bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on Cell Performance and Inconsistency Evolution of Series and Parallel Lithium‐Ion Battery Modules
Authors: Wang Xueyuan , Fang Qiaohua , Dai Haifeng , Chen Qijun , Wei Xuezhe
Published: April 2021

Lithium‐ion battery cells are usually connected in series or parallel to form modules to meet power and energy requirements for specific applications. Inconsistency of the cells’ performance, i.e., capacity and internal resistance, is initially formed during production. Then the inconsistency evolves in the lifespan. Herein, the performance and inconsistency evolution of the series and parallel modules for the design and management guide are investigated. A quantitative analysis of the performance and inconsistency is made. The performance and inconsistency evolution are investigated experimentally. Based on it, the trend judgment of the inconsistency evolution is derived. It is found that the cell performance in series modules is self‐divergent, especially in the later stage of the aging process. And the divergence becomes more severe with an unreasonable equalization, such as the traditional cell voltage equalization. Equalization of the cell performance is needed to cut off the vicious circle. For the parallel module, self‐convergence of the performance exists. The better‐performing cells in the module withstand a larger current, making their performance decay faster and finally becoming consistent with the cells with worse initial performance. Meanwhile, the parallel module performance also decays significantly. Therefore, maintaining the cells’ consistency is still necessary for the parallel modules.
Determinants of Legacy Persistent Organic Pollutant Levels in the European Pond Turtle (Emys orbicularis) in the Camargue Wetland, France
Authors: Burkart Louisiane , Olivier Anthony , Lourdais Olivier , Vittecoq Marion , Blouin-Demers Gabriel , Alliot Fabrice , Le Gac Clément , Martin Nicolas , Goutte Aurélie
Published: April 2021

Many banned persistent organic pollutants (POPs) remain for decades in the aquatic environment and can have harmful effects on long-lived predators because of their high bioaccumulation and biomagnification potentials. We investigated the occurrence and levels of 18 polychlorinated biphenyls (PCBs) and 16 organochlorine pesticides in European pond turtles (n = 174) from April to July 2018 in the Camargue wetland, France. Although the Camargue was highly contaminated in previous decades, plasma occurrence and levels of POPs were very low: we were able to quantify only 3 of the 34 compounds we analyzed in >10% of the turtles. The burdens from POPs did not differ between males and females and were uncorrelated with sampling date and body mass. We observed differences in POP burdens between turtles from the 2 sampling sites. One possible explanation is that the sampling sites were in different agricultural hydraulic systems: plasma occurrence and levels were higher for PCB-52 and hexachlorobenzene in turtles captured in drainage channels and for PCB-153 at the site that receives irrigation. Finally, the occurrence and levels of PCB-153 in turtles increased with age, likely because of bioaccumulation and much higher exposure 20 to 30 yr ago than now. Environ Toxicol Chem 2021;40:2261–2268. © 2021 SETAC
Deconvoluting Thermodynamics from Biology in the Aquatic Food Web Model
Authors: Ghosh Upal , Bokare Mandar , Gobas Frank A.P.C.
Published: April 2021

Bioaccumulation of hydrophobic pollutants in an aquatic food web is governed by exposure concentrations in sediment and water phases and by complex trophic interactions among the various species. We demonstrate that biological interactions and exposure from the chemical environment can be deconvoluted for aquatic food webs to allow clearer assessments of the role of thermodynamic drivers from the sediment and surface water phases. We first demonstrate the feasibility of this deconvolution mathematically for hypothetical food webs with 3 and 4 interacting species and for more realistic real-world food webs with >10 species of aquatic organisms (i.e., the freshwater lake food web in Western Lake Erie [ON, Canada] and the marine food web in New Bedford Harbor [MA, USA]). Our results show both mathematically (for the simple food webs) and computationally (for the more complex food webs) that a deconvoluted food web model parameterized for site-specific conditions can predict the bioaccumulation of polychlorinated biphenyls in aquatic organisms same as existing complex food web models. The merit of this approach is that once the thermodynamic and biological contributions to food web bioaccumulation are computed for an ecosystem, the deconvoluted model provides a relatively simple approach for calculating concentrations of chemicals in organisms for a range of possible surface water and sedimentary concentrations. This approach is especially useful for calculating bioaccumulation of pollutants from freely dissolved concentrations measured using passive sampling devices or predicted by fate and transport models. The deconvoluted approach makes it possible to develop regulatory guidelines for a set of surface water and sediment (or porewater) concentration combinations for a water body that is able to achieve a risk-based target for fish concentration. Environ Toxicol Chem 2021;40:2145–2155. © 2021 SETAC.

Abstract

Thermodynamic influences of surface water and porewater separated mathematically from complex food web interactions. Csw and Cpw = dissolved concentrations of the hydrophobic organic contaminants in surface water and sediment porewater, respectively; fsw and fpw = fractional influence of surface water and porewater, respectively; BAFfish,A = bioaccumulation factor for Fish A.
Effect of temperature on mechanical properties of ultra‐high performance concrete
Authors: Banerji Srishti , Kodur Venkatesh
Published: April 2021

High temperature mechanical property data are needed for evaluating fire resistance of structural members. Being a relatively new construction material, there is a lack of temperature‐dependent mechanical property data on ultra‐high performance concrete (UHPC). To address this knowledge gap, this paper presents results from an experimental study on the effect of temperature on mechanical properties of UHPC. Specimens made of two UHPC mixes: one with only steel fibers (UHPC‐S) and the other with hybrid fibers, that is, both steel and polypropylene (UHPC‐H), were tested under different heating conditions in 20 to 750°C temperature range. Compressive strength, tensile strength, stress‐strain response, and elastic modulus of UHPC were evaluated at various temperatures. Results generated from these property tests on UHPC were compared with property relations specified in design codes for conventional normal strength concrete (NSC) and high strength concrete (HSC). The comparisons show that UHPC experiences faster degradation in compressive strength and elastic modulus as compared to conventional concrete. However, UHPC exhibits slower degradation in tensile strength and ductility at elevated temperatures due to the presence of steel fibers. Data generated from these property tests were utilized to propose relations for expressing the mechanical properties of UHPC as a function of temperature and these relations can be used as input to numerical models for evaluating fire resistance of structures made of UHPC.
Chemical composition and biological activities of essential oils from Calendula officinalis L. flowers and leaves
Authors: Ak Gunes , Zengin Gokhan , Ceylan Ramazan , Fawzi Mahomoodally Mohamad , Jugreet Sharmeen , Mollica Adriano , Stefanucci Azzurra
Published: April 2021

Calendula officinalis L., commonly known as pot marigold, is a popular ornamental and highly medicinal plant. In fact, it is well recognized for its wide‐ranging therapeutic effects conducive to wound healing and for treating various illnesses. In this study, the essential oils from flowers and leaves of C. officinalis were analysed for their chemical constituents and screened for their in vitro antioxidant and enzyme inhibitory properties. Thirty compounds were found in common in both essential oils, with the sesquiterpene alcohol, α‐cadinol as the most abundant compound (leaf: 32.3% and flower: 31.3%, respectively). Besides, the essential oils were found to possess antioxidant capacity through free radical scavenging and reducing mechanisms (DPPH: 2.94, 1.52 mg trolox equivalent (TE)/g of oil; ABTS: 20.72, 2.86 mg TE/g; CUPRAC: 31.16, 47.98 mg TE/g; FRAP: 24.84, 23.42 mg TE/g; phosphomolybdenum: 4.01, 4.68 mmol TE/g for leaves and flowers essential oils, respectively). Moreover, the essential oils (leaves and flowers, respectively) were found to inhibit all the tested enzymes, namely amylase (0.46, 0.42 mmol acarbose equivalent (ACAE)/g), glucosidase (1.35, 1.31 mmol ACAE/g), acetylcholinesterase (2.48, 2.36 mg galantamine (GALAE)/g) and butyrylcholinesterase (8.13, 8.20 mg GALAE/g) and tyrosinase (47.73, 54.36 mg kojic acid equivalent/g). Molecular docking was also performed revealing the compounds neophytadiene and α‐humulene to show the highest binding affinity with tyrosinase. Therefore, the obtained results demonstrated some appealing activities of C officinalis essential oils as natural pharmacological agents that could be valuable for the potential development of phyto‐formulations against the herein targeted diseases and especially for cosmeceutical applications.
Genomic and transcriptomic characterization of desmoplastic small round cell tumors
Authors: Sydow Saskia , Versleijen‐Jonkers Yvonne M. H. , Hansson Magnus , van Erp Anke E. M. , Hillebrandt‐Roeffen Melissa H. S. , van der Graaf Winette T. A. , Piccinelli Paul , Rissler Pehr , Flucke Uta E. , Mertens Fredrik
Published: April 2021

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue tumor primarily affecting children and young adults. Most cases display a pathognomonic EWSR1‐WT1 gene fusion, presumably constituting the primary driver event. Little is, however, known about secondary genetic changes that may affect tumor progression. We here studied 25 samples from 19 DSRCT patients using single nucleotide polymorphism arrays and found that all samples had copy number alterations. The most common imbalances were gain of chromosomes/chromosome arms 1/1q and 5/5p and loss of 6/6q and 16/16q, all occurring in at least eight of the patients. Five cases showed homozygous deletions, affecting a variety of known tumor suppressor genes, for example, CDKN2A and NF1. As almost all patients died of their disease, the impact of individual imbalances on survival could not be evaluated. Global gene expression analysis using mRNA sequencing on fresh‐frozen samples from seven patients revealed a distinct transcriptomic profile, with enrichment of genes involved in neural differentiation. Two genes ‐ GJB2 and GAL ‐ that showed higher expression in DSRCT compared to control tumors could be further investigated for their potential as diagnostic markers at the protein level.
Application of Artificial Intelligence for Diagnosis and Risk Stratification in NAFLD and NASH: The State of the Art
Authors: Dinani Amreen M. , Kowdley Kris V. , Noureddin Mazen
Published: April 2021

The diagnosis of nonalcoholic fatty liver disease and associated fibrosis is challenging given the lack of signs, symptoms and nonexistent diagnostic test. Furthermore, follow up and treatment decisions become complicated with a lack of a simple reproducible method to follow these patients longitudinally. Liver biopsy is the current standard to detect, risk stratify and monitor individuals with nonalcoholic fatty liver disease. However, this method is an unrealistic option in a population that affects about one in three to four individuals worldwide. There is an urgency to develop innovative methods to facilitate management at key points in an individual’s journey with nonalcoholic fatty liver disease fibrosis. Artificial intelligence is an exciting field that has the potential to achieve this. In this review, we highlight applications of artificial intelligence by leveraging our current knowledge of nonalcoholic fatty liver disease to diagnose and risk stratify NASH phenotypes.
Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.
Authors: Genêt Jean‐Pierre , Phansavath Phannarath , Ratovelomanana‐Vidal Virginie
Published: April 2021

This personal account focuses on the development of atropisomeric ligands and chiral transition metal complexes and their applications to the asymmetric hydrogenation of alkenes, ketones and heteroaromatics using Ru(II) and Ir(III) catalysts in‐house developed. Particularly, effective scaled‐up development syntheses of SYNPHOS and DIFLUORPHOS have been successfully achieved and their steric and electronic profiling established. Going further, we demonstrated the utility of such homogeneous catalytic process highlighted with examples of industrial applications and total syntheses of biorelevant targets. Asymmetric hydrogenation provides a powerful tool for performing precise stereocontrolled transformations on valuable complex molecules.
Maternal death related to COVID‐19: A systematic review and meta‐analysis focused on maternal co‐morbidities and clinical characteristics
Authors: La Verde Marco , Riemma Gaetano , Torella Marco , Cianci Stefano , Savoia Fabiana , Licciardi Federico , Scida Serena , Morlando Maddalena , Colacurci Nicola , De Franciscis Pasquale
Published: April 2021

Background

Besides reducing the quality of obstetric care, the direct impact of COVID‐19 on pregnancy and postpartum is uncertain.

Objective

To evaluate the characteristics of pregnant women who died due to COVID‐19.

Search strategy

Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021.

Selection criteria

Studies that compared deceased and survived pregnant women with COVID‐19.

Data collection and analysis

Relevant data were extracted and tabulated. The primary outcome was maternal co‐morbidity.

Main results

Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41–4.36, I2 = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77–42.44, I2 = 94%) or asthma (RR 2.05, 95% CI 0.81–5.15, I2 = 0%). Overall, at least one severe co‐morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77–2.89, I2 = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00–12.98, I2 = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23–1.48, I2 = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96–19.60, I2 = 58%).

Conclusion

COVID‐19 with at least one co‐morbidity increases risk of intensive care and mortality.
Regulatory role of TIGAR on endothelial metabolism and angiogenesis
Authors: He Xiaochen , Zeng Heng , Cantrell Aubrey C. , Chen Jian‐Xiong
Published: April 2021

Endothelial glycolytic metabolism plays an important role in the process of angiogenesis. TP53‐induced glycolysis and apoptosis regulator (TIGAR) is a significant mediator of cellular energy homeostasis. However, the role of TIGAR in endothelial metabolism, angiogenesis, and coronary flow reserve (CFR) has not been studied. The present study investigated whether knockout (KO) of TIGAR improves endothelial glycolytic function and angiogenesis. In vitro, aortic endothelial cells (ECs) from TIGAR KO mice exhibited increased expression of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform‐3 (PFKFB3) and increased glycolytic function. These were accompanied by increased mitochondrial basal/maximal respiration and ATP production. Furthermore, knockout of TIGAR in ECs enhanced endothelial proliferation, migration, and tube formation. Knockout of TIGAR also significantly increased aortic sprouting ex vivo. In vivo, knockout of TIGAR increased the expression of proangiogenic factor, angiopoietin‐1 (Ang‐1) in mouse hearts. Knockout of TIGAR also significantly increased coronary capillary density with enhanced CFR in these hearts. Furthermore, TIGAR KO mice subjected to pressure overload (PO), a common model to study angiogenesis and cardiac hypertrophy, exhibited elevated expression of Ang‐1, VEGF, and PFKFB3 than that of the wild‐type (WT) mice. WT mice subjected to PO exhibited a significant reduction of coronary capillary density and impaired CFR, but TIGAR KO mice did not. In addition, knockout of TIGAR blunted TAC‐induced cardiac hypertrophy and dysfunction seen in the WT mice. In conclusion, knockout of TIGAR improves endothelial angiogenetic capabilities by enhancing the endothelial glycolytic function, mitochondrial respiration, and proangiogenic signaling, which leads to increased coronary capillary density and vascular function and protects against chronic stress.
Employing machine learning and microscopy images of AIB1‐stained biopsy material to assess the 5‐year survival of patients with colorectal cancer
Authors: Theodosi Angeliki , Ouzounis Sotiris , Kostopoulos Spiros , Glotsos Dimitris , Kalatzis Ioannis , Asvestas Pantelis , Tzelepi Vassiliki , Ravazoula Panagiota , Cavouras Dionisis , Sakellaropoulos George
Published: April 2021

Our purpose was to employ microscopy images of amplified in breast cancer 1 (AIB1)‐stained biopsy material of patients with colorectal cancer (CRC) to: (a) find statistically significant differences (SSDs) in the texture and color of the epithelial gland tissue, between 5‐year survivors and non‐survivors after the first diagnosis and (b) employ machine learning (ML) methods for predicting the CRC‐patient 5‐year survival. We collected biopsy material from 54 patients with diagnosed CRC from the archives of the University Hospital of Patras, Greece. Twenty‐six of the patients had survived 5 years after the first diagnosis. We selected regions of interest containing the epithelial gland at different microscope lens magnifications. We computed 69 textural and color features. Furthermore, we identified features with SSDs between the two groups of patients and we designed a supervised ML system for predicting the CRC‐patient 5‐year survival. Additionally, we employed the VGG16 pretrained convolution neural network to extract deep learning (DL) features, the support vector machines classifier, and the bootstrap cross‐validation method for boosting the accuracy of predicting 5‐year survival. Fourteen features sustained SSDs between the two groups of patients. The supervised ML system achieved 87% accuracy in predicting 5‐year survival. In comparison, the DL system, using images from all magnifications, gave 97% classification accuracy. Glandular texture in 5‐year non‐survivors appeared to be of lower contrast, coarseness, roughness, local pixel correlation, and lower AIB1 variation, all indicating loss of textural definition. The supervised ML system revealed useful information regarding features that discriminate between 5‐year survivors and non‐survivors while the DL system displayed superior accuracy by employing DL features.
Palyno‐morphological characterization of selected allergenic taxa of family Poaceae from Islamabad‐Pakistan using microscopic techniques
Authors: Ullah Izhar , Ahmad Mushtaq , Jabeen Asma , Yusuf M. Osman , Arfan Muhammad , Kilic Omer , Bagci Eyüp , Zafar Muhammad , Sultana Shazia , Khan Siraj , Usma Anwer
Published: April 2021

Statistics around the world show an increased risk of high allergies associated with plants. The role of allergenic pollen is now well known. The most serious allergenic diseases are asthma and rhinitis, which affect 5–30% of the population of industrialized countries. This work focuses on the exploration of allergenic grass species of Islamabad, Pakistan and use microscopic techniques to correctly identify them. This study contains 11 species of grasses which showed variations in pollen morphological features. The dominant pollen shape was prolate, prolate‐spheroidal and sub oblate. The largest polar diameter was calculated for Echinochloa crus‐galli (56.00 μm) while the largest equatorial diameter was found in Cenchrus ciliaris (45.00 μm). Exine ornamentation varied from Gemmate–verrucate, Scabrate–reugulate, Verrucate–reticulate, Gemmate–Scabrate, Fine–Gemmate, Gemmate–rugulate, Gemmate–reticulate, Gemmate–scabrate, Scabrate–verrucate, and Scabrate. Maximum exine thickness was found in Eleusine indica (4.90 μm) while in C. ciliaris (1.50 μm) the minimum thickness of exine was measured. In E. crus‐galli (1.54 μm), the largest P to E value was measured and the smallest value was noticed in Setaria verticillata (0.86 μm). The study was performed with an aim to identify the allergenic plant species in Islamabad‐Pakistan using pollen morphological studies. This study provides significant information, to arrange the pollen types within their defined classes and to discuss various pollen features for developing an allergenic pollen atlas.
Evolutionary insights into sexual behavior from whiptail lizards
Authors: O'Connell Lauren A. , Crews David
Published: April 2021

Is the brain bipotential or is sex‐typical behavior determined during development? Thirty years of research in whiptail lizards transformed the field of behavioral neuroscience to show the brain is indeed bipotential, producing behaviors along a spectrum of male‐typical and female‐typical behavior via a parliamentary system of neural networks and not a predetermined program of constrained behavioral output. The unusual clade of whiptail lizards gave these insights as there are several parthenogenetic all‐female species that display both male‐typical and female‐typical sexual behavior. These descendant species exist alongside their ancestors, allowing a unique perspective into how brain–behavior relationships evolve. In this review, we celebrate the over 40‐year career of David Crews, beginning with the story of how he established whiptails as a model system through serendipitous behavioral observations and ending with advice to young scientists formulating their own questions. In between these personal notes, we discuss the discoveries that integrated hormones, neural activity, and gene expression to provide transformative insights into how brains function and reshaped our understanding of sexuality.
Seventy‐year disruption of seasons characteristics in the Arabian Peninsula
Authors: Ajjur Salah Basem , Al‐Ghamdi Sami G.
Published: April 2021

Climate change has significantly influenced the characteristics of seasons and negatively affected ecosystems and socio‐economic life. This study presents a new, objective definition for seasons in the Arabian Peninsula. Specifically, the study determines disruptions in the onset, cessation, and duration of winter, spring, summer, and autumn based on mean intra‐annual changes of 12 climatological parameters from 1950 to 2019. Data for climatological parameters were obtained from the National Centers for Environmental Prediction (NCEP)/National Center for Atmospheric Research (NCAR) reanalysis. These data were analysed using two multivariate statistical methods: principal component analysis and cluster analysis. The results show that the characteristics of the four seasons differ from conventionally defined seasons. The differing characteristics of the four seasons are (a) that winter extends for 91 days, between 2 November (the previous year) and 31 January; (b) spring extends for 111 days, until 22 May; (c) summer extends for 106 days, until 5 September and, finally; (d) autumn completes the cycle, extending for 57 days. To investigate the decadal disruption of seasons' characteristics, the analysis was performed on the data collected during five overlapping 30‐year periods: 1950–1979, 1960–1989, 1970–1999, 1980–2009, and 1990–2019. The most remarkable changes were noticed during the last 30 years. Compared to the 70‐year analysis, the 1990–2019 analysis showed extra prolongation in the duration of summer and a shortage in winter, which aligns with the recent warming and drying of the Arabian Peninsula. Summer (winter) lasts for 126 (76) days. All analyses propose that all seasons start earlier, compared with the astronomical definition. The findings of this study are key to understanding the consequences of seasons changes in the Arabian Peninsula. These consequences include impacts on agriculture, water deficits, ecosystems, and land cover.
Diurnal cycle of summer precipitation over the North China Plain and associated land–atmosphere interactions: Evaluation of ERA5 and MERRA‐2
Authors: Song Yuanyuan , Wei Jiangfeng
Published: April 2021

The diurnal cycle of precipitation is influenced by the dynamic and thermodynamic processes of the land–atmosphere system and is a gateway for understanding land–atmosphere interactions. Here, we use satellite‐based precipitation data from CMORPH and TRMM 3B42 to evaluate the ability of ERA5 and MERRA‐2 reanalyses to depict the diurnal cycle of summer precipitation over the North China Plain (NCP). The observed diurnal cycles generally have a peak time in the afternoon or in the night to early morning, depending on the region. Both ERA5 and MERRA‐2 can reproduce the observed night to early morning precipitation peak, but the observed afternoon precipitation peak is only shown in ERA5. Moisture flux convergence is the main driver for night and early morning precipitation, while local land surface evapotranspiration and moisture flux convergence jointly drive afternoon rainfall. Compared with ERA5, the land surface is more strongly coupled with the atmosphere in MERRA‐2, and MERRA‐2 precipitation is more sensitive to precipitable water. The low‐level wind field is more divergent in MERRA‐2 than in ERA5 during afternoon, which causes weaker ascending motions, less precipitable water, and lower precipitation efficiency. The less favourable atmospheric conditions for precipitation, exacerbated by the strong land–atmosphere coupling, lead to the absence of afternoon rainfall in MERRA‐2.
Lake Neor reveals how mountain vegetation responded to 7000 years of hydroclimate variability in northwestern Iran
Authors: Alinezhad Khadijeh , Ramezani Elias , Djamali Morteza , Sharifi Arash , Naqinezhad Alireza , Aubert Cyril , Gandouin Emmanuel , Pourmand Ali
Published: April 2021

Palynological and geochemical analyses provide valuable information about modern and past climatic regimes and vegetation. The impact of climate and humans on past vegetation in the semi‐arid areas of northwestern Iran has received increased interest in the wake of warming temperatures in the Middle East. Palynological and down‐core XRF elemental abundances from a peat core from Lake Neor enabled a reconstruction of vegetational changes of the past 7000 years over the highlands of northwestern Iran. Periods of increased arboreal pollen (AP) types and high (Artemisia + Poaceae)/Chenopodiaceae ratios along with low titanium abundances, high percentages of total organic carbon, more negative δD values, and higher carbon accumulation rates suggest a relatively wet climate. These conditions have persisted during the periods 6700–6200, 5200–4450 and 3200–2200 cal a bp. The overall low AP values, substantial rise of Chenopodiaceae, high Ti abundances and low values of palaeo‐redox proxies, are all evidences of a drier climate, as has been reconstructed for the periods 6200–5200 and 4030–3150 cal a bp and the last 2200 years. An important feature of the last centuries is the increase of anthropogenic and pastoral indicator pollen types. Our results may provide basic data to predict future trends in vegetation dynamics under future climate change in western Asia.
Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR‐targeting agents to treat head and neck squamous cell carcinoma
Authors: Zaryouh Hannah , De Pauw Ines , Baysal Hasan , Peeters Marc , Vermorken Jan Baptist , Lardon Filip , Wouters An
Published: April 2021

Resistance to therapies targeting the epidermal growth factor receptor (EGFR), such as cetuximab, remains a major roadblock in the search for effective therapeutic strategies in head and neck squamous cell carcinoma (HNSCC). Due to its close interaction with the EGFR pathway, redundant or compensatory activation of the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway has been proposed as a major driver of resistance to EGFR inhibitors. Understanding the role of each of the main proteins involved in this pathway is utterly important to develop rational combination strategies able to circumvent resistance. Therefore, the current work reviewed the role of PI3K/Akt pathway proteins, including Ras, PI3K, tumor suppressor phosphatase and tensing homolog, Akt and mammalian target of rapamycin in resistance to anti‐EGFR treatment in HNSCC. In addition, we summarize PI3K/Akt pathway inhibitors that are currently under (pre)clinical investigation with focus on overcoming resistance to EGFR inhibitors. In conclusion, genomic alterations in and/or overexpression of one or more of these proteins are common in both human papillomavirus (HPV)‐positive and HPV‐negative HNSCC tumors. Therefore, downstream effectors of the PI3K/Akt pathway serve as promising drug targets in the search for novel therapeutic strategies that are able to overcome resistance to anti‐EGFR treatment. Co‐targeting EGFR and the PI3K/Akt pathway can lead to synergistic drug interactions, possibly restoring sensitivity to EGFR inhibitors and hereby improving clinical efficacy. Better understanding of the predictive value of PI3K/Akt pathway alterations is needed to allow the identification of patient populations that might benefit most from these combination strategies.
Sulforaphane Balances Ca2+ Homeostasis Injured by Excessive Fat via Mitochondria‐Associated Membrane (MAM)
Authors: Tian Sicong , Lei Peng , Zhang Jing , Sun Yao , Li Baolong , Shan Yujuan
Published: April 2021

Scope

Mitochondria‐associated membrane (MAM) connects endoplasmic reticulum (ER) and mitochondria plays a significant role in lipid metabolism and Ca2+ homeostasis. Albeit sulforaphane (SFN) shows potential in ameliorating excessive fat accumulation and mitochondrial function; whether MAM is a target of SFN and its underlying mechanisms are still unclear.

Methods and Results

High‐fat‐intake models are established both in vivo and in vitro. SFN widens the distance between ER and mitochondria and down‐regulates MAM tether protein mitofusin‐2. SFN reverses the increase of Ca2+ induced by fatty acid and inhibits the Ca2+ channel inositol‐1,4,5‐trisphosphate receptor (IP3R). Compared with high fat group, SFN alleviates Ca2+ overload in the mitochondria and suppresses mitochondrial calcium uniporter (MCU). Furthermore, SFN increases mitochondrial DNA quantities and mitochondria membrane potential, while decreasing reactive oxygen species (ROS) production. Finally, SFN increases mitochondria complexes IV content and ATP synthesis.

Conclusion

These results suggest that SFN balances the Ca2+ homeostasis in the MAM through regulating Ca2+ flux by Ca2+ channel IP3R and MCU.
Prevalence of low computed tomography–measured skeletal muscle index and handgrip strength in a general medical population
Authors: Van Jacobs Amanda , Coltman Anne , Gomez‐Perez Sandra L. , Bienia Benjamin , Sclamberg Joy S. , Peterson Sarah J.
Published: April 2021

Background

Sarcopenia is defined as the loss of muscle mass and function and has been associated with worsened outcomes, including disability and mortality. The aim of this study was to describe the prevalence of sarcopenia in patients who had an abdominal computed tomography (CT) scan completed within 7 days of hospital admission.

Methods

A retrospective study was conducted. Adult patients admitted to either the general medical or surgical floor were included. Muscle function was assessed using handgrip strength (HGS, kg), completed within the first 48 hours of admission. Skeletal muscle index (SMI, kg/m2) at the third lumber region was calculated among patients who had an abdominal CT scan completed within 7 days of admission. Sarcopenia was identified by the combination of low SMI and HGS. The primary outcome was the percentage of patients diagnosed with sarcopenia.

Results

A total of 1318 patients were admitted; 11% (n = 141) had an abdominal CT scan completed within 7 days of admission. Only race and prevalence of malnutrition were different between patients who did and did not have a CT completed. The overall prevalence of sarcopenia was 13% (n = 18/141). Additionally, 39% of the sample was at risk for sarcopenia, with either low SMI (n = 13/141) or low HGS (n = 42/141).

Conclusions

Overall prevalence of sarcopenia was low, but more than one‐third of patients had either low SMI or low HGS. Minimal differences were observed between patients who did and did not have an abdominal CT scan completed upon admission.
Layer by layer controlled synthesis at room temperature of tri‐modal (MRI, fluorescence and CT) core/shell superparamagnetic IO/human serum albumin nanoparticles for diagnostic applications
Authors: Ganguly Sayan , Neelam  , Grinberg Igor , Margel Shlomo
Published: April 2021

Magnetic nanoparticles (NPs) are drawing attention since few decades because of its tunable properties. It is well known that the degradation of plasma proteins like albumin in cancer cells is significantly faster than in normal cells. Hereby, we combined the advantages of human serum albumin (HSA) and iron oxide NPs (IO NPs) to prepare mono‐, bi‐ and tri‐modal IO/HSA core‐shell NPs for diagnostic applications, to promote the smooth and precise assessment of signals obtained from diagnostic machines. HSA is well known as a physiological carrier for many biomaterials (e.g., fatty acids, metal ions, amino acids, peptides, drugs, etc.). Mono‐modal magnetic resonance imaging (MRI) IO NPs were prepared via nucleation at room temperature of IO layers onto IO‐HSA nuclei. Mono‐modal IO/HSA NPs were produced by heating the IO NPs aqueous HSA dispersion to 80°C, followed by HSA precipitation via cooling to RT. Bi‐modal (MRI and fluorescence [FL]) IO/HSA NPs were prepared similarly, substituting the HSA for Cy7‐conjugated HSA. Tri‐modal (MRI, FL and computed tomography (CT) IO/HSA were prepared similarly, substituting the aqueous continuous phase for aqueous continuous phase containing iohexol (a water‐soluble CT contrast agent), thereby entrapping the iohexol within the precipitated HSA. Cytotoxicity tests in HCT116 (colon), MCF7 (breast) and A127 (glioblastoma) cells showed that the IO/HSA NPs are non‐toxic toward these cells. Moreover, these non‐cytotoxic NPs were incubated with HCT116 cells and tested against three different diagnostic tools (FL, MRI and CT). The calibration and signal assessment of the results showed almost identical intensities obtained from these diagnostic tools that could promote these NPs as the multi‐modal probe.
Rapid analysis and identification of dianthrone glycosides in Polygoni Multiflori Caulis based on enrichment of macroporous absorbent resin and UPLC‐Q‐TOF‐MS/MS
Authors: Bo Rui , Wu Jian , Wu Jiacai , Bai Lisha , Ye Mingzhu , Huang Li , Chen Hongyuan , Rui Wen
Published: April 2021

Introduction

Polygoni Multiflori Caulis (PMC) has been used as a traditional Chinese medicine for a long time in China. However, hepatotoxic events of PMC have been reported in recent years, but the potential toxic compounds have remained unclear. Dianthrones as the secondary plant metabolites were revealed to potential hepatotoxicity in a previous study. However, no reports focused on dianthrones in PMC.

Objective

In the quest for exploring potential hepatotoxic compounds in PMC, the aim of this work was to undertake a comprehensive characterisation of dianthrones in PMC.

Methods

A simple and effective macroporous absorbent resin column chromatography method was established in this study to enrich the minor dianthrones from PMC extracts. Exploration and characterisation of dianthrones in PMC was conducted by an ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS/MS) method and information dependent acquisition (IDA) mode. The aglycones of dianthrone glycosides were further verified by acid hydrolysis method.

Results

Seventy‐two dianthrone glycosides and their five aglycones were discovered and tentatively characterised in PMC for the first time, of which 29 dianthrones were identified as potential new compounds. Dianthrone glycosides could be classified into three types according to their aglycone structures, and their fragmentation pathway rules and diagnosed ions were also summarised comprehensively.

Conclusion

This was the first comprehensive investigation on dianthrones in PMC. The result would help to fully understand the phytochemical constituents and toxic components in PMC, and highlight the need for further toxicological investigations of the dianthrones in PMC due to their potential hepatotoxicity correlation.
Investigating whole‐brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury
Authors: Lin Joanne C. , Mueller Christina , Campbell Kelsey A. , Thannickal Halle H. , Daredia Altamish F. , Sheriff Sulaiman , Maudsley Andrew A. , Brunner Robert C. , Younger Jarred W.
Published: April 2021

Background

Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions.

Objective

To measure whole‐brain metabolites in chronic stages of TBI.

Design

Observational study.

Setting

University.

Participants

Eleven men with a moderate or severe TBI more than 12 months prior and 10 age‐matched healthy controls completed whole‐brain spectroscopic imaging.

Main Measures

Ratios of N‐acetylaspartate (NAA), choline (CHO), and myo‐inositol (MI) to creatine (CR) were measured in whole‐brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion.

Results

There were no differences in metabolite ratios within whole‐brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls.

Conclusion

Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.
The clinical management of extralobar pulmonary sequestration in children
Authors: Huang Dongmei , ･ Habuding Aerxin , Yuan Miao , Yang Gang , Cheng Kaisheng , Luo Dengke , Xu Chang
Published: April 2021

Introduction

The treatment of extralobar pulmonary sequestration (ELS) remains divergent. This study aims to demonstrate the characters of ELS in children for optimal clinical management in the future.

Material and Methods

A retrospective analysis was conducted for ELS patients' treatment in our center from January 2013 to April 2020.

Results

In total, 85 patients were included, containing 70 upper‐diaphragmatic, 7 intra‐diaphragmatic, and 8 infra‐diaphragmatic ELS. Eight patients' pathology results showing inflammation without symptoms preoperation and two patients had chest pain for torsion. All the upper‐diaphragmatic and intra‐diaphragmatic ELS patients accepted thoracoscopic surgery resection. The intraoperative operation time and blood loss volume of intra‐diaphragmatic ELS were significantly more than that of the upper‐diaphragmatic (40.14 ± 9.92  vs. 23.07 ± 6.79 min; 9.29 ± 3.45  vs. 3.18 ± 4.94 ml; all p < .05). No chest tubes were inserted in both subgroups. No complications were found in the postoperative follow‐up of operative ELS patients at least 3 months. A total of eight infra‐diaphragmatic ELS patients except for one (7/8) had conservative therapy and follow‐up by the outpatient clinic or phone call eventually. There were no symptoms occurring and no size increasing of observation infra‐diaphragmatic ELS.

Conclusions

The ELS has the potential risk of infection and torsion in this study. Thoracoscopic surgery might be optimal management of upper‐diaphragmatic ELS for its minimal invasion and low perioperative risks, which could be developed into a day operation with safe and quick recovery. The intra‐diaphragmatic and infra‐diaphragmatic ELS need a larger sample size and multiple center data to get a better management approach.
Positive bronchoalveolar lavage pepsin assay associated with viral and fungal respiratory infections in children with chronic cough
Authors: Martin Corey N. , Barnawi Zhour , Chorvinsky Elizabeth , Pillai Dhruv , Gatti Meagan , Collins Maura E. , Krakovsky Gina M. , Bauman Nancy M. , Sehgal Sona , Pillai Dinesh K.
Published: April 2021

Objective

To assess the association between commonly obtained endoscopic and serologic data and bronchoalveolar lavage pepsin assay (BAL) results in children with chronic cough.

Study Design

We performed a retrospective chart review of 72 children with a BAL pepsin obtained through our Aerodigestive Center over an 18‐month period. BAL outcomes include evidence of viral, bacterial, or fungal infection, presence of lipid‐laden macrophages, and cytology (eosinophils, neutrophils, and lymphocytes). Gastrointestinal outcomes include esophagogastroduodenoscopy (EGD) and pH impedance probe findings. Other characteristics include serum eosinophils, neutrophils, and lymphocytes; spirometry; FeNO; and IgE.

Results

Seventy‐two patients underwent BAL pepsin testing. Median age was 4.9 years, 30.6% had severe persistent asthma, and 59.2% were on reflux medication. There was an association between positive BAL pepsin assay and positive viral panel (p = .002) or fungal culture (p = .027). No significant association found between positive BAL bacterial culture; BAL cytology; the presence of BAL lipid‐laden macrophages; IgE; spirometry; FeNO; CBC neutrophil, eosinophil, or lymphocytes; pH impedance testing parameters; or EGD pathology.

Conclusions

BAL pepsin is associated with a positive BAL viral PCR or fungal culture. Lack of correlation between pepsin‐positivity and pH‐impedance parameters or EGD pathology suggests microaspiration may be due to an acute event (such as a respiratory infection) rather than chronic gastroesophageal reflux disease. This may be especially true in the presence of a positive viral panel or fungal culture when a BAL pepsin is obtained.
Comparing two different low‐intensity shockwave therapy frequency protocols for nonbacterial chronic prostatitis/chronic pelvic pain syndrome: A two‐arm, parallel‐group randomized controlled trial
Authors: Mykoniatis Ioannis , Pyrgidis Nikolaos , Kalyvianakis Dimitrios , Zilotis Filimon , Kapoteli Paraskevi , Fournaraki Agrippina , Hatzichristou Dimitrios
Published: April 2021

Background

Despite encouraging results, the optimal low‐intensity shockwave therapy (LiST) protocol in patients with chronic prostatitis/chronic pelvic pain syndrome (CPPS) remains unknown. We conducted a two‐arm, parallel‐group, randomized controlled trial aiming to compare the efficacy and safety of six LiST sessions applied once or twice weekly.

Methods

Fifty patients with CP/CPPS type IIIb were randomly assigned to six LiST sessions once (Group A, n = 25) or twice weekly (Group B, n = 25). Both groups followed the same treatment protocol in terms of LiST application, impulses (5000/session), energy flux density (0.096 mJ/mm2) and frequency (5 Hz). Subsequently, all participants were evaluated at 1 and 3 months after completion of LiST protocol.

Results

At the follow‐up evaluations, LiST significantly improved the National Institutes of Health‐Chronic Prostatitis Symptom Index (NIH‐CPSI) total, pain and quality of life scores, as well as the International Index of Erectile Function–Erectile Domain (IIEF‐ED) in both groups (p < .001 for all measures). Comparing between the two groups, no significant differences were demonstrated in the NIH‐CPSI total, pain, urinary and quality of life scores, as well as in the International Prostate Symptom Score, IIEF–ED, and LiST‐induced pain at both follow‐up evaluations. Accordingly, no adverse events and no dropouts were observed in both groups.

Conclusion

Six sessions of LiST applied once weekly for 6 weeks or twice weekly for 3 weeks seem to be equally safe and effective in patients with CP/CPPS. Nevertheless, further studies are necessary, since LiST gradually gains its place for the management of CP/CPPS.
Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
Authors: Ding Liang , Zhang Fang‐bin , Liu Hui , Gao Xiang , Bi Hui‐chang , Huang Ling , Wang Xue‐ding , Chen Bai‐li , Zhang Yu , Lv Chuanzhu , Hu Pin‐jin , Huang Min
Published: April 2021

Xanthine oxidase (XO) competes with thiopurine S‐methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6‐mercaptopurine (6‐MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine‐induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6‐MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu‐like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu‐like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine‐induced toxicity.