bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional analyses of maize leaves in response to high‐density planting
Authors: Zhao Chenghao , Ji Shuwen , Ge Chao , Su Yujing , Shi Zhongxian , Cui Zhenhai , Zhang Ao , Wang Zuoying , Ruan Yanye , Zhang Lijun , Ma Xinglin
Published: July 2021

Maize (Zea mays L.) is one of the major cereal crops worldwide. Increasing planting density is an effective way to improve crop yield. However, plants grown under high‐density conditions compete for water, nutrients, and light, which often leads to changes in productivity. To date, few studies have determined the transcriptomic differences in maize leaves in response to different planting densities. This study examined the whole‐genome expression patterns in the leaves of maize planted under high and low densities to identify density‐regulated genes. Leaves at upper, ear, and lower stem nodes were collected at the grain‐filling stage of the maize hybrid Xianyu335 grown under low‐density planting and high‐density planting. In total, 72, 733, and 1,739 differentially expressed genes (DEGs) were identified in the respective upper, ear, and lower leaves under HDP. Upregulated and downregulated DEGs in the upper and lower leaves were similar in number, whereas upregulated DEGs in the ear leaves were significantly higher in number than the downregulated DEGs. Functional analysis indicated that genes responding to HDP‐related stresses were mediated by pathways involving four phytohormones responsible for metabolism and signaling, osmoprotectant biosynthesis, transcription factors, and fatty acid biosynthesis and protein kinases, which suggested that these pathways are affected by the adaptive responses of maize plants grown at high density. Research findings elucidated the molecular mechanisms underlying the physiological and biochemical responses of the leaves of maize planted at high density.
Comparative establishment and yield of bioenergy sorghum and maize following pre‐emergence waterlogging
Authors: von Haden Adam C. , Burnham Mark B. , Yang Wendy H. , DeLucia Evan H.
Published: July 2021

Biofuel feedstocks grown on marginal lands, such as those that experience ephemeral waterlogging, reduce interference with food agriculture. As early‐season extreme precipitation events in the U.S. Midwest continue to increase, waterlogging tolerance may play an important role in the productivity of annual biofuel cropping systems. We assessed the establishment and yield of photoperiod‐sensitive sorghum [Sorghum bicolor (L.) Moench] and maize (Zea mays L.) after extreme early‐season rainfall events in central Illinois. We used paired sorghum and maize transects, spanning from low‐lying poorly drained areas to higher better drained areas, to evaluate the response of both cropping systems throughout the 2020 growing season. Sorghum maintained 25% mean emergence rates in areas that experienced the most severe waterlogging, but maize failed to establish under the same conditions. Despite the low establishment, sorghum yields in the poorly drained areas were upwards of 50% of those found in the better drained, whereas maize yields were zero areas in the poorly drained locations. The yield compensation in sorghum resulted from increased tillering, higher productivity per stem, and subsequently higher productivity per plant, which illustrates the greater phenotypic plasticity of sorghum compared to maize. Land managers who are currently seeking to grow annual cellulosic feedstocks on soils that are vulnerable to transient soil waterlogging will likely have more success with photoperiod‐sensitive bioenergy sorghum than maize.
Ring Origami: Snap‐Folding of Rings with Different Geometries
Authors: Wu Shuai , Yue Liang , Jin Yi , Sun Xiaohao , Zemelka Cole , Qi H. Jerry , Zhao Ruike
Published: July 2021

Origami folding and thin structure buckling are intensively studied for structural transformations with large packing ratio for various biomedical, robotic, and aerospace applications. The folding of circular rings has shown bistable snap‐through deformation under simple twisting motion and demonstrates a large area change to 11% of its undeformed configuration. Motivated by the large area change and the self‐guided deformation through snap‐folding, it is intended to design ring origami assemblies with unprecedented packing ratios. Herein, through finite‐element analysis, snap‐folding behaviors of single ring with different geometries (circular, elliptical, rounded rectangular, and rounded triangular shapes) are studied for ring origami assemblies for functional foldable structures. Geometric parameters' effects on the foldability, stability, and the packing ratio are investigated and are validated experimentally. With different rings as basic building blocks, the folding of ring origami assemblies including linear‐patterned rounded rectangular rings, radial‐patterned elliptical rings, and 3D crossing circular rings is further experimentally demonstrated, which show significant packing ratios of 7% and 2.5% of the initial areas, and 0.3% of the initial volume, respectively. It is envisioned that the reported snap‐folding of origami rings will provide alternative strategies to design foldable/deployable structures and devices with reliable self‐guided deformation and large area change.
What is normal body weight? Perceptions around “average” and “healthy” body weight among adolescents in Indiana
Authors: Cullin Jennifer M.
Published: July 2021

Objectives

Biological normalcy is a framework that investigates relationship(s) between statistical norms and normative views/beliefs around particular traits. This study assessed the relationships between perceptions of average body weight, healthy body weight, and weight status among adolescents.

Methods

Adolescents recruited in southcentral Indiana, United States (n = 123) completed online questionnaires for demographics and body weight perceptions. Silhouettes from the Stunkard Figure Rating Scale measured perceived weight status, perceived average body weight, and perceived healthy body weight. Height and weight were measured to calculate body mass index‐for‐age percentiles. A subsample (n = 11) provided descriptions of “average,” “healthy,” and “normal” bodies during semi‐structured interviews.

Results

As perceived average body weight increased, selections of “healthy” silhouettes shifted downward, with smaller female silhouettes being marked healthy more often and larger male silhouettes being marked healthy less often. Additionally, perceived weight status was positively associated with perceptions around average body weight and lowest body weight perceived to be healthy for female and male silhouettes. Qualitative data demonstrated significant overlap in adolescents' descriptions of “average,” “healthy,” and “normal” bodies as well as dual meanings for the term “normal” in adolescents' views of body weight.

Conclusions

Perceived weight status appears to play a role in adolescents' conceptualizations of average and healthy body weight. Additionally, Qualitative and quantitative data indicated that perceived body weight norms were associated with normative perceptions around what healthy bodies look like. This study demonstrates relationships between statistical norms and normative views around body weight, underscoring the duality in how body weight is understood to be “normal” among adolescents.
Synthesis of a 1,4‐Bis[2‐(5‐thiophen‐2‐yl)‐1‐benzothiophene]‐2,5‐dioctyloxybenzene Pentamer for Creatinine Detection
Authors: Hidayah Azeman Nur , Asif Ahmad Khushaini Muhammad , Daik Rusli , Ismail Ahmad Ghadafi , Yeop Majlis Burhanuddin , Mat Salleh Muhammad , Aziz Tg Hasnan Tg Abdul , Bakar Ahmad Ashrif A , Md Zain Ahmad Rifqi , Teh Chin‐Hoong
Published: July 2021

The synthesis of novel material 1,4‐bis[2‐(5‐thiophen‐2‐yl)‐1‐benzothiophene]‐2,5‐dioctyloxybenzene pentamer (BOBzBT2) was carried out via Williamson etherification, bromination, and Suzuki coupling. Functionalization was carried out via the incorporation of dioctyloxy‐substituents on phenylene moiety to improve its solubility. The elongation of the π‐conjugation backbone was carried out through the addition of benzo[b]thiophene rings of BOBzBT2 to accelerate cation radicals′ formation. In FTIR, the disappearance of the stretching peak of υ(CBr) at 657 cm−1 confirms the coupling of benzo[b]thiophene rings end‐capped the BOBzBT2 UV‐visible shows the appearance of two broad bands at 343 nm and 422 nm, that related to π‐π* transition between thiophene and bithiophene groups with 2,5‐bis(dioctyloxy)benzene moiety in the π‐conjugated backbone, respectively. DSC shows that the BOBzBT2 is a high purity compound. A gradual relaxation occurred between BOBzBT2 with creatinine as observed in UV‐visible analysis. It is expected that the BOBzBT2 sensed creatinine via NH−S and NH−O hydrogen bonding interactions.
Common evolutionary patterns in the human nasal region across a worldwide sample
Authors: Tran Cathy Ngọc Hân , Schroeder Lauren
Published: July 2021

Objectives

Variation in the external nasal region among human populations has long been proposed in the literature to reflect adaptations to facilitate thermoregulation, air conditioning, and moisture retention in local climates and environments. More specifically, adaptations in populations living in colder climates have often been assumed due to correlational relationships found between variation in the nasal region and climatic variables. Here, we test this hypothesis by applying a quantitative genetics approach based on the Lande model to assess whether variation in the nasal region can be explained by random neutral processes (e.g., genetic drift) or if non‐random forces (i.e., adaptation) have contributed significantly to its diversity.

Materials and methods

A mixed‐sex sample representing 28 population groups from Howells' craniometric dataset were analyzed (n = 2504). Twenty standard measurements were chosen to reflect the external skeletal morphology of the nasal region. We apply statistical tests developed from evolutionary quantitative genetics theory to analyze patterns of within‐ and between‐population divergence under a null hypothesis of genetic drift.

Results

This study finds a rejection of genetic drift in all analyses, across tests that involve all 28 populations, exclusively cold‐climate populations, and with cold‐climate populations excluded, indicating that non‐random evolutionary forces have contributed significantly to variation in the nasal region overall.

Discussion

These results show that nasal region adaptation is not exclusive to cold‐climate populations, which have often been implicated in the literature to drive nasal variation, instead suggesting that the propensity for adaptation in the nasal region is shared among all human populations.
Self‐healing in high impact polystyrene (HIPS) composites via embedded non‐toxic solvent‐filled microcapsules
Authors: Shinde Vinita V. , Shelke Shreyas D. , Celestine Asha‐Dee N. , Beckingham Bryan S.
Published: July 2021

Polymer composites are widely used in many industries due to their desirable, and commonly superior properties. However, the replacement of damaged composite materials can be very costly and time‐consuming, motivating the development of self‐healing composites that recover their properties after a damage event. This work demonstrates the microcapsule‐based self‐healing of compression molded thermoplastic high impact polystyrene (HIPS) composites using a non‐toxic and environmentally friendly solvent, ethyl phenylacetate (EPA). EPA is incorporated within double‐walled polyurethane‐poly(urea‐formaldehyde) (PU/UF) microcapsules which are then integrated within the HIPS specimens. Flexure and fracture behavior, with and without microcapsules, is used to investigate the microcapsules' impact on composite physical properties and to determine the composite's self‐healing efficiency (up to 64%) after healing in response to fracture. Overall, this work demonstrates the inclusion of self‐healing properties in a commercially important polymer material with a non‐toxic and environmentally friendly solvent and motivates further development of thermoplastic self‐healing composites for industrial applications.
Accelerated weathering effects on mechanical, thermal and viscoelastic properties of kenaf/pineapple biocomposite laminates for load bearing structural applications
Authors: Kumar Santosh , Saha Abir , Bhowmik Sumit
Published: July 2021

Natural fibers are exceptional renewable resources to develop biocomposite materials for reducing the negative effects on the environment and producing economical and lightweight materials for load bearing semi‐structural applications. The present study is an attempt to develop kenaf/pineapple reinforced bio‐epoxy biocomposite and investigates thermo‐mechanical and viscoelastic properties under accelerated weathering conditions. The compression molding technique is used to develop biocomposite with four different arrangements of kenaf/pineapple laminates. To perform accelerated weathering, laminates are exposed to ultraviolet radiation and humidity conditions with extreme temperature in weathering tester machine. The tensile, flexural, impact, thermogravimetric analysis, thermal conductivity, viscoelastic properties, and water absorption tests are performed before and after accelerated weathering. The results revealed that the hybridization of kenaf/pineapple laminates showed better interfacial strength and stiffness while reducing the moisture sensitivity under accelerated weathering conditions. The morphology and fracture behavior of biocomposites are examined with scanning electron microscopy.
Three‐dimensional solubility parameters of natural rubber and its predictive power in diffusion coefficients
Authors: Jing Yuanrong , Cui Ziwen , Zou Huimin , Tu Jieyun , Jiang Xingwang , Shi Xinghui , Yong Zhanfu , Liu Susu , Liu Guangyong
Published: July 2021

Equilibrium swelling test is employed to study the swelling responses of natural rubber (NR) in various solvents, and to determine the total Hildebrand solubility parameter (δt) of NR. The three‐dimensional solubility parameters (HSP) of NR is obtained by virtue of software package as the result of being δd = 17.50 MPa1/2, δp = 3.20 MPa1/2, δh = 1.40 MPa1/2, and δt = 17.85 MPa1/2, respectively. The swelling ratio (q) is correlated with the energy difference (Ra) in order to deeply understand the swelling principle of NR, and the results turn out that q decreased with the increase of the Ra and it can be used to explain the abnormal swelling phenomena of methyl acetate and ethyl acetate. One of the possible applications of Ra is the prediction or explanation of diffusion behaviors of small liquids in the rubber matrix. Therefore, the diffusion coefficient (D) is calculated in accordance with the Fick's law model and attempted to correlate with the Ra value. Two qualitative relationships between D and Ra and χHSP can be preliminarily established now, which can provide an easy way to predict the diffusion behavior of fluids in rubber matrix.
Efficient removal of methyl orange by nanocomposite aerogel of polyethyleneimine andβ‐cyclodextringrafted cellulose nanocrystals
Authors: Li Qian , Li Yujie , Li Yuehu , Chen Yifan , Wu Qiang , Wang Siqun
Published: July 2021

Owing to the high specific surface area and lightweight, aerogels exhibit excellent adsorption capacity that can be tailored for the fabrication of high‐performance environmental purification materials. Cellulose nanocrystal (CNC) is an abundant, bio‐based, low‐density one dimensional (1D) nanomaterials with high‐respect ratio. In this work, CNC is first chemically grafted with polyethylenimine (PEI) and further byβ‐cyclodextrin (β‐CD), which is subsequently crosslinked by polyacrylamide (PAM) to prepare the composted aerogel (CNC‐PEI‐CD/PAM), and being endowed high‐adsorption capacity for methyl orange (MO) (155.93 mg g−1) and removal rate (97.46%). Our unique strategy overcomes the low graft efficiency ofβ‐CD directly onto CNC by connecting PEI. Besides, CNC‐PEI‐CD/PAM not only shows superior adsorption performance to methyl orange, attributing to the unique “selective” cavity structure ofβ‐CD and dense surface charge of PEI, but also displays the desired reusability. This material shows the huge potential in water purification.
Fabrication of high transparent, mechanical strong, and flame retardant waterborne polyurethane composites by incorporating phosphorus‐silicon functionalized cellulose nanocrystals
Authors: Du Weining , Ge Xinguo , Huang Hao , Zhang Tianhao , Zhang Zejiang , Shang Xiang
Published: July 2021

To manufacture transparent waterborne polyurethane composite coatings that possess desirable mechanical and flame retardancy properties is still a challenge. Herein, we first synthesized phosphorus‐silicon functionalized cellulose nanocrystals (FCNC) filler, and further introduced it into waterborne polyurethane (WPU) matrix to prepare composite. The phosphorus‐silicon‐containing components were grafted covalently on the surface of FCNC, and the FCNC showed good dispersion level in water and WPU matrix. Moreover, the inserted FCNC could not only maintain the high transparency of WPU‐FCNCs composites, but also remarkably enhancing the mechanical and flame retardancy performances. Noticeably, the WPU‐FCNC3 composite containing 3 wt% of FCNC showed balanced mechanical (σb = 16.7 MPa, εb = 557.5%), limiting oxygen index (22.9%), and a UL‐94 rating of V‐2 among prepared films. Additionally, WPU‐FCNC3 composite exhibited significantly reductions in heat release during combustion, and also showed a high transmittance of 92.2%. The present research supplies promising way for developing transparent, toughness, and flame retardant composite coatings.
Increasing smallholder farmers’ market participation through technology adoption in rural Timor‐Leste
Authors: Akter Sonia , Chindarkar Namrata , Erskine William , Spyckerelle Luc , Imron Julie , Branco Lucia Viana
Published: July 2021

This study examines the role of high‐yielding maize varieties as one of the key drivers of smallholder farmers’ market participation in a highly subsistence rural economy. The analysis is based on the End‐of‐Program Survey data collected by the Seeds of Life program in 2016 covering 700 households in rural Timor‐Leste. The results reveal significant positive impacts of technology adoption on farmers’ market participation. Households where women are relatively more active in agriculture than men are more likely to engage in agricultural commerce. The results also show a positive impact of technology adoption on maize productivity. These findings present the first empirical evidence of the causal link between technology adoption and market participation choices.
Sharing information about health‐related resources: Observations from a community resource referral intervention trial in a predominantly African American/Black community
Authors: Lindau Stacy Tessler , Makelarski Jennifer A. , Abramsohn Emily M. , Beiser David G. , Boyd Kelly , Huang Elbert S. , Paradise Kelsey , Tung Elizabeth L.
Published: July 2021

CommunityRx is a theory‐driven, information technology‐based intervention, developed with and in a predominantly African American/Black community, that provides patients with personalized information (a “HealtheRx”) about self‐management and social care resources in their community. We described patient and clinician information sharing after exposure to the intervention during a clinical trial. Survey data from 145 patients (ages 45–74) and 121 clinicians were analyzed. Of patients who shared information at least once (49%), 47% reported sharing ≥3 times (range 1–14). Patient sharers were in poorer physical health (mean PCS 37.6 vs. 40.8, p = .05) than nonsharers and more likely to report going to a resource on their HealtheRx (79 vs. 41%, p ≤ .05). Most patient sharers provided others a look at or copy of their HealtheRx, keeping the original. Patients used the HealtheRx to promote credibility of the information and communicate that resources were disease‐specific and local. Half of clinicians shared HealtheRx resource information with peers; sharers were 3 times more likely than nonsharers to feel they were well‐informed about resources to address social needs (55 vs. 18%, p < .01). Information sharing by clinicians and patients is an understudied mechanism that could amplify the effects of a growing class of community resource referral information technologies.
A Simple Effective SCF Method for Computing Optical Gaps in Organic Chromophores
Authors: Roy Raj , Ghosal Abhisek , Roy Amlan K.
Published: July 2021

Photoluminescence effects in organic chromophores are of significant importance and requires precise description of low lying excited states. In this communication, we put forward an alternative time‐independent DFT scheme for computing lowest single‐particle excitation energy, especially for singlet excited state. This adopts a recently developed “virial“‐theorem based model of singlet‐triplet splitting which requires a DFT calculation on closed shell ground state and a restricted open‐shell triplet excited state, followed by a simple
integral evaluation. This produces vertical excitation energies in small molecules, linear and non‐linear polycyclic aromatic hydrocarbon and organic dyes in comparable accuracy to the TDDFT. We also explore the functional dependency of present method with three different functionals (B3LYP, wB97X and CAM‐B3LYP) for polyenes and linear acenes. A systematic comparison with literature value illustrates the validity and usefulness of the present scheme in determining optical gap with fair computational cost.
Impurity profiling and stability‐indicating method development and validation for the estimation of assay and degradation impurities of midostaurin in softgel capsules using HPLC and LC–MS
Authors: Lakka Narasimha Swamy , Kuppan Chandrasekar , Ravinathan Poornima
Published: July 2021

Midostaurin (MDS) is used for the treatment of acute myeloid leukemia, myelodysplastic syndrome, and advanced systemic mastocytosis. MDS softgel capsule samples were subjected to stress testing per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines for impurity profiling study. MDS underwent extensive degradation under stress testing (acid, alkaline, oxidative, photolytic, thermolytic, and hydrolysis conditions) and formed four degradation products (DPs). MDS and its DPs were separated well from one another with good resolution using reserved‐phase HPLC using an Inertsil ODS‐3V column (250 × 4.6 mm, 5 μm) and a mobile phase of ammonium formate (40 mM) and acetonitrile. The stability‐indicating characteristic of the newly developed method was proven for the estimation of MDS assay, and its organic impurities were free from interference. The validated method exhibited excellent linearity, accuracy, precision, specificity, detection limit, and quantitation limit within 25 min run time. Stress testing, robustness, and solution stability were performed to ensure the continuous performance of the developed method. The peak fractions of DPs formed under stress testing were isolated and characterized using LC–MS, 1H and 13C NMR, IR, and UV–Vis. The structure of the major DPs was predicted as DP1 based on the spectral data. The proposed method is effectively used for MDS in bulk drug and finished formulations in the pharmaceutical industry.
Justifying environmental sustainability in small‐ and medium‐sized enterprises: An analysis of complementary assets in the printing industry
Authors: Reyes‐Rodríguez Juan Felipe , Ulhøi John Parm
Published: July 2021

Contrary to large enterprises, the environmental impact from small‐ and medium‐sized enterprises (SMEs) has not, to the same extent, attracted stakeholder attention and engagement. A similar lack of attention seems to have dominated management scholars who seem to have predominantly focused on the competitive implications of environmental sustainability of large enterprises. To fill up some of that gap, this study draws on the resource‐based view of the firm and the innovation‐value‐capturing‐framework to identify and characterise complementary assets utilised to materialise the competitive advantage of environmental management practices (EMP) in SMEs. Based on a multifirm case study among Danish SMEs in the printing and graphic industry, we demonstrate why and how SMEs' strategic involvement in EMP can be justified. This research complements existing insights in the field by exposing how SMEs operating under conditions of weak appropriability can justify investment in EMP thus highlighting their role in pursuing corporate sustainability.
Characterizing the relationships between tertiary and community cancer providers: Results from a survey of medical oncologists in Southern California
Authors: Salgia Nicholas J. , Chehrazi‐Raffle Alexander , Hsu JoAnn , Zengin Zeynep , Salgia Sabrina , Chawla Neal S. , Meza Luis , Malhotra Jasnoor , Dizman Nazli , Muddasani Ramya , Ruel Nora , Cianfrocca Mary , Gong Jun , Anand Sidharth , Chiu Victor , Yeh James , Pal Sumanta K.
Published: July 2021

Background

Tertiary cancer centers offer clinical expertise and multi‐modal approaches to treatment alongside the integration of research protocols. Nevertheless, most patients receive their cancer care at community practices. A better understanding of the relationships between tertiary and community practice environments may enhance collaborations and advance patient care.

Methods

A 31‐item survey was distributed to community and tertiary oncologists in Southern California using REDCap. Survey questions assessed the following attributes: demographics and features of clinical practice, referral patterns, availability and knowledge of clinical trials and precision medicine, strategies for knowledge acquisition, and integration of community and tertiary practices.

Results

The survey was distributed to 98 oncologists, 85 (87%) of whom completed it. In total, 52 (61%) respondents were community practitioners and 33 (38%) were tertiary oncologists. A majority (56%) of community oncologists defined themselves as general oncologists, whereas almost all (97%) tertiary oncologists reported a subspecialty. Clinical trial availability was the most common reason for patient referrals to tertiary centers (73%). The most frequent barrier to tertiary referral was financial considerations (59%). Clinical trials were offered by 97% of tertiary practitioners compared to 67% of community oncologists (p = 0.001). Most oncologists (82%) reported only a minimal‐to‐moderate understanding of clinical trials available at regional tertiary centers.

Conclusions

Community oncologists refer patients to tertiary centers primarily with the intent of clinical trial enrollment; however, significant gaps exist in their knowledge of trial availability. Our results identify the need for enhanced communication and collaboration between community and tertiary providers to expand patients’ access to clinical trials.
Identification of the prognostic value of elevated ANGPTL4 expression in gallbladder cancer‐associated fibroblasts
Authors: Wang Fang‐Tao , Li Xin‐Ping , Pan Mu‐Su , Hassan Mohamed , Sun Wei , Fan Yue‐Zu
Published: July 2021

Background

Cancer‐associated fibroblasts (CAFs) with different gene profiles from normal fibroblasts (NFs) have been implicated in tumor progression. Angiopoietin‐like protein 4 (ANGPTL4) has been shown to regulate tumor angiogenesis and metastasis, and predict poor prognosis. However, the ANGPTL4 expression in CAFs, especially in gallbladder CAFs (GCAFs) and its relationship with patient prognosis is unclear.

Methods

Affymetrix gene profile chip analysis in vitro was performed to detect the different gene expression profiles between GCAFs and NFs. RT‐qPCR, immunohistochemistry, and western blotting were performed to investigate the different expression levels of ANGPTL4 in GCAFs/NFs in vitro and in an in vivo nude mouse model of xenograft tumors. Finally, the ANGPTL4 expression was investigated in the stroma of different lesion tissues of the human gallbladder by immunohistochemistry, especially the expression in GCAFs in vivo by co‐immunofluorescence, and their prognostic significance in patients with gallbladder cancer (GBC) was assessed.

Results

ANGPTL4 was upregulated in both GCAFs in vitro and in the xenograft stroma of nude mice in vivo, and its expression was also significantly upregulated in human GBC stroma co‐localized with the interstitial markers fibroblast secreted protein‐1 and α‐smooth muscle actin. In addition, the elevated ANGPTL4 expression in GCAFs was correlated with tumor differentiation, liver metastasis, venous invasion and Nevin staging, and GBC patients with an elevated ANGPTL4 expression in GACFs were found to have a lower survival rate.

Conclusions

Increased ANGPTL4 expression in GCAFs correlates with poor patient prognosis, which indicates a potential therapeutic target for human GBCs.
Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis
Authors: Wang Jingyun , Sun Zhuang , Wang Jing , Tian Qihai , Huang Runda , Wang Hanyu , Wang Xiaohui , Han Fei
Published: July 2021

Background

PLEK2 (pleckstrin) could bind to membrane‐bound phosphatidylinositols and further promote cell spread. Recently, several studies have noted the importance of PLEK2 in tumor metastasis. However, the role of PLEK2 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated.

Methods

The PLEK2 expression in HNSCC was identified using Oncomine, Gene Expression Omnibus (GEO), UALCAN databases, and western blot analysis. Prognosis analysis was performed using Kaplan–Meier plotter, DriverDBv3, UALCAN, UCSC Xena, and GEO databases. Single‐cell functional analysis was further performed using the cancerSEA database. The PLEK2‐related co‑expressed genes were identified, and gene set enrichment analysis was performed using LinkedOmics. Furthermore, the top 10 hub genes were identified using the cytoHubba plug‐in of Cytoscape. Then, gene enrichment analysis, pathway activity, and drug sensitivity analyses of the hub genes were performed using the R package “clusterProfiler” and GSCAlite. Finally, the UCSC Xena browser was utilized to explore the hub gene most likely to play a synergic role with PLEK2 in HNSCC.

Results

Elevated expression of PLEK2 was observed in HNSCC and even in HNSCC subgroups based on diverse clinicopathological features, portending a poor prognosis in HNSCC. PLEK2 was correlated with metastasis and hypoxia in HNSCC, and the PLEK2‐related co‐expressed genes were mainly involved in the focal adhesion pathway. The top 10 hub genes were primarily enriched in focal adhesion, HPV infection, ECM‐receptor interaction, and PI3K‐AKT signaling pathway, and epithelial–mesenchymal transition pathway was activated. Furthermore, the expression levels of the hub genes were associated with sensitivity and resistance to various small molecules and anti‐cancer drugs. Further study suggested that ITGA3 and PLEK2 might be viewed as inextricably linked in facilitating HNSCC metastasis.

Conclusions

In general, PLEK2 might serve as a potential biomarker for the diagnosis of HNSCC and guide the development of targeted therapies for HNSCC.
Treating eating disorders in groups: A pilot study on the role of a structured intervention on perfectionism on group climate
Authors: Margherita Giorgia , Gargiulo Anna , Gaudioso Rosita , Esposito Giovanna
Published: July 2021

Several studies have shown the efficacy of group treatments for patients with eating disorders (EDs) who have negative attitudes towards their bodies, also using the group climate as an indicator of process. Within this field of study, perfectionism has been examined as a factor that maintains eating disorders. This study proposes to comprehend what kind of treatment favours a better group climate, by providing a within‐person comparison between two short group treatments of ED patients, where one was not focused on a specific topic and the other was structured around the topic of clinical perfectionism. Two groups of young adult patients with eating disorders were monitored for three months. Group climate was measured both with the Group Climate Questionnaire, which was administered at the end of each session, and through the clinical accounts written by an observer. The findings revealed that the perfectionism group, in comparison with the control group, presented a significantly higher level of engagement and avoidance, along with a lower level of conflict. In particular, the engagement of the perfectionism group increased in accordance with the therapeutic process, whilst in the control group, it remained relatively constant. The conflict decreased in both groups whilst avoidance increased alongside the sessions of the perfectionism group and decreased in the control group. The group on perfectionism, despite its enhanced high levels of avoidance, was effective in promoting a positive group climate. The clinical implications of structured group treatment for eating disorders, which manage the theme of mind‐body splitting, will be discussed.
Interventions for benzodiazepine withdrawal: Perceptions of benzodiazepine counsellors
Authors: Wurf Gerald , Swing Alice
Published: July 2021

Governments have been urged to adopt real‐time prescription monitoring in order to manage and reduce risks associated with the long‐term use of sleep and anti‐anxiety medications. Given this imperative, accessible psychological interventions for benzodiazepine (BZD) dependency and withdrawal are essential. The aim of this study was to understand how counsellors support clients assessed as suitable for community‐based drug withdrawal services to reduce their BZD use. Six BZD counsellors and two service coordinators were interviewed. Counsellors collaborated with their clients and prescribing doctors to develop individualised taper schedules that were in line with recommended clinical guidelines. Psychoeducation underscored a range of evidence‐based interventions, and a trauma‐informed approach was considered essential in working with clients to reduce their use of BZDs. Continuity in care was affected by the degree of prescribing doctor support for the taper. Counsellors reported that workforce sustainability was enhanced by quality clinical supervision and professional development opportunities. The role of counsellors in providing accessible, community‐based interventions for clients to reduce their use of BZDs was supported. Psychosocial support, combined with a medically supervised taper, has a strong evidence base and implications for client‐centred interventions are discussed.
Final 3‐year clinical outcomes following transcatheter aortic valve implantation with a supra‐annular self‐expanding repositionable valve in a real‐world setting: Results from the multicenter FORWARD study
Authors: Van Mieghem Nicolas M. , Windecker Stephan , Manoharan Ganesh , Bosmans Johan , Bleiziffer Sabine , Modine Thomas , Linke Axel , Scholtz Werner , Tchétché Didier , Finkelstein Ariel , Ito Saki , Eisenberg Ruth , Grube Eberhard
Published: July 2021

Objectives

The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3‐year clinical follow up of the FORWARD study.

Background

Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long‐term clinical outcome data with the Evolut R platform are scarce.

Methods

FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart‐Team assessment. TAVR was attempted in 1039 patients.

Results

Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all‐cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all‐cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all‐cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low.

Conclusions

The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve‐related adverse events were low.
Ultrahigh Rate Capability and Lifespan MnCo2O4/Ni‐MOF Electrode for High Performance Battery‐Type Supercapacitor
Authors: Yang Fan , Guo Hao , Chen Yuan , Xu Mengni , Yang Wenhu , Wang Mingyue , Yang Meng , Zhang Junye , Sun Lei , Zhang Tingting , Yang Wu
Published: July 2021

MnCo2O4 is derived from a Co/Mn bimetallic metal‐organic framework (MOF). Then Ni‐MOF is directly grown on the surface of the obtained MnCo2O4 to form a nano‐flower structure with small balls. A large surface area, abundant active sites of MnCo2O4 and porosity of Ni‐MOF allow the prepared MnCo2O4/Ni‐MOF composite material to deliver an excellent electrochemical performance. At the same time, an appropriate thermal treatment temperature of the MnCo2O4 precursor is also very important for controlling the morphology of the obtained MnCo2O4 and electrochemical performances of the resulted composite material including electric conductivity, specific capacitance and rate performance. The prepared MnCo2O4‐600/Ni‐MOF shows an ultrahigh rate performance (when the current density increases from 1 to 10 A g−1, the capacitance retention rate is as high as 93.41 %) and good cycle stability (the assembled asymmetric supercapacitor advice delivers a capacitance retention rate of 94.74 % after 20 000 charge and discharge cycles) as well as a relatively high specific capacitance. These excellent electrochemical properties indicate that MnCo2O4/Ni‐MOF has a good application prospect in the market.
Mathematical Modeling of Drying Processes of Selected Fruits and Vegetables
Authors: Reppich Marcus , Jegla Zdeněk , Grondinger Jakob , Azouma Yaovi Ouézou , Turek Vojtěch
Published: July 2021

This study investigates the behavior of fruit and vegetable samples during drying. The experimental data are fitted to several different thin‐layer drying models. Regression analysis is used to determine model parameters, while statistical indicators serve to evaluate the goodness of fit. The power function model gives the best fit for all examined samples. Based on this model, different drying and heat storage technologies can be combined to ensure that the required residual moisture content of an agricultural product is reached. It is demonstrated on the case of a specific Togolese processing plant that under favorable conditions, fossil fuel consumption can be decreased by 33 %.
Improved bilayer convolution transfer learning neural network for industrial fault detection
Authors: Wang Jing , Zhang Wenqian , Wu Haiyan , Zhou Jinglin
Published: July 2021

Machine learning methods have achieved outstanding results in the fault detection of industrial processes when the training and test data follow the same distribution or originate from the same situation. However, the pre‐trained detection model fails when the operation status changes or unknown fault occurs during the actual production. Therefore, this paper proposes a novel bilayer convolutional transfer learning neural network (BCTLNN) to improve the generalization of detection model. BCTLNN is a bilayer network (local and global level) in order to extract the fault features. Transfer learning strategies (fine‐tuning and domain adaptation) are introduced to learn the domain invariant features by minimizing the divergence between different domain data. Experiments on the benchmark bearing data and the agglomeration fault data from an actual polyethylene process are employed to verify the effectiveness of the proposed method.
Myosin's powerstroke occurs prior to the release of phosphate from the active site
Authors: Scott Brent , Marang Christopher , Woodward Mike , Debold Edward P.
Published: July 2021

Myosins are a family of motor proteins responsible for various forms of cellular motility, including muscle contraction and vesicular transport. The most fundamental aspect of myosin is its ability to transduce the chemical energy from the hydrolysis of ATP into mechanical work, in the form of force and/or motion. A key unanswered question of the transduction process is the timing of the force‐generating powerstroke relative to the release of phosphate (Pi) from the active site. We examined the ability of single‐headed myosin Va to generate a powerstroke in a single molecule laser trap assay while maintaining Pi in its active site, by either elevating Pi in solution or by introducing a mutation in myosin's active site (S217A) to slow Pi‐release from the active site. Upon binding to the actin filament, WT myosin generated a powerstoke rapidly (≥500 s−1) and without a detectable delay, both in the absence and presence of 30 mM Pi. The elevated levels of Pi did, however, affect event lifetime, eliminating the longest 25% of binding events, confirming that Pi rebound to myosin's active site and accelerated detachment. The S217A construct also generated a powerstroke similar in size and rate upon binding to actin despite the slower Pi release rate. These findings provide direct evidence that myosin Va generates a powerstroke with Pi still in its active site. Therefore, the findings are most consistent with a model in which the powerstroke occurs prior to the release of Pi from the active site.
Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment‐Based Approach
Authors: Feder Daniel , Mohd‐Pahmi Siti H. , Hussein Waleed M. , Guddat Luke W. , McGeary Ross P. , Schenk Gerhard
Published: July 2021

Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone‐related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug‐like molecules bound near the active site is available. Herein, we used a fragment‐based design approach using structures of a mammalian PAP in complex with the MaybridgeTMfragment CC063346, the amino acid L‐glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug‐like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action.
Update on ICH E14/S7B Cardiac Safety Regulations: The Expanded Role of Preclinical Assays and the “Double‐Negative” Scenario
Authors: Lester Robert M.
Published: July 2021

For nearly 2 decades, regulators have adopted a harmonized approach to drug development, which has succeeded in bringing new pharmaceuticals to market without significant cardiac liability. Ushered in by technological advancements and better understanding of cellular electrophysiology, the initial paradigm detailed in the 2005 International Conference for Harmonization E14 and S7B documents has undergone evolutionary changes designed to streamline drug development and improve regulatory decision‐making and product labeling. The intent of this review is to summarize the new US Food and Drug Administration (FDA) Question and Answer update from August 2020 and key messaging from a subsequent FDA webinar describing best practices for preclinical and clinical data integration into a QT risk prediction model.
Metformin Stimulates Intestinal Glycolysis and Lactate Release: A single‐Dose Study of Metformin in Patients With Intrahepatic Portosystemic Stent
Authors: Rittig Nikolaj , Aagaard Niels K. , Sundelin Elias , Villadsen Gerda E. , Sandahl Thomas D. , Holst Jens J. , Hartmann Bolette , Brøsen Kim , Grønbæk Henning , Jessen Niels
Published: July 2021

The pharmacodynamic effects of metformin remain elusive, but several lines of evidence suggest a critical role of direct effects in the gastrointestinal (GI) tract. We investigated if metformin stimulates intestinal glucose metabolism and lactate release in the prehepatic circulation. We included eight patients with transjugular intrahepatic portosytemic stent in an open label study. Portal and arterialized peripheral blood was obtained before and 90 minutes after ingestion of 1,000 mg metformin. Metformin increased lactate concentrations by 23% (95% confidence interval (CI): 6–40) after 90 minutes in the portal vein. The plasma concentration of glucose, insulin, and C‐peptide was higher in the portal vein compared with arterialized blood (P < 0.05, all) and was lowered at both sampling sites following metformin ingestion (P < 0.01, all). Plasma concentration of GLP‐1 was 20% (95% CI: 2–38) higher in the portal vein at baseline and metformin increased the concentration with 11% (1.5 pM, P = 0.05). The median concentration of growth differentiation factor 15 was 10% (95% CI: 1–19) higher in the portal vein compared with arterialized blood. Ninety minutes after metformin administration, the median portal vein concentration increased to around 3,000 ng/mL with a mean portal/arterial ratio of 1.5 (95% CI: 1.2–1.8). Non‐targeted metabolomics showed that metformin acutely affected benzoate‐hippurate metabolism. A single‐dose of metformin directly affects substrate metabolism in the upper GI tract in humans with direct stimulation of nonoxidative glucose metabolism. These data suggest glucose lowering effects of metformin can be intrinsically linked with the GI tract without hepatic uptake of the drug.
Non‐neoplastic inflammatory pseudotumor of the lung after immunotherapy for melanoma: A diagnostic pitfall on fine needle aspiration biopsy of lung
Authors: Nelson Blessie Elizabeth , Hong Angelina , Okereke Ike , Markowitz Avi , Willis Maurice , Muthukumarana Palawinnage V. , Nawgiri Ranjana
Published: July 2021

Nivolumab is commonly used as monotherapy or in combination therapy for management of locally advanced or metastatic melanoma; however, it is also associated with immunotherapy‐related adverse events concerning for disease progression or tumor flare reaction. This report presents a case of a non‐neoplastic pseudotumor of the lung initially mistaken for malignancy that occurred in a patient receiving adjuvant nivolumab therapy following complete resection of stage IIIB melanoma. The diagnosis was made by lung biopsy and confirmed by a wedge resection, with findings consistent with organizing pneumonia type of pulmonary inflammatory pseudotumor rather than malignancy.