bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of ABCC2 Haplotypes to Mycophenolic Acid Pharmacokinetics in Stable Kidney Transplant Recipients
Authors: Brazeau Daniel , Meaney Calvin J. , Consiglio Joseph D. , Wilding Gregory E. , Cooper Louise M. , Venuto Rocco C. , Tornatore Kathleen M.
Published: June 2021

Mycophenolic acid exhibits significant interpatient pharmacokinetic variability attributed to factors including race, sex, concurrent medications, and enterohepatic circulation of the mycophenolic acid glucuronide metabolite to mycophenolic acid. This conversion by enterohepatic circulation is mediated by the multidrug resistance‐associated protein 2, encoded by ABCC2. This study investigated ABCC2 haplotype associations with mycophenolic acid pharmacokinetics in 147 stable kidney transplant recipients receiving mycophenolic acid in combination with calcineurin inhibitors. The role of the ABCC2 genotypes ‐24C>T (rs717620), 1249C>T (rs2273697), and 3972C>T (rs3740066) were evaluated in prospective, cross‐sectional pharmacokinetic studies of stable recipients receiving mycophenolic acid and either tacrolimus or cyclosporine. Haplotype phenotypic associations with mycophenolic acid pharmacokinetic parameters were computed using THESIAS (v. 3.1). Four ABCC2 haplotypes with estimated frequencies greater than 10% were identified (H1:CGC [wild type], H9:CGT, H2:CAC, H12:TGT). There were no differences in haplotype frequencies by either race or sex. There were significant associations of pharmacokinetic parameters with ABCC2 haplotypes for mycophenolic acid clearance (L/h), mycophenolic acid AUC0‐12h (mg·h/L), and the ratio of mycophenolic acid glucuronide to mycophenolic acid AUC0‐12h. The wild‐type haplotype ABCC2 CGC had greater mycophenolic acid AUC0‐12h (P = .017), slower clearance (P = .013), and lower mycophenolic acid glucuronide to mycophenolic acid AUC0‐12h ratio (P = .047) compared with the reduced function ABCC2 haplotype CGT. These differences were most pronounced among patients receiving tacrolimus cotreatment. No phenotypic associations were found with the cyclosporine‐mycophenolic acid regimen. Variation in ABCC2 haplotypes contributes to subtherapeutic mycophenolic acid exposure and influences interpatient variability in pharmacokinetic phenotypes based on concurrent calcineurin inhibitor treatment.
Synthesis and bioactivity evaluation of eugenol hybrids obtained by Mannich and 1,3 dipolar cycloaddition reactions
Authors: Buduma Komuraiah , Kumar A Niranjana , Srinivas KVN Satya , Kumar J Kotesh , Chinde Srinivas , Domatti Anand Kumar , Kumar Yogesh , Grover Paramjit , Tiwari Ashok , Khan Feroz
Published: June 2021

Design, synthesis, and bioactivity evaluation of novel mannich bases (2a‐2j) and triazole‐chalcone derivatives (7a‐7k) of Eugenol 1 were reported. Among all the derivatives tested for antiproliferative activity, di‐amine manich derivative 2b (32.92 μM), and 4‐methoxy chalcone triazole derivative 7d (33.05 μM) significantly inhibited HepG2 cell lines when compared to the standard doxorubicin (37.29 μM). Whereas most of the compounds such as diethylamine 2a (17.75 μM), (aminomethyl) methane diamine 2b (17.02 μM), and bis (chloromethyl) amine 2c (20.12 μM) showed moderate to better inhibition towards MCF‐7 cell lines. The synthesized analogues were also tested for antidiabetic and antiobesity potentials. Compounds 2f (55.50%), 2c (54.34%), 7g (55.5%), and 2a (55.5%) have shown moderate inhibitory potentials toward intestinal α‐glucosidase enzyme when compared to the standard Acarbose (72.86%). Likewise, compounds 7d (82.95%), 7f (76.19%), 7g (74.81%), 7e (74.81%), and 2g (72.50%) have shown significant to moderate inhibitory potentials toward Pancreatic lipase enzyme when compared to the standard orlistat (91.10%). ROS induces life‐threatening diseases like diabetes, cancer, etc., and antioxidants play a major role in controlling their production. Compounds 2c (99.81%), 2i (99.80%), 2d (99.26%), 2g (98.79%), and 2f (98.42%) have shown significant antioxidant profiles in ABTS assay when compared to the standard Trolox (99.07%). Further, In silico Molecular docking and pharmacokinetic screening of the eugenol derivatives complemented the in vitro results indicating the drug likeness of the obtained active compounds.
Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID‐19: A case study
Authors: Karakaş Çelik Sevim , Çakmak Genç Güneş , Pişkin Nihal , Açikgöz Bilgehan , Altinsoy Bülent , Kurucu İşsiz Başak , Dursun Ahmet
Published: June 2021

Coronavirus disease 2019 (COVID‐19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Angiotensin‐converting enzyme (ACE2) has been recognized as the specific receptor of the SARS‐CoV‐2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS‐CoV‐2 susceptibility and COVID‐19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID‐19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR‐based restriction fragment length polymorphism methods, respectively, in 155 COVID‐19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID‐19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID‐19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID‐19 severity. Interindividual differences in COVID‐19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID‐19 pathogenesis such as pro‐inflammatory cytokines and coagulation indicators.
A systematic review of the malnutrition prevalence in hospitalized hip fracture patients and its associated outcomes
Authors: Foo Melody Xuan En , Wong Gabriel Jun Yung , Lew Charles Chin Han
Published: June 2021

Background

Malnutrition is associated with poorer outcomes in hospitalized patients. However, in hip fracture patients, the associations between malnutrition and poorer outcomes are unclear because of the use of nonestablished nutrition assessment tools in previous studies that may have some degree of misclassification bias. Therefore, this review aims to determine (1) the prevalence of malnutrition diagnosed in hospitalized hip fracture patients using established nutrition assessment tools and (2) the outcomes associated with malnutrition given some of the nonestablished nutrition assessment tools used in previous studies.

Methods

Four electronic databases were used. Studies that used established nutrition assessment tools to diagnose malnutrition in hip fracture patients within 48 h of hospital admission were included.

Results

Nine studies were included (n = 1665). Patients’ mean age ranged from 79.9 to 86.1 years. Eight studies reported the frequencies of each sex, and for females, it ranged from 70% to 81.8%. The prevalence of malnutrition was 4.0% to 39.4%. Malnutrition was independently associated with (1) increased mortality and (2) functional dependence. There was also a trend towards more supported living arrangements and impaired mobility in the longer term. Malnutrition was not associated with (1) hospital length of stay, (2) hospital readmissions, and (3) incidence of complications.

Conclusion

The prevalence of malnutrition in hip fracture patients is highly variable and is associated with poorer outcomes. Therefore, identifying malnourished hip fracture patients using established nutrition assessment tools is important, and adequate resources can be allocated to prevent malnutrition through early screening and intervention.
Prospective evaluation of the family's health‐related quality of life in pediatric intestinal failure
Authors: Neam Victoria C. , Faino Anna , O'Hara Michael , Wendel Danielle , Horslen Simon P. , Javid Patrick J.
Published: June 2021

Background

Due to altered nutrition regimens and complex medical needs, pediatric intestinal failure (IF) may have a powerful impact on health‐related quality of life (HRQOL). Studies have shown that children with IF experience lower HRQOL. Data on the HRQOL of families of children with IF are lacking.

Methods

We performed a prospective analysis of the HRQOL of families of children with IF in a regional intestinal rehabilitation program from 2011 to 2018. The Pediatric Quality of Life Family Impact Module (FIM) was administered annually to parents. FIM scores were regressed on risk factors using linear mixed‐effect models that accounted for repeated surveys within families.

Results

A total of 117 families completed 272 surveys. FIM scores increased with patient age across nearly all survey dimensions. Total FIM scores were lower when compared to families of healthy children (median differences = –5, P = .01) and similar to families of chronically ill children. While IF families reported major deficits in the Communication (–11, P < .001) and Worry (–17, P < .001) dimensions, they also reported higher Family Relationship scores (+7, P < .01). On multivariable regression, presence of a major comorbidity and four or more hospital admissions in the prior year were associated with lower family HRQOL (P < .05). Parenteral nutrition dependence was independently associated with lower scores in the Communication (–7, P = .03) and Daily Activities (–10, P = .02) dimensions.

Conclusion

Families of children with IF experience a decreased HRQOL that may improve with patient age. Intestinal rehabilitation programs should address the HRQOL of families in addition to patients.
Hypoglycemic peptide‐enriched hydrolysates of Corbicula fluminea and Chlorella sorokiniana possess synergistic hypoglycemic activity through inhibiting α‐glucosidase and dipeptidyl peptidase‐4 activity
Authors: Huang Tse‐Hung , Liu Pi‐Yu , Lin Yu‐Ling , Tsai Jenn‐Shou
Published: June 2021

BACKGROUND

The prevalence of diabetes mellitus worldwide has increased in recent decades. Maintaining the level of blood glucose is the most basic and important issue for diabetics. This study aimed to investigate the hypoglycemic activity of a combination of hypoglycemic peptide‐enriched hydrolysates of Corbicula fluminea (ACH) and Chlorella sorokiniana (PCH).

RESULTS

Combined supplementation of ACH and PCH synergistically inhibited α‐glucosidase and DPP4 activities in vitro. After 4 weeks of treatment with ACH and/or PCH, the plasma glucose concentration and insulin, homeostasis model assessment‐estimated insulin resistance (HOMA‐IR), total cholesterol (TC) and triglyceride (TG) levels significantly decreased. The hypoglycemic peptides in ACH and PCH were purified and assayed for α‐glucosidase and DPP4 activity. The hypoglycemic peptides in ACH and PCH effectively decreased α‐glucosidase and DPP4 activities. In silico assays showed that these two peptide types have different docking poses, which determined their inhibitory effect against α‐glucosidase and DPP4 activity.

CONCLUSION

Combined treatment with hypoglycemic peptide‐enriched ACH and PCH could modulate blood glucose by synergistically inhibiting α‐glucosidase and DPP4 activities. © 2021 Society of Chemical Industry.
Effect of using an infiltration hole and mulching in fish‐scale pits on soil water, nitrogen, and organic matter contents: Evidence from a 4‐year field experiment
Authors: Wang Ke , Zhang Xiaoyuan , Li Gaoliang , Ma Jiangbo , Zhang Suiqi , Zheng Jiyong
Published: June 2021

Soil water, nitrogen, and organic matter contents are among the main limiting factors for successful vegetation restoration on degraded slopes in arid and semi‐arid areas. Combining slope engineering measures for revegetation is considered an effective eco‐rehabilitation practice used to restore degraded slopes. However, a single slope measure is insufficient to efficiently utilize runoff and sediments to improve soil water, nitrogen, and organic matter for revegetation. In this study, four treatments were implemented on a hilly slope in a temperate continental semiarid area slope engineered with fish‐scale pits (semicircle‐shaped pit, 1.0 m in diameter, 0.5 m in radius, and 0.2 m deep), namely: with gravel mulching (GM), straw mulching (SM), infiltration hole (IH), and without other measures (CK). The effects of the combined measures on soil water, nitrogen, and organic matter contents were analyzed over 4 years. The results showed that the soil water storage (0–100 cm) showed no significant differences among all treatments; however, the soil (100–260 cm) of GM/SM/IH treatment increased by 11.65%/8.62%/7.10% compared with CK (p < 0.05). The soil organic matter and nitrogen (0–100 cm) under IH were 73.34%/81.29%/98.32% and 77.37%/80.27%/85.31% higher than CK/SM/GM, respectively (p < 0.05). Overall, IH is the most effective measure for increasing nitrogen and organic matter, and it is equally effective with GM and SM to increase the water replenishment of deep soils in semiarid areas. Our findings provide the combined measures to combat soil water, nitrogen, and organic matter deficits for slope revegetation in arid and semiarid areas.
Nexus between corporate social responsibility and earnings management: Sustainable or opportunistic
Authors: Ehsan Sadaf , Tariq Adeel , Nazir Mian Sajid , Shabbir Malik Shahzad , Shabbir Rizwan , Lopez Lydia Bares , Ullah Wasim
Published: June 2021

This study examines the association between corporate social responsibility (CSR) and earnings management (EM) among manufacturing firms from a developing economy, Pakistan. To deal with the CSR measurement and data bias, a multimethod approach has applied to measure CSR (both qualitative and quantitative approaches). This research has also established CSR disclosure indices and CSR monetary spending ratio (CSR MSR). Moreover, this research examines both types of EM (accrual‐based as well as real activities‐based) and used annual data set from 2009 to 2018 for 160 nonfinancial firms. For empirical analysis, the two‐stage least square (2SLS) and pooled ordinary least square (POLS) regressions are used. This study finds a negative relationship between CSR and EM, and it supports the notion that firms' commitment to CSR is largely driven by long‐term perspective. However, with respect to each measure of EM and CSR, this relationship is asymmetric.
The Hill event examines increasing mental health, SUD issues amid COVID‐19
Authors: Canady Valerie A.
Published: June 2021

For every suicide in this country, there are at least 29 attempts. Heroin addiction and overdose deaths have been on the rise since the pandemic began, which is not a coincidence, given that many people are using drugs as a way of self‐medicating to mask mental health issues. These observations by the co‐chair of the Mental Health Caucus and its Suicide Prevention Task Force were heard during a livestreamed event last week led by The Hill and sponsored by The Hartford.
NP Navigator: A New Look at the Natural Product Chemical Space
Authors: Zabolotna Yuliana , Ertl Peter , Horvath Dragos , Bonachera Fanny , Marcou Gilles , Varnek Alexandre
Published: June 2021

Natural products (NPs), being evolutionary selected over millions of years to bind to biological macromolecules, remained an important source of inspiration for medicinal chemists even after the advent of efficient drug discovery technologies such as combinatorial chemistry and high‐throughput screening. Thus, there is a strong demand for efficient and user‐friendly computational tools that allow to analyze large libraries of NPs. In this context, we introduce NP Navigator – a freely available intuitive online tool for visualization and navigation through the chemical space of NPs and NP‐like molecules. It is based on the hierarchical ensemble of generative topographic maps, featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. NP Navigator allows to efficiently analyze different aspects of NPs ‐ chemotype distribution, physicochemical properties, biological activity and commercial availability of NPs. The latter concerns not only purchasable NPs but also their close analogs that can be considered as synthetic mimetics of NPs or pseudo‐NPs.
Integral representation formulae for the solution of a wave equation with time‐dependent damping and mass in the scale‐invariant case
Authors: Palmieri Alessandro
Published: June 2021

This paper is devoted to deriving integral representation formulae for the solution of an inhomogeneous linear wave equation with time‐dependent damping and mass terms that are scale invariant with respect to the so‐called hyperbolic scaling. Yagdjian's integral transform approach is employed for this purpose. The main step in our argument consists in determining the kernel functions for the different integral terms, which are related to the source term and to initial data. We will start with the one‐dimensional case (in space). We point out that we may not apply in a straightforward way Duhamel's principle to deal with the source term since the coefficients of lower order terms make our model not invariant by time translation. On the contrary, we shall begin with the representation formula for the inhomogeneous equation with vanishing data by using a revised Duhamel's principle. Then, we will derive the representation of the solution in the homogeneous case with nontrivial data. After deriving the formula in the one‐dimensional case, the classical approach by spherical means is used in order to deal with the odd‐dimensional case. Finally, using the method of descent, the representation formula in the even‐dimensional case is proved.
Fast tracking of polarization impairments using DSP algorithms in fiber for a coherent optical communication system
Authors: Cui Nan , Zhang Xiaoguang
Published: June 2021

In a 100G coherent optical fiber communication system, the equalization algorithm of polarization effects in fibers is generally integrated in digital signal processing (DSP) using a multiple input/multiple output (MIMO) equalizer to overcome the impairment due to the polarization effects in fiber. However, it was found in some extreme scenarios, such as the lightning strikes near the fiber cables, the Kerr effect and Faraday effect would induce very fast time‐varying state‐of‐polarization (SOP) and transient variation of principal‐state‐of‐polarization (PSP) of polarization mode dispersion (PMD) which would result in the coherent receivers unlocking. Faced with the difficulty, we propose a 3‐parameter RSOP model and design a window‐split structured Kalman filter equalization scheme instead of conventional MIMO equalizer to cope with this extreme scenario of large PMD combined with ultra‐fast rotation of SOP in presence of residual chromatic dispersion (RCD). The proposed equalization method has an excellent performance and can cope with RCD in the range of ±820 ps/nm under RSOP from 100 krad/s to 3 Mrad/s and DGD = 200 ps.
A direct Jacobian total Lagrangian explicit dynamics finite element algorithm for real‐time simulation of hyperelastic materials
Authors: Zhang Jinao
Published: June 2021

This article presents a novel direct Jacobian total Lagrangian explicit dynamics (DJ‐TLED) finite element algorithm for real‐time nonlinear mechanics simulation. The nodal force contributions are expressed using only the Jacobian operator, instead of the deformation gradient tensor and finite deformation tensor, for fewer computational operations at run‐time. Owing to this proposed Jacobian formulation, novel expressions are developed for strain invariants and constant components, which are also based on the Jacobian operator. Results show that the proposed DJ‐TLED consumed between 0.70× and 0.88× CPU solution times compared to state‐of‐the‐art TLED and achieved up to 121.72× and 94.26× speed improvements in tetrahedral and hexahedral meshes, respectively, using GPU acceleration. Compared to TLED, the most notable difference is that the notions of stress and strain are not explicitly visible in the proposed DJ‐TLED but embedded implicitly in the formulation of nodal forces. Such a force formulation can be beneficial for fast deformation computation and can be particularly useful if the displacement field is of primary interest, which is demonstrated using a neurosurgical simulation of brain deformations for image‐guided neurosurgery. The present work contributes towards a comprehensive DJ‐TLED algorithm concerning isotropic and anisotropic hyperelastic constitutive models and GPU implementation.
Application of solubility parameters in the preparation of PMMA with permanent antistatic, high toughness, and excellent optical properties
Authors: Chen Si , Xu Changbo , Ma Meng , Shi Yanqin , He Huiwen , Yuan Kaiyun , Xu Ruqing , Wang Xu
Published: June 2021

In this paper, a novel kind of PMMA copolymer, P(MMA‐co‐MAA‐co‐SPMA), with permanently antistatic, high toughness, and high transparent properties, was synthesized via radical copolymerization. Herein, we selected the appropriate compatibilizer α‐methacrylic acid (MAA) and release agent (lauryldiethanolamine) through the calculation of solubility parameters for industrial mass production. What is more, the polymer's molecular weight was increased by improving the polymer's synthesis process. The structure and properties of the obtained copolymer were characterized. With 0.6 wt% of the 3‐sulfopropyl methacrylate potassium salt (SPMA), the copolymer exhibits nearly unchanged transparency with neat PMMA, and its unnotched impact strength reaches 16 kJ/m2. The surface resistance of the copolymer could be reduced to 1010 Ω, which could be considered as antistatic materials. Finally, the antistatic mechanism was analyzed. The main reason is that the hydrophilic group absorbs water to form a conductive layer on the surface, and 3‐sulfopropyl methacrylate potassium salt (SPMA) is an ionic monomer that can form ion channels in water molecules, further accelerating the leakage of accumulated electrostatic charges and improving the antistatic properties of the copolymer. The method of selecting compatibilizers and release agents through solubility parameters provides more opportunities for the development of PMMA with excellent comprehensive performance.
The Effect of Nanometer‐Scale V‐Pit Layer on the Carrier Recombination Mechanisms and Efficiency Droop of GaN‐Based Green Light‐Emitting Diodes
Authors: Jia Chuanyu , Hu Xiduo , Wang Qi , Liang Zhiwen
Published: June 2021

The effects of nanometer‐scale V‐pits layer with different parameters on the carrier recombination mechanisms and efficiency droop of GaN‐based green light‐emitting diodes (LEDs) are investigated. Under optimized growth conditions, the threading dislocations (TDs) are surrounded by V‐pits layer with six (10–11) side wall facets. The V‐pits layer contains sidewall multiple quantum wells (MQWs) with bandgap several hundred millielectronvolts higher than that of c‐plane MQWs. This higher bandgap acts as a barrier for carriers and prevents them from reaching the dislocations, which can effectively suppress the nonradiative recombination. Analysis suggests that the V‐pits enhance hole injection into deeper MQWs, which is confirmed by the secondary ion mass spectroscopy profiles of Mg and Al. With the aid of the V‐pits layer, holes can be injected into deeper MQWs, which reduce the carrier concentration within individual QWs. Therefore, the Auger‐related efficiency droop can be suppressed. The results show that LED with 200 nm LT‐GaN + 40 nm n‐GaN V‐pits layer is able to deliver an improvement in the light output power by 189% as compared with reference LED without V‐pits layer. At 200 mA, the efficiency droop for LED with200 nm LT‐GaN + 40 nm n‐GaN V‐pits is 25.9%, which is much smaller than 34.7% for reference LED without V‐pits.
Large‐scale tandem mass spectrum clustering using fast nearest neighbor searching
Authors: Bittremieux Wout , Laukens Kris , Noble William Stafford , Dorrestein Pieter C.
Published: June 2021

Rationale

Advanced algorithmic solutions are necessary to process the ever‐increasing amounts of mass spectrometry data that are being generated. In this study, we describe the falcon spectrum clustering tool for efficient clustering of millions of MS/MS spectra.

Methods

falcon succeeds in efficiently clustering large amounts of mass spectral data using advanced techniques for fast spectrum similarity searching. First, high‐resolution spectra are binned and converted to low‐dimensional vectors using feature hashing. Next, the spectrum vectors are used to construct nearest neighbor indexes for fast similarity searching. The nearest neighbor indexes are used to efficiently compute a sparse pairwise distance matrix without having to exhaustively perform all pairwise spectrum comparisons within the relevant precursor mass tolerance. Finally, density‐based clustering is performed to group similar spectra into clusters.

Results

Several state‐of‐the‐art spectrum clustering tools were evaluated using a large draft human proteome data set consisting of 25 million spectra, indicating that alternative tools produce clustering results with different characteristics. Notably, falcon generates larger highly pure clusters than alternative tools, leading to a larger reduction in data volume without the loss of relevant information for more efficient downstream processing.

Conclusions

falcon is a highly efficient spectrum clustering tool, which is publicly available as an open source under the permissive BSD license at https://github.com/bittremieux/falcon.
Square Planar trans‐N2O2 Cu(II) Complex: Synthesis, Crystal Structure, Hirshfeld Surface, DFT, Antimicrobial and Docking Studies
Authors: Udaya Kumar Allampura H. , Kumara Karthik , Harohally Nanishankar V. , Pampa Kudigana J. , Lokanath Neratur K.
Published: June 2021

SL ligand [(E)‐2‐(((2‐(tert‐butylthio) phenyl) imino)methyl)‐4‐chlorophenol)] and its Cu(II) complex [Cu(C14H12ClNOS)2] are synthesized and characterized by FTIR, SEM, EDX and TGA. Single crystal X‐ray diffraction studies revealed that the ligand and Cu(II) complex crystallizes in identical space group and the copper complex exhibits square planar geometry (τ4=0). SL and copper complex show C−Cl⋯π and C−H⋯π interaction respectively enables the formation of multi‐dimensional supramolecular architecture and its nature of interactions is quantified by Hirshfeld surface analysis. The strength of the interaction and 3D topology of crystal packing are visualized through an energy framework. Further, the physical nature of intramolecular interactions is assessed by QTAIM and NCI index model. DFT was employed to evaluate the optimized electronic structure, HOMO‐LUMO, energy gap, molecular properties and global parameters. The copper complex exhibited good antibacterial activity against the S.aureus and MRSA and compared with the standard drug (gentamicin). The molecular docking studies of the copper complex show a high affinity towards penicillin‐binding protein 2 and topoisomerase II DNA gyrase.
Synthesis and Application of Ionic Liquid‐Supported Carbodiimides
Authors: Liu Zi‐Ying , Hsu Jun‐Hao , Lin Cheng‐Kun
Published: June 2021

A series of ionic liquid‐supported carbodiimides was synthesized and applied in coupling reactions. The key features for the synthetic route included the click reaction of 3‐azidobenzyl chloride to introduce the imidazolium moiety and the Staudinger reaction with different isothiocyanates to furnish novel carbodiimides, which showed good reactivity toward (thio)esterifications (76–99 %) and other acylations (79–93 %) and the resulting urea can be easily removed.
Cu‐Catalyzed Aerobic Oxidative Coupling of Tetrahydro‐β‐carbolines with Indoles
Authors: Chen Haijun , Qiao Panpan , Luo Yining , Hu Jing , Gao Yu
Published: June 2021

A copper‐catalyzed aerobic oxidative coupling reaction of tetrahydro‐β‐carbolines (THβCs) with indoles is reported for the first time. This room‐temperature catalytic strategy offers an efficient synthesis of the complex scaffold with an excellent chemoselectivity profile under mild reaction conditions.
Metal‐Free Selective C−S Bond Cleavage of Thioethers to Access β‐Alkoxy Carbonyl Compounds
Authors: Li Yi , Hu Qingyue , Zhang Feiyang , Li Zhengyi , Sun Xiaoqiang , Yang Ke
Published: June 2021

A metal‐free C(sp3)−S bond cleavage of β‐alkylthio carbonyl compounds in the presence of Selectfluor is described. This novel strategy realizes the C−S bond cleavage and subsequent C−O bond formation, providing a facile and efficient method to construct different important β‐alkoxy carbonyl compounds with moderate to good yields and good functional groups tolerance. Moreover, our mechanistic studies also prove that two different mechanisms including the oxidant and thionium ion intermediate pathway may exist in this process.
Ultrasensitive Multiparameter Phenotyping of Rare Cells Using an Integrated Digital‐Molecular‐Counting Microfluidic Well Plate
Authors: Su Shiuan‐Haur , Song Yujing , Newstead Michael W. , Cai Tao , Wu MengXi , Stephens Andrew , Singer Benjamin H. , Kurabayashi Katsuo
Published: June 2021

Integrated microfluidic cellular phenotyping platforms provide a promising means of studying a variety of inflammatory diseases mediated by cell‐secreted cytokines. However, immunosensors integrated in previous microfluidic platforms lack the sensitivity to detect small signals in the cellular secretion of proinflammatory cytokines with high precision. This limitation prohibits researchers from studying cells secreting cytokines at low abundance or existing at a small population. Herein, the authors present an integrated platform named the “digital Phenoplate (dPP),” which integrates digital immunosensors into a microfluidic chip with on‐chip cell assay chambers, and demonstrates ultrasensitive cellular cytokine secretory profile measurement. The integrated sensors yield a limit of detection as small as 0.25 pg mL−1 for mouse tumor necrosis factor alpha (TNF‐α). Each on‐chip cell assay chamber confines cells whose population ranges from ≈20 to 600 in arrayed single‐cell trapping microwells. Together, these microfluidic features of the dPP simultaneously permit precise counting and image‐based cytometry of individual cells while performing parallel measurements of TNF‐α released from rare cells under multiple stimulant conditions for multiple samples. The dPP platform is broadly applicable to the characterization of cellular phenotypes demanding high precision and high throughput.
Synchronized Reagent Delivery in Double Emulsions for Triggering Chemical Reactions and Gene Expression
Authors: Stucki Ariane , Jusková Petra , Nuti Nicola , Schmitt Steven , Dittrich Petra S.
Published: June 2021

Microfluidic methods for the formation of single and double emulsion (DE) droplets allow for the encapsulation and isolation of reactants inside nanoliter compartments. Such methods have greatly enhanced the toolbox for high‐throughput screening for cell or enzyme engineering and drug discovery. However, remaining challenges in the supply of reagents into these enclosed compartments limit the applicability of droplet microfluidics. Here, a strategy is introduced for on‐demand delivery of reactants in DEs. Lipid vesicles are used as reactant carriers, which are co‐encapsulated in double emulsions and release their cargo upon addition of an external trigger, here the anionic surfactant sodium dodecyl sulfate (SDS). The reagent present inside the lipid vesicles stays isolated from the remaining content of the DE vessel until SDS enters the DE lumen and solubilizes the vesicles’ lipid bilayer. The versatility of the method is demonstrated with two critical applications chosen as representative assays for high‐throughput screening: the induction of gene expression in bacteria and the initiation of an enzymatic reaction. This method not only allows for the release of the lipid vesicle content inside DEs to be synchronized for all DEs but also for the release to be triggered at any desired time.
Location of obstetric anal sphincter injury scars on translabial tomographic ultrasound
Authors: Dietz H. P. , Kreft M. , Subramaniam N. , Robledo K.
Published: June 2021

Objective

Obstetric anal sphincter injury (OASI) is a common preventable cause of anal incontinence. Both diagnosis and primary repair of OASI are often suboptimal, partly owing to the absence of effective clinical audit. The aim of this study was to evaluate the location of scars or defects of the external anal sphincter (EAS), diagnosed by translabial ultrasound (TLUS), following primary OASI repair.

Methods

This was a retrospective analysis of 309 women who were seen at a tertiary obstetric unit after primary repair of OASI between June 2012 and May 2019. All women underwent a standardized interview, including St Mark's incontinence score, followed by clinical examination and TLUS assessment within 2–9 months after OASI repair. Postprocessing of TLUS volume datasets was performed by an investigator who was blinded to all other information. Tomographic ultrasound imaging was used to evaluate the presence of a scar or defect in the proximal and distal parts of the EAS. Women were classified into four groups according to the imaging findings: (1) no visible defect or distortion (likely false positive); (2) only proximal OASI; (3) only distal OASI; and (4) both proximal and distal OASI.

Results

Of the 309 women seen during the study period, 34 were excluded because they were referred for reasons other than recent (< 1 year) OASI, 16 owing to missing data and four owing to poor image quality, leaving 255 patients for analysis. Women were seen on average 0.25 ± 0.1 years after the index birth, and their mean age at delivery was 29.1 ± 4.6 years. Anal incontinence was reported by 97 (38.0%) women. A scar or defect was seen only in the proximal part of the EAS in 64 (25.1%) women and only in the distal part in 19 (7.5%) (P < 0.001). In 165 (64.7%) women, the damage affected both the proximal and distal EAS.

Conclusions

EAS scars after primary OASI repair commonly affect the entire length of the EAS; however, partial tears seem to be more likely to occur proximally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Evaluation of Wall‐Barriers to Manage Human Conflict with Asian Elephants in India
Authors: Natarajan Lakshminarayanan , Kumar Ankit , Qureshi Qamar , Desai Ajay A , Pandav Bivash
Published: June 2021

The Terai Arc Landscape (TAL) in the foothills of the Himalayas is one of the four major elephant ranges in India. In response to the escalating problem of crop raiding by elephants, the State Forest Department of Uttarakhand (UKFD) has built walls along the forest boundary in several protected areas and multiple‐use forest divisions. Given the high costs of constructing walls and the growing demand from farmers, the UKFD solicited an evaluation of wall efficacy. In response, we surveyed 98.4 km of walls in the TAL to assess frequency of breaches. We used generalized linear models to examine the influence of 7 explanatory variables on variation in breach frequencies between stretches of the wall. We observed 598 breaches and 87 weak spots in the 98.4 km of walls. Elephants caused 48% of the breaches, suggesting that walls in the TAL were not effective barriers against elephants. Explanatory variables of wall length, forest division, relative density of elephants, and land use along the wall stretches explained variation in wall breach frequencies. Based on our results, walls would only reduce elephant intrusion on 9 stretches (>1 km) totaling 11.8 km (approximately 12% of the wall stretches built in TAL). © 2021 The Wildlife Society.
Use of EDXRF elemental fingerprinting for discrimination of botanical and geographical origin of Slovenian bee pollen
Authors: Lilek Nataša , Kandolf Borovšak Andreja , Bertoncelj Jasna , Vogel Mikuš Katarina , Nečemer Marijan
Published: June 2021

Bee pollen contains proteins, amino acids, carbohydrates, fats, fatty acids, vitamins, polyphenols, and mineral nutrients that make it useful as a good nutritional supplement in the human diet. It has the richest elemental composition among bee products which is not uniform and consequently varies greatly depending on botanical and geographical origin. In polyfloral and selected monofloral bee pollen samples: sweet chestnut, maple, dandelion, rapeseed, flowering ash, buckwheat, common ivy, and plantain, the concentrations of P, S, Cl, K, Ca, Mn, Fe, Zn, Br, Rb, and Sr were determined. A non‐destructive energy dispersive X‐ray fluorescence spectrometry was used for elemental fingerprinting. The most abundant elements in Slovenian bee pollen are K, P, S, Ca, and Cl followed by Fe, Mn, Zn, Rb, Br, and Sr. Several statistically significant differences in the content of analysed elements were found between studied groups according to the botanical and geographical origin which can be related to soil and plant elemental composition and plant metabolism. The obtained data extend our previous chemical profiling of Slovenian bee pollen and contribute to a more precise evaluation of some essential mineral nutrients in bee pollen to cover recommended dietary allowances in human nutrition. Additionally, this work contributes to a better understanding of mineral nutrient requirements in honey bee nutrition and of the environmental and agricultural impact of this product.
Probing QCD dynamics and the standard model with $$ {D}_{(s)}^{+}\to {P}_1^{+}{P}_2^0\gamma $$ decays
Authors: Adolph Nico , Hiller Gudrun
Published: June 2021

Abstract

We compute 10 radiative three-body decays of charged charmed mesons $$ {D}^{+}\to {P}_1^{+}{P}_2^0\gamma $$

D
+

→

P
1
+

P
2
0

γ
and $$ {D}_s\to {P}_1^{+}{P}_2^0\gamma $$

D
s

→

P
1
+

P
2
0

γ
, P1,2 = π, K, in leading order QCDF, HHχPT and the soft photon approximation. We work out decay distributions and asymmetries in the standard model and with new physics in the electromagnetic dipole operators. The forward-backward asymmetry is suitable to probe the QCD frameworks, in particular the s-channel dependent weak annihilation contributions in QCDF against the markedly different resonance structure in HHχPT. These studies can be performed with Cabibbo-favored modes Ds → π+π0γ, $$ {D}^{+}\to {\pi}^{+}{\overline{K}}^0\gamma $$

D
+

→

π
+

K
¯

0

γ
and $$ {D}_s\to {K}^{+}{\overline{K}}^0\gamma $$

D
s

→

K
+

K
¯

0

γ
with $$ \mathcal{O}\left({10}^{-4}-{10}^{-3}\right)\hbox{-} \mathrm{level} $$
O

10

−
4

−

10

−
3

‐
level
branching ratio, which are standard model-like and induced by different hadronic dynamics. Understanding of the latter can therefore be improved in a data-driven way and sharpens the interpretation of standard model tests. Singly Cabibbo-suppressed modes such as D+ → π+π0γ, Ds → π+K0γ, Ds → K+π0γ with branching ratios within ∼ 10−5–10−4 are sensitive to new physics that can be signalled in the forward-backward asymmetry and in the CP-asymmetry of the rate, ideally in the Dalitz region but also in single differential distributions. Results complement those with neutral D0→ P1P2γ decays.
DeRAS I – deutsche Situation der robotisch assistierten Chirurgie – eine Online-Survey-Studie
Authors: Krüger C. M. , Rückbeil O. , Sebestyen U. , Schlick T. , Kürbis J. , Riediger H.
Published: June 2021

Hintergrund

Die robotische Assistenz hat sich in der Chirurgie etabliert, ist aber noch kein Standard. Der aktuelle Stand der klinischen Verbreitung in Deutschland ist weiter unklar. Industrieunabhängige Quellen sind rar.

Ziel der Arbeit

Ziel dieser Umfrage ist es, den aktuellen Stand der robotisch assistierten Chirurgie (RAS) fachübergreifend in Deutschland im Zeitraum von 2014 bis 2018 zu untersuchen.

Materialien und Methoden

Mit einer Internetrecherche wurden Krankenhäuser (KH) und Fachabteilungen (FA) mit Zugang zur RAS identifiziert. Die FA wurden aufgefordert, ihre Daten aus den Jahren 2014 bis 2018 zu teilen. Neben klinischen Daten wurden Daten zu Nutzung, Implementierung, Training und Finanzierung abgefragt.

Ergebnisse

Am 31.12.2018 wurde die RAS an 121 KH in Deutschland angeboten. 383 FA mit Zugang zur RAS wurden identifiziert. 26 % (n = 98) der FA haben geantwortet. Im Mittel verfügte jede FA über zwei Konsolenchirurgen. 10 % der KH verfügten über mehr als 1 RAS-System. 100 % der erfassten RAS-Systeme stammten von der Firma Intuitive Surgical Inc., CA, USA. Die RAS wurde zu 65 % in der Urologie implementiert, zu 12 % in der Viszeralchirurgie (VC). 21 % der Programme erfolgten interdisziplinär und 4 % multidisziplinär (> 3). 83 % der Systeme wurden gekauft, 17 % anderweitig finanziert. Bei den Operationsmehrkosten gaben 74 % der Kliniken an, diese selbst zu tragen. 14 % wählten eine Umlage. Seit 2014 steigerten sich die Eingriffe um den Faktor 4 auf ca. 8000. Der Anteil der VC steigerte sich um das Fünffache seit 2016.

Schlussfolgerung

Die RAS erlebte in Deutschland bis 2018 ein starkes Wachstum. Das Eingriffsspektrum entspricht dem der Laparoskopie. Bei aktuell fehlender Kostenerstattung für den technischen Mehraufwand, wird die RAS überwiegend im mittel- und hochkomplexen Bereich eingesetzt. Der Online-Survey ist eine gute Methode, ohne hohen administrativen Aufwand unabhängige Daten zu erheben.
Prognosefaktoren für das Gesamtüberleben bei Oropharynxkarzinomen in Abhängigkeit vom HPV-Status
Authors: Riders A. , Oberste M. , Abbaspour B. , Beule A. , Rudack C.
Published: June 2021

Hintergrund

Aufgrund der unterschiedlichen Karzinogenese, Prognose und klinischen Manifestation werden seit der 8. Auflage des TNM-Klassifikationssystems der UICC/AJCC (UICC 8) humane Papillomavirus (HPV)-assoziierte und HPV-negative oropharyngeale Plattenepithelkarzinome (OSCC) als 2 Entitäten separat klassifiziert.

Material und Methoden

Insgesamt 524 Patienten mit einem im Zeitraum von 2000–2016 in der HNO-Klinik des Universitätsklinikums Münster behandelten OSCC wurden hinsichtlich des Nachweises von HPV-Typ-16-spezifischer DNA (HPV16-DNA), des Nikotin- und Alkoholkonsums sowie des Therapieeinflusses auf das Gesamtüberleben (GÜ) untersucht.

Ergebnisse

Ein signifikanter Anstieg der jährlichen Prävalenz der HPV16-DNA-positiven OSCC von 40 % (n = 12/30) im Jahr 2000 auf 46 % (n = 18/39) im Jahr 2016 wurde verzeichnet (p = 0,025, β = 0,539). 89 % (n = 212) der HPV16-DNA-positiven OSCC wurden anhand der UICC 8 gegenüber der UICC 7 herabgestuft. Im Gesamtkollektiv zeigten der häufige Alkohol- und Nikotinkonsum (≥ 10 Packungsjahre) einen statistisch relevanten negativen Einfluss auf das GÜ (p = 0,004 und p = 0,009). Auch häufiger Alkoholkonsum war in der HPV16-DNA-negativen Gruppe prognoserelevant (p = 0,049). In der HPV16-DNA-positiven Gruppe zeigte sich bezüglich des GÜ zwischen den UICC-Stadien I und II (p = 0,481) sowie zwischen III und IV (p = 0,439) gemäß UICC 8 kein statistischer Unterschied.

Schlussfolgerungen

Die UICC 8 verbessert zwar die Prognosestratifikation der OSCC durch die Trennung von HPV-positiven und HPV-negativen Tumoren im Vergleich zu UICC 7, die prognostische Aussagekraft der UICC 8 für die HPV-assoziierten OSCC ist jedoch weiterhin unzureichend. Der Noxenkonsum könnte zukünftig Einfluss auf die UICC-Klassifikation nehmen, um die prognostische Aussagekraft weiter zu verbessern.
Capability accumulation and product innovation: an agent-based perspective
Authors: Gräbner Claudius , Hornykewycz Anna
Published: June 2021

This paper studiesthe relevance of productheterogeneity and relatedness for the accumulation ofcapabilities in firms, as well as their implications for innovation dynamics. The existing literature has produced extensive evidence on the relevance of capability accumulation for innovation processes. Yet, an assessment of prior attempts to model these processes indicates that when it comes to the final consumption good sector, the evolutionary macroeconomic literature has focused on process rather than product innovation. To facilitate the consideration of empirical and microeconomic insights on product innovation in these models, this paper introduces a simple agent-based model, which may later serve as an innovation module in macroeconomic models. In the model, firms accumulate capabilities to produce final consumption goods that are heterogeneous in terms of their complexity and differ in their relatedness to each other. The model is used to study theoretical implications of different topological structures underlying product relatedness by conducting simulations with different ‘product spaces’. The analysis suggests that the topological structure of the product space, the assumed relationship between product complexity and centrality, as well as the relevance of product complexity in price setting dynamics have significant but nontrivial implications and deserve further attention in evolutionary macroeconomics.
Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression
Authors: Paprottka K. J. , Kleiner S. , Preibisch C. , Kofler F. , Schmidt-Graf F. , Delbridge C. , Bernhardt D. , Combs S. E. , Gempt J. , Meyer B. , Zimmer C. , Menze B. H. , Yakushev I. , Kirschke J. S. , Wiestler B.
Published: June 2021

Purpose

To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma.

Material and methods

At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier’s performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments.

Results

In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77–0.93 (sensitivity 0.91, 95% CI 0.81–0.97; specificity 0.71, 95% CI 0.44–0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72–0.9), 0.81 for [18F]-FET-PET (95% CI 0.7–0.89), and 0.81 for expert consensus (95% CI 0.7–0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities.

Conclusion

Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.