY‐ and piperidine‐cured epoxies decreased with increasing rubber content. The results of fracture toughness tests for both types of cured epoxies indicated that the J‐integral (Jc) values of the DICY‐cured epoxy containing rubber particles were ~0.3–0.5 times that of the piperidine‐cured epoxy, which implied that the fracture toughness of the rubber‐modified epoxies decreased with decreasing deformability of the matrix phase. In addition, the ratio of Jc for CLR‐modified epoxies to those of Jc for CSR‐modified epoxies for piperidine cured epoxies were about 1.5 times greater than those of DICY cured ones. Microscopy observations were conducted to explore the effect of the deformability of the matrix phase on the fracture mechanism.
“Fun slipping into the doctor's role”—The relationship between sonoanatomy teaching and professional identity formation before and during the Covid‐19 pandemic
Authors: Darici Dogus , Missler Markus , Schober Anna , Masthoff Max , Schnittler Hans , Schmitz Martina
Published: March 2022

The various psychological dimensions of professional identity formation (PIF) are an important aspect of the study course for undergraduate medical students. Anatomical learning environments have been repeatedly shown to play a critical role in forming such an identity; however, relevance of PIF during sonoanatomical training remains underexplored. At the end of their basic anatomy studies, third‐semester medical students took part in a four‐day block course on anatomy and imaging. Anatomical content was revised in small groups using peer teaching and imaging methods, including one hour of hands‐on sonoanatomy sessions each day. On‐site sonoanatomy was identified as an excellent format to support students' transition from the pre‐clinical to clinical phase as medical experts‐to‐be. Students enjoyed practical exercises and the clinical input, which increased their interest in the medical profession and their academic studies. This study further examined the effects of the transition into an online‐only format, necessitated by the current Covid‐19 pandemic. A comparison was made between the quantitative and qualitative evaluation data, and the written results of examinations of several on‐site (n = 1096, mean age = 22.4 years ± 2.18), and online‐only cohorts (n = 230, mean age = 22.6 years ± 2.21). The online‐only transition led to a reduction of all PIF‐related variables measured, losing identity‐related variables, increasing students' stress levels, and reducing their long‐term academic performance. Together, this study demonstrates presence of PIF in undergraduate sonoanatomy teaching, and cautions against the uncritical online‐only substitution of hands‐on learning environments.
H∞optimal preview tracking control problem with disturbance attenuation
Authors: Liu Tao , Liu Ling , Lu Yanrong
Published: March 2022

In this paper, theH∞optimal preview tracking control problem of continuous‐time linear system with external disturbance is studied, where the reference signal is previewed and its amplitude does not decay. First, an augmented system with error vector, original system state derivative, and internal model state derivative is constructed, which transforms the tracking problem into theH∞optimal output regulation problem. Second, theH∞optimal control method is used to design the controller, and the output regulation of the augmented system is achieved by finding the upper bound of the discount factor. Then the optimal controller, including error integral, preview feed‐forward compensation, and internal model compensation, is obtained for the original problem, and meanwhile the sufficient conditions are also provided to guarantee the existence of the controller. Finally, both theoretical and simulation results show that under the proposed controller, the closed‐loop system can achieve asymptotic tracking and has robustness against the disturbance.
Exome sequencing identifies variants in infants with sacral agenesis
Authors: Pitsava Georgia , Feldkamp Marcia L. , Pankratz Nathan , Lane John , Kay Denise M. , Conway Kristin M. , Hobbs Charlotte , Shaw Gary M. , Reefhuis Jennita , Jenkins Mary M. , Almli Lynn M. , Moore Cynthia , Werler Martha , Browne Marilyn L. , Cunniff Chris , Olshan Andrew F. , Pangilinan Faith , Brody Lawrence C. , Sicko Robert J. , Finnell Richard H. , Bamshad Michael J. , McGoldrick Daniel , Nickerson Deborah A. , Mullikin James C. , Romitti Paul A. , Mills James L. ,   UW Center for Mendelian Genomics, NISC Comparative Sequencing Program and the National Birth Defects Prevention Study
Published: March 2022

Background

Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non‐syndromic SA.

Methods

Using buccal cell specimens from families of children with non‐syndromic SA, exomes of 28 child–parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child–father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced.

Results

Three children had heterozygous missense variants in ID1 (Inhibitor of DNA Binding 1), with CADD scores >20 (top 1% of deleterious variants in the genome); two children inherited the variant from their fathers and one from the child's mother. Rare missense variants were also detected in PDZD2 (PDZ Domain Containing 2; N = 1) and SPTBN5 (Spectrin Beta, Non‐erythrocytic 5; N = 2), two genes previously suggested to be associated with SA etiology. Examination of variants with autosomal recessive and X‐linked recessive inheritance identified five and two missense variants, respectively. Compound heterozygous variants were identified in several genes. In addition, 12 de novo variants were identified, all in different genes in different children.

Conclusions

To our knowledge, this is the first study reporting a possible association between ID1 and non‐syndromic SA. Although maternal pregestational diabetes has been strongly associated with SA, the missense variants in ID1 identified in two of three children were paternally inherited. These findings add to the knowledge of gene variants associated with non‐syndromic SA and provide data for future studies.
Bio‐analytically fluorimetric method for estimation of ertapenem in real human plasma and commercial samples; application to pharmacokinetics study
Authors: Salman Baher I. , Saraya Roshdy E.
Published: March 2022

Ertapenem (EPM) has been recently approved by the United States Food and Drug Administration (US‐FDA) as an antimicrobial drug. EPM has a broad spectrum of action against different bacterial strains and is most commonly prescribed in Egypt for the treatment of Klebsiella pneumonia. In this study, EPM was estimated using a sensitive and selective spectrofluorimetric method for human plasma and pharmaceutical vials. The measured fluorescence (at 540 nm) was obtained from reaction of EPM with 0.05% w/v benzofurazan (NBD‐Cl) using 0.1 M borate buffer pH 8.8 after excitation at 460 nm. The fluorometric linear range was stable from 10 to 350 ng ml−1. The lower limit of detection and the lower limit of quantitation were found to be 2.13 and 6.47 ng ml−1 respectively. Many factors such as pH, temperature, heating time, and NBD‐Cl concentration were optimized. The presented work was validated according to International Council for Harmonisation guidelines and bio‐analytically validated using FDA recommendations. The significant finding of this study, sensitivity, was successfully applied in Egypt for a pharmacokinetic application and commercial vials. Pharmacokinetic parameters were studied and the result, recorded as Cmax of EPM, was found to be 83.60 μg ml−1 after infusion of 0.5 g of Invanz® for 30 min. AUC0‐∞ was found to be 320 ± 30.2 μ.h ml−1.
A gadolinium‐based magnetic ionic liquid for supramolecular dispersive liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma
Authors: Abdallah Inas A. , Hammad Sherin F. , Bedair Alaa , Abdelaziz Mohamed A. , Danielson Neil D. , Elshafeey Ahmed H. , Mansour Fotouh R.
Published: March 2022

Favipiravir is a potential antiviral medication that has been recently licensed for Covid‐19 treatment. In this work, a gadolinium‐based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid–liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd‐magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd‐based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 105 ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.
Characteristics of anal canal cancer in Japan
Authors: Yamada Kazutaka , Saiki Yasumitsu , Komori Koji , Shiomi Akio , Ueno Masashi , Ito Masaaki , Hida Koya , Yamamoto Seiichiro , Shiozawa Manabu , Ishihara Soichiro , Kanemitsu Yukihide , Ueno Hideki , Kinjo Tatsuya , Maeda Kotaro , Kawamura Junichiro , Fujita Fumihiko , Takahashi Keiichi , Mizushima Tsunekazu , Shimada Yasuhiro , Sasaki Shin , Sunami Eiji , Ishida Fumio , Hirata Keiji , Ohnuma Shinobu , Funahashi Kimihiko , Watanabe Jun , Kinugasa Yusuke , Yamaguchi Shigeki , Hashiguchi Yojiro , Ikeda Masataka , Sudo Takeshi , Komatsu Yoshito , Koda Keiji , Sakamoto Kazuhiro , Okajima Masazumi , Ishida Hideyuki , Hisamatsu Yuichi , Masuda Taiki , Mori Shinichiro , Minami Kazuhito , Hasegawa Seiji , Endo Shungo , Iwashita Akinori , Hamada Madoka , Ajioka Yoichi , Usuku Koichiro , Ikeda Tokunori , Sugihara Kenichi
Published: March 2022

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.
Comparison of sampling methods for next generation sequencing for patients with lung cancer
Authors: Kunimasa Kei , Matsumoto Shingo , Nishino Kazumi , Honma Keiichiro , Maeda Noboru , Kuhara Hanako , Tamiya Motohiro , Inoue Takako , Kawamura Takahisa , Kimura Toru , Maniwa Tomohiro , Okami Jiro , Goto Koichi , Kumagai Toru
Published: March 2022

Introduction

Success of next generation sequencing (NGS) analysis is becoming indispensable in the treatment of advanced lung cancer. However, the advantages and disadvantages of each sampling method in the NGS analysis have not yet been clarified.

Methods

We compared the success rates of NGS analysis, and DNA and RNA yields for transbronchial biopsy (TBB), endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), computed tomography (CT)‐guided biopsy, fluid sample, and surgical biopsy for NGS analysis in patients through the lung cancer genomic screening project for individualized medicine (LC‐SCRUM)‐Asia, a nationwide NGS screening project. In case, sufficient samples could not be collected by TBB and EBUS‐TBNA, re‐biopsy (genome re‐biopsy) was performed.

Results

A total of 223 patients were enrolled and success rates of NGS analysis were not different between samples obtained through TBB, EBUS‐TBNA, and CT‐guided biopsy; however, success rates for fluid samples and surgical biopsy samples were significantly higher than those of other methods. The risk of genome re‐biopsy was higher with TBB for centrally located lesions. CT‐guided biopsy yielded more samples but had a lower success rate for analysis of RNA‐based NGS than TBB.

Conclusions

TBB is the mainstay of sampling methods, but for centrally located lesions, EBUS‐TBNA may be a better strategy. For CT‐guided biopsy, the success rate of RNA‐based NGS analysis is low. Fluid samples are expected to yield successful results as surgical biopsy samples, but the latter are better for sample preservation. Determining the optimal method for genome biopsy for each case is important.
Power‐VR: Interactive 3D virtual environment to increase motivation levels of powerlifters during training sessions
Authors: Gulec Ulas , Isler Ilkin Sevgi , Doganay Mehmet Harun , Gokcen Muruvet , Gozcu Mert Ali , Nazligul Merve Denizci
Published: March 2022

Motivation is one of the important factors that increase the success of athletes, especially who lift weights. It increases not only the success of the athletes but also influences other notions such as increasing self‐confidence, decreasing anxiety, and improving endurance. Although motivation has a key role in the performance of athletes, most of the athletes may be fully motivated only in competition environments. However, being motivated only in competition environments is not enough for athletes since they spend most of their time in training. If they are motivated in training environments as motivated as in competition environments, they can increase their performance, however, being motivated during training sessions is not easy since there are not enough motivational factors, such as spectators, in training environments. In order to solve this problem, this study aims to increase the motivation levels of powerlifters during training sessions by developing a virtual competition environment. In this environment, the athletes experience a virtual competition environment by using HTC Vive. To understand the efficiency of the virtual environment, it was tested with 32 professional athletes. The findings illustrated that using VR technology was beneficial to increase the level of motivation of powerlifters during training sessions.
Nephrotic syndrome associated with metastatic melanoma: a case report
Authors: Bienes Fabiana Almeida Antonio , de Brito Germana Alves , Alves Joubert Araujo , Baptista Aline Lourenco , Andrade Luis André Silvestre , Imanishe Marina Harume , Pereira Benedito Jorge
Published: March 2022

Nephrotic syndrome (NS) may occur after or concomitantly with malignancy. The use of immunosuppressive approaches in patients with cancer and NS is controversial, especially when the association between the pathologies is unclear. The aim of this study was to report the case of a patient with metastatic melanoma who developed NS and to examine the association between NS and neoplasia. A 56‐year‐old woman diagnosed with right hallux melanoma, removed by marginal resection with no sign of metastasis, developed NS after 6 months without the detection of another associated disease. The histological diagnosis was focal and segmental glomerulosclerosis (FSGS). The patient was older than most patients with FSGS and was treated with immunosuppressive agents (prednisone and cyclosporine) concomitantly with melanoma treatment. Nephrotic syndrome was the first manifestation of metastatic melanoma recurrence in this patient. Proteinuria was controlled adequately after immunosuppression and melanoma treatment. Although NS has been associated with cancer, laboratory and histological markers correlating it with melanoma are needed.
Production of Styrene from Dehydrogenation of Ethylbenzene
Authors: Gupta Rahul , Uslu Hasan , Majumder Subhajit
Published: March 2022

A pseudo‐homogeneous model based on intrinsic rate equations for dehydrogenation of ethylbenzene to styrene in an adiabatic fixed‐bed reactor is developed. Steam and ethylbenzene are the main reactants with styrene as the desired product, and benzene and toluene as by‐products. Styrene production is an endothermic reaction depends on various factors such as temperature, pressure, steam to ethylbenzene ratio, styrene to ethylbenzene ratio in feed. These factors affects the properties like styrene selectivity, ethylbenzene and by‐product conversion etc. The development of the mathematic model includes the application of mass balance, energy balance, and basic thermodynamic relations, momentum balance, Langmuir and Hinshelwood model, Ergun relation, etc. The effects of temperature as well as of the steam‐to‐ethylbenzene and styrene‐to‐ethylbenzene molar ratios in the feed on the selectivity for styrene, ethylbenzene conversion, and conversion to by‐products are also evaluated. The maximum selectivity for styrene can be achieved at increased steam‐to‐ethylbenzene feed ratio and a lower ethylbenzene conversion.
Near‐IR Intramolecular Charge Transfer in Strongly Interacting Diphenothiazene‐TCBD and Diphenothiazene‐DCNQ Push‐Pull Triads
Authors: Yadav Indresh S. , Jang Youngwoo , Rout Yogajivan , Thomas Michael B. , Misra Rajneesh , D'Souza Francis
Published: March 2022

Three types of phenothiazines dimers (PTZ‐PTZ, 1–3), covalently linked with one or two acetylene linkers, were synthesized by copper‐mediated Eglinton and Pd‐catalyzed Sonogashira coupling reactions in excellent yields. The dimers 1–3 were further engaged in [2+2] cycloaddition‐retroelectrocyclization reactions with strong electron acceptors, tetracyanoethylene (TCNE) and 7,7,8,8‐tetracyanoquinodimethane (TCNQ) to yield tetracyanobutadiene (TCBD, 1 a–3 a), and dicyanoquinodimethane (DCNQ, 1 b–3 b) functionalized donor‐acceptor (D‐A) conjugates, respectively. The conjugates were examined by a series of spectral, computational, and electrochemical studies. Strong ground state polarization leading to new optical transitions was witnessed in both series of D‐A conjugates. In the case of DCNQ derived D‐A system 1 b, the optical coverage extended until 1200 nm in benzonitrile, making this a rare class of D‐A ICT system. Multiple redox processes were witnessed in these D‐A systems, and the frontier orbitals generated on DFT optimized structures further supported the ICT phenomenon. Photochemical studies performed using femtosecond pump‐probe studies confirmed solvent polarity dependent excited state charge transfer and separation in these novel multi‐modular D‐A conjugates. The charge‐separated states lasted up to 70 ps in benzonitrile while in toluene slightly prolonged lifetime of up to 100 ps was witnessed. The significance of phenothiazine dimer in wide‐band optical capture all the way into the near‐IR region and promoting ultrafast photoinduced charge transfer in the D‐A‐D configured multi‐modular systems, and the effect of donor‐acceptor distance and the solvent polarity was the direct outcome of the present study.
Organic Base Enabled Nickel‐Catalyzed Mono‐α‐Arylation of Feedstock Solvents
Authors: MacMillan Joshua W. M. , McGuire Ryan T. , Stradiotto Mark
Published: March 2022

We report on our successful development of the first metal‐catalyzed mono‐α‐arylation of carbonyl compounds employing a soluble organic base. The scope of these Ni/DalPhos‐catalyzed transformations encompasses a range of (hetero)aryl halides (Cl, Br, I) and phenol‐derived electrophiles (sulfonates, carbonates, carbamates, sulfamates), including active pharmaceutical ingredients (chloroquine, clozapine), in combination with the typically problematic feedstock small molecule substrates acetone, dimethylacetamide, and for the first time with any metal catalyst/base, ethyl acetate.
Optimal knee osteoarthritis diagnosis using hybrid deep belief network based on Salp swarm optimization method
Authors: Balasubramanian Kishore , Kishore Ramya , Krishnamoorthy Gayathri Devi
Published: March 2022

Osteoarthritis (OA) damages the articular cartilage of the knee and is a severe degenerative joint condition. Currently, OA diagnosis is carried out by symptom analysis and progressive evaluation of the radiographs, although the method is subjective. This work presents a novel computer aided diagnostic system to diagnose the severity of the disease in its early stages. The proposed method comprises of stages that include image pre‐processing, extraction of features based on discrete wavelet decomposition, histogram, GLCM and texture features, and classification by stacked up‐RBM Deep Belief Networks (Hybrid DBN) finally. The performance of HDBN is improved by optimizing the hyper parameters with the Salp Swarm Optimization Algorithm (SSA). Experiments conducted on the Kaggle database consisting of 7503 images demonstrated an overall accuracy of 99.45% with 100% sensitivity and specificity. The impact on isolated and combined feature contributions is also analyzed using 10‐fold cross validation (CV). The robustness of the algorithm is tested on degraded images of salt‐pepper, Gaussian, and Poisson noise, which proved the effectiveness of the method. Comparison of the method proposed with similar techniques is done by employing different optimization algorithms and classifiers.
Virtual research environments co‐creation: The D4Science experience
Authors: Assante Massimiliano , Candela Leonardo , Castelli Donatella , Cirillo Roberto , Coro Gianpaolo , Dell'Amico Andrea , Frosini Luca , Lelii Lucio , Lettere Marco , Mangiacrapa Francesco , Pagano Pasquale , Panichi Giancarlo , Piccioli Tommaso , Sinibaldi Fabio
Published: March 2022

Virtual research environments are systems called to serve the needs of their designated communities of practice. Every community of practice is a group of people dynamically aggregated by the willingness to collaborate to address a given research question. The virtual research environment provides its users with seamless access to the resources of interest (namely, data and services) no matter what and where they are. Developing a virtual research environment thus to guarantee its uptake from the community of practice is a challenging task. In this article, we advocate how the co‐creation driven approach promoted by D4Science has proven to be effective. In particular, we present the co‐creation options supported, discuss how diverse communities of practice have exploited these options, and give some usage indicators on the created VREs.
Leveraging Real‐World Data for EMA Qualification of a Model‐Based Biomarker Tool to Optimize Type‐1 Diabetes Prevention Studies
Authors: Podichetty Jagdeep T. , Lang Patrick , O’Doherty Inish M. , David Sarah E. , Muse Rhoda N. , Karpen Stephen R. , Song Laura Sue , Romero Klaus , Burton Jackson K. ,   the Type‐1 Diabetes Consortium (T1DC)
Published: March 2022

The development of therapies to prevent or delay the onset of type 1 diabetes (T1D) remains challenging, and there is a lack of qualified biomarkers to identify individuals at risk of developing T1D or to quantify the time‐varying risk of conversion to a diagnosis of T1D. To address this drug development need, the T1D Consortium (i) acquired, remapped, integrated, and curated existing patient‐level data from relevant observational studies, and (ii) used a model‐based approach to evaluate the utility of islet autoantibodies (AAs) against insulin/proinsulin autoantibody, GAD65, IA‐2, and ZnT8 as biomarkers to enrich subjects for T1D prevention. The aggregated dataset was used to construct an accelerated failure time model for predicting T1D diagnosis. The model quantifies presence of islet AA permutations as statistically significant predictors of the time‐varying probability of conversion to a diagnosis of T1D. Additional sources of variability that greatly improved the accuracy of quantifying the time‐varying probability of conversion to a T1D diagnosis included baseline age, sex, blood glucose measurements from the 120‐minute timepoints of oral glucose tolerance tests, and hemoglobin A1c. The developed models represented the underlying evidence to qualify islet AAs as enrichment biomarkers through the qualification of novel methodologies for drug development pathway at the European Medicines Agency (EMA). Additionally, the models are intended as the foundation of a fully functioning end‐user tool that will allow sponsors to optimize enrichment criteria for clinical trials in T1D prevention studies.
Gel‐Based and Gel‐Free Phosphoproteomics to Measure and Characterize Mitochondrial Phosphoproteins
Authors: Thongboonkerd Visith , Chaiyarit Sakdithep
Published: March 2022

The mitochondrion is a key intracellular organelle regulating metabolic processes, oxidative stress, energy production, calcium homeostasis, and cell survival. Protein phosphorylation plays an important role in regulating mitochondrial functions and cellular signaling pathways. Dysregulation of protein phosphorylation status can cause protein malfunction and abnormal signal transduction, leading to organ dysfunction and disease. Investigating the mitochondrial phosphoproteins is therefore crucial to better understand the molecular and pathogenic mechanisms of many metabolic disorders. Conventional analyses of phosphoproteins, for instance, via western blotting, can be done only for proteins for which specific antibodies to their phosphorylated forms are available. Moreover, such an approach is not suitable for large‐scale study of phosphoproteins. Currently, proteomics represents an important tool for large‐scale analysis of proteins and their post‐translational modifications, including phosphorylation. Here, we provide step‐by‐step protocols for the proteomics analysis of mitochondrial phosphoproteins (the phosphoproteome), using renal tubular cells as an example. These protocols include methods to effectively isolate mitochondria and to validate the efficacy of mitochondrial enrichment as well as its purity. We also provide detailed protocols for performing both gel‐based and gel‐free phosphoproteome analyses. The gel‐based analysis involves two‐dimensional gel electrophoresis and phosphoprotein‐specific staining, followed by protein identification via mass spectrometry, whereas the gel‐free approach is based on in‐solution mass spectrometric identification of specific phosphorylation sites and residues. In all, these approaches allow large‐scale analyses of mitochondrial phosphoproteins that can be applied to other cells and tissues of interest. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Mitochondrial isolation/purification from renal tubular cells

Support Protocol: Validation of enrichment efficacy and purity of mitochondrial isolation

Basic Protocol 2: Gel‐based phosphoproteome analysis

Basic Protocol 3: Gel‐free phosphoproteome analysis
Unraveling the Role of Nitrogen‐Doped Carbon Nanowires Incorporated with MnO2 Nanosheets as High Performance Cathode for Zinc‐Ion Batteries
Authors: Li Xiaohui , Zhou Qiancheng , Yang Ze , Zhou Xing , Qiu Dan , Qiu Huajun , Huang Xintang , Yu Ying
Published: March 2022

Manganese‐based cathode materials are considered as a promising candidate for rechargeable aqueous zinc‐ion batteries (ZIBs). Suffering from poor conductive and limited structure tolerance, various carbon matrix, especially N‐doped carbon, were employed to incorporate with MnO2 for greatly promoted electrochemical performances. However, the related underlying mechanism is still unknown, which is unfavorable to guide the design of high performance electrode. Herein, by incorporating layered MnO2 with N‐doped carbon nanowires, a free‐standing cathode with hierarchical core‐shell structure (denoted as MnO2@NC) is prepared. Benefiting from the N‐doped carbon and rational architecture, the MnO2@NC electrode shows an enhanced specific capacity (325 mAh g−1 at 0.1 A g−1) and rate performance (90 mAh g−1 at 2 A g−1), as well as improved cycling stability. Furthermore, the performance improvement mechanism of MnO2 incorporated by N‐doped carbon is investigated by X‐ray photoelectron spectroscopy (XPS), Raman spectrums and density functional theory (DFT) calculation. The N atom elongates the Mn‐O bond and reduces the valence of Mn4+ ion in MnO2 crystal by delocalizing its electron clouds. Thus, the electrostatic repulsion will be weakened when Zn2+/H+ insert into the host MnO2 lattices, which is profitable to more cation insertion and faster ion transfer kinetics for higher capacity and rate capability. This work elucidates a fundamental understanding of the functions of N‐doped carbon in composite materials and shed light on a practical pathway to optimize other electrode materials.
Association of chronic heart failure with mortality in old intensive care patients suffering from Covid‐19
Authors: Bruno Raphael Romano , Wernly Bernhard , Wolff Georg , Fjølner Jesper , Artigas Antonio , Bollen Pinto Bernardo , Schefold Joerg C. , Kindgen‐Milles Detlef , Baldia Philipp Heinrich , Kelm Malte , Beil Michael , Sviri Sigal , van Heerden Peter Vernon , Szczeklik Wojciech , Topeli Arzu , Elhadi Muhammed , Joannidis Michael , Oeyen Sandra , Kondili Eumorfia , Marsh Brian , Andersen Finn H. , Moreno Rui , Leaver Susannah , Boumendil Ariane , De Lange Dylan W. , Guidet Bertrand , Flaatten Hans , Jung Christian ,   COVIP study group
Published: March 2022

Aims

Chronic heart failure (CHF) is a major risk factor for mortality in coronavirus disease 2019 (COVID‐19). This prospective international multicentre study investigates the role of pre‐existing CHF on clinical outcomes of critically ill old (≥70 years) intensive care patients with COVID‐19.

Methods and results

Patients with pre‐existing CHF were subclassified as having ischaemic or non‐ischaemic cardiac disease; patients with a documented ejection fraction (EF) were subclassified according to heart failure EF: reduced (HFrEF, n = 132), mild (HFmrEF, n = 91), or preserved (HFpEF, n = 103). Associations of heart failure characteristics with the 30 day mortality were analysed in univariate and multivariate logistic regression analyses. Pre‐existing CHF was reported in 566 of 3917 patients (14%). Patients with CHF were older, frailer, and had significantly higher SOFA scores on admission. CHF patients showed significantly higher crude 30 day mortality [60% vs. 48%, P < 0.001; odds ratio 1.87, 95% confidence interval (CI) 1.5–2.3] and 3 month mortality (69% vs. 56%, P < 0.001). After multivariate adjustment for confounders (SOFA, age, sex, and frailty), no independent association of CHF with mortality remained [adjusted odds ratio (aOR) 1.2, 95% CI 0.5–1.5; P = 0.137]. More patients suffered from pre‐existing ischaemic than from non‐ischaemic disease [233 vs. 328 patients (n = 5 unknown aetiology)]. There were no differences in baseline characteristics between ischaemic and non‐ischaemic disease or between HFrEF, HFmrEF, and HFpEF. Crude 30 day mortality was significantly higher in HFrEF compared with HFpEF (64% vs. 48%, P = 0.042). EF as a continuous variable was not independently associated with 30 day mortality (aOR 0.98, 95% CI 0.9–1.0; P = 0.128).

Conclusions

In critically ill older COVID‐19 patients, pre‐existing CHF was not independently associated with 30 day mortality.

Trial registration number: NCT04321265.
Oxidation‐resistant Cu‐based metallisation for Si solar cells
Authors: Son Hyung Jin , Hong Kuen Kee , Ju Byeong‐Kwon , Kim Sung Hyun
Published: March 2022

Herein, the oxidation resistance effect of B on the high‐temperature sintering of Cu‐based metallisation for crystalline Si solar cells is described. Atmospheric sintering of B‐containing Cu–Ag core‐shell paste printed on a Si wafer is performed at high temperatures (up to 800°C). The oxidation of Cu is effectively prevented by B, affording a brown bulky Cu–Ag film with low electrical resistivity (order of 10−6 Ω cm). The Cu–Ag film formation is monitored via microscopic and crystallographic analyses. The Cu–Ag film exhibits increased electrical conductivity with increasing B content from 0 to 5 wt.%. X‐ray photoelectron spectroscopy data reveal that the B2O3 formed on the Cu–Ag film surface prevents external oxygen diffusion into the bulk. The developed paste is applied to a crystalline Si solar cell, affording a maximum efficiency of 17.55%. These results show the practical applicability of Cu‐based electrodes in the solar cell industry.
Enhanced social network search algorithm with powerful exploitation strategy for PV parameters estimation
Authors: Shaheen A. M. , Elsayed A. M. , Ginidi A. R. , El‐Sehiemy R. A. , Elattar E.
Published: March 2022

In this paper, an enhanced social network search algorithm (ESNSA) has been proposed to model the solar photovoltaic (PV) modules accurately and efficiently. The proposed algorithm is introduced to minimize the least root‐mean‐square error (RMSE) between the calculated and experimental data for the single, double, and triple diode models of Kyocera KC200GT, STM6(40/36), and Photowatt‐PWP201 modules. The original SNSA was inspired by users on social networks and their many moods, including imitation, conversation, disputation, and innovation mood. Two strategies are presented for the ESNSA. The first strategy is the powerful exploitation strategy (PES), which is intended to increase the SNSA's performance by boosting searching around the best view of all users. The second strategy is to suggest an adaptable parameter to aid in the exploitation of iterations in the end. Diverse comparisons and statistical analyses for validation purposes are carried out for mono‐crystalline STM6(40/36), multicrystalline KC200GT, and polycrystalline photowatt‐PWP201 modules. The comparative studies and statistical measures show the consistency and accurateness of the proposed ESNSA. As a numerical application, for the mono‐crystalline STM6(40/36) PV module, the proposed ESNSA achieves the least RMSE of 1.751631E−3, 1.769953E−3, and 1.696504E−3, respectively for the three models. Also, it shows high robustness compared to the original SNSA as it acquires the least standard errors for the three models of 2.56E−18, 1.76E−6, and 1.24E−5, respectively. Moreover, the proposed ESNSA provides a higher convergence speed where it is approximately reached to the least RMSE in less than 60%, 50%, and 60% of the iterations for the three models, respectively. Nevertheless, the proposed ESNSA provides better performance than miscellaneous published approaches in minimizing the RMSE, with high robust indices.
Mechanical integrity of tubing string in high‐temperature and high‐pressure ultra‐deep gas wells based on uncertainty theory
Authors: Zhang Zhi , Ding Jian , Zheng Yushan , Sang Pengfei , Chen Lili , Fan Yu , Li Yufei
Published: March 2022

During the manufacturing process of tubing and casing, manufacturing deviations can occur in quality parameters, such as yield strength, outer diameter, and wall thickness, which can lead to uncertainty in the actual strength of the tubing string. Specifically, tubing string failures periodically occur in high‐temperature, high‐pressure, and ultra‐deep gas wells owing to the uncertainty in string strength, attenuation of high‐temperature material properties, and influence of complex load fluctuations. Therefore, in this study, Monte Carlo method is adopted to simulate the local fluctuation of downhole actual load, and the load variation rule of tubing string in high‐temperature and high‐pressure ultra‐deep well is obtained. By considering the effect of manufacturing tolerance and corrosion, variation law of string strength is obtained. Additionally, the influence of load, temperature, manufacturing tolerance, and other uncertainties on the strength and stress of the tubing string is analyzed, and a quantitative evaluation method for the mechanical integrity of the tubing string is established. The calculation results show that the uncertainty of complex loads and influence of high temperature increase the failure probability of the mechanical integrity of tubing string. Furthermore, a failure risk can potentially exist under conditions wherein conventional verification results denote no failure. It is determined via sensitivity analysis that temperature, corrosion rate, and steel grade are the main factors for the failure of the tubing string mechanical integrity. By considering the influence of high temperature, the failure probability of the tubing string is increased by 25.33% when compared to the original basis. However, considering the manufacturing tolerance of tubing string, the actual yield strength of tubing string is higher than the nominal yield strength, which reduces the failure probability of the tubing string. This implies that reduction of the subjective influence in the risk assessment process can lead to precise and quantitative analysis of the failure risk of the tubing string mechanical integrity and optimization of the structure of the tubing string in high‐temperature, high‐pressure, and ultra‐deep gas wells.
Learning‐based deep neural network inference task offloading in multi‐device and multi‐server collaborative edge computing
Authors: Cui Enfang , Yang Dong , Wang Hongchao , Zhang Weiting
Published: March 2022

Deep neural network (DNN) inference task offloading is an essential problem of edge intelligence, which faces the challenges of limited computing resources shortage of edge devices and the dynamics of edge networks. In this article, the DNN inference task offloading problem in queue‐based multi‐device and multi‐server collaborative edge computing is investigated. To support efficient collaborative inference, we formulate a multi‐objective optimization problem that minimizes the average delay and maximizes average inference accuracy. Due to time‐varying queue load states and random task arrival, it is challenging to solve this optimization problem. Thus, a deep reinforcement learning based task offloading algorithm, named LSTM‐TD3, is proposed to solve the formulated problem. Specifically, LSTM‐TD3 incorporates the long short‐term memory (LSTM) and twin delayed deep deterministic policy gradient algorithm (TD3), and can leverage long‐term environment information to efficiently explore the optimal task offloading solution. Finally, we compared the performance of LSTM‐TD3 with TD3 (without LSTM) and random offloading algorithms, and simulation results show the LSTM‐TD3 reduce the average inference delay by up to , and the accuracy is better than other algorithms.
Ultrasonic‐assisted extraction of bioactive chlorogenic acid from heilong48 soybean variety: Parametric optimization and evaluation of physicochemical and bioactive properties
Authors: Akpabli‐Tsigbe Nelson Dzidzorgbe Kwaku , Ma Yongkun , Ekumah John‐Nelson , Osabutey Juliet , Hu Jie , Xu Manqing , Johnson Nana Adwoa Nkuma , Mintah Benjamin Kumah
Published: March 2022

Chlorogenic acid (CA), especially that found in soybeans, is a rich bioactive compound but has received very little attention in research settings in past decades. Ultrasonic‐assisted extraction (UAE) could be an efficient method to increase CA release from soybeans. Hence, this study aimed to optimize UAE parameters for CA extraction from heilong48 soybean (HS) variety and evaluate the physicochemical and bioactive properties of the soybean. Optimization of ultrasound parameters with a Box–Behnken design found a frequency of 20.0 kHz, a power density of 30.0 W/L), a temperature of 37.9°C, and a time of 28.0 min to be the best conditions, which gave a CA yield of 5.007 ± 0.033 mg/g and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity of 93.197 ± 0.213 μmol of AA eq/g dry sample; these were higher than those of a non–ultrasound‐treated (raw) HS sample (CA yield of 1.627 ± 0.528 mg/g and DPPH radical scavenging activity of 10.760 ± 0.207 μmol of AA eq/g dry sample). A satisfactory model was obtained. Scanning electron microscopy results confirmed the structural changes of the HS variety caused by the optimized UAE parameters. High total polyphenol contents (TPCs; 4.726 ± 0.002 mg GAE/g) and total phenolic acids (1.883 ± 0.005 mg GAE/g) and low total flavonoid contents (0.040 ± 0.008 mg RE/g) were obtained. A positive linear correlation between antioxidant activity and TPC was established. A protein–phenolic interaction in the HS variety was observed. The results established that polyphenols should be considered a significant component of the HS variety. Likewise, the HS variety could be used for CA extraction.