bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and segmentation of melanoma skin cancer in dermoscopy images using modified Alexnet convolutional neural network‐morphological methodology
Authors: Govindaswamy Bharathi , Mallappa Malleswaran
Published: August 2022

Melanoma is most vicious and dangerous type of skin cancer that its early detection can save patients' lives. Computer‐aided methods can be used for this early detection with acceptable performance. In this article, the melanoma skin cancer dermoscopy images are detected and cancer regions are segmented using the proposed modified AlexNet convolutional neural network‐morphological segmentation (CNN‐MS) method. This proposed work consists of enhancement stage, feature matrix construction stage, CNN classification stage, and segmentation stage. In enhancement stage, the skin pixels are contrast enhanced by histogram equalization technique and then non‐sub sampled contourlet transform (NSCT) is applied on the enhanced skin image to obtain the decomposed coefficients. Further, local ternary pattern (LTP) features are computed from the enhanced image and the feature matrix (FM) is constructed by integrating the NSCT coefficients and the LTP features. This constructed FM is fed to the CNN model for the classification of Melanoma skin cancer images from the normal skin images. Finally, morphological functions are applied on the classified melanoma skin image to segment the cancer regions. The performance of this developed model for skin cancer detection is analyzed on international skin imaging collaboration (ISIC) dataset images and achieves 98.11% of Se, 98.5% of Sp, 99.11% of Acc, and 0.96 of MCC. Also, the performance of this developed model for skin cancer detection is analyzed on SIIM‐ISIC dataset images and achieves 98.04% Se, 98.46% Sp, 99.12% Acc, and 0.97 MCC.
Alternate wetting and moderate soil drying could increase grain yields in both main and ratoon rice crops
Authors: Zhang Qiang , Liu Xiangchen , Yu Guilong , Duan Bin , Wang Hao , Zhao Haiying , Feng Daqing , Gu Mengxuan , Hu Yang , Chen Yingxia , Liu Lijun
Published: August 2022

Alternate wetting and drying irrigation is a widely used irrigation method for water‐savings and high‐yielding in rice (Oryza sativa L.) production; however, its effect on grain yield (GY) in the main and ratoon crops is unclear. With two rice cultivars as materials, the effects on GY in the main and ratoon crop of three irrigation regimes, that is, conventional flooding irrigation (CI), alternate wetting and moderate soil drying irrigation (WMD), and alternate wetting and severe soil drying irrigation (WSD), during grain filling of the main crop were investigated. Compared with CI, WMD increased GY by 6.0∼6.5% in the main crop by increasing the 1,000‐grain weight and filled grain rate, whereas the ratoon crop GY increased by 13.3∼14.6% via increased panicle number. The WSD had no significant effects on the main crop GY, but significantly decreased ratoon crop GY by decreasing panicle number. A higher leaf photosynthetic rate, leaf area index, root oxidation activity, dry matter accumulation and nonstructural carbohydrate (NSC) translocation under WMD primarily drove the increased 1,000‐grain weight and filled grain rate in the main crop. Under WMD, higher soluble sugar contents catalysed by high amylase activity and higher zeatin + zeatin riboside in stems of the main crop promoted the growth of regenerated buds and increased the ratoon crop panicle number. In conclusion, WMD during grain filling of the main crop improved the growth and development of the main crop and promote the germination of regenerated buds, thereby increasing the GY of both main and ratoon crops.
Exploring the bidirectional relationships between night eating, loss of control eating, and sleep quality in Chinese adolescents: A four‐wave cross‐lagged study
Authors: Weng Hongbin , Barnhart Wesley R. , Cheng Yawei , Chen Gui , Cui Tianxiang , Lu Tom , He Jinbo
Published: August 2022

Objective

This study examined the bidirectional relationships between sleep quality, loss of control (LOC) eating, and night eating in Chinese adolescents using longitudinal data over an 18‐month study period.

Method

Four‐waves of data measurement (Waves 1–4), at 6‐month intervals, were conducted with 2566 adolescents aged 11–17 years at baseline. A set of questionnaires were used to assess night eating, LOC eating, and sleep quality at each wave of data collection. Cross‐lagged models were applied to analyze the bidirectional relationships between night eating, LOC eating, and sleep quality.

Results

Results indicated that higher night eating scores consistently predicted poorer sleep quality and higher LOC eating scores at Waves 1, 2, and 3. Furthermore, poorer sleep quality predicted higher night eating scores at Wave 1 and Wave 3, and higher LOC eating scores predicted higher night eating scores at Wave 1 and Wave 2.

Discussion

These findings highlight that night eating, LOC eating, and sleep quality were interrelated across time in Chinese adolescents. Improving sleep quality and reducing LOC eating might be promising in the prevention of night eating in adolescents. Similarly, reducing night eating might be promising in improving sleep quality and reducing LOC eating in adolescents.

Public Significance

This study explored the bidirectional relationship between night eating, LOC eating, and sleep quality in Chinese adolescents using cross‐lagged models. Findings indicate bidirectional relationships between these variables and highlight the potential utility in incorporating sleep, LOC eating, and night eating interventions in eating pathology prevention designs for adolescents.
Monosaccharide profiling of glycoproteins by capillary electrophoresis with contactless conductivity detection
Authors: Tomnikova Alice , Kozlík Petr , Křížek Tomáš
Published: August 2022

Saccharides form one of the major constituents of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response and receptor activation are regulated by glycosylation. In this work, we optimized a capillary electrophoresis method with capacitively coupled contactless conductivity detection for the separation of eight monosaccharides commonly found in glycoproteins, namely D‐glucose, D‐galactose, D‐mannose, N‐acetyl‐D‐glucosamine, N‐acetyl‐D‐galactosamine, D‐fucose, N‐acetylneuraminic acid, and D‐xylose. A highly alkaline solution of 50 mM sodium hydroxide, 22.5 mM disodium phosphate, and 0.2 mM CTAB (pH 12.4) was used as a background electrolyte in a 10 µm id capillary. To achieve baseline separation of all analytes, a counter‐directional pressure of –270 kPa was applied during the separation. The limits of detection of our method were below 7 µg/ml (i.e., 1.5 pg or 1 mg/g protein) and the limits of quantification were below 22 µg/ml (i.e., 5 pg or 3 mg/g protein). As a proof of concept of our methodology, we performed an analysis of monosaccharides released from fetuin glycoprotein by acid hydrolysis. The results show that, when combined with an appropriate pre‐concentration technique, the developed method can be used as a monosaccharide profiling tool in glycoproteomics and complement the routinely used LC‐MS/MS analysis.
Sediment supply control on morphodynamic processes in gravel‐bed river widenings
Authors: Rachelly Cristina , Vetsch David F. , Boes Robert M. , Weitbrecht Volker
Published: August 2022

Reach‐scale widening of channelized rivers can locally reactivate morphodynamic processes and increase habitat heterogeneity. Following process‐based restoration principles, construction efforts are often limited to bank protection removal and local bank erosion initiation. Despite significant advances in our understanding of fluvial processes, the influence of sediment supply on widening morphodynamics is still inadequately understood. Using mobile‐bed laboratory experiments, we studied the morphological development of river widenings in channelized subalpine gravel‐bed rivers in response to different sediment supply levels. The initial setup included a channel with a longitudinal slope of around 1% and a floodplain on one side, which was 25 channel widths long and three wide. After removing the fixed bank, the floodplain was available for erosion and channel shifting. Seven experimental series with sequences of steady bed‐forming discharge and unsteady larger floods were conducted. Sediment was supplied at rates of 20%, 60%, 80%, and 100% of the initial channel's transport capacity. The laboratory experiments were combined with two‐dimensional hydrodynamic numerical simulations to closely track both the morphological development and the resulting flow conditions. Sediment supply was found to be a critical driver of morphodynamic activity in river widenings, with sediment supply rates close to channel transport capacity promoting active channel widening, sediment relocation, and lateral channel‐floodplain connectivity. In contrast, low sediment supply maintained a stable, single‐thread channel disconnected from its floodplain. Further, our results indicate that an increase in sediment supply or structural measures triggering local flow deflection can reactivate morphodynamic processes in previously sediment‐starved reaches after a transition period of several years to decades. Our results highlight the fundamental importance of sediment transport in reach‐scale river restoration.
Reliability‐based offloading strategy for deadline‐constrained taskflows in vehicular edge computing environments
Authors: Li Bo , Li Kun , Jin Shicheng , Qian Rongrong , Ding Hongwei
Published: August 2022

Vehicular edge computing (VEC) offers a new paradigm for improving vehicular services and enhancing vehicle capabilities. In the VEC environments, vehicles can offload tasks to edge servers deployed in roadside units or other vehicles via wireless networks to enhance their computation capability. However, the high mobility of vehicles will lead to constant change of the network topology among resources, which will affect the completion time and the reliability of offloaded tasks. Therefore, we proposes a reliability‐based offloading strategy by considering task attributes, resource state, completion time, and reliability to map task flows to resources that can satisfy the time constraints with high reliability. The experimental results show that, compared with existing typical algorithms, the proposed strategy not only reduces the average completion time of tasks, but also ensures the reliability of tasks.
Muscarinic and N‐methyl‐D‐aspartate receptor blockade reveal differences in hippocampal local field potentials in mice with low cholinergic tone
Authors: Leung L. Stan , Moallem Shahin , Prado Marco A. M. , Prado Vania F. , Chu Liangwei
Published: August 2022

We hypothesize that hippocampal local field potentials in acetylcholine (ACh)‐deficient mutant mice, compared to wild‐type (WT) mice, will show lower sensitivity to muscarinic cholinergic antagonist scopolamine (5 mg/kg i.p.) but higher sensitivity to NMDA receptor antagonist 3‐(2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphonic acid (CPP, 10 mg/kg i.p.). Recordings were made during walk and awake‐immobility (IMM) in WT mice, and in mice with forebrain knockout (KO) of the vesicular acetylcholine transporter (VAChT) gene, or heterozygous knockdown of VAChT gene (KD). Scopolamine or CPP did not significantly alter walk theta frequency, which was higher in KD than WT/KO mice. Scopolamine decreased theta power peak rise during walk in WT/KD mice but not in KO mice, while CPP suppressed theta peak rise more in WT/KO mice than KD mice. During IMM, scopolamine decreased gamma1 (γ1, 30–58 Hz) power more in KD/WT mice than KO mice, while delta (1–4 Hz) power and delta‐gamma cross‐frequency coherence (CFC) were increased in all mouse groups during IMM or walk. During walk, scopolamine increased delta and beta (13–30 Hz) power and decreased gamma2 (γ2, 62–100 Hz) power and theta‐γ2 CFC more in WT/KD than KO mice. Theta‐γ2, but not theta‐γ1, CFC increased with theta‐peak‐frequency in WT/KD mice, and was suppressed by scopolamine at high theta (8–10 Hz) frequency; theta‐γ2 CFC in KO mice was not significantly altered by scopolamine. CPP decreased beta and gamma power more in KD/KO mice compared to WT mice, while delta power and delta‐gamma CFC were increased in all mouse groups. ACh deficiency exacerbates the attenuation of beta and gamma power by CPP. We conclude that both muscarinic and NMDA transmission contribute toward hippocampal theta, beta, and gamma power, and a decrease in gamma power or theta‐gamma CFC may be associated with loss of arousal and cognitive functions.
A configurational analysis of IT governance: A study of the financial services sector in Ghana
Authors: Asmah Alexander , Kyobe Michael
Published: August 2022

This study seeks to answer the question, what is the right configuration of IT Governance mechanisms that will improve performance? Although few studies have addressed how governance mechanisms improve performance, these studies have adopted a linear approach in assessing the relationships among governance mechanisms. The nature of the linear relationships has not answered the lingering question making this study crucial. The study follows the configurational theories that for IT governance to improve performance, all the governance mechanisms much be implemented coherently. We used Cluster analysis to assess the nature of the configuration in the Ghanaian Financial Services Sector using 7 companies. Our findings confirm our theory that to improve performance, IT Governance mechanisms must be implemented coherently. However, in a fast‐changing environment, there is the need to increase focus on technological mechanisms to provide timely information for decision making, collaboration and reduce information asymmetry. As a contribution to practice, this study recommends that policy makers in the financial space should emphasize the need for adequate IT Governance implementations with the right configuration. Companies in the pension and savings and loan sectors should be encouraged to adopt more technological mechanisms.
The beneficial therapeutic effects of plant‐derived natural products for the treatment of sarcopenia
Authors: Bagherniya Mohammad , Mahdavi Atena , Shokri‐Mashhadi Nafiseh , Banach Maciej , Von Haehling Stephan , Johnston Thomas P. , Sahebkar Amirhossein
Published: August 2022

Sarcopenia is an age‐related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes of sarcopenia in the elderly have been proposed. However, the exact mechanisms involved in sarcopenia, as well as effective treatments for this condition, are not fully understood. The purpose of this article was to conduct a comprehensive review of previous evidence regarding the definition, diagnosis, risk factors, and efficacy of plant‐derived natural products for sarcopenia. The methodological approach for the current narrative review was performed using PubMed, Scopus, and Web of Science databases, as well as Google Scholar (up to March 2021) in order to satisfy our objectives. The substantial beneficial effects along with the safety of some plant‐derived natural products including curcumin, resveratrol, catechin, soy protein, and ginseng on sarcopenia are reported in this review. Based on clinical studies, nutraceuticals and functional foods may have beneficial effects on physical performance, including handgrip and knee‐extension strength, weight‐lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, muscle fatigue, mean muscle fibre area, and total number of myonuclei. In preclinical studies, supplementation with herbs and natural bioactive compounds resulted in beneficial effects including increased plantaris mass, skeletal muscle mass and strength production, increased expression of anabolic factors myogenin, Myf5 and MyoD, enhanced mitochondrial capacity, and inhibition of muscle atrophy and sarcopenia. We found that several risk factors such as nutritional status, physical inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history of chronic disease, mental health, and genetic factors are linked or associated with sarcopenia. The substantial beneficial effects of some nutraceuticals and functional foods on sarcopenia, including curcumin, resveratrol, catechin, soy protein, and ginseng, without any significant side effects, are reported in this review. Plant‐derived natural products might have a beneficial effect on various components of sarcopenia. Nevertheless, due to limited human trials, the clinical benefits of plant‐derived natural products remain inconclusive. It is suggested that comprehensive longitudinal clinical studies to better understand risk factors over time, as well as identifying a treatment strategy for sarcopenia that is based on its pathophysiology, be undertaken in future investigations.
Geranylgeranyl pyrophosphate depletion by statins compromises skeletal muscle insulin sensitivity
Authors: Wang Lai , Zheng Zuguo , Zhu Lijun , Meng Lingchang , Liu Hanling , Wang Keke , Chen Jun , Li Ping , Yang Hua
Published: August 2022

Background

Statins are widely prescribed cholesterol‐lowering drugs but have been shown to increase the risk of type 2 diabetes mellitus. However, the molecular mechanisms underlying the diabetogenic effect of statins are still not fully understood.

Methods

The effects of geranylgeranyl transferase I and II (GGTase I and II) inhibition on insulin‐stimulated glucose uptake and GLUT4 translocation, and the dependence of these effects on insulin signalling were investigated in skeletal muscle cells. The protective effects of geranylgeranyl pyrophosphate (GGPP) and its precursor geranylgeraniol (GGOH) on simvastatin‐induced insulin resistance were evaluated in vitro and in vivo. The effect of GGTase II inhibition in skeletal muscle on insulin sensitivity in vivo was confirmed by adeno‐associated virus serotype 9 (AAV9)‐mediated knockdown of the specific subunit of GGTase II, RABGGTA. The regulatory mechanisms of GGTase I on insulin signalling and GGTase II on insulin‐stimulated GLUT4 translocation were investigated by knockdown of RhoA, TAZ, IRS1, geranylgeranylation site mutation of RhoA, RAB8A, and RAB13.

Results

Both inhibition of GGTase I and II mimicked simvastatin‐induced insulin resistance in skeletal muscle cells. GGPP and GGOH were able to prevent simvastatin‐induced skeletal muscle insulin resistance in vitro and in vivo. GGTase I inhibition suppressed the phosphorylation of AKT (Ser473) (−51.3%, P < 0.01), while GGTase II inhibition had no effect on it. AAV9‐mediated knockdown of RABGGTA in skeletal muscle impaired glucose disposal without disrupting insulin signalling in vivo (−46.2% for gastrocnemius glucose uptake, P < 0.001; −52.5% for tibialis anterior glucose uptake, P < 0.001; −17.8% for soleus glucose uptake, P < 0.05; −31.4% for extensor digitorum longus glucose uptake, P < 0.01). Inhibition of RhoA, TAZ, IRS1, or geranylgeranylation deficiency of RhoA attenuated the beneficial effect of GGPP on insulin signalling in skeletal muscle cells. Geranylgeranylation deficiency of RAB8A inhibited insulin‐stimulated GLUT4 translocation and concomitant glucose uptake in skeletal muscle cells (−42.8% for GLUT4 translocation, P < 0.01; −50.6% for glucose uptake, P < 0.001).

Conclusions

Geranylgeranyl pyrophosphate regulates glucose uptake via GGTase I‐mediated insulin signalling‐dependent way and GGTase II‐mediated insulin signalling‐independent way in skeletal muscle. Supplementation of GGPP/GGOH could be a potential therapeutic strategy for statin‐induced insulin resistance.
Accumulation of recalcitrant dissolved organic matter in aerobic aquatic systems
Authors: Cotner James B. , Anderson N.J. , Osburn Christopher
Published: August 2022

An oxygenated atmosphere changed life on Earth but it also provided a negative feedback to organic matter accumulation by increasing decomposition rates. Nonetheless, dissolved organic carbon (DOC) is a huge carbon pool (> 750 Pg) and it can accumulate to high concentrations (20–100 mg C L−1) in some freshwater aquatic systems, yet it is not clear why. Here, we examine DOC in several Greenland lakes with varying DOC concentrations and identify processes that could alter its composition to make it increasingly recalcitrant. Δ14C aging of DOC corresponded with increased DOC concentrations, slower degradation rates, changes in isotope ratios and optical properties, all suggesting that photochemical and microbial degradation processes contributed to recalcitrance. Young DOC degradation was stimulated by phosphorus, but older DOC was not, suggesting an important role for nutrients early in degradation. Photochemical processing coupled with decreased habitat diversity in hydrologically isolated systems may enable recalcitrant DOC to accumulate with important implications for Earth's carbon and oxygen cycles.
BrainMRIin the Decision for Liver Transplantation in Pediatric Neurological Wilson's Disease
Authors: Pinto Catarina , Malaquias Maria João , Miranda Helena Pessegueiro , Temudo Teresa , Silva Ermelinda , Ramos Cristina , Magalhães Marina
Published: August 2022

Background

Neurological Wilson's disease (WD) presentation in the pediatric population is rare, and liver transplantation (LT) in these patients remains controversial. The aim of the present study was to assess the role of brain magnetic resonance imaging (MRI) in predicting reversion of brain lesions and neurological outcomes in pediatric WD patients after LT.

Methods

Patients with confirmed WD (Leipzig score ≥4), disease onset in pediatric age (<18 years), neurological involvement, and submitted to LT were selected. Clinical records and pre‐ and post‐LT brain MRI were evaluated.

Results

Six patients met the pre‐defined inclusion criteria, one of whom died shortly after LT and was excluded. The indication for LT was end‐stage liver disease in two patients and neurological worsening despite optimized treatment in three patients. After LT, the neurological picture progressively improved in all patients. Pre‐LT brain MRI showed T1‐weighted hyperintensities in four patients, which quickly resolved afterward. T2‐weighted hyperintensities were observed in four patients before LT, completely resolving in one patient, stabilizing in two, and improving in one after LT. A direct correlation could not be found between clinical and neuroradiological improvement. Progressive clinical improvement was observed even in patients with irreversible brain MRI changes. Conversely, some patients with normal MRI had only slight neurological improvement.

Conclusions

The pattern of T2‐weighted hyperintensities after LT was unpredictable and did not correlate with neurological outcomes, suggesting that these changes may not entail irreversible clinical damage. Therefore, brain MRI does not seem to have prognostic value for assessing clinical response to LT.
MolPredictX: Online Biological Activity Predictions by Machine Learning Models
Authors: Tullius Scotti Marcus , Herrera‐Acevedo Chonny , Barros de Menezes Renata Priscila , Martin Holli‐Joi , Muratov Eugene N. , Ítalo de Souza Silva Ávilla , Faustino Albuquerque Emmanuella , Ferreira Calado Lucas , Coy‐Barrera Ericsson , Scotti. Luciana
Published: August 2022

Here we report the development of MolPredictX, an innovate and freely accessible web interface for biological activity predictions of query molecules. MolPredictX utilizes in‐house QSAR models to provide 27 qualitative predictions (active or inactive), and quantitative probabilities for bioactivity against parasitic (Trypanosoma and Leishmania), viral (Dengue, Sars‐CoV and Hepatitis C), pathogenic yeast (Candida albicans), bacterial (Salmonella enterica and Escherichia coli), and Alzheimer disease enzymes. In this article, we introduce the methodology and usability of this webtool, highlighting its potential role in the development of new drugs against a variety of diseases. MolPredictX is undergoing continuous development and is freely available at https://www.molpredictx.ufpb.br/.
Development and interinstitutional validation of an automatic vertebral‐body misalignment error detector for cone‐beam CT‐guided radiotherapy
Authors: Luximon Dishane C. , Ritter Timothy , Fields Emma , Neylon John , Petragallo Rachel , Abdulkadir Yasin , Charters John , Low Daniel A. , Lamb James M.
Published: August 2022

Background

In cone‐beam computed tomography (CBCT)‐guided radiotherapy, off‐by‐one vertebral‐body misalignments are rare but serious errors that lead to wrong‐site treatments.

Purpose

An automatic error detection algorithm was developed that uses a three‐branch convolutional neural network error detection model (EDM) to detect off‐by‐one vertebral‐body misalignments using planning computed tomography (CT) images and setup CBCT images.

Methods

Algorithm training and test data consisted of planning CTs and CBCTs from 480 patients undergoing radiotherapy treatment in the thoracic and abdominal regions at two radiotherapy clinics. The clinically applied registration was used to derive true‐negative (no error) data. The setup and planning images were then misaligned by one vertebral‐body in both the superior and inferior directions, simulating the most likely misalignment scenarios. For each of the aligned and misaligned 3D image pairs, 2D slice pairs were automatically extracted in each anatomical plane about a point within the vertebral column. The three slice pairs obtained were then inputted to the EDM that returned a probability of vertebral misalignment. One model (EDM1) was trained solely on data from institution 1. EDM1 was further trained using a lower learning rate on a dataset from institution 2 to produce a fine‐tuned model, EDM2. Another model, EDM3, was trained from scratch using a training dataset composed of data from both institutions. These three models were validated on a randomly selected and unseen dataset composed of images from both institutions, for a total of 303 image pairs. The model performances were quantified using a receiver operating characteristic analysis. Due to the rarity of vertebral‐body misalignments in the clinic, a minimum threshold value yielding a specificity of at least 99% was selected. Using this threshold, the sensitivity was calculated for each model, on each institution's test set separately.

Results

When applied to the combined test set, EDM1, EDM2, and EDM3 resulted in an area under curve of 99.5%, 99.4%, and 99.5%, respectively. EDM1 achieved a sensitivity of 96% and 88% on Institution 1 and Institution 2 test set, respectively. EDM2 obtained a sensitivity of 95% on each institution's test set. EDM3 achieved a sensitivity of 95% and 88% on Institution 1 and Institution 2 test set, respectively.

Conclusion

The proposed algorithm demonstrated accuracy in identifying off‐by‐one vertebral‐body misalignments in CBCT‐guided radiotherapy that was sufficiently high to allow for practical implementation. It was found that fine‐tuning the model on a multi‐facility dataset can further enhance the generalizability of the algorithm.
The effect of a tight control regime with monthly follow‐up on remission rates and reported pain in early rheumatoid arthritis
Authors: Aronsson Maria , Teleman Annika , Bergman Stefan , Lindqvist Elisabet , Forslind Kristina , Andersson Maria L. E.
Published: August 2022

Objective

To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6 months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA).

Methods

In this single‐centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2 years.

Results

The patients in the TC cohort had lower 28‐ joints disease activity score (DAS28) at three, six, 12 and 24 months, compared with the conventionally managed cohort, p ≤ 0.001. At 12 months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28 < 2.6) and at 24 months 68% versus 49% respectively, p < 0.05. The TC cohort reported less pain at three, six, 12 and 24 months, p < 0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24 months and with acceptable pain at 24 months.

Conclusion

The intensive follow‐up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.
Noncovalent functionalization of boron nitride via chelation of tannic acid with Fe ions for constructing high thermally conductive polymeric composites
Authors: Wang Hailong , Hao Jian , Yang Dan
Published: August 2022

With the advancement of integration and miniaturization of precise instruments, the heat accumulating in electronic components is urgently needed to dissipate for ensuring their service life. In this work, boron nitride (BN) was functionalized with tannic acid/ferric ions (TA/Fe) chelate complexes to synthesize high thermally conductive natural rubber (NR) composites (NR@TA/Fe‐BN). The stable TA/Fe chelate complexes improved the interfacial compatibility between BN and NR and enhanced the BN dispersion in the NR matrix, which led to the reduction of interfacial thermal resistance and the construction of heat transfer channels in NR composites. As a result, a relative high thermal conductivity (0.327 W/(mK)) by 30 vol% NR@TA/Fe‐BN composite was achieved, being 2.44 times that of pure NR (about 0.134 W/(mK)). In addition, the insulating NR@TA/Fe‐BN composites showed outstanding elongation at break (686%) and tensile strength (15.2 MPa). This highly efficient and green TA inspired modification is expected to find application in industrial manufacturing of thermally conductive polymeric composites.
Preparation and properties of glass fiber reinforced nylon56 composites
Authors: Zhao Yanhui , Wang Liyan , Chong Yunsheng , Chen Yanming , Zheng Rongrong , Zhang Longyun
Published: August 2022

Glass fiber (GF) reinforced nylon56 composites (nylon56/GF) were prepared by melting and blending through twin‐screw extruder with continuous fiber feeding. The structure and properties of the composites were characterized by electron density tester, polarizing microscope, scanning electron microscope, electro‐mechanical universal testing machine and thermal analyzer. The results showed that the density of the prepared composites is less than 1.37 g/cm3. There is strong interface adhesion between glass fiber and nylon56 matrix in the composite system, and the glass fiber length in the system is 0.47–0.61 mm. With the increase in the content of high‐performance glass fiber, the mechanical properties of the composite are significantly improved. When four bundles of GF are added, the properties of the nylon56/GF composite are the best. The tensile strength of nylon56/GF composite reaches 160 MPa, 86.9% higher than that of nylon56. The bending strength is 180 MPa and increases by 98.7% more than that of nylon56. The flexural modulus is 7100 MPa and rises by 125.6% compared with nylon56, and the impact strength is 11 kJ/mm2, which is 307.4% higher than that of nylon56. The nylon56/GF composite has a low density and excellent performance and can be widely used in locomotive and wind power.
An international study on implementation and facilitators and barriers for parent‐infant closeness in neonatal units
Authors: van Veenendaal Nicole R. , Labrie Nanon H.M. , Mader Silke , van Kempen Anne A. M. W. , van der Schoor Sophie R. D. , van Goudoever Johannes B. ,   CROWN Study Group
Published: August 2022

Importance

Parent‐infant closeness and active parent participation in neonatal care are important for parent and infant health.

Objective

To give an overview of current neonatal settings and gain an in‐depth understanding of facilitators and barriers to parent‐infant closeness, zero‐separation, in 19 countries.

Methods

Neonatal intensive care unit (NICU) professionals, representing 45 NICUs from a range of geographic regions in Europe and Canada, were purposefully selected and interviewed June–December 2018. Thematic analysis was conducted to identify, analyze and report patterns (themes) for parent‐infant closeness across the entire series of interviews.

Results

Parent‐infant separation during infant and/or maternity care is very common (42/45 units, 93%), despite the implementation of family integrated care (FICare) practices, including parent participation in medical rounds (17/45, 38%), structured education sessions for parents (16/45, 36%) and structured training for healthcare professionals (22/45, 49%). NICU professionals encountered four main themes with facilitators and barriers for parent‐infant closeness on and between the hospital, unit, staff, and family level: Culture (jointly held characteristics, values, thinking and behaviors about parental presence and participation in the unit), Collaboration (the act of working together between and within different levels), Capacities (resources and policies), and Coaching (education to acquire and transfer knowledge and skills).

Interpretation

Implementing parent‐infant closeness in the NICU is still challenging for healthcare professionals. Further optimization in neonatal care towards zero‐separation and parent‐infant closeness can be achieved by enforcing the ‘four Cs for Closeness’: Culture, Collaboration, Capacities, and Coaching.
Dynamic regulation of Zn(II) sequestration by calgranulin C
Authors: Wang Qian , Kuci Deniz , Bhattacharya Shibani , Hadden‐Perilla Jodi A. , Gupta Rupal
Published: August 2022

Calgranulin C performs antimicrobial activity in the human immune response by sequestering Zn(II). This biological function is afforded with the aid of two structurally distinct Ca(II)‐binding EF hand motifs, wherein one of which bears an unusual amino acid sequence. Here, we utilize solution state NMR relaxation measurements to investigate the mechanism of Ca(II)‐modulated enhancement of Zn(II) sequestration by calgranulin C. Using C13/N15 CPMG dispersion experiments we have measured pH‐dependent major and minor state populations exchanging on micro‐to‐millisecond timescale. This conformational exchange takes place exclusively in the Ca(II)‐bound state and can be mapped to residues located in the EF‐I loop and the linker between the tandem EF hands. Molecular dynamics (MD) simulations spanning nano‐to‐microsecond timescale offer insights into the role of pH‐dependent electrostatic interactions in EF‐hand dynamics. Our results suggest a pH‐regulated dynamic equilibrium of conformations that explore a range of “closed” and partially “open” sidechain configurations within the Zn(II) binding site. We propose a novel mechanism by which Ca(II) binding to a non‐canonical EF loop regulates its flexibility and tunes the antimicrobial activity of calgranulin C.
A methodology for creating thermostabilized mutants of G‐protein coupled receptors by combining statistical thermodynamics and evolutionary molecular engineering
Authors: Sugaya Kanna , Yasuda Satoshi , Sato Shingo , Sisi Chen , Yamamoto Taisei , Umeno Daisuke , Matsuura Tomoaki , Hayashi Tomohiko , Ogasawara Satoshi , Kinoshita Masahiro , Murata Takeshi
Published: August 2022

We constructed a methodology for thermostabilizing a G‐protein coupled receptor (GPCR) in the inactive state whose wild‐type (WT) structure is unknown solely by multiple amino‐acid mutations without the ligand binding. It is a combination of our recently developed theory based on statistical thermodynamics and site‐directed saturation mutagenesis, a method often employed in evolutionary molecular engineering. First, the WT structure is predicted using the homology modeling. Second, a key residue is determined by our statistical‐thermodynamics theory using suitably modeled mutant structures. Many of 19 different single mutations for the key residue are expected to produce significantly higher stabilization. Third, we undertake to mutate not only the key residue but also a few more residues whose side chains are close to the side chain of the key residue. The whole mutational space is then efficiently explored by introducing site‐directed saturation mutations, and a gene (mutant) library is constructed using the small‐intelligent and fully automatic single‐tube recombination methods. Each mutant is expressed in Escherichia coli cells, and highly stabilized mutants are sorted out using a fluorescence‐screening technique. The methodology was illustrated for the serotonin 2A receptor, 5‐HT2AR, for stabilizing its inactive state. We could identify a double mutant whose apparent midpoint temperature of thermal denaturation is higher than that of a thermostabilized double mutant previously reported by ~8.9°C and that of the WT by over 15°C. Moreover, it exhibits higher binding affinity for spiperone, an antagonist which was previously proved to stabilize 5‐HT2AR in the inactive state.
CHARMM‐GUIhigh‐throughput simulator for efficient evaluation of protein–ligand interactions with different force fields
Authors: Guterres Hugo , Park Sang‐Jun , Zhang Han , Perone Thomas , Kim Jongtaek , Im Wonpil
Published: August 2022

Molecular docking is one of the most popular computational tools for the hit discovery step in drug design. However, there is ample room for improvement of docking's ability to identify correct binding modes and discriminate active from decoy compounds. Molecular dynamics (MD) simulations of protein–ligand docking structures have been shown to be effective in improving docking results. Here, we present CHARMM‐GUI high‐throughput simulator (HTS) that prepares MD simulation systems and inputs for multiple protein–ligand complex structures in a high‐throughput manner. HTS supports commonly used MD programs (NAMD, GROMACS, AMBER, OpenMM, GENESIS, Desmond, LAMMPS, and Tinker) along with various force field combinations for protein and ligand, including CHARMM36m, Amber (ff19SB/ff14SB), OPLS‐AA/M, CGenFF, GAFF2, and OpenFF. Validation tests using Miller and the directory of useful decoys‐enhanced (DUD‐E) datasets demonstrate that short MD simulations using HTS‐generated systems and simple ligand RMSD calculations consistently outperform docking results. Specifically, MD simulations can better identify correct ligand‐binding modes among top 10 binding poses as compared to docking scores. In addition, MD simulations can better discriminate active from decoy compounds in the DUD‐E dataset than docking scores for both soluble and membrane proteins. We expect that HTS can be a useful tool to facilitate the hit discovery process in drug design by improving docking results.
Asymptotic output tracking control with prescribed transient performance of nonlinear systems in the presence of unknown dynamics
Authors: Liu Yong‐Hua , Chen Lang‐Lei , Zhou Qi , Su Chun‐Yi
Published: August 2022

In this article, we address the problem of asymptotic output tracking control with prescribed transient performance for a class of nonlinear systems in the presence of unknown dynamics. By fusing the funnel control approach and the tool of barrier Lyapunov function, a smooth adaptive tracking control strategy is developed in a recursive manner. In the proposed design, a new barrier Lyapunov function is adopted to eliminate the effects of unknown nonlinear dynamics, ensuring the prescribed transient behavior of the output tracking. The distinctive characteristic of the proposed method is that the designed control algorithm can guarantee not only prescribed output tracking performance but also global asymptotic stability without incorporating any prior knowledge of nonlinear dynamics or even corresponding bounding functions. Three illustrative examples are provided to testify the effectiveness of the proposed method.
Dual H2O2‐Amplified Nanofactory for Simultaneous Self‐Enhanced NIR‐II Fluorescence Activation Imaging and Synergistic Tumor Therapy
Authors: Zheng Ziliang , Chen Xuejiao , Ma Yanchun , Dai Rong , Wu Shutong , Wang Tong , Xing Jun , Gao Jinnan , Zhang Ruiping
Published: August 2022

Activatable fluorescence imaging in the second near‐infrared window (NIR‐II FL, 1000–1700 nm) is of great significance for accurate tumor diagnosis and targeting therapy. However, the clinical translation of most stimulus‐activated nanoprobes is severely restricted by insufficient tumor response and out‐of‐synchronization theranostic process. Herein, an intelligent nanofactory AUC‐GOx/Cel that possesses the “external supply, internal promotion” dual H2O2‐amplification strategy for homologous activated tumor theranostic is designed. This nanofactory is constructed via a two‐step biomineralization method using Au‐doped Ag2S as a carrier for glucose oxidase (GOx) and celastrol, followed by the growing of CuS to “turn off” the NIR‐II FL signal. In the overexpressed H2O2 tumor‐microenvironment, the CuS featuring a responsive‐degradability behavior can effectively release Cu ions, resulting in the “ON” state of NIR‐II FL and Fenton‐like activity. The exposed GOx can realize the intratumoral H2O2 supply (external supply) via the effective conversion of glucose, and mediating tumor‐starvation therapy; the interaction of celastrol and mitochondria can offer a substantial increase in the endogenous H2O2 level (internal promotion), thereby significantly promoting the chemodynamic therapy (CDT) efficacy. Meanwhile, the dual H2O2‐enhancement performance will in turn accelerate the degradation of AUC‐GOx/Cel, and achieve a positive feedback mechanism for self‐reinforcing CDT.
Identification of late blight resistance quantitative trait loci in Solanum pimpinellifolium accession PI 270441
Authors: Sullenberger Matthew T. , Jia Mengyuan , Gao Sihui , Ashrafi Hamid , Foolad Majid R.
Published: August 2022

Late blight (LB), caused by the oomycete Phytophthora infestans, is one of the most destructive diseases of the cultivated tomato (Solanum lycopersicum L.) and potato (Solanum tuberosum L.) worldwide. Genetic changes in the pathogen have resulted in the emergence of new genotypes, overcoming formerly effective fungicides or host resistance genes. We previously reported the identification of a LB‐resistant accession (PI 270441) of the wild tomato species S. pimpinellifolium L. and the high heritability of its resistance. In the present study, an F2 population (n = 1,209), derived from a cross between PI 270441 and a LB‐susceptible tomato breeding line (Fla. 8059), was screened for response to LB infection. Extreme resistant (n = 44) and susceptible (n = 39) F2 individuals were selected and used in a trait‐based marker analysis (TBA; a.k.a selective genotyping) to identify and map quantitative trait loci (QTLs) conferring LB resistance. Reduced representation libraries (RRLs) of Fla. 8059 and PI 270441 were constructed, sequenced, and mapped to the tomato genome. A total of 13,054 single‐nucleotide polymorphisms (SNPs) were identified, of which, 200 were used to construct a genetic linkage map and locate QTLs. Four LB resistance QTLs were identified on chromosomes 1, 10, and 11 of PI 270441. The markers associated with these QTLs can be used to transfer LB resistance from PI 270441 into new tomato cultivars and to develop near‐isogenic lines for fine mapping of the QTL.
Fostering Civic Reasoning Through Disciplinary Literacy
Authors: Zhang Jie , Lee Grace , Iluore Azizah Curry , Relyea Jackie Eunjung , Wui Ma. Glenda L.
Published: August 2022

In this article, the authors introduce ways to use disciplinary literacy (DL) instructional strategies to foster civic engagement and reasoning for middle‐grade multilingual students. Four phases of DL strategies—framing, reading, discussion, and writing—are illustrated with examples from an intervention project with sixth‐grade multilingual students. The intervention features a 4‐week Space Exploration unit designed for students to address a contestable and relevant civic question: Should the government increase or decrease funding for space exploration? Teacher instructional moves, reading selections, student discussion excerpts, and writing samples are presented to highlight the language‐rich disciplinary teaching and learning in action and the benefits of multilingual students in their science, language, and literacy learning.
Nonwoven viscose fabric‐polyvinyl alcohol based flexible composite
Authors: Chatterjee Arobindo , Singh Harwinder , Chaudhary Khushboo
Published: August 2022

Development of ecofriendly packaging materials is still a challenging area. Researchers are continuously working to improve the mechanical and barrier properties of the different polymers which are used in the packaging industry. Selection of reinforcement and matrix for any composite are based upon end use applications. The novelty of the work is development of fully biodegradable, flexible, lightweight biocomposite by reinforcing needle punched flexible nonwoven viscose fabric to the PVA solution. The effect of PVA concentration and areal density of viscose fabric on the properties of prepared composite is examined. The composite thus prepared is assessed in terms of mechanical, thermal, breathability, and UV blocking properties. The nonwoven viscose‐PVA composite shows excellent improvement in tensile strength of 100% to 300% with respect to PVA film of equivalent concentration for two different areal densities of viscose fabric. The composite also exhibits improved thermal stability and UV blocking property with respect to parent components. However, a reduction in flexibility (with respect to PVA film) as well as breathability (with respect to viscose fabric) of the composite is observed. Based upon the improved performance of the viscose‐PVA composite in terms of mechanical properties, UV and water vapor permeability, it seems that the composite has a strong potential for application in the packaging sector as a flexible as well as biodegradable composite.