bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
Authors: McLoughlin Niall M. , Kuepper Arne , Neubacher Saskia , Grossmann Tom N. 
Published: April 2021

AbstractBiomolecular assemblies composed of proteins and oligonucleotides play a central role in biological processes. While in nature, oligonucleotides and proteins usually assemble via non‐covalent interactions, synthetic conjugates have been developed which covalently link both modalities. The resulting peptide‐oligonucleotide conjugates have facilitated novel biological applications as well as the design of functional supramolecular systems and materials. However, despite the importance of concerted protein/oligonucleotide recognition in nature, conjugation approaches have barely utilized the synergistic recognition abilities of such complexes. Herein, the structure‐based design of peptide‐DNA conjugates that bind RNA through Watson‐Crick base pairing combined with peptide‐mediated major groove recognition is reported. Two distinct conjugate families with tunable binding characteristics have been designed to adjacently bind a particular RNA sequence. In the resulting ternary complex, their peptide elements are located in proximity, a feature that was used to enable an RNA‐templated click reaction. The introduced structure‐based design approach opens the door to novel functional biomolecular assemblies.
Interstellar Enolization‐Acetaldehyde (CH3CHO) and Vinyl Alcohol (H2CCH(OH)) as a Case Study
Authors: Kleimeier N. Fabian , Kaiser Ralf I. 
Published: April 2021

AbstractOwing to the unique conditions in cold molecular clouds, enols—the thermodynamically less stable tautomers of aldehydes and ketones—do not undergo tautomerization to their more stable tautomers in the gas phase because they cannot overcome tautomerization barriers at the low temperatures. Laboratory studies of interstellar analog ices have demonstrated the formation of several keto–enol tautomer pairs in astrochemically relevant ice mixtures over the last years. However, so far only one of them, acetaldehyde−vinyl alcohol, has been detected in deep space. Due to their reactivity with electrophiles, enols can play a crucial role in our understanding of the molecular complexity in the interstellar medium and in comets and meteorites. To study the enolization of aldehydes in interstellar ices by interaction with galactic cosmic rays (GCRs), we irradiated acetaldehyde ices with energetic electrons as proxies of secondary electrons generated in the track of GCRs while penetrating interstellar ices. The results indicate that GCRs can induce enolization of acetaldehyde and that intra‐ as well as intermolecular processes are relevant. Therefore, enols should be ubiquitous in the interstellar medium and could be searched for using radio telescopes such as ALMA. Once enols are detected and abundances are established, they can serve as tracers for the non‐equilibrium chemistry in interstellar ices thus eventually constraining fundamental reaction mechanisms deep inside interstellar ices.
Green Esterification of Carboxylic Acids Promoted bytert‐Butyl Nitrite
Authors: Zheng Yonggao , Zhao Yanwei , Tao Suyan , Li Xingxing , Cheng Xionglve , Jiang Gangzhong , Wan Xiaobing 
Published: April 2021

AbstractIn this work, the green esterification of carboxylic acids promoted bytert‐butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.
Conditional spectrum record selection faithful to causative earthquake parameter distributions
Authors: Spillatura Andrea , Kohrangi Mohsen , Bazzurro Paolo , Vamvatsikos Dimitrios 
Published: April 2021

AbstractIn performance‐based earthquake wngineering, record selection comes into play at the interface of seismic hazard and structural analysis aiming to repair any loss of essential seismological dependencies caused by the choice of an insufficient intensity measure to be used for structural response prediction. Site‐specific selection is best exemplified by the prominent conditional spectrum (CS) approach that attempts to ensure a hazard‐consistent response prediction by involving site hazard disaggregation. Specifically, CS utilizes a target spectrum (with mean and dispersion) that, in its latest formulation, accounts for all the scenarios (in terms of magnitude, M, and closest to rupture distance, R) contributing to the hazard of the site at a given intensity level. The ground motion records, however, are selected to match this target spectrum–based solely on their spectral shape but with no explicit consideration to their underlying M‐R characteristics. The main focus of this study is to explore whether the reintroduction of M‐R criteria in the selection process preserves hidden dependencies that may otherwise be lost through a spectral‐shape‐only proxy. The proposed record selection method, termed CS‐MR, offers a simple approach to maintain a higher order of hazard consistency able to indirectly account for metrics that depend on M‐R (e.g., duration, Arias intensity) but are not captured in the response spectra. Herein the CS‐MR response prediction is favorably compared to CS and to the generalized conditional intensity measure methods that select records according to, respectively, spectral shape only and, for the case at hand, to spectral shape plus duration.
European legislation for veterinary medicines: Would a monograph system improve the environmental risk assessment?
Authors: de la Casa-Resino Irene , Haro Castuera Amparo , Casimiro Elena Ramiro , Rubio Montejano Consuelo , Carapeto García Ricardo 
Published: April 2021

Abstract
The environmental risk assessment (ERA) of veterinary medicinal products (VMPs) has been a regulatory requirement in the European Union (EU) since 1993. However, in the last few years, the potential impact of human and veterinary medicines on the environment has become a growing concern worldwide. Indeed, the legal requirements for VMPs in the EU are changing. Regulation (EU) 2019/6, which will be applied from January 28, 2022, aims to update the regulatory framework for VMPs and replaces Directive 2001/82/EC. This paper analyzes the ability of both legislations to ensure a high level of protection of the environment while authorizing VMPs. Consideration is also given to the impact on administrative burdens in both the legislations. We conclude that the Regulation improves the Directive by reducing to a certain extent the regulatory burdens for the applicants and authorities. However, the knowledge of the environmental risks of all authorized VMPs and the consistency of the assessments remain quite similar between both legislations. Nevertheless, the new Regulation proposes to examine the feasibility and applicability of an assessment system based on the critical review of properties of the active substances (“monographs”) or other potential alternatives. With this in mind, two proposals (a basic and an enhanced approach) for developing a monograph system are presented and their main advantages and disadvantages are explored. Integr Environ Assess Manag 2021;17:1274–1285. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
KEY POINTS
The environmental risk assessment (ERA) of veterinary medicinal products (VMPs) performed according to the Directive 2001/82/EC does not allow the systematic review of the environmental risks of all the VMPs authorized and supposes a lack of harmonization among equal active substances. The forthcoming legislation (Regulation [EU] 2019/6) improves the Directive in terms of ERA. However, the issues related to the lack of information on the environmental risks of all the VMPs in the market and the issues related to consistency remain. Article 156 of the Regulation gives the opportunity to study the feasibility of an active substance-based review system (the so-called “monographs”) or other potential alternatives for the environmental risk assessment of VMPs. The development of a monograph system could be a good opportunity to solve the shortcomings detected in the ERA of VMPs of the current and forthcoming legislation.
A retrospective study for investigating the outcomes of endometrial cancer treated with radiotherapy
Authors: Sakai Kensuke , Yamagami Wataru , Machida Hiroko , Ebina Yasuhiko , Kobayashi Yoichi , Tabata Tsutomu , Kaneuchi Masanori , Nagase Satoru , Enomoto Takayuki , Aoki Daisuke , Mikami Mikio 
Published: April 2021

AbstractObjectiveTo clarify the role of radiotherapy for endometrial cancer.MethodsData were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011.ResultsThe rates of 5‐year overall survival (5y‐OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y‐OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors.ConclusionPatients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.
Changes of cytokine levels and T cell surface molecules in patients with chronic hepatitis B and the association with functional cure
Authors: Xu Zhen , Lin Ji‐zong , Zeng Ying‐fu , Yang Xiao‐hua , Wu Zhe‐bin , Hu Zhao‐xia , Zhao Qi‐yi , Liu Jing , Gao Zhi‐liang 
Published: April 2021

AbstractThis study aimed to examine changes in levels of cytokine and T cell surface molecules in chronic hepatitis B (CHB) patients receiving sequential interferon therapy following 1‐year nucleos(t)ide analogs (NAs) treatment. Cytokine levels were measured in 30 patients, and T cell surface molecule expression was measured in 48 patients receiving sequential interferon therapy and 24 patients only receiving NA mono‐therapy. An HBsAg titer of <0.05 IU/ml was defined as a “functional cure.” In the cured group (HBsAg < 0.05 IU/ml), a decreasing probability was observed in IFN‐γ (after Week 0), and IL‐22 and IP‐10 (after Week 12). In the non‐cured group (HBsAg ≥ 0.05 IU/ml), a probability of slightly decreasing was observed for IFN‐γ (after Week 12), and a probability of increasing IP‐10 concentration (after Week 0) was observed. Generalized estimating equation (GEE) analyses showed significant differences in the levels of IL‐10, IL‐23, CCL‐3, IL‐1β, IL‐2, and IL‐12P70 between the two groups. In GEE analysis, there were significant differences in expressions of CD45RO+ between the cured group and the non‐cured group. The frequencies of T cells expressing Tim‐3, CD62L, and CD152 were significantly lower in the sequential interferon therapy group than in the NA mono‐therapy group. Changes in cytokine levels (IFN‐γ, IP‐10, IL‐10, IL‐23, CCL‐3, IL‐1β, IL‐2, and IL‐12P70) and T cell surface molecules (CD45RO+) may predict HBsAg seroconversion in CHB patients receiving sequential interferon therapy. The period from Weeks 12 to 24 during sequential interferon therapy may be a critical time of immune status change.
Evaluation of the diagnostic performance of nine commercial RT‐PCR kits for the detection of SARS‐CoV‐2 in Colombia
Authors: Hernández Carolina , Florez Carolina , Castañeda Sergio , Ballesteros Nathalia , Martínez David , Castillo Adriana , Muñoz Marina , Gomez Sergio , Rico Angelica , Pardo Liseth , Paniz‐Mondolfi Alberto , Ramírez Juan David 
Published: April 2021

AbstractThe ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic has led to the design and development of multiple reverse‐transcription polymerase chain reaction kits aimed to facilitate the rapid scale‐up of molecular testing for massive screening. We evaluated the diagnostic performance of nine commercial kits, which showed optimal performance and high discriminatory power. However, we observed differences in terms of sensitivity, specificity, and E gene Ct Values and discuss these results in light of the influence of SARS‐CoV‐2 genetic variability and its potential impact in current molecular diagnostic assays.
Participating mechanism of a major contributing gene ysnE for auxin biosynthesis in Bacillus amyloliquefaciens SQR9
Authors: Shao Jiahui , Li Yucong , Li Zunfeng , Xu Zhihui , Xun Weibing , Zhang Nan , Feng Haichao , Miao Youzhi , Shen Qirong , Zhang Ruifu 
Published: April 2021

AbstractThe phytohormone indole‐3‐acetic acid (IAA) has been demonstrated to contribute to the plant growth‐promoting effect of rhizobacteria, but the IAA biosynthesis pathway in rhizobacteria remains unclear. The ysnE gene, encoding a putative tryptophan acetyltransferase, has been demonstrated to be involved in and strongly contribute to IAA production in Bacillus, but the mechanism is unknown. In this study, to investigate how ysnE participates in IAA biosynthesis in the plant growth‐promoting rhizobacterium Bacillus amyloliquefaciens SQR9, differences in the produced IAA biosynthesis intermediates between wild‐type SQR9 and ΔysnE were analyzed and compared, and the effects of different intermediate compounds on the production of IAA and the accumulation of other intermediates were also investigated. The results showed that the mutant ΔysnE produced more indole‐3‐lactic acid (ILA) and tryptamine (TAM) than the SQR9 wild‐type strain (nearly 1.6‐ and 2.1‐fold), while the production of tryptophol (TOL) was significantly decreased by 46%. When indole‐3‐pyruvic acid (IPA) served as the substrate, the concentration of ILA in the ΔysnE fermentation broth was much higher than that of the wild type, while IAA and TOL were significantly lower, and ΔysnE was lower than SQR9 in IAA and TOL with the addition of TAM. The TOL content in the ΔysnE fermentation broth was much lower than that in the wild‐type SQR9 with the addition of ILA. We suggest that ysnE may be involved in the IPA and TAM pathways and play roles in indole acetaldehyde (IAAld) synthesis from IPA and TAM and in the conversion of ILA to TOL.
Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model
Authors: Marston Scott , Mirick Mueller Gudrun , Sabin Arick , Hansen Glen T. , Lindgren Bruce , Aparicio Conrado , Armstrong Alexandra R. , Larsen Ole H. , Schmidt Andrew , Kyle Richard , Gustilo Ramon , Tsukayama Dean , Bechtold Joan , Bue Mats 
Published: April 2021

AbstractWe studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4‐week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50‐μl, 104 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups.
Terminal sterilization influences the efficacy of an extracellular matrix‐blood composite for treating posttraumatic osteoarthritis in the rat model
Authors: Karamchedu Naga Padmini , Fleming Braden C. , Proffen Benedikt L. , Sant Nicholas J. , Portilla Gabriela , Parola Lauren R. , Molino Janine , Murray Martha M. 
Published: April 2021

AbstractThe objective was to determine if an intra‐articular injection of an extracellular matrix (ECM) powder and blood composite (ECM‐B) after anterior cruciate ligament (ACL) injury would have a mitigating effect on posttraumatic osteoarthritis and if that effect would be different with terminal sterilization of the ECM powder before use. Eighty Lewis rats underwent ACL transection and were divided into four groups: (1) intra‐articular injection with phosphate‐buffered saline (PBS; n = 20), (2) intra‐articular injection of ECM‐B using aseptically processed ECM (ASEPTIC; n = 20), (3) intra‐articular injection of the ECM‐busing ECM powder sterilized with 15 kGy electron beam irradiation (EBEAM; n = 20), and (4) intra‐articular injection of the ECM‐B using ECM powder sterilized with ethylene oxide (EO; n = 20). Twenty additional animals received capsulotomy only (SHAM). The animals were followed for 6 weeks and evaluations of gait, radiographs, and joint cartilage histology were performed. At 6 weeks, when compared to the SHAM group, the group treated with PBS had significantly worse gait and histologic changes, while the ASEPTIC group was not different from SHAM for either of these outcomes. When compared to the SHAM group, the EO group had similar gait outcomes, but greater histologic damage, and the EBEAM group had significantly worse gait and histological outcomes. The ECM‐B composite produced using aseptically processed ECM powder mitigated the gait and histologic changes associated with osteoarthritis after ACL transection in the rat; however, care must be taken when selecting a terminal sterilization method as this may affect the effectiveness of treatment.
Treatment of advanced pseudomyxoma peritonei using cytoreductive surgery including total gastrectomy and perioperative chemotherapy
Authors: Sugarbaker Paul H. , Chang David 
Published: April 2021

AbstractBackgroundPseudomyxoma peritonei is a disease caused by the widespread distribution of mucinous tumor into the peritoneal space from a perforated appendiceal neoplasm.MethodsAll patients in this study had cytoreductive surgery with total gastrectomy plus perioperative intraperitoneal chemotherapy. A high diverting jejunostomy was used on all patients. Patient characteristics, adverse events, and survival were accumulated prospectively.ResultsFifty‐eight patients were available for long‐term follow‐up. In the univariate analysis, features associated with a less favorable outcome included female gender (p = 0.0127), intestinal obstruction before treatment (p = 0.00791), and prior surgical score (PSS) (p = 0.0054). In the multivariate analysis, the two significant variables were grade (p = 0.0458) and PSS (p = 0.0041). Median survival was 12 years with a 5‐, 10‐, and 20‐year survival of 76%, 58%, and 37%, respectively. There were two postoperative deaths (3.4%) and Grades 3 and 4 adverse events in 20 (34.5%) patients.ConclusionsA 10‐year survival after cytoreductive surgery, total gastrectomy with temporary high diverting jejunostomy, and perioperative chemotherapy occurred in 58% of these patients with advanced pseudomyxoma peritonei. High‐grade disease and extensive prior surgery with a high PSS were associated with reduced benefit.
Separation and anti‐inflammatory evaluation of phytochemical constituents from Pleurospermum candollei (Apiaceae) by high‐speed countercurrent chromatography with continuous sample load
Authors: Ali Iftikhar , Mu Yan , Atif Muhammad , Hussain Hidayat , Li Jinping , Li Dandan , Shabbir Muhammad , Bankeu Jean Jules Kezetas , Cui Li , Sajjad Shahida , Wang Daijie , Wang Xiao 
Published: April 2021

AbstractPleurospermum (Apiaceae) species possess a wide range of biological properties viz. analgesic, anti‐inflammatory, antimalarial, and so on. Pleurospermum candollei (DC.) Benth. Ex C. B. Clark. is reported to cure diarrhea, gastric, respiratory, stomach, abdominal, joint, and back pain problems. In addition, it is also used for both male and female infertility. The present study deals with an efficient technique using high‐speed countercurrent chromatography for separation of chemical components from the methanol extract of P. candollei. Notably, nine main compounds namely luteolin 7‐O‐glucoside (1), oxypeucedanin hydrate (2), pabulenol (3), bergapten (4), heptadecanoic acid (5), (E)‐isoelemicin (6), trans‐asarone (7), α‐linolenic acid (8), and isoimperatorin (9) were very efficiently separated and isolated in pure form. Multiple injections were applied followed by two off‐line recycling high‐speed countercurrent chromatography. The inhibitory effect of nitric oxide production of all compounds was tested in the presence of 200 ng/mL lipopolysaccharide in RAW264.7 mice macrophage cells. The results demonstrated that compounds 7 and 8 effectively inhibited nitric oxide production, with IC50 values of 28.44 and 53.18 μM, respectively. This study thus validates the traditional claim of using P. candollei. Taken together, these findings will be useful in future research to find a potential candidate with anti‐inflammatory properties.
Ultrathin Broadband Reflective Optical Limiter
Authors: Wan Chenghao , Zhang Zhen , Salman Jad , King Jonathan , Xiao Yuzhe , Yu Zhaoning , Shahsafi Alireza , Wambold Raymond , Ramanathan Shriram , Kats Mikhail A. 
Published: April 2021

AbstractOptical limiters are nonlinear devices that feature decreasing transmittance with increasing incident optical intensity, and thus can protect sensitive components from high‐intensity illumination. The ideal optical limiter reflects rather than absorbs light in its active (“limiting”) state, minimizing risk of damage to the limiter itself. Previous efforts to realize reflective (rather than absorbing) limiters were based on embedding nonlinear layers into relatively thick multilayer photonic structures, resulting in substantial fabrication complexity, reduced speed and, in some instances, limited working bandwidth. In this paper, these tradeoffs are overcome by using the insulator‐to‐metal transition (IMT) in vanadium dioxide (VO2) to achieve intensity‐dependent modulation of resonant transmission through aperture antennas. Due to the large change of optical properties across the IMT, low‐quality‐factor resonators are sufficient to achieve high on–off ratios in the transmittance of the limiter. As a result, our ultrathin reflective limiter (thickness ≈1/100 of the free‐space wavelength) is broadband in terms of operating wavelength (>2 µm at 10 µm) and angle of incidence (up to ≈50° away from the normal). Our analysis of the experimental results via opto‐thermal simulations provides insight into limiter performance and is a useful guidance for further engineering efforts.