bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription, Reverse Transcription, and Amplification of Backbone‐Modified Nucleic Acids with Laboratory‐Evolved Thermophilic DNA Polymerases
Authors: Song Ping , Zhang Rujie , He Chuanping , Chen Tingjian
Published: July 2021

Backbone‐modified nucleic acids are usually more stable enzymatically than their natural counterparts, enabling their broad application as potential diagnostic or therapeutic agents. Moreover, the development of nucleic acids with unnatural backbones has expanded the pool of genetic information carriers and paved the way toward synthetic xenobiology. However, synthesizing these molecules remains very challenging due to the requirement for harsh reaction conditions and the low coupling efficiency during their traditional solid‐phase synthesis. Although enzymatic synthesis provides an attractive alternative that also allows the replication and artificial evolution of these molecules, it is crucially dependent on the availability of polymerases capable of synthesizing these backbone‐modified nucleotides. Previously, a series of thermostable polymerases that can efficiently synthesize or even amplify backbone‐modified DNA or RNA have been evolved through a polymerase evolution method based on phage display. Herein we summarize protocols to use these evolved polymerase mutants to transcribe, reverse transcribe, and PCR amplify backbone‐modified nucleic acids. We also outline the polymerase chain transcription method, developed later for the rapid production of RNA or backbone‐modified RNA with one of these evolved polymerases, SFM4‐3. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Transcription/synthesis of modified DNA/RNA from DNA templates with evolved polymerases SFM4‐3 or SFM4‐6

Basic Protocol 2: Reverse transcription of modified DNA/RNA with evolved polymerase SFM4‐9

Basic Protocol 3: PCR amplification of modified DNA with evolved polymerase SFM4‐3

Basic Protocol 4: Polymerase chain transcription for the production of RNA/modified RNA oligonucleotides with evolved polymerase SFM4‐3
Time point‐dependent concordance and prognostic significance of flow cytometry and real time quantitative PCR for measurable/minimal residual disease detection in acute myeloid leukemia with t(8;21)(q22;q22.1)
Authors: Shang Lei , Cai Xiaojin , Sun Wanchen , Cheng Qingnian , Mi Yingchang
Published: July 2021

Background

Flow cytometry (FCM) and PCR are reliable methods for assessing minimal residual disease (MRD) in acute myeloid leukemia with t(8;21)(q22;q22.1). The aim of this study was to analyze the concordant rate of these two methods and their prognostic significance.

Methods

PCR and FCM were simultaneously used for MRD analysis at four different time points on 450 BM samples from 124 patients with AML with t(8;21)(q22;q22.1). The four monitoring time points included post‐induction (first), after the first consolidation (second) and the second consolidation (third), and at the end of chemotherapy or before Allo/Auto stem cell transplantation (fourth).

Results

The concordant rates of the two methods were 33.06%, 25.81%, 49.59%, and 75.31%, respectively, and the main discordant cases were FCM‐/PCR+ cases. At all monitoring time points, the MRD level ≥ 10−4 by FCM indicated a poor 3‐year Relapse‐Free Survival (RFS) (p < 0.001). More than 2‐log MRD reduction by PCR after induction and more than 3‐log reduction by PCR after the first consolidation remained the significant predictors of better RFS (p < 0.001). After the second consolidation, the negative MRD by PCR (<10–5) was also associated with improved RFS (p = 0.002). A > 1‐log increase in PCR can effectively predict recurrence after molecular remission (p < 0.001). In the multivariate analysis, MRD≥0.01% by.

FCM and less than 2‐log MRD reduction by PCR after induction remained the significant predictors of poor RFS (p < 0.05).

Conclusions

FCM+ always indicates a poor prognosis. Sequential monitoring by PCR is of significance for evaluating prognosis. Our findings suggest a complementary role of two analyses in optimizing risk stratification in clinical practice.
Integrins in cardiac hypertrophy: lessons learned from culture systems
Authors: Bildyug Natalya
Published: July 2021

Heart growth and pathological changes are accompanied by extracellular matrix‐dependent alterations in integrins and integrin‐associated proteins, suggesting their role in heart development and disease. Most of our knowledge on the involvement of integrins in heart pathology is provided by the in vivo experiments, including cardiac hypertrophy models. However, in vivo studies are limited by the complex organization of heart tissue and fail to discern cell types and particular integrins implicated in hypertrophic signalling. This problem is being addressed by isolated cardiomyocyte primary cultures, which have been successfully used in different in vitro disease models. This review aimed to analyse the general approaches to studying integrins and integrin‐associated signalling pathways in cardiac hypertrophy focusing on the in vitro systems. The lessons learned from culture experiments on the models of hypertrophy induced by stretch, stimulating factors, and/or extracellular matrix components are summarized, demonstrating the major involvement of integrin‐mediated signalling in cardiac hypertrophic response and its apparent crosstalk with signal pathways induced by stretch or hypertrophy stimulating factors. The benefits and perspectives of using cardiomyocyte primary culture as a hypertrophy model are discussed.
O‐Isopropylferrocenesulfonate: Synthesis of Polysubstituted Derivatives and Electrochemical Study
Authors: Erb William , Wen Min , Pierre Hurvois Jean , Mongin Florence , Halauko Yury S. , Ivashkevich Oleg A. , Matulis Vadim E. , Roisnel Thierry
Published: July 2021

Few studies have been reported on the synthesis of ferrocenesulfonates up to now. Here, we describe the use of ortho‐deprotometalation and “halogen dance” reactions to easily reach original derivatives. Further functionalizations using cross‐coupling and metal/halogen exchange were also performed from iodinated derivatives. Finally, while the electrochemical properties of selected ferrocenesulfonates were evaluated and compared with the corresponding sulfonamide derivatives, halogen bonds were observed at the solid state for iodinated derivatives of ferrocenesulfonates.
Rapid assessment of integrated nuclear cogeneration projects using multi‐criteria indices
Authors: Bhattacharyya Rupsha , Khalid Farrukh
Published: July 2021

Nuclear power plants provide clean, carbon free, stable, reliable electricity and can offer nonelectric products and services via cogeneration operations to multiple sectors. This contributes to decarbonization of the current energy and industrial systems, supports climate change mitigation and adaptation efforts and ensures sustainable development over the long term, according to the United Nations Sustainable Development Goals (UN SDGs) framework and the provisions of the Conference of Parties 21 (COP21) Paris Agreement, 2015. This work surveys the potential role of nuclear cogeneration projects in meeting these objectives based on the current technological landscape. It focuses on nuclear assisted desalination for freshwater production and electrolytic hydrogen production as the use cases and suggests an assessment framework for their holistic evaluation. New integrated metrics and multi‐criteria performance indicators beyond the levelized cost of production are developed to quantify the likely multi‐dimensional impacts of such projects. The use of these for screening alternatives illustrates the fact that depending on weightage given to different criteria, different technologies may appear to be better suited to deployment under given set of conditions. These metrics are expected to be useful for creation of a decision support system for deployment of nuclear cogeneration projects.
Structure of ruthenium nanocatalysts of bismuth, investigation of its effect on hydrolysis performance and kinetic studies
Authors: Avci Hansu Tulin , Caglar Aykut , Demir Kivrak Hilal , Sahin Omer
Published: July 2021

In this study, a new nanocatalyst, RuBi/carbon nanotube, was synthesized to be used in the hydrolysis reaction of sodium boron hydride. The sodium boron hydride hydrolysis performance was investigated by adding bismuth to the structure of ruthenium nanocatalysts. Hydrolysis experiments were carried out by adding bismuth at different atomic proportions to ruthenium. The best atomic ratio was determined to be 90:10. These catalysts are characterized by scanning electron microscopy with energy‐dispersive X‐ray analysis, X‐ray diffraction, and transmission electron microscopy. The parameters affecting hydrolysis such as temperature, catalyst amount, sodium hydroxide concentration, and sodium borohydride concentration were examined. The reusability of the catalyst was tested five times. In the calculations, the reaction order was calculated as n, 0.73, and activation energy Ea, 49657 kJ/mol.
An integrated geotechnical and geophysical investigation of a catastrophic landslide in the Northeast Himalayas of Pakistan
Authors: Khan Muhammad Asim , Basharat Muhammad , Riaz Muhammad Tayyib , Sarfraz Yasir , Farooq Muhammad , Khan Ali Yousaf , Pham Quoc Bao , Ahmed Khawaja Shoaib , Shahzad Amir
Published: July 2021

Landslides are a complex geohazard, and the key parameters that have a prominent effect on their nature are variations in slope angle and fluctuations in groundwater. The focus of this research was to analyse the prevailing conditions of the Danna‐Sahotar landslide in the south of Muzaffarabad district, Sub‐Himalayas, Pakistan, and evaluating how different conditions effect the stability of the landslide with the integration of geotechnical, geophysical, and slope stability analysis. The geotechnical investigations revealed that the surface layer is mainly sandy with clayey and silty content. The two‐dimensional (2D) electrical resistivity tomography (ERT) demarcated the presence of a possible slip surface situated in the portion where the resistivity values clearly change. The ERT of the crown is characterized by low resistivity due to the presence of water seepages, which increase the degree of saturation and pore water pressure hence, leading to the slope failure. It was proved that the presence of high moisture content has played an influential role in triggering the landslide. Thorough analysis of integrated research yielded reliable and accurate information on the geotechnical and geological aspects of the landslide. The outcomes were used in slope stability limit equilibrium method (LEM) analysis using GeoStudio software. The slip surface predicted from the LEM was almost circular, which was confirmed by the geotechnical and ERT method. The factor of safety Fs (0.830) along the longitudinal profile of the landslide was calculated, indicating that the slopes along the profile are unstable. The geotechnical survey in combination with ERT and slope stability analysis helped to understand the failure mechanism of the landslide and to improve the layout of the future monitoring experiment, which may be used as a key for the observation of similar slope investigation.
New material of Aprotodon lanzhouensis (Perissodactyla, Rhinocerotidae) from the Early Miocene in Northwest China
Authors: Li Zhaoyu , Li Yongxiang , Zhang Yunxiang , Xie Kun , Li Zhichao , Chen Yu
Published: July 2021

Aprotodon is an extinct genus of the family Rhinocerotidae with a peculiar morphology that is mainly embodied in the wide mandibular symphysis and a pair of prominent second low incisors. The genus once lived on the vast grasslands of Asia, from Pakistan, and Kazakhstan to China, during the Late Eocene to the Early Miocene. The scarcity and incompleteness of the record, however, make the morphological characteristics of Aprotodon rather perplexing. Here, we report on a better mandible fossil with an intact second right incisor from the Xianshuihe Formation from the Early Miocene age (approximately 21–20 Ma) in the Lanzhou Basin, Gansu Province, China. Several important features, notably the elongated strongly curved tusk‐like incisors and mandibular symphysis, which widens sharply in the anterior part of the mandible, support attribution to A. lanzhouensis. Compared with previous specimens, the material described here is distinct in the lack of p1, horizontal ramus, and the ventral morphology of the mandible symphysis. Based on the new fossil specimen, we provide new material for the understanding of this extinct peculiar rhinoceros.
Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy
Authors: Chen Qian , Lv Han , Wang Zhaodi , Wei Xuan , Liu Jiao , Zhao Pengfei , Yang Zhenghan , Gong Shusheng , Wang Zhenchang
Published: July 2021

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network‐level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting‐state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory‐related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory‐related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network‐level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.
Automated Measurements of Body Composition in Abdominal CT Scans Using Artificial Intelligence Can Predict Mortality in Patients With Cirrhosis
Authors: Zou Winnie Y. , Enchakalody Binu E. , Zhang Peng , Shah Nidhi , Saini Sameer D. , Wang Nicholas C. , Wang Stewart C. , Su Grace L.
Published: July 2021

Body composition measures derived from already available electronic medical records (computed tomography [CT] scans) can have significant value, but automation of measurements is needed for clinical implementation. We sought to use artificial intelligence to develop an automated method to measure body composition and test the algorithm on a clinical cohort to predict mortality. We constructed a deep learning algorithm using Google’s DeepLabv3+ on a cohort of de‐identified CT scans (n = 12,067). To test for the accuracy and clinical usefulness of the algorithm, we used a unique cohort of prospectively followed patients with cirrhosis (n = 238) who had CT scans performed. To assess model performance, we used the confusion matrix and calculated the mean accuracy of 0.977 ± 0.02 (0.975 ± 0.018 for the training and test sets, respectively). To assess for spatial overlap, we measured the mean intersection over union and mean boundary contour scores and found excellent overlap between the manual and automated methods with mean scores of 0.954 ± 0.030, 0.987 ± 0.009, and 0.948 ± 0.039 (0.983 ± 0.013 for the training and test set, respectively). Using these automated measurements, we found that body composition features were predictive of mortality in patients with cirrhosis. On multivariate analysis, the addition of body composition measures significantly improved prediction of mortality for patients with cirrhosis over Model for End‐Stage Liver Disease alone (P < 0.001). Conclusion: The measurement of body composition can be automated using artificial intelligence and add significant value for incidental CTs performed for other clinical indications. This is proof of concept that this methodology could allow for wider implementation into the clinical arena.
Conflicts of interest in oncology expanded access studies
Authors: Borysowski Jan , Lewis Anna C. F. , Górski Andrzej
Published: July 2021

Expanded access is a treatment use of investigational drugs, biologicals or medical devices outside of clinical trials. The purpose of our study was to assess self‐reported conflicts of interest (COIs) in oncology expanded access studies. One hundred fifty‐eight oncology expanded access studies published from 2013 through 2020 were included. The pharmaceutical industry funded either completely or in part 94 studies (59.49%). The authors disclosed mostly financial COIs, while the number of the reported nonfinancial conflicts was relatively small (3528 and 57 COIs, respectively). The number of articles in which at least one author had a financial COI was 118 (74.68%). The most common financial COI types included advisory board membership/consulting (1471 COIs; 41.7%), followed by honoraria (570 COIs; 16.16%) and research funding (441 COIs; 12.5%). Logistic regression was performed to identify predictors of disclosing financial COIs and positive study's conclusions. On univariate analysis, financial COIs were more likely to occur in studies with at least one center located in the United States (odds ratio [OR], 5.62; 95% confidence interval [CI], 1.57‐35.98; P = .02). We also found that positive conclusions about the studied treatments were less likely in studies without industry funding (OR, 0.26; CI, 0.08‐0.77; P = .01). Most of the research on COIs in oncology performed to date focused on other types of studies, especially clinical trials. To our knowledge, our study is the first to evaluate COIs in oncology expanded access studies.
Tracing the Maps of Our Lives: A Review of Apple (Skin to the Core)
Authors: Sheahan Annmarie
Published: July 2021

Searing in content and ambitious in form, Eric Gansworth’s (2020) multimodal memoir, Apple (Skin to the Core), compels practitioners to widen the voices that students encounter in school and to position students as critical consumers of multimodal texts. Laced with images, prose, and repurposed pop cultural allusions, Gansworth’s memoir provides a model by which students can honor their own stories. This review highlights the importance of centering diverse Indigenous voices in school and community spaces while arguing for artistic creation as both an act and declaration of survival.
Efficient electrosorption of uranyl ions by a homemade amidoxime‐modified carbon paper‐based electrode in acidic aqueous condition
Authors: Pan Meng , Zhang Dongxiang , Xu Xiyan , Reda Alemtsehay Tesfay , Li Jinying
Published: July 2021

BACKGROUND

Electrosorption efficiency for uranyl ion (UO22+) capture is low in acid solution due to the adverse effect caused by protons. This requires novel electrodes effective at acid conditions for UO22+ electrosorption in highly acidic industrial effluents such as spent nuclear fuel treatment.

RESULTS

In the current study, UO22+ electrosorption was conducted using an amidoxime‐modified carbon paper (CP‐AO) electrode. The effects of voltage and frequency, pH, UO22+ initial concentration, and competing ions on UO22+ electrosorption were investigated. The reusability and electrochemical properties of the CP‐AO electrode were studied. The experimental results showed that the current CP‐AO electrode worked well in acidic conditiona (pH = 3) with a square wave periodic voltage (SWPV, −4 V, 1000 Hz), and outperformed a previously used carbon felt‐based electrode. The CP‐AO electrode showed considerable selectivity toward UO22+ in the presence of competitive ions. After seven rounds of continuous electrosorption–desorption, the CP‐AO electrode still showed good UO22+ uptake efficiency. The electrosorption mechanisms were studied in‐depth based on experimental and characterization results. The electrosorption of UO22+ by the CP‐AO electrode was due mainly to the electric field force moving UO22+ to the surface of the electrode, leading to electrodeposition of uranium compounds and the formation of electrically neutral substances.

CONCLUSIONS

The results indicated that based on SWPV electrosorption the CP‐AO could be a desirable treatment approach for acidic uranium‐containing wastewater with promising practical applications.
Management of systemic risk factors ahead of dental implant therapy: A beard well lathered is half shaved
Authors: Yu Hui , Zhou Anqi , Liu Jiayi , Tang Yufei , Yuan Quan , Man Yi , Xiang Lin
Published: July 2021

As the most successful therapy for missing teeth, dental implant has become increasingly prevalent around the world. A lot of papers have reported diverse local risk factors affecting the success and survival rate of dental implants, either for a short or a long period. However, there are also many types of systemic disorders or relatively administrated medicine that may jeopardize the security and success of dental implant treatment. Additionally, the coronavirus disease 2019 pandemic also poses a challenge to dental implant clinicians. Some of these risk factors are clinically common but to some extent unfamiliar to dentists, thus optimal measurements are often lacking when they occur in dental clinics. In this review, we analyze potential systemic risk factors that may affect the success rate of dental implants. Some of them may affect bone mineral density or enhance the likelihood of local infection, thus impeding osseointegration. Others may even systemically increase the risk of the surgery and threaten patients’ life. In order to help novices receive high-risk patients who need to get dental implant treatment in a more reasonable way, we accordingly review recent research results and clinical experiments to discuss promising precautions, such as stopping drugs that impact bone mineral density or the operation, and addressing any perturbations on vital signs.
The role of angiopoietin‐2 and surfactant protein‐D levels in SARS‐CoV‐2‐related lung injury: A prospective, observational, cohort study
Authors: Alay Handan , Laloglu Esra
Published: July 2021

Introduction

Coronavirus disease‐2019 (COVID‐19) is a respiratory disease whose clinical manifestation ranges from asymptomatic to severe respiratory failure. The purpose of this study was to investigate the place of serum surfactant‐D (SP‐D) and angiopoetin‐2 (Ang‐2) levels in predicting severity of disease in patients diagnosed with COVID‐19.

Methods

Sixty‐four patients diagnosed with COVID‐19 between September 2020 and February 2021, 50 patients diagnosed with community‐acquired pneumonia and a 50‐member healthy control group were included in the study. Plasma samples and clinical data were collected within 72 h after admission, during hospital stay. Serum SP‐D and Ang‐2 concentrations were measured using the enzyme‐linked immunosorbent assay.

Results

SP‐D and Ang‐2 levels were significantly higher in the mild–moderate pneumonia and severe/critical patient groups compared to the asymptomatic and noncomplicated COVID‐19 patients (p < 0.001 for all groups). Serum SP‐D and Ang‐2 levels of severe‐critical COVID‐19 patients were significantly higher than CAP patients (p < 0.001). Powerful correlation was present between clinical severity of COVID‐19 and SP‐D and Ang‐2 levels (r = 0.885 p < 0.001 and r = 0.913 p < 0.001, respectively). Cut‐off values of 37.7 ng/ml (AUC = 0.763, p < 0.001, 95% confidence interval [CI] = 0.667–0.860) for SP‐D and 4208.3 pg/ml (AUC = 0.659, p = 0.004, 95% CI = 0.554–0.763) for Ang‐2 were identified as predictors of COVID‐19 disease at receiver operating characteristic curve analysis.

Conclusion

SP‐D and Ang‐2 are predictive factors in differentiating COVID‐19 patients and determining severity of disease. These data may be important for the initiation of treatment in the early stage of the disease in patients with COVID‐19.
A Randomized Controlled Pilot Study: Combined 595‐nm Pulsed Dye Laser Treatment and Oxymetazoline Hydrochloride Topical Cream Superior to Oxymetazoline Hydrochloride Cream for Erythematotelangiectatic Rosacea
Authors: Sodha Pooja , Suggs Amanda , Munavalli Girish S. , Friedman Paul M.
Published: July 2021

Background and Objectives

We evaluated if oxymetazoline therapy combined with 595‐nm pulsed dye laser (PDL) will be more beneficial than topical oxymetazoline alone for the improvement of erythematotelangiectatic rosacea.

Study Design/Materials and Methods

This was a randomized, controlled, prospective clinical trial approved by an independent Institutional Review Board, which enrolled 34 patients with moderate to severe clinical erythema (CEA) into a two‐arm study of PDL with concomitant oxymetazoline cream (Arm 1) and oxymetazoline cream alone (Arm 2). Patients in Arm 1 were treated with 3 monthly laser sessions, which were started after 1 month of topical oxymetazoline cream. Thirty subjects continued with the study, and 25 subjects (Arm 1: 14, Arm 2: 11) completed the 6‐month follow‐up. With photographic comparison to baseline images, efficacy endpoints were based on clinical on‐site grading by both the investigator and the patient, using the grading tools for CEA, Global Aesthetic Improvement (GAI) assessment, vessel size improvement, and subject self‐assessment. These scales were assessed at baseline and/or at each clinical follow‐up at 1, 2, 3, and 6 months. Subject satisfaction as well as post‐treatment immediate response and treatment‐associated pain scores were also evaluated.

Results

Statistically significant improvement in CEA was seen in both arms at the 1‐, 2‐, and 3‐month post‐baseline visits (P < 0.01). Only Arm 1 presented statistically significant improvement in CEA (P < 0.001) at 6 months post baseline with a mean score of 1.6 (almost clear‐mild) compared with 3.2 at baseline. Arm 1 showed significantly greater mean vessel size improvement at 3 months (P < 0.01) and 6 months (P < 0.05) post baseline compared to Arm 2. Significantly greater improvement (P < 0.05) in the investigator GAI score was reported at the 2‐ and 6‐month follow‐ups compared with Arm 2. Subject GAI scores showed statistically significant greater improvement in Arm 1 compared with Arm 2 at both the 3‐ and 6‐month follow‐ups (P < 0.01). There were no complications or long‐term effects associated with PDL or topical oxymetazoline treatments.

Conclusion

The prospective trial verifies a safe, enhanced clinical outcome with the combination of PDL therapy and topical oxymetazoline for the treatment of erythematotelangiectatic rosacea patients. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.
On the optimality of competition within a team
Authors: Aytimur R. Emre
Published: July 2021

This paper studies the optimal team contract when the principal observes a noisy ranking of the efforts of the two team members. The objective of this paper is to understand whether it is optimal to use this competition‐promoting noisy ranking in a team setting. It is shown that noisy ranking is always part of the optimal contract both in static and repeated settings. Even though noisy ranking promotes competition between team members, it does not have a negative effect on peer monitoring incentives in a repeated setting. In summary, competition does not need to be damaging in a team setting.
The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study
Authors: Chida Keigo , Kotani Daisuke , Masuishi Toshiki , Kawakami Takeshi , Kawamoto Yasuyuki , Kato Kyoko , Fushiki Kunihiro , Sawada Kentaro , Kumanishi Ryosuke , Shirasu Hiromichi , Matsubara Yuki , Yuki Satoshi , Komatsu Yoshito , Yamazaki Kentaro , Yoshino Takayuki
Published: July 2021

Background

KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC.

Materials and Methods

We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations.

Results

Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04–1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01–2.00; p = .044).

Conclusion

We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.

Implications for Practice

Among patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.01; p = .015) and OS (HR, 1.50; 95% CI, 1.08–2.08; p = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.
Polyelectrolyte complexes of chitosan and sodium alginate as a drug delivery system for diclofenac sodium
Authors: Nikolova Denitsa , Simeonov Marin , Tzachev Christo , Apostolov Anton , Christov Lachezar , Vassileva Elena
Published: July 2021

Polyelectrolyte complexes (PECs) have unique physicochemical properties which make them very interesting for pharmaceutical applications and particularly as drug delivery systems. The aim of this work was to obtain PECs based on the biocompatible and biodegradable biopolymers chitosan and sodium alginate and to apply them as a drug delivery system for sustained release of diclofenac sodium. Three complexes with different ratios between the two polyions were obtained. Their structure and properties were investigated using dynamic light scattering, microscopy methods (optical, scanning and transmission electron microscopy), infrared spectroscopy, X‐ray diffraction. The drug entrapment efficiency of the various PECs was assessed and the release profiles were monitored. In this way the relationship between the composition of the PECs and the drug release profiles was outlined. The fibrillar form of the chitosan/alginate PECs was demonstrated to exert specific control over the diclofenac release which makes these materials appropriate as vehicles for controlled diclofenac sodium release. © 2021 Society of Industrial Chemistry.
Silk fibroin/chitosan hydrogel with antibacterial, hemostatic and sustained drug‐release activities
Authors: Xu Zhangpeng , Chen Tuying , Zhang Ke‐Qin , Meng Kai , Zhao Huijing
Published: July 2021

Hydrogels are viable wound dressing materials that have gained increasing attention due to their specific physicochemical properties, biocompatibility and environmental responsiveness. In addition to keeping a wound area moist, hydrogels characterized by a porous network structure and regulated drug‐release capacity promote the various phases of wound healing by effectively loading a drug and inducing anti‐infection activity. In this study, we prepared a multifunctional hydrogel with antibacterial, hemostatic and sustained drug‐release activities by chemically crosslinking silk fibroin (SF) and chitosan (CS) biomacromolecules. Results of characterization revealed that the synthesized hydrogel presents higher swelling and in vitro degradation rates under acidic conditions than in a neutral environment. Moreover, the three‐dimensional network structure of the material and the transformation of the SF secondary structure resulted in enhanced compressive mechanical properties (maximum compressive stress of 50–130 kPa). In vitro studies of drug loading and release, antibacterial assay, cytotoxicity studies, and coagulation assay were performed. Results showed that the prepared hydrogel exhibits good bacteriostatic and hemostatic properties, and it is not toxic towards human skin fibroblasts. Therefore, the designed SF/CS hydrogel constitutes an excellent candidate material for wound dressings. © 2021 Society of Industrial Chemistry.
The mobilities and immobilities of rural gentrification: Staying put or moving on?
Authors: Smith Darren P. , Phillips Martin , Culora Andreas , Kinton Chloe
Published: July 2021

This paper analyses census data for England and Wales to explore the ties between processes of rural gentrification and recent internal migration. Internal migrants are defined as individuals who moved subnationally to their current address in the previous 12 months, as indicated by the replies to the 2001 and 2011 census question about usual address 1 year ago. Our analysis reveals declining rural in‐migration rates between 2001 and 2011, in parallel with other recent studies of internal migration. At the same time, uneven geographies of rural in‐migration are identified. In rural places with declining in‐migration rates, we emphasise the immobilities of settled gentrifiers that are caused by predilections to ‘stay put’ within prized, rural places for age‐related personal/emotional, social/support and economic reasons. This is limiting the supply pipeline of housing for latent in‐migrants and slowing flows of migration per se in saturated rural housing markets. By contrast, rural places with increasing in‐migration rates may signify new frontiers of gentrification, providing channels of entry for recent migrants that are not able to buy into exclusive high‐cost gentrified markets. Our novel argument is that despite gentrification being inherently a process of migration, when viewed in a broader temporal perspective, mature and exclusive forms of gentrification can also stifle migration and be the catalyst for immobilities.
An initialisation scheme for tropical cyclones in the South China Sea
Authors: Huang Yanyan , Feng Yerong , Dai Guangfeng , Zhang Chengzhong , Zheng Bin
Published: July 2021

We propose an initialisation scheme for weak tropical cyclones (TCs) in the South China Sea (SCS) by combining composite and analysis vortices to improve forecasts of weak TCs in the region. The composite vortex is obtained from good samples of analyses of TCs in the SCS, and the analysis vortex is obtained from either European Centre for Medium‐Range Weather Forecasts (ECMWF) analysis data or an operational assimilation system. The new scheme has been applied to 57 cases of weak TCs, and the effect on the forecasting of four tropical storms has been studied in detail. It can be concluded that the proposed scheme can reduce track errors and intensity errors of weak TCs, compared with the control experiment. The possible reasons for these results are investigated in a case study for Linfa. Results of batch experiments show that the new method significantly improves TC track forecasting of tropical storms, severe tropical storms and typhoons, and demonstrates significant advantages in forecasting intensity of tropical storms, compared with the control experiment. It also performs better in predicting intensity of TCs in the SCS compared with ECMWF Atmospheric Model high resolution.
Influences of North Pacific anomalies on Indian summer monsoon onset
Authors: Choudhury Devanil , Tian Yurun , Chen Wen , Gao Yongqi
Published: July 2021

This study finds a significantly decreasing (increasing) trend (1979–2018) of sea level pressure (SLP) over coastal East Asia (far North Pacific) during May and June, which resembles the negative (positive) Pacific Decadal Oscillation (PDO) (North Pacific Oscillation, NPO)‐like pattern. Thus, we examine May composite differences between early and late Indian summer monsoon (ISM) onset years. Sea surface temperature (SST) differences show that early (late) ISM onset is accompanied by a negative (positive) PDO‐like state. Whereas, in SLP, an intense low pressure over northwestern India, the Arabian Sea to Southeast Asia (far North Pacific, East Asia) is associated with the early (late) onset. During the early onset, warm surface air temperature (SAT) anomalies over southeast Russia propagate towards Central Asia to the Middle East and the northwest Indian subcontinent, strengthening the land‐sea thermal contrast, which subsequently strengthens the monsoon low. We thus show how the positive NPO, negative PDO, and high spring Bering Sea ice link with the SAT anomalies. In the early onset, more wave packets generated in response to these North Pacific anomalies propagate towards the Atlantic and European region, reaching and converging over the northwest Indian subcontinent. The warm surface anomalies possibly draw eastward‐propagating waves towards northwest India, thus intensifying the monsoon low there. Meanwhile, in the CAM5 PDO simulation, we observe a similar pattern of atmospheric responses, where warm SAT anomalies associated with stationary Rossby wave trains propagate from the North Pacific towards the North Atlantic to Central Asia and the northwest Indian subcontinent, strengthening the monsoon low. Terefore, our study highlights the crucial role of the North Pacific anomalies in modulating the ISM onset processes via atmospheric pathways.
Disturbance‐observer based antiwindup control for singularly perturbed switched systems
Authors: Zhou Linna , Zhang Ying , Ma Lei , Yang Chunyu , Wang Guoqing
Published: July 2021

This article investigates the antiwindup control problem for a class of saturated singularly perturbed switched systems (SPSSs) with external disturbances. A novel antiwindup control architecture is first devised for the SPSSs by using the disturbance observer technique, which contains a state feedback controller, an antiwindup compensator and a disturbance observer. By constructing a singular perturbation parameter (SPP) dependent Lyapunov function, a set invariance condition is established, under which the antiwindup controller gain matrices can be derived, for any SPP less than or equal to a predefined upper bound. An optimization algorithm is formulated to enlarge the invariant set to reduce conservativeness. Then, an optimization problem is proposed in order to improve the disturbance refection ability. Moreover, the explicit parameterization of the disturbance rejection capacity is given by the solutions to a set of optimization algorithms with a guaranteed basin of attraction. Finally, a numerical example is provided to verify the effectiveness of the proposed antiwindup control strategy.
Finite‐time disturbance observer‐based modified super‐twisting algorithm for systems with mismatched disturbances: Application to fixed‐wing UAVs under wind disturbances
Authors: Nguyen Ngo Phong , Oh Hyondong , Kim Yoonsoo , Moon Jun , Yang Jun , Chen Wen‐Hua
Published: July 2021

This article proposes a finite‐time disturbance observer‐based modified super‐twisting algorithm (FDO‐STA) for disturbed high‐order integrator‐chain systems under matched and mismatched disturbances. We first design a finite‐time observer for disturbance estimation, in which we show the finite‐time convergence of disturbance estimation errors to zero. Second, by employing the estimates of disturbances and their derivatives, a new dynamic sliding surface is derived, which ensures the finite‐time convergence of the controlled output to zero in the sliding phase. Then, based on the estimates of disturbances and their derivatives, the designed sliding surface, and a modified super‐twisting algorithm, we develop the FDO‐STA, which guarantees the finite‐time convergence of the sliding variable to zero in the reaching phase. Rigorous analysis is provided to show the finite‐time stability of the overall closed‐loop system under the proposed control scheme. We finally apply the proposed FDO‐STA framework to the path following control for fixed‐wing UAVs under wind disturbances. Various simulation results are provided to show the effectiveness of the proposed controller, compared with the existing control approaches.
The governance of a community garden with a food cycle in suburban Tokyo
Authors: Shimpo Naomi
Published: July 2021

Urbanites can learn more about food cycles by growing vegetables and fruits and composting food residues within a community garden (CG). Case studies are necessary for developing theories about the sustainable governance of CGs containing food cycles. In particular, Asian cities have high potential to establish food cycles because of their mixture of urban and rural land use. This paper discusses the governance of a suburban‐Tokyo CG, where neighborhood kitchen wastes were collected and used as direct fertilizer for the soil. The quantitative and qualitative data obtained through interviews and internal material of the garden was analyzed to grasp the garden's history, stakeholders' involvement, and the relationships between gardeners and kitchen waste providers. The results showed that the founder started the garden in a bottom‐up way and overcame challenges by maintaining a strong motivation and a flexible attitude. The gardeners provided work opportunities to people with disabilities and education materials to children. These collaborations may have corroborated the necessity of the garden existence. Most of the gardeners and all the waste providers live within 2 km of the garden and the close communication between them was possible, which may have maintained the kitchen waste quality. This study demonstrates advantages and challenges in the governance of Japanese CGs; however, further case studies are necessary for improving the generalizability of this study's findings.
Introduction: Advances in Research on Shared Physical Custody by Interdisciplinary Approaches
Authors: Bernardi Laura , Mortelmans Dimitri
Published: July 2021

This introductory chapter provides the rationale for adopting an interdisciplinary approach to study the implications of shared physical custody arrangements for families and their members. The Chapter gives a rapid overview of the current state of the literature on shared physical custody in the legal, sociological and psychological literature and highlights the uncertainties and controversial aspects still open to exploration in this field. It addresses the specific research needs in order to move forward from the current situation, where evidence on shared physical custody produce results that are scattered across disciplines and hard to compare across contexts. It concludes by arguing that the complexity of shared physical custody implications in terms of health, educational, relational and living standards requires research from different disciplinary fields in order to agree on a comprehensive theoretical perspective, standardize definitions and collect longitudinal and comparable data on the custody arrangements and their normative environments.
Postdivorce Parent-Child Contact and Child Outcomes: The Role of Spatial Mobility
Authors: Poortman Anne-Rigt
Published: July 2021

Shared physical custody, or more generally, frequent contact with both parents is often assumed to benefit children, but having to move back and forth between parents’ homes may also be harmful, particularly when parents live far apart. This study examined the role of spatial mobility in the association between frequent parent-child contact and multiple child outcomes. Using the New Families in the Netherlands survey, analyses firstly showed that frequent parent-child contact, on average, was found to be not or modestly associated with better child outcomes. Second, spatial mobility mattered, but in varying ways. Long travel times were negatively associated with children’s contact with friends and their psychological well-being, but positively related to educational performance. Furthermore, frequent commutes were negatively associated with how often children saw their friends, but positively associated with child psychological well-being. Third, and most importantly, the impact of parent-child contact and frequent commutes on child outcomes were found to be dependent on traveling time. For child psychological well-being and contact with friends, frequent parent-child contact and/or frequent commutes were found to have positive effects when travel distances were short, but these positive effects disappeared when traveling times increased.
Psychological Perspectives on Joint Physical Custody
Authors: Emery Robert E.
Published: July 2021

This overview discusses key findings, questions, and controversies about joint physical custody (JPC) emphasizing psychological issues for research and practice. Children living in JPC are slightly better adjusted, on average, but it is not clear whether this is a consequence of the arrangement or due to nonrandom selection into it. Moreover, no consistent evidence links specific variations in JPC to better or worse child adjustment, including equal or some other pattern of shared time. Parental conflict/cooperation is the factor most firmly, if still somewhat tenuously, established as a moderator of JPC effects. Other important moderators include logistics (e.g., geographical distance between parents), developmental stage (very young children and older adolescents may fare less well), and personality (a factor only beginning to be explored). The clearest implication for policy and practice is that children will fare better if their parents cooperate in crafting a parenting plan designed to meet their individual needs.
The SOHI: Operationalizing a New Model for Studying Teenagers’ Sense of Home in Post-divorce Families
Authors: Merla Laura , Dedonder Jonathan , Nobels Bérengère , Murru Sarah
Published: July 2021

This chapter explores the important question of whether, and under which conditions, children alternating between two distinct family dwellings can develop a sense of home that might nourish a sense of belonging to their sometimes, complex family configurations. We first present a theoretical framework to understand the various dimensions that influence children’s sense of home in shared custody arrangements, building on Hashemnezhad et al. (2013)’s work. We then show how this framework can be operationalized in quantitative research. For this purpose, we introduce the Sense of Home Instrument (SOHI), a new instrument for measuring the impact of material and behavioral-relational dimensions on teenagers’ sense of home at their mothers’ and fathers’. We then illustrate its relevance and value with supporting analyses of data collected through a survey conducted with Belgian adolescents aged between 11 and 18. In doing so, we propose new avenues for research on the consequences of divorce and separations for children’s identity construction and belonging, where the spatiality of family life is taken into-account.