bluuebunny/crossref_metadata_2025 huggingface dataset:
Alleviation of Liver Dysfunction, Oxidative Stress, and Inflammation Underlines the Protective Effects of Polysaccharides from Cordyceps cicadae on High Sugar/High Fat Diet‐Induced Metabolic Syndrome in Rats
Authors: Zhang Xiao , Li Jinpeng , Yang Bo , Leng Qina , Li Ji , Wang Xintuan , Lu Junyao , Olatunji Opeyemi Joshua , Tang Jian
Published: March 2021

This study investigated the protective effects of two polysaccharides (CPA‐1 and CPB‐2) from Cordyceps cicadae against high fructose/high fat diet (HF/HFD) induced obesity and metabolic disorders in rats. Rats were either fed with normal diet or HF/HFD and treated with CPA‐1 and CPB‐2 (100 and 300 mg/kg) for 11 weeks. Administration of CPA‐1 and CPB‐2 significantly and dose dependently reduced body and liver weight, insulin and glucose tolerance, serum insulin and glucose levels. Furthermore, serum and hepatic lipid profiles, liver function enzymes and proinflammatory cytokines (TNF‐α, IL‐1β and IL‐6) were markedly reduced. Additionally, CPA‐1 and CPB‐2 treatment alleviated hepatic oxidative stress by reducing lipid peroxidation level (MDA) and upregulating glutathione peroxidase (GSH‐Px), superoxide dismutase (SOD) and catalase (CAT) activities as well as ameliorated histological alterations through the reduction of hepatic lipid accumulation. These results suggested that the polysaccharides from C. cicadae showed protective effects against HF/HFD induced metabolic disturbances and may be considered as a dietary supplement for treating obesity.
SOX‐17 is involved in invasion and apoptosis of colorectal cancer cells through regulating miR‐302b‐3p expression
Authors: Hu Fan , Li Mei , Mo Li , Xiao You , Wang Xiaoyan , Xie Biao
Published: March 2021

The prognosis of advanced colorectal cancer (CRC) is currently still very poor, which suggests that the biological mechanisms of CRC oncogenesis are not fully understood. This study was conducted to explore the regulatory effect of SOX‐17 on the expression of microRNA (miR)‐302b‐3p, and the involvement of SOX‐17 in the invasion and apoptosis of CRC cells. The expression of SOX‐17 and miR‐302a,b,c,d‐3p in colorectal cancer and normal colon epithelial cell lines was measured by real‐time polymerase chain reaction and/or western blot. The regulatory effects of SOX‐17 on miR‐302b‐3p gene in HT29 and LoVo cells were tested using the ChiP assay. The biological activities of SOX‐17 and miR‐302b‐3p were evaluated by invasion and apoptosis assay. Results showed that transfection of SOX‐17 small interfering RNA (siSOX‐17) significantly increased, whereas transfection of SOX‐17 overexpression vector (oeSOX‐17) significantly decreased, miR‐302b expression in HT29 and LoVo cells. Cotransfection of oeSOX‐17 and miR‐302b‐3p inhibitor (INmiR‐302b) significantly blocked the effects of SOX‐17 in HT29 and LoVo cells. ChIP experiments showed that SOX‐17 bonded to the miR‐302b‐3p promoter in HT29 and LoVo cells. Transfection of oeSOX‐17 and miR‐302b‐3p mimics (MImiR‐302b) significantly decreased, whereas transfection of siSOX‐17 and INmiR‐302b significantly increased, the invasion of HT29 and LoVo cells. In contrast, transfection of oeSOX‐17 and MImiR‐302b significantly increased, while transfection of siSOX‐17 and INmiR‐302b significantly decreased, apoptosis in HT29 and LoVo cells. Cotransfection of oeSOX‐17 and INmiR‐302b significantly blocked the effects of oeSOX‐17 on cell invasion and apoptosis in HT29 and LoVo cells. These results suggested that SOX‐17 can bind to the promoter of miR‐302b‐3p gene to regulate its expression, while both SOX‐17 and miR‐302b regulate the invasion and apoptosis in colorectal cancer cells.
Long‐term follow‐up of salvage therapy using a combination of inotuzumab ozogamicin and mini–hyper‐CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome–negative acute lymphoblastic leukemia
Authors: Jabbour Elias , Sasaki Koji , Short Nicholas J. , Ravandi Farhad , Huang Xuelin , Khoury Joseph D. , Kanagal‐Shamanna Rashmi , Jorgensen Jeffrey , Khouri Issa F. , Kebriaei Partow , Jain Nitin , Alvarado Yesid , Kadia Tapan M. , Paul Shilpa , Garcia‐Manero Guillermo , Dabaja Bouthaina S. , Burger Jan A. , DiNardo Courtney D. , Daver Naval A. , Montalban‐Bravo Guillermo , Yilmaz Musa , Ohanian Maro , Ferrajoli Alessandra , Jacob Jovitta , Rostykus Meagan , Garris Rebecca , O’Brien Susan , Kantarjian Hagop M.
Published: March 2021

BACKGROUND

The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low‐intensity mini–hyper‐CVD (mini‐hyper‐CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL.

METHODS

We used lower intensity chemotherapy, mini‐hyper‐CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) compared to conventional hyper‐CVAD.

RESULTS

Ninety‐six patients with a median age of 37 years (range, 18‐87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty‐four (46%) patients underwent later allogeneic stem cell transplantation. Veno‐occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower‐dose inotuzumab and sequential blinatumomab. With a median follow‐up of 36 months, the median overall survival (OS) was 13.4 months, with 3‐year OS rates of 33%. The 3‐year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%.

CONCLUSION

The combination of inotuzumab and low‐intensity mini‐hyper‐CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.
Synthesis and 15N NMR Signal Amplification by Reversible Exchange of [15N]Dalfampridine at Microtesla Magnetic Fields
Authors: Chukanov Nikita V. , Salnikov Oleg G. , Trofimov Ivan A. , Kabir Mohammad S. H. , Kovtunov Kirill V. , Koptyug Igor V. , Chekmenev Eduard Y.
Published: March 2021

Signal Amplification by Reversible Exchange (SABRE) technique enables nuclear spin hyperpolarization of wide range of compounds using parahydrogen. Here we present the synthetic approach to prepare 15N‐labeled [15N]dalfampridine (4‐amino[15N]pyridine) utilized as a drug to reduce the symptoms of multiple sclerosis. The synthesized compound was hyperpolarized using SABRE at microtesla magnetic fields (SABRE‐SHEATH technique) with up to 2.0 % 15N polarization. The 7‐hour‐long activation of SABRE pre‐catalyst [Ir(IMes)(COD)Cl] in the presence of [15N]dalfampridine can be remedied by the use of pyridine co‐ligand for catalyst activation while retaining the 15N polarization levels of [15N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on 15N polarization levels of free and equatorial catalyst‐bound [15N]dalfampridine were investigated. Moreover, we studied 15N polarization build‐up and decay at magnetic field of less than 0.04 μT as well as 15N polarization decay at the Earth's magnetic field and at 1.4 T.
Construction and Quantitation of a Selectable Protein Splicing Sensor Using Gibson Assembly and Spot Titers
Authors: Woods Daniel , LeSassier Danielle S. , Egbunam Ikechukwu , Lennon Christopher W.
Published: March 2021

Inteins (intervening proteins) are translated within host proteins and removed through protein splicing. Conditional protein splicing (CPS), where the rate and accuracy of splicing are highly dependent on environmental cues, has emerged as a novel form of post‐translational regulation. While CPS has been demonstrated for several inteins in vitro, a comprehensive understanding of inteins requires tools to quantitatively monitor their activity within the cellular context. Here, we describe a method for construction of a splicing‐dependent system that can be used to quantitatively assay for conditions that modulate protein splicing. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Construction of an intein‐containing KanR2 library using Gibson assembly

Basic Protocol 2: Phenotype determination using quantitative spot titers

Support Protocol 1: Preparation of LB agar plates for spot titers

Support Protocol 2: Preparation and transformation of competent M. smegmatis cells
Relativistic study of electromagnetic electron cyclotron instability based on trapped electrons in kappa‐Maxwellian auroral plasmas
Authors: Nazeer M. , Qureshi M.N.S. , Shen C.
Published: March 2021

The presence of relativistic electrons in the Earth's magnetosphere may excite EMEC waves via resonant interaction. The understanding of EMEC waves induced by such electrons requires relativistic treatment. Therefore, we present here the investigation of EMEC waves based on relativistic trapped electrons represented by kappa‐Maxwellian distribution in auroral plasmas. The analytical expressions of real frequency and relativistic growth rate are derived. Our numerical outcomes report that relativistic approximation increases the wave growth and causes reduction in the threshold value of drift velocity of trapped electrons for instability. The wave frequency that corresponds to the maximum growth decreases as we go from nonrelativistic limit to relativistic. The maximum growth increases with the increment in plasma frequency, perpendicular thermal velocity, drift velocity of trapped electrons, and Lorentz factor γ. Moreover, the relativistic effects on maximum growth are more pronounced for smaller values of drift velocity and perpendicular thermal velocity.
A distributed fault‐tolerant mechanism for mission‐oriented unmanned aerial vehicle swarms
Authors: Wang Huibin , Chen Ming , Fu Ping
Published: March 2021

Unmanned aerial vehicle (UAV) swarm consists of a number of autonomous and collaborative UAV nodes. The purpose of the research is to address the hypotheses: an efficient centralized resources management scheme should be adopted to meet the mission‐oriented feature of UAV swarms, while a distributed fault‐tolerant mechanism should be adopted to meet the characteristics of complex environment and address the issue of high failure rate of UAV nodes. By using an experimental modeling method, this paper proposes a management model and related mechanisms fitting for UAV swarms with the feature of “centralized decision making and distributed task execution.” The model allows UAV nodes to manage their own resources autonomously and execute centralized decisions accordingly. The advantage of the model is that the master node of a UAV swarm is able to perceive all the resources of the system and the status of all (or some) of the UAVs efficiently; therefore, it provides a supportive environment for the UAV swarm application to make centralized decisions and optimize those decisions. Additionally, this paper proposes a distributed fault‐tolerant model and related mechanisms to address the issue of high failure rate of UAV nodes, as well as the system vulnerability caused by harsh environment. Finally, this study developed a prototype system designed and implemented by OMNeT++ to confirm the truth of the hypotheses. The analysis of the experimental data and simulation results of the prototype validated the feasibility and usability of the distributed fault‐tolerant mechanism and demonstrated its value for the mission‐oriented UAV swarms.
Experimental rain prints and gas escape structures as a framework for interpreting circular imprints in shales of the Pottsville Formation (Pennsylvanian, Alabama)
Authors: Bartley Julie K. , Gilliland Patrick J.
Published: March 2021

Coal‐bearing, fine‐grained clastic rocks of the Pennsylvanian Pottsville Formation contain well‐preserved vertebrate and invertebrate trace fossils and disarticulated plant fossils. These fossil‐bearing rocks also contain small, circular imprints that resemble raindrop impressions but have also been interpreted as structures formed by gas bubble escape from wet sediment. Because rain prints are associated with arid, subaerially exposed depositional conditions and gas escape structures with water‐saturated, organic rich sediments, the interpretation of the circular structures profoundly impacts the palaeoenvironmental reconstruction and interpretation of the life habits of the trace‐makers. In this project, rain prints and gas escape structures were produced to compare these two hypotheses regarding mode of formation and to gain insight into interpretations of similar circular pits in the geological record. The results indicate that gas escape structures form most readily in fine‐grained sediment under water‐saturated conditions, in contrast to rain prints, which form most readily in unsaturated sand. A comparison with experimental structures suggests that the Pottsville shales preserve gas escape structures, not raindrop impressions, suggesting that the environment was rarely desiccated. Because rain prints and gas escape structures are superficially similar, genetic interpretations should not be based on these similarities, but rather on the differences observed between them. Reexamination of circular pits in the sedimentary rock record might require adjustment of environmental interpretations.
Dynamics of total volume of pancreatic α‐ and β ‐cells under the influence sulfonylureas and their combination with dipeptidyl peptidase‐4 inhibitors
Authors: Taisiia Pavlovna Tuchina , Kseniia Petrovna Skotnikova , Anna Anatolievna Vtorushina , Ivan Sergeyevich Uskov , Olga Vladimirovna Rogoza , Roman Viktorovich Grozov , Alina Yurievna Babenko , Mikhail Mikhailovich Galagudza
Published: March 2021

Objective

Sulfonylureas and dipeptidyl peptidase‐4 inhibitors have a multidirectional effect on pancreatic cells. We aimed to evaluate the effects of these drugs on β‐ and α‐cells in rats aged 12 months with type 2 diabetes mellitus when administered in combination with various sulfonylureas.

Methods

Streptozotocin‐nicotinamide induced type 2 diabetes mellitus was induced in rats aged 12 months. Animals received the sulfonylureas gliclazide or glibenclamide for 24 weeks alone or in combination with the dipeptidyl peptidase‐4 inhibitor vildagliptin or vildagliptin monotherapy. Blood glucose and animal weights were measured before and during the experiment. The oral glucose tolerance test was conducted before therapy initiation. Immunohistochemical analyses were conducted after the end of the experiment using glucagon and insulin antibodies. The total volumes of α and β cells were estimated in relation to the volume of the pancreatic islets.

Results

The total volumes of β‐cells did not differ between the sulfonylurea group and the untreated type 2 diabetes mellitus group. The addition of dipeptidyl peptidase‐4 inhibitors to sulfonylureas normalized the total volumes of β cells. The total volumes of α‐cells in the gliclazide group and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor was comparable to that in the control group of intact animals, in contrast with the glibenclamide group.

Conclusion

The combination of vildagliptin to both sulfonylureas contributed to the normalisation of β‐cells number. Normalisation of the total volumes of α‐cells was observed with gliclazide therapy and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor.
P(III)‐Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids
Authors: Meng Haiwen , Sun Kunhui , Xu Zhimin , Tian Lifang , Wang Yahui
Published: March 2021

An external oxidant‐free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri‐substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N‐based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.
Study on the flow characteristics of fire extinguishing agent FK‐5‐1‐12 in the pipeline release process
Authors: Fan Weipeng , Gao Zheming , Wang Dapeng , Yang Yuzhuo , Gao Ye
Published: March 2021

Studying the flow characteristics of FK‐5‐1‐12 in the pipeline during the release process is important for appropriate hydraulic calculations and fire extinguishing efficiency evaluation. This work proposes a well‐documented dataset of flow results to investigate the flow state and characteristics. Through comparing the evaporation properties of FK‐5‐1‐12 and those of other typical extinguishers, the flow state of FK‐5‐1‐12 was assumed to be a single‐phase flow, and hydraulic calculations were carried out using single‐phase fluid formulas. The calculated values were compared with experimental data. The release tests of water (pure single‐phase flow), Halon1301 (two‐phase flow), and FK‐5‐1‐12 were carried out under the same piping system, and the flow characteristics of the three media were compared to further verify the piping flow state. The experimental results show that the release process of FK‐5‐1‐12 in the cylinder has a single‐phase flow similar to water, but differs in density and expansion performance. However, FK‐5‐1‐12 only conformed to single‐phase flow in the more upstream sections of the pipeline, but presented obvious two‐phase flow state in the main pipe and the more downstream sections. When the vaporization is the most serious, the density of the mixture is only 1/26 of that of liquid FK‐5‐1‐12.
Brain age prediction: A comparison between machine learning models using region‐ and voxel‐based morphometric data
Authors: Baecker Lea , Dafflon Jessica , da Costa Pedro F. , Garcia‐Dias Rafael , Vieira Sandra , Scarpazza Cristina , Calhoun Vince D. , Sato João R. , Mechelli Andrea , Pinaya Walter H. L.
Published: March 2021

Brain morphology varies across the ageing trajectory and the prediction of a person's age using brain features can aid the detection of abnormalities in the ageing process. Existing studies on such “brain age prediction” vary widely in terms of their methods and type of data, so at present the most accurate and generalisable methodological approach is unclear. Therefore, we used the UK Biobank data set (N = 10,824, age range 47–73) to compare the performance of the machine learning models support vector regression, relevance vector regression and Gaussian process regression on whole‐brain region‐based or voxel‐based structural magnetic resonance imaging data with or without dimensionality reduction through principal component analysis. Performance was assessed in the validation set through cross‐validation as well as an independent test set. The models achieved mean absolute errors between 3.7 and 4.7 years, with those trained on voxel‐level data with principal component analysis performing best. Overall, we observed little difference in performance between models trained on the same data type, indicating that the type of input data had greater impact on performance than model choice. All code is provided online in the hope that this will aid future research.
Opposing relationships of childhood threat and deprivation with stria terminalis white matter
Authors: Banihashemi Layla , Peng Christine W. , Verstynen Timothy , Wallace Meredith L. , Lamont Daniel N. , Alkhars Hussain M. , Yeh Fang‐Cheng , Beeney Joseph E. , Aizenstein Howard J. , Germain Anne
Published: March 2021

While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress‐related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n= 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post‐traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.
Deep‐learning based fully automatic segmentation of the globus pallidus interna and externa using ultra‐high 7 TeslaMRI
Authors: Solomon Oren , Palnitkar Tara , Patriat Re'mi , Braun Henry , Aman Joshua , Park Michael C. , Vitek Jerrold , Sapiro Guillermo , Harel Noam
Published: March 2021

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson's disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep‐learning based neural network, which we term GP‐net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP‐net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP‐net performs 3D inference in a patient‐specific manner, alleviating the need for atlas‐based segmentation. GP‐net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state‐of‐the‐art atlas‐based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP‐net.
Yttrium‐90 Radioembolization for the Treatment of Solitary, Unresectable HCC: The LEGACY Study
Authors: Salem Riad , Johnson Guy E. , Kim Edward , Riaz Ahsun , Bishay Vivian , Boucher Eveline , Fowers Kirk , Lewandowski Robert , Padia Siddharth A.
Published: March 2021

Background and Aims

Locoregional therapies, including yttrium‐90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y‐90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium‐90 glass microspheres.

Approach and Results

LEGACY is a multicenter, single‐arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child‐Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0‐1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative‐level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan‐Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1‐8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow‐up time was 29.9 months by reverse Kaplan‐Meier. ORR (best response) was 88.3% (CI: 82.4‐92.4), with 62.2% (CI: 54.1‐69.8) exhibiting a DoR ≥ 6 months. Three‐year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver.

Conclusions

In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.
Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group
Authors: Rigolin Gian Matteo , Cavazzini Francesco , Piciocchi Alfonso , Arena Valentina , Visentin Andrea , Reda Gianluigi , Zamprogna Giulia , Cibien Francesca , Vitagliano Orsola , Coscia Marta , Farina Lucia , Gaidano Gianluca , Murru Roberta , Varettoni Marzia , Paolini Rossella , Sportoletti Paolo , Pietrasanta Daniela , Molinari Anna Lia , Quaglia Francesca M. , Laurenti Luca , Marasca Roberto , Marchetti Monia , Mauro Francesca R. , Crea Enrico , Vignetti Marco , Gentile Massimo , Montillo Marco , Foà Robin , Cuneo Antonio ,   GIMEMA Group
Published: March 2021

Because the efficacy of new drugs reported in trials may not translate into similar results when used in the real‐life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression‐free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0–1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p < 0.01). Treatment breaks ≥14 days were recorded in 96% of patients and adverse events mirrored those reported in trials. In conclusion, this real‐life analysis showed that IR treatment duration was longer at experienced centers, that the ECOG PS and ≥3 lines of previous therapy are strong prognostic factor and that the overall outcome with this regimen was superimposable to that reported in a randomized trial.
From Black Wednesday to Brexit: Macroeconomic shocks and correlations of equity returns in France, Germany, Italy, Spain, and the United Kingdom
Authors: Gottschalk Sylvia
Published: March 2021

This paper investigates whether macroeconomic shocks, such as the UK's referendum decision to leave the European Union (“Brexit”), the 2008 Financial Crisis, the 1992 ERM Crisis (“Black Wednesday”), and the 1987 stock market crash (“Black Monday”), had a positive impact on portfolio risk diversification. We estimate weekly dynamic conditional correlations and then optimal sectoral portfolio allocations between 1973 and 2019. Our results show that correlations of equity returns increased as a consequence of economic integration among European countries from the mid‐1980s until the late 2000s, and decreased in the United Kingdom after Black Wednesday and the Brexit referendum. We tested the existence of a correlation change‐point on June 27, 2016 by applying Wied et al. (2012)'s [Econometric Theory, 28(3), 570–589] correlation structural break test, which we modified to account for dynamic conditional correlations. Application of this test confirms that the referendum date was a break‐point in nearly all UK manufacturing industries. The failure of Lehman Brothers and the 1987 stock market crash were also identified as structural breaks in equity correlations. Moreover, our findings suggest that the Brexit vote may constitute a long‐term trend reversal of the convergence of equity return correlations in European markets, akin to Black Wednesday, rather than a shock like the 1987 and 2008 financial crises, which merely intensified a historical upward trend in correlations of European equity returns.
Left‐behind children's social adjustment and relationship with parental coping with children's negative emotions during the COVID‐19 pandemic in China
Authors: Wang Yining , Liu Wen , Wang Weiwei , Lin Shuang , Lin Danhua , Wang Hongli
Published: March 2021

Using data collected from two provinces in China through an online survey, the current study aimed to investigate left‐behind children's emotional and academic adjustment during the COVID‐19 pandemic in China. The participants included 1780 left‐behind (960 boys) and 1500 non‐left‐behind (811 boys) children in elementary and junior high school with a mean age of 11.23. Self‐reported questionnaires concerning children's depression, loneliness, anxiety, and academic adjustment, and parents' coping with children's negative emotions were completed. The results suggested that compared with non‐left‐behind children, left‐behind children's depression and anxiety symptoms were more severe and their academic adjustment was poorer. However, left‐behind children had lower levels of loneliness than non‐left‐behind children. Additionally, supportive coping types, especially emotion‐focused and problem‐focused reactions, were significantly negatively correlated with children's depression and anxiety. Unsupportive coping types, especially distress and punitive reactions, were significantly positively correlated with children's depression and anxiety symptoms. Moreover, the relationships between punitive reactions and depression, ignoring and loneliness and problem‐focused reactions and academic adjustment were significantly stronger in left‐behind children. Hence, during the pandemic, left‐behind children were still at a disadvantage even with their parents' company. However, parents' coping style towards left‐behind children's negative emotions played a significant role in their adjustment.
Increasing passive compliance to wearing a facemask in children with autism spectrum disorder
Authors: Lillie Madelynn A. , Harman Michael J. , Hurd Maisie , Smalley Miranda R.
Published: March 2021

The current study taught 6 children with autism spectrum disorder (ASD) to increase passive compliance of wearing a facemask across sequentially increasing durations of time. A changing‐criterion design embedded within a nonconcurrent multiple baseline design was used to evaluate the effectiveness of a resetting differential reinforcement of other behavior (DRO) without escape extinction procedure on passive compliance. Terminal probe sessions determined DRO fading intervals. Results showed that 2 participants acquired mastery level passive compliance (30 min) without fading during the initial baseline sessions. The remaining 4 participants acquired mastery level passive compliance following fading intervals within the DRO intervention. Participants' passive compliance generalized across 2 novel settings. This study replicates previous studies and extends empirical support for the use of DRO without escape extinction interventions for increasing passive compliance with medical devices in children with ASD.
Effect of amphotericin B‐deoxycholate (Fungizone) on the mitochondria of Wistar rats' renal proximal tubules cells
Authors: Alenazi Shehab Ahmed , Elmorsy Ekramy , Al‐Ghafari Ayat , El‐Husseini Amr
Published: March 2021

Amphotericin B‐deoxycholate (Fungizone [FZ]) is a widely used potent antimycotic drug in spite of its nephrotoxic effect via different mechanisms. The effect of FZ on renal cell bioenergetics is not clear. The current study evaluated the effect of FZ on the bioenergetics of albino rats' isolated renal proximal tubule cells (PTCs). The cytotoxic effect of FZ on the isolated renal cells was assessed by MTT and lactate dehydrogenase (LDH) assays. The effect of FZ on the PTCs uptake (OAT1 and OCT2) and efflux (P‐gp and MRP2) transporters was evaluated. Then, the effect of FZ on mitochondria was assessed by studying complexes I–IV activities, lactate assay, oxygen consumption rates (OCR), and western blotting for all mitochondrial complexes. Moreover, the effect of FZ on mitochondrial membrane fluidity (MMF) and fatty acids composition was evaluated. Additionally, the protective effect of coenzyme q10 was studied. Outcomes showed that FZ was cytotoxic to the PTCs in a concentration and time‐dependent patterns. FZ significantly inhibited the studied uptake and efflux tubular transporters with inhibition of the mitochondrial complexes activities and parallel increase in lactate production and decrease in OCRs. Finally, FZ significantly reduced the expression of all mitochondrial complexes in addition to significant increase in MMF and MMFA concentration. Coenzyme Q10 was found to significantly decrease FZ‐induced cytotoxicity and transporters impairment in the PTC. FZ significantly inhibits bioenergetics of PTC, which may stimulate the cascade of cell death and clinical nephrotoxicity.
Infectious Osteomyelitis: Marrying Bone Biology and Microbiology to Shed New Light on a Persistent Clinical Challenge
Authors: Veis Deborah J , Cassat James E
Published: March 2021

Infections of bone occur in a variety of clinical settings, ranging from spontaneous isolated infections arising from presumed hematogenous spread to those associated with skin and soft tissue wounds or medical implants. The majority are caused by the ubiquitous bacterium Staphyloccocus (S.) aureus, which can exist as a commensal organism on human skin as well as an invasive pathogen, but a multitude of other microbes are also capable of establishing bone infections. While studies of clinical isolates and small animal models have advanced our understanding of the role of various pathogen and host factors in infectious osteomyelitis (iOM), many questions remain unaddressed. Thus, there are many opportunities to elucidate host-pathogen interactions that may be leveraged toward treatment or prevention of this troublesome problem. Herein, we combine perspectives from bone biology and microbiology and suggest that interdisciplinary approaches will bring new insights to the field. © 2021 American Society for Bone and Mineral Research (ASBMR).
Ecomorphological, space, and mineral relations of dermal denticles in angular angel shark (Squatina guggenheim)
Authors: de Lima Viliod Marcela Coffacci , Rangel Bianca de Sousa , Rocha Lara Caetano , dos Santos Domingos Júlia Ferreira , Malavasi‐Bruno Carlos Eduardo , de Amorim Alberto Ferreira , Watanabe Ii‐Sei , Ciena Adriano Polican
Published: March 2021

Shark skin is predominantly specialized for swimming and protection, with the dermal denticle being the main structure associated with these abilities. The dermal denticle is a mineral structure with a unique morphology for each species, which allows its use as a taxonomic tool. Few studies have investigated the microscopy aspects of skin and dermal denticles, considering the high diversity of sharks. Here, we investigated the three‐dimensional morphoquantitative aspects and mineral composition of dermal denticles in different regions of the angular angel shark, Squatina guggenheim, using scanning electron microscopy and dispersive energy system. With the microscopy, we were able to observe that the dermal denticle morphology changes according to the area it is located. It was possible to describe the dermal denticles individually, from root to the crown, highlighting all of their individualities. Through the dispersive energy system, we showed the proportions of each mineral found in the denticle, by area, demonstrating the composition and the particularities of crown, body, and root, where whitlockite was described for the first time in elasmobranchs. In this way, the present study presented the specificities of the dermal denticles of S. guggenheim, as well sought to understand the different structure functions for the animal, thus assisting future research in animal morphology.
In a mouse model of INCL reduced S‐palmitoylation of cytosolic thioesterase APT1 contributes to microglia proliferation and neuroinflammation
Authors: Sadhukhan Tamal , Bagh Maria B. , Appu Abhilash P. , Mondal Avisek , Zhang Wei , Liu Aiyi , Mukherjee Anil B.
Published: March 2021

S‐palmitoylation is a reversible posttranslational modification in which a 16‐carbon saturated fatty acid (generally palmitate) is attached to specific cysteine residues in polypeptides via thioester linkage. Dynamic S‐palmitoylation (palmitoylation‐depalmitoylation), like phosphorylation‐dephosphorylation, regulates the function of numerous proteins, especially in the brain. While a family of 23 palmitoyl‐acyl transferases (PATS), commonly known as ZDHHCs, catalyze S‐palmitoylation of proteins, the thioesterases, localized either in the cytoplasm (eg, APT1) or in the lysosome (eg, PPT1) mediate depalmitoylation. Previously, we reported that APT1 requires dynamic S‐palmitoylation for shuttling between the cytosol and the plasma membrane. APT1 depalmitoylated H‐Ras to regulate its signaling pathway that stimulates cell proliferation. Although we demonstrated that APT1 catalyzed its own depalmitoylation, the ZDHHC(s) that S‐palmitoylated APT1 had remained unidentified. We report here that ZDHHC5 and ZDHHC23 catalyze APT1 S‐palmitoylation. Intriguingly, lysosomal Ppt1‐deficiency in Cln1−/− mouse, a reliable animal model of INCL, markedly reduced ZDHHC5 and ZDHHC23 levels. Remarkably, in the brain of these mice decreased ZDHHC5 and ZDHHC23 levels suppressed membrane‐bound APT1, thereby, increasing plasma membrane‐localized H‐Ras, which activated its signaling pathway stimulating microglia proliferation. Increased inflammatory cytokines produced by microglia together with increased complement C1q level contributed to the transformation of astrocytes to neurotoxic A1 phenotype. Importantly, neuroinflammation was ameliorated by treatment of Cln1−/− mice with a PPT1‐mimetic small molecule, N‐tert(Butyl)hydroxylamine (NtBuHA). Our results revealed a novel pathway to neuropathology in an INCL mouse model and uncovered a previously unrecognized mechanism of the neuroprotective actions of NtBuHA and its potential as a drug target.
Back to normal; serological testing for COVID‐19 diagnosis unveils missed infections
Authors: Tsuchida Tomoya , Nitahara Yuko , Suzuki Shotaro , Komase Yuko , Candray Katherine , Kido Yasutoshi , Nakagama Yu , Yamasaki Yukitaka , Imamura Mitsuru , Kawahata Kimito , Kunishima Hiroyuki , Fujitani Shigeki , Mineshita Masamichi , Matsuda Takahide
Published: March 2021

Background

The gold standard for coronavirus disease (COVID‐19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID‐19 may offer advantages in detecting possibly overlooked infections by NAAT.

Methods

To evaluate seroconversion of NAAT‐negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS‐CoV‐2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein.

Results

Eight suspected but unconfirmed COVID‐19 pneumonia patients (median age, 39 years; range, 21–55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2–27 days). None of them had tested positive for SARS‐CoV‐2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS‐CoV‐2. The median period between onset and blood sampling was 26.5 days (7–51 days).

Conclusion

Eight patients with COVID‐19 pneumonia, initially tested negative for SARS‐CoV‐2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID‐19.
Effect of femoral head material on head‐to‐trunnion impaction motion and taper
Authors: Grosso Matthew J. , Choo Kevin J. , Rajaravivarma Raga , Hozack William
Published: March 2021

The purpose of this study was to evaluate the effect of femoral head material on the impaction force, relative motion, and stability of the trunnion. There were three groups with different head materials (n = 5 per group)—CoCr Group: 36 mm CoCr heads, Ceramic Group: 36 mm ceramic heads, Ceramic + Sleeve Group: 36 mm ceramic heads with a titanium sleeve—that were all impacted twice and disengaged onto titanium alloy (Ti6al4V) trunnions in in vitro conditions. A high‐speed camera system was utilized to characterize relative displacement behavior of the head‐trunnion junction motion. The first impact force of Ceramic + Sleeve Group (14,241    SD, 935) was significantly lower than the first impact force in Ceramic Group (14,961 N, SD = 184). Ceramic + Sleeve Group had a lower magnitude bounce‐back displacement following the first impact (17.7 μm, SD = 11), p < 0.05) compared to CoCr Group (298.8 μm, SD = 84) and Group 2 (196.5 μm, SD = 31). Ceramic + Sleeve Group sat further on the trunnion (cumulative final displacement, 366.8 μm, SD = 71, p < 0.001) compared to CoCr Group (142.5 μm, SD = 41.8) and Ceramic Group (183.8 μm, SD = 30). Ceramic + Sleeve Group demonstrated two distinct disengagement patterns—(a) the sleeve disengaged from the trunnion (pull‐off force 6810 N), and (b) the femoral head disengaged from the sleeve (pull‐off force 18,620 N), with large fluctuations in pull‐off force. The presence of a titanium sleeve with a ceramic head resulted in significant differences in impaction force on the trunnion, motion and displacement, and unique mechanisms for disengagement. Further investigation is required to determine potential clinical impact.
Electrochemical corrosion behavior and microstructural characteristics of electron beam welded UNS S32205 duplex stainless steel
Authors: Singh Jastej , Shahi A. S.
Published: March 2021

Different electrochemical techniques were used to study the corrosion behavior of UNS S32205 duplex stainless steel (DSS) welded autogenously using a single‐pass by electron beam welding process, supplemented by microstructural characterization. Furthermore, a comparative study was also performed between multipass gas tungsten arc (GTA)‐welded and EB‐welded DSS for their microstructure and corrosion behavior. The differences in weld thermal cycle and chemical composition influenced the fusion zone microstructure of both the welds and eventually their corrosion properties. The general corrosion resistance of the EB weld was lower than the base metal and higher than the GTA weld despite its weld zone being characterized by a relatively unbalanced phase ratio (α/γ) in comparison to the GTA weld. However, the EB weld showed relatively higher susceptibility to pitting corrosion than the base metal and GTA weld due to its poor repassivation characteristics and poor resistance to pit growth.
Microcellular Conductive Carbon Black or Graphene/PVDF Composite Foam with 3D Conductive Channel: A Promising Lightweight, Heat‐Insulating, and EMI‐Shielding Material
Authors: Jia Li Jiang , Phule Ajit Dattatray , Geng Yue , Wen Shibao , Li Lin , Zhang Zhen Xiu
Published: March 2021

In this study, a lightweight microcellular carbon‐based filler/poly(vinylidene fluoride) (PVDF) composite foam is fabricated with a 3D conductive network that is thermally insulating, electrically conductive, and fabricated on a large scale. This composite can be used for high‐efficiency thermal insulation and electromagnetic interference (EMI) shielding applications. The prepared composite demonstrates low density, high electrical conductivity, and excellent thermal insulation properties. The structure and density of the conductive network and the carbon‐based filler content has a significant influence on the electrical conductivity of the prepared composite foam. Although the composite comprises microcellular PVDF beads of the same density, the conductivity of the composite‐comprising strip beads is greater than that comprising spherical beads. In the same conductive network structure, as the size of the microcellular PVDF beads decrease, the conductive network becomes denser, which results in a higher conductivity. Furthermore, with an increase in the conductive filler content, the conductivity improves significantly. Excellent EMI shielding materials with optimal filler content and particle shapes, exhibiting EMI shielding effectiveness of up to 40–50 dB, are developed. The prepared composite foam possesses excellent application potential in the fields of ultra‐light thermal insulation, conductivity, and EMI shielding.
Reinforcement of bio‐based network polymer with wine pomace
Authors: Morinaga Hisatoyo , Haibara Shunsuke , Ashizawa Satoki
Published: March 2021

Polymer materials prepared using renewable resources such as agricultural and food wastes would lead to a sustainable society. Our target was a synthesis of fiber‐reinforced network polymer derived from citrus oil and wine pomace. Lignocellulose nanofiber (LCNF) was successfully prepared from wine pomace by mechanical fibrillation using disk mill grinder under wet condition, followed by freeze‐drying. The resultant LCNF with coarse powder‐like (the untreated LCNF) enabled to reinforce bio‐based network polymer derived from limonene oxide even though heterogeneously dispersed LCNF was observed in the polymer matrix. Polymer/LCNF composite material with almost homogeneously dispersed LCNF was obtained using LCNF prepared from alcohol‐exchange process prior to freeze‐drying (the alcohol‐exchanged LCNF). Tensile strength of the network polymer reinforced by 2% of alcohol‐exchanged LCNF was around 3.2 times higher than that of the polymer without any LCNF. Dynamic mechanical analysis measurement exhibited that cross‐link density of the network polymer reinforced by 2% of alcohol‐exchanged LCNF was around 1.4 times higher than that of the neat polymer. It is noted that the cross‐linker for bio‐based network polymer, branched polyethyleneimine, likely acted as a dispersing agent for LCNF.