bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemiconvulsion–hemiplegia–epilepsy syndrome with 5q33.3q34 microdeletion: Causal or chance association
Authors: Xue Jiao , Song Zhenfeng , Yi Zhi , Yang Chengqing , Li Fei , Liu Kaixuan , Zhang Ying
Published: April 2021

Hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. We presented a girl with global developmental delay with history and brain MRI consistent with the diagnosis of HHE syndrome. The cytogenetic microarray (CMA) showed 9.1 Mb deletion in 5q33.3q34 region. Along with HHE syndrome, the patient also had global developmental delay. Clinical phenotype of this microdeletion region has not been described in association with HHE syndrome in the literature. We compared the patient's phenotype with other patients in previously published papers of a common region of deletion spanning 157501989–164166203. GABRA1, GABRB2, GABRG2, CYFIP2, and THG1 are the important genes in the present deleted region, which may be responsible for the fever sensitivity and global developmental delay. This is the first case of HHE syndrome in which CMA showed a microdeletion of 5q33.3q34 region. This case report links HHE syndrome and global developmental delay to microdeletion of 5q33.3q34, which has never been reported in literature. The cause of HHE syndrome remains unexplained in present case and HHE may be a causal or chance co‐occurrence.
Metal‐free multicomponent synthesis and in vitro antioxidant activity of indolylpyrazolopyrimidines
Authors: Nadiveedhi Maheshwara Reddy , Shaik Mahammad Sadik , Krishnammagari Suresh Kumar , Cirandur Suresh Reddy
Published: April 2021

Multisubstituted indolylpyrazolopyrimidines were synthesized in good yields with base promoted one‐pot multicomponent system from aldehyde, ketone, and indolylpyrazolamine. Milder and cost‐effective conditions are the highlights of the present protocol. Among the synthesized compounds (4a‐j) 4b, 4c, 4e, and 4f have shown significant better in vitro antioxidant activity compared to standard ascorbic acid.
Electrocatalytic multicomponent one‐pot approach to tetrahydro‐2′H,4H‐spiro[benzofuran‐2,5′‐pyrimidine] scaffold
Authors: Elinson Michail N. , Ryzhkova Yuliya E. , Vereshchagin Anatoly N. , Ryzhkov Fedor V. , Egorov Mikhail P.
Published: April 2021

The new electrocatalytic multicomponent transformation has been found: the electrolysis of arylaldehydes, N,N′‐dimethylbarbiturate, and cycloxehane‐1,3‐diones in alcohols in the presence of sodium bromide as a mediator in an undivided cell results in the formation of substituted unsymmetric spirobarbituric dihydrofurans in 62%–76% yields. The optimized reaction conditions and a mechanistic rationale for this electrocatalytic multicomponent transformation are presented. This new electrocatalytic process is a facile and efficient way to produce substituted unsymmetric spirobarbituric dihydrofurans containing both barbituric and 3,5,6,7‐tetrahydro‐1‐benzofuran‐4(2H)‐one fragments, which are promising compounds for different biomedical applications, among them are anticonvulsants, anti‐AIDS agents, and antiinflammatory remedies. The scaffold approach was employed to find a protein, which may be influenced by the synthesized compounds—human aldose reductase was proposed. It was shown by molecular docking studies that such a scaffold search is beneficial and tetrahydro‐2′H,4H‐spiro[benzofuran‐2,5′‐pyrimidines] used in this approach are promising for the development of novel aldose reductase inhibitors.
An efficient ultrasonic synthetic approach, DFT study, and molecular docking of 6a‐hydroxy‐9‐nitro‐6,6a‐dihydro‐isoindolo[2,1‐a] quinazoline‐5,11‐dione derivatives as algaecides for refining wastewater
Authors: El‐Banna Mohamed G. , El‐Hashash Maher A. , Elnaggar Abeer M. , El‐Badawy Azza A. , Rizk Sameh A.
Published: April 2021

In the present work, reaction of 3‐nitrophthalic anhydride with anthranilic acid to afford the corresponding anthranil that is treated with acetic anhydride that yielded the 2‐benzoxazinonyl‐5‐nitrobenzoic acid (BNBA) could be isomerized to the stereogenic 9‐nitrobenzoxazinone[2,3‐a]isoindolinone acetate (NBIA) via basic reaction conditions. A reaction of the BNBA→NBIA was allowed with series of nitrogen nucleophiles such as formamide and hydrazine derivatives, for example, hydrazine hydrate, hydroxyl amine, acetic hydrazide, thiosemicarbazide, thiocarboihydrazide, and some amino acid, for example, glycine, alanine, and some aliphatic amine, for example, octyl amine, decyl amine, and aromatic amine, for example, aniline, o‐toluidine, 4‐aminobenzoic acid, and carbon nucleophiles such as malononitrile and diethylmalonate. The basicity of previous nucleophiles and thermal stability of the products can be controlled on the course of reaction. The chemical structure of the synthesized compounds can be confirmed by micro‐analytical, spectral data, and they are optimized by quantum chemical parameters (DFT study) to identify the thermal stability of the products. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. A novel sequence of quinazoline derivatives were synthesized, evaluated for their algaecides activity against compounds 1, 2b, and 6 that showed the highest algaecides activities of this series with relatively low toxicity in the median lethal dose test. The obtained results proved that the most active compounds could be useful models for future design, adaptation, and investigation to construct more active analogs.
HDAC11 regulates expression of C/EBPβ and immunosuppressive molecules in myeloid-derived suppressor cells
Authors: Chen Jie , Cheng Fengdong , Sahakian Eva , Powers John , Wang Zi , Tao Jianguo , Seto Edward , Pinilla-Ibarz Javier , Sotomayor Eduardo M
Published: April 2021

Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous population of immature myeloid cells derived from bone marrow and negatively regulate both innate and adaptive immunity in the tumor microenvironment. Previously we have demonstrated that MDSCs lacking histone deacetylase 11 (HDAC11) displayed an increased suppressive activity against CD8+ T-cells. However, the mechanisms of HDAC11 that contribute to the suppressive function of MDSCs remain unclear. Here, we show that arginase activity and NO production is significantly higher in HDAC11 knockout MDSCs when compared with wild-type (WT) controls. In the absence of HDAC11, elevated arginase level and enzymatic activity were observed preferentially in the tumor-infiltrated granulocytic MDSCs, whereas iNOS expression and NO production were increased in the tumor-infiltrated monocytic MDSCs. Of note and for the first time, we demonstrated an association between the elevated expression of immunosuppressive molecules with up-regulation of the transcription factor C/EBPβ in MDSCs lacking HDAC11. Interestingly, the highest expression of C/EBPβ was observed among CD11b+ Gr-1+ MDSCs isolated from tumor-bearing mice. The additional demonstration that HDAC11 is recruited to the promoter region of C/EBPβ in WT MDSCs suggests a novel molecular mechanism by which HDAC11 influence the expression of immunosuppressive molecules in MDSCs through regulation of C/EBPβ gene expression.
A review of signaling and transcriptional control in T follicular helper cell differentiation
Authors: Hart Andrew P , Laufer Terri M
Published: April 2021

T follicular helper (Tfh) cells are a critical component of adaptive immunity and assist in optimal Ab-mediated defense. Multiple effector functions of Tfh support germinal center B cell survival, Ab class switching, and plasma cell maturation. In the past 2 decades, the phenotype and functional characteristics of GC Tfh have been clarified allowing for robust studies of the Th subset including activation signals and environmental cues controlling Tfh differentiation and migration during an immune response. A unique, 2-step differentiation process of Tfh has been proposed but the mechanisms underlying transition between unstable Tfh precursors and functional mature Tfh remain elusive. Likewise, newly identified transcriptional regulators of Tfh development have not yet been incorporated into our understanding of how these cells might function in disease. Here, we review the signals and downstream transcription factors that shape Tfh differentiation including what is known about the epigenetic processes that maintain Tfh identity. It is proposed that further evaluation of the stepwise differentiation pattern of Tfh will yield greater insights into how these cells become dysregulated in autoimmunity.
ER stress protein PERK promotes inappropriate innate immune responses and pathogenesis during RSV infection
Authors: Narayanan Samanthi , Elesela Srikanth , Rasky Andrew J , Morris Susan H , Kumar Surinder , Lombard David , Lukacs Nicholas W
Published: April 2021

The activation of dendritic cells (DC) during respiratory viral infections is central to directing the immune response and the pathologic outcome. In these studies, the effect of RSV infection on development of ER stress responses and the impact on innate immunity was examined. The upregulation of ER stress was closely associated with the PERK pathway through the upregulation of CHOP in RSV infected DC. The inhibition of PERK corresponded with decreased EIF2a phosphorylation but had no significant effect on Nrf2 in DC, two primary pathways regulated by PERK. Subsequent studies identified that by blocking PERK activity in infected DC an altered ER stress response and innate cytokine profile was observed with the upregulation of IFNβ and IL-12, coincident to the down regulation of IL-1β. When mitochondria respiration was assessed in PERK deficient DC there were increased dysfunctional mitochondria after RSV infection that resulted in reduced oxygen consumption rates (OCR) and ATP production indicating altered cellular metabolism. Use of a CD11c targeted genetic deleted murine model, RSV infection was characterized by reduced inflammation and diminished mucus staining as well as reduced mucus-associated gene gob5 expression. The assessment of the cytokine responses showed decreased IL-13 and IL-17 along with diminished IL-1β in the lungs of PERK deficient infected mice. When PERK-deficient animals were assessed in parallel for lung leukocyte numbers, animals displayed significantly reduced myeloid and activated CD4 and CD8 T cell numbers. Thus, the PERK activation pathway may provide a rational target for altering the severe outcome of an RSV infection through modifying immune responses.
Improved decadal predictions of East Asian summer monsoon with a weakly coupled data assimilation scheme
Authors: Li Feifei , Wang Bin , He Yujun , Huang Wenyu , Xu Shiming , Liu Li , Liu Juanjuan , Li Lijuan , Wang Yong
Published: April 2021

The East Asian summer monsoon (EASM) has undergone significant decadal variations since the late 1970s, which greatly affects regional economic and societal activities. However, most available EASM predictions are limited to seasonal to interannual scales, with indistinctive improvements. This study significantly improves decadal prediction skills of the 10‐year‐averaged EASM index (EASMI) and related decadal variations of the East China summer precipitation anomalies (ECSPAs) in the 10‐member decadal prediction experiments started once a year from 1960 to 2005 using a coupled climate model. These improvements are mainly attributed to the use of more realistic and well‐balanced initial conditions (ICs) from a weakly coupled data assimilation system that incorporates the monthly mean atmospheric reanalysis data into the model using the dimension‐reduced projection four‐dimensional variational data assimilation approach, a kind of four‐dimensional ensemble‐variational hybrid method. The atmospheric initialization ameliorates the ICs of Pacific Decadal Oscillation (PDO) through the air‐sea coupling, and thus leads to better PDO hindcasts and forecasts (under the representative concentration pathway 4.5). The improved PDO hindcasts (forecasts) result in more accurate hindcasts (forecasts) of land‐sea thermal contrast, and thus have significant impacts on the EASMI. The improved decadal predictions of the EASMI then contribute to the ameliorated prediction on decadal variations of the spatial distribution of ECSPAs. This study highlights the importance of ICs for a coupled model in reasonably presenting decadal variabilities of the EASMI.
Relationships between subseasonal‐to‐seasonal predictability and spatial scales in tropical rainfall
Authors: Moron Vincent , Robertson Andrew W.
Published: April 2021

Subseasonal to seasonal (S2S) tropical rainfall predictability is assessed both from an analysis of the spatial scales of observed rainfall variability data, as well as from an S2S model reforecast skill. Observed spatial scales are quantified from gridded observed daily rainfall data, in terms of the size (area) of daily contiguous wet grid‐points (referred to as ‘wet patches’), as well as from the spatial autocorrelations of 7–91‐day running averages of rainfall. Model S2S reforecast skill is measured using the anomaly correlation coefficient between observed and simulated weekly and monthly rainfall from an 11‐member ensemble of European Centre for Medium‐Range Weather Forecasts (ECMWF) reforecasts (1998–2017). Both measures of S2S predictability are found to be systematically lower over land than sea, usually peaking at the start or end of the rainy season and decreasing during the core. Small spatial scales and low skill over equatorial/northern tropical Africa and western Amazonia coincide with small daily rainfall patch size and strong synoptic‐scale (≤7 days) variability there. Over most of South and SE Asia, daily wet patches are larger and strongly modulated by intraseasonal oscillations, boosting S2S rainfall predictability, while this is offset by large daily mean rainfall intensities that increase the noise. In consequence, S2S rainfall skill here generally remains low. Several land areas (as around Maritime Continent from the Philippines to Northern Australia, Eastern and Southern Africa, Eastern South America) exhibit larger spatial scales and skill, especially where the relative amplitude of SST‐forced interannual variations is strong. Most of the Maritime Continent illustrates such behaviour, but even here, the time‐averaged spatial scales and skill drop during the core of the rainy season.
Theoretical study of Raman scattering in MoS2xSe2(1 − x) layered alloys
Authors: Romaniuk Yurii A. , Golovynskyi Sergii , Li Baikui , Qu Junle
Published: April 2021

Two‐dimensional layered crystals have attracted great attention due to their unique properties and practical interests for the application in nano‐optoelectronics. This work theoretically studies the effect of intralayer interaction on the Raman scattering in MoS2xSe2(1 − x) layered alloy, in particular, the change of intensity and position of the in‐plane and out‐of‐plane mode bands as a function of the concentration of S or Se atoms. The theory of Raman scattering in the layered alloys is developed, where the Green's function method is used to obtain the Raman scattering intensity. The Raman intensity is a function of the concentration of S or Se atoms in the layers and also a function of the parameters of intralayer and interlayer interactions. The modeling and numerical calculations show that the Raman spectrum mostly depends on the parameter describing the intralayer interaction between the unit cells containing S or Se atoms in the layer. The spectrum exhibits the two‐mode character when the intralayer interaction is weak while conserves the one‐mode character when the intralayer interaction increases to be comparable with the wavenumber position of the bands. The developed microscopic theoretical approach is versatile and can also be applied to interpret Raman spectra and explain some of their features in bulk and two‐dimensional layered alloys.
Venous thromboembolism rates in patients with bone and soft tissue sarcoma of the extremities following surgical resection: A systematic review
Authors: Krzyzaniak Halli , You Daniel Z. , Mosca Giulianna , Monument Michael J. , Schneider Prism S.
Published: April 2021

Background

Patients undergoing an orthopedic surgery for bone or soft tissue sarcoma are at increased venous thromboembolism (VTE) risk. Unfortunately, there is a lack of thromboprophylaxis guidelines in this population. The purpose of this systematic review was to determine the soft tissue and bone sarcoma VTE rate and to explore the thromboprophylaxis regimens used.

Methods

The databases MEDLINE, EMBASE, and CENTRAL were queried using keywords related to VTE and long bone malignancy requiring surgical intervention to 2020. Included studied reported VTE rate in patients with surgically managed extremity sarcoma. Descriptive statistics and weighted mean totals were calculated.

Results

A total of 2082 studies were screened and 23 studies were included. The overall VTE rate was 2.9%, with a rate of 3.7% and 1.4% in patients with bone and soft tissue sarcomas, respectively. Low‐molecular‐weight heparin was the most commonly used chemoprophylaxis.

Conclusions

There is a high VTE rate following sarcoma surgery. The VTE rate is higher in bone sarcoma surgery, which may be attributed to differences in surgery and postoperative recovery. There was no consensus on the duration or type of thromboprophylaxis used. Future research is needed to determine the most effective thromboprophylaxis regimen in patients with sarcoma and whether individualized thromboprophylaxis is required.
Initial clinical experiences using the intraoperative probe‐based parathyroid autofluorescence identification system—PTeye™ during thyroid and parathyroid procedures
Authors: Kiernan Colleen M. , Thomas Giju , Baregamian Naira , Solόrzano Carmen C.
Published: April 2021

Background and Objective

The Food and Drug Administration has cleared a probe‐based near‐infrared autofluorescence (NIRAF) detection system called PTeye™ as an adjunct tool for label‐free intraoperative parathyroid gland (PG) identification. Since PTeye™ has been investigated only in a “blinded” manner to date, this study describes the preliminary impressions of PTeye™ when used by surgeons without being blinded to the device output.

Methods

Patients undergoing thyroid and parathyroid procedures were prospectively recruited. Target tissues were intraoperatively assessed with PTeye™. The surgeon's confidence in PG identification was recorded concomitantly with NIRAF parameters that were output in real‐time from PTeye™.

Results

A retrospective review of prospectively collected data on 83 patients was performed. PTeye™ was used for interrogating 336 target tissues in 46 parathyroid and 37 thyroid procedures. PTeye™ yielded an overall accuracy of 94.3% with a positive predictive value of 93.0% and a negative predictive value of 100%. An increase in confidence for intraoperative PG identification with PTeye™ was observed by all three participating high‐volume surgeons, irrespective of their level of accrued surgical experience.

Conclusions

Probe‐based NIRAF detection with PTeye™ can be a valuable adjunct device to intraoperatively identify PGs for surgeons of varied training and experience.
Pharmacokinetic studies of six major 2‐(2‐phenylethyl) chromones in rat plasma using ultra high performance liquid chromatography with tandem mass spectrometry after oral administration of agarwood ethanol extract
Authors: Xie Bin , Luo Huitai , Huang Xiaolan , Huang Fang , Zhang Qiuyan , Wu Xuefeng , Zhou Xi , Wu Huiqin
Published: April 2021

In this study, a simple, quick, sensitive and reliable method utilizing ultra‐high performance liquid chromatography with tandem mass spectrometry method was validated for simultaneous quantification of six main 2‐(2‐phenylethyl) chromones, including agarotetrol, isoagarotetrol, (5S,6R,7R,8S)‐5,6,7,8‐tetrahydroxy‐(4‐methoxyphenethyl)‐5,6,7,8‐tetrahydro‐4H‐chromen‐4‐one, 8‐chloro‐2‐(2‐phenyl ethyl)‐5,6,7‐trihydroxy‐5,6,7,8‐tetrahydrochromone, 6,7‐dimethoxy‐2‐(2‐phenylethyl) chromone, and 2‐(2‐phenylethyl) chromone in rat plasma after oral administration of agarwood ethanol extract. Separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) using gradient elution with mobile phase of 0.2% formic acid‐water and acetonitrile. The tandem mass was performed in the multiple reaction monitoring mode with positive ionization. The calibration curves indicated good linearity (r2 > 0.99) over the corresponding concentration range. The precision and accuracy were within the acceptable range. Mean absolute recoveries of all analytes were between 73.31% and 94.76%, and the relative standard deviations of matrix effects were not higher than 15%. The six analytes were proven to be stable during sample storage and analysis procedures. The validated method was successfully applied to pharmacokinetic study of six 2‐(2‐phenylethyl) chromones in rat after oral administration of agarwood ethanol extract for the first time. This study could serve as a reference and provide theoretical guidance for further pharmacodynamic research and clinical applications of agarwood.
Extraction of stabilizers from polymers: Separation of oligomeric hindered amine light stabilizers and phenolic antioxidants from polyolefins using liquid chromatography and high‐temperature solid‐phase extraction
Authors: Kot David , Arndt Jan‐Hendrik , Macko Tibor , Brüll Robert
Published: April 2021

The extraction of different stabilizers from a polymer matrix and the subsequent separation of said stabilizers is one of the most important as well as challenging undertakings in polymer chemistry. A multitude of stabilizers exists, each of which may be hard to extract, be difficult if not impossible to separate from other stabilizers or necessitate very selected and time‐consuming intermediate stages for separation. Certain polymer matrices even pose additional challenges, such as polyolefins being only soluble at elevated temperatures. One of the most well‐established approaches for the extraction of stabilizers is Soxhlet extraction. However, even this highly successful approach shows only limited success with regard to the extraction of the ever more relevant oligomeric stabilizers or the extraction of multiple stabilizers in a one‐shot approach. Moreover, performing Soxhlet extractions often necessitates ≥24 h. For these reasons, alternative approaches for the extraction of stabilizers from polymers are highly sought after. An approach with enormous potential is solid‐phase extraction, which allows the selective retention and enrichment of stabilizers. Herein, the very first application of high‐temperature solid‐phase extraction for the extraction of stabilizers from polyolefin matrices is described; as with other extraction techniques, the identification and quantification of the stabilizers is then allowed. At temperatures of 140–160°C, it was possible to adsorb common polyolefin stabilizers selectively on a silica solid phase from their polyolefin matrix. To predict high‐temperature solid‐phase extraction test conditions, first LC tests are necessary, offering an elegant approach for the separation of polyolefins from oligomeric stabilizers, which was not achievable until now.
Polyimide removal, cleaving, and fusion splicing of cylindrical and square fused silica capillaries for new separation and detection layouts in capillary electrophoresis and chromatography
Authors: Paiva Raul Dias , Mallmann Ana Maria M. C. , Santos Josemir C. , Kist Tarso B. Ledur
Published: April 2021

Fusion splicing is an already mature technology used to join the ends of optical fibers in the telecommunication industry. However, there is a lack of reliable and well‐described protocols to join the ends of fused silica microtubes or capillaries using fusion splicing. In this work, a step‐by‐step procedure is proposed and demonstrated to find the optimal operation conditions to splice the ends of fused silica capillaries by fusion. The two most appropriate and known technologies were tested and optimized: the microfurnace technique (or hot filament technique) and the electric arc technique. It is shown that both produce good splices when the capillaries are well cleaved. For this reason, the removal of the external coating, which is important for good cleavage, was also revised. The cleaving techniques were also compared among themselves. As a result, fusion splices of cylindric‐to‐cylindric, cylindric‐to‐square, and square‐to‐square capillaries are demonstrated. They have potential applications in new detection schemes and separation layouts in capillary electrophoresis, electrophoresis‐based hydrodynamic concentrators, chromatography, cell sorters, and microfluidics in general.
Efficacy and Safety of Endoscopic Balloon Placement for Weight Loss in Patients With Cirrhosis Awaiting Liver Transplantation
Authors: Watt Kymberly D. , Heimbach Julie K. , Rizk Monika , Jaruvongvanich Pete , Sanchez William , Port John , Venkatesh Sudhakar K. , Bamlet Heather , Tiedtke Kathryn , Malhi Harmeet , Acosta Cardenas Andres , Grothe Karen , Clark Matthew , Mundi Manpreet S. , Abu Dayyeh Barham K.
Published: April 2021

The efficacy and safety of a fluid‐filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End‐Stage Liver Disease–sodium (MELD‐Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD‐Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short‐term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow‐up are required.
HET0016 attenuates the stemness of breast cancer cells through targeting CYP4Z1
Authors: Liu Hai , Qin Hai , Zhou Yi , Yuan Yin , Liu Yichen , Chen Ying , Yang Yue , Ni Haiwei , Xi Tao , Zheng Lufeng
Published: April 2021

Ours and other previous studies have shown that CYP4Z1 is specifically and highly expressed in breast cancer, and acts as a promoter for the stemness of breast cancer cells. Here, we explored whether targeting CYP4Z1 could attenuate the stemness of breast cancer cells using HET0016, which has been confirmed to be an inhibitor of CYP4Z1 by us and others. Using the transcriptome‐sequencing analysis, we found that HET0016 suppressed the expression of cancer stem cell (CSC) markers and stem cell functions. Additionally, HET0016 indeed reduced the stemness of breast cancer cells, as evident by the decrease of stemness marker expression, CD44+/CD24− subpopulation with stemness, mammary‐spheroid formation, and tumor‐initiating ability. Moreover, HET0016 suppressed the metastatic capability through in vitro and in vivo experiments. Furthermore, we confirmed that HET0016 suppressed CYP4Z1 activity, and HET0016‐induced inhibition on the stemness and metastasis of breast cancer cells was rescued by CYP4Z1 overexpression. Thus, our results demonstrate that HET0016 can attenuate the stemness of breast cancer cells through targeting CYP4Z1.
Commissioning of an ultra‐high dose rate pulsed electron beam medical LINAC for FLASH RT preclinical animal experiments and future clinical human protocols
Authors: Moeckli Raphaël , Gonçalves Jorge Patrik , Grilj Veljko , Oesterle Roxane , Cherbuin Nicolas , Bourhis Jean , Vozenin Marie‐Catherine , Germond Jean‐François , Bochud François , Bailat Claude
Published: April 2021

Purpose

To present the acceptance and the commissioning, to define the reference dose, and to prepare the reference data for a quality assessment (QA) program of an ultra‐high dose rate (UHDR) electron device in order to validate it for preclinical animal FLASH radiotherapy (FLASH RT) experiments and for FLASH RT clinical human protocols.

Methods

The Mobetron® device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short‐ and long‐term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements.

Results

The acceptance tests were all within the tolerances of the company's acceptance protocol. The linearity with pulse width was within 1.5% in all cases. The pulse repetition frequency did not affect the delivered dose more than 2% in all cases but 90 Hz, for which the larger difference was 3.8%. The reference dosimetry showed a good agreement within the alanine and films with variations of 2.2% or less. The short‐term (resp. long‐term) stability was less than 1.0% (resp. 1.8%) and was the same in both CONV and UHDR modes. PDDs, profiles, and reference dosimetry were measured at two positions, providing data for two specific dose rates (about 9 Gy/pulse and 3 Gy/pulse). Maximal beam size was 4 and 6 cm at 90% isodose in the two positions tested. There was no difference between CONV and UHDR mode in the beam characteristics tested.

Conclusions

The device is commissioned for FLASH RT preclinical biological experiments as well as FLASH RT clinical human protocols.
Management of plantar heel pain in general practice in Australia
Authors: Whittaker Glen A. , Menz Hylton B. , Landorf Karl B. , Munteanu Shannon E. , Harrison Christopher
Published: April 2021

Background

Studies have described general practitioner (GP) management of plantar heel pain from some countries; however, there is limited information from Australian general practice.

Objectives

To describe patient and GP characteristics, and management actions for plantar heel pain in Australian general practice.

Design

Secondary analysis of data from the Bettering the Evaluation and Care of Health (BEACH) dataset.

Methods

Data were summarised using descriptive analysis and robust 95% confidence intervals (CIs) were calculated around point estimates. Multivariate logistic regression identified predictors of plantar heel pain management.

Results

From 1,568,100 encounters between April 2000 and March 2016, plantar heel pain was managed at 3007 encounters. GPs manage plantar heel pain approximately once every 500 encounters, which extrapolates to 271,100 encounters in 2015–2016. Patient factors independently associated with plantar heel pain encounters included female sex (OR 1.27, 95% CI 1.17–1.34 cf. males), being aged 45–64 (OR 3.44, 95% CI 2.94–4.01 cf. aged 75+) and patients from a non‐English speaking background (OR 1.22, 95% CI 1.07–1.39). Plantar heel pain was frequently managed using medication (45.1 per 100), with non‐steroidal anti‐inflammatory drugs the most common (22.8 per 100). GPs also commonly provided counselling/advice/education (32.4 per 100), and referrals for diagnostic imaging (19.1 per 100) and to podiatrists (12.0 per 100).

Conclusions

Plantar heel pain is a frequently managed foot condition in Australian general practice. GPs use medication, counselling and education, diagnostic imaging and referral to podiatrists for management. Further research is required to understand the drivers of these management actions and whether they are effective.
On a novel full decoupling, linear, second‐order accurate, and unconditionally energy stable numerical scheme for the anisotropic phase‐field dendritic crystal growth model
Authors: Yang Xiaofeng
Published: April 2021

The anisotropic phase‐field dendritic crystal growth model is a highly nonlinear system that couples the anisotropic Allen–Cahn equation and the thermal equation together. Due to the high anisotropy and nonlinear couplings in the system, how to develop an accurate and efficient, especially a fully decoupled scheme, has always been a challenging problem. To solve the challenge, in this article, we construct a novel fully decoupled numerical scheme which is also linear, energy stable, and second‐order time accurate. The key idea to realize the full decoupling structure is to introduce an ordinary differential equation to deal with the nonlinear coupling terms satisfying the so‐called “zero‐energy‐contribution” property. This scheme is very effective and easy to implement since only a few fully decoupled elliptic equations with constant coefficients need to be solved at each time step. We rigorously prove the solvability of each step and the unconditional energy stability, and perform a large number of numerical simulations in 2D and 3D to demonstrate its stability and accuracy numerically.
Scale development for consumer repulsion: A consumers' individual identity‐expressiveness perspective
Authors: Bu Huimei , Shi Guicheng , Liu Matthew Tingchi
Published: April 2021

In a number of emerging markets such as China, native consumers may avoid certain domestic products when foreign products are available. However, the studies on the unfavorable attitudes toward the products of one's own country are not sufficient. This article aims to develop a construct to explain this phenomenon. The measurement scale was developed and validated using responses from 318 Chinese consumers with respect to electronics and clothing. The judgment sampling method produced representative distributions in terms of age and gender. The items were first generated and refined based on the content validity. Exploratory factor analysis, confirmatory factor analysis, and convergent and discriminant validity were then established. Finally, this study investigates relationships among consumer repulsion, domestic product ownership, and negative word of mouth, to confirm the nomological validity. This study develops a construct—consumer repulsion—that can be used to articulate native consumers' unfavorable attitudes toward domestic products from consumers' individual identity‐expressiveness perspective. First, this study develops a scale for consumer repulsion. The scale shows good reliability, unidimensionality, convergent validity, discriminant validity, and nomological validity. The scale helps explain the nature and impact of country biases, and integrates and expands current studies in this field, which should prove helpful in further research on this topic. Furthermore, this study proposes a three‐dimensional model of consumer repulsion consisting of affective repulsion, cognitive repulsion, and conative repulsion. Finally, these findings have shown that linking domestic products to social identity and self‐identity will likely influence domestic product ownership and word of mouth of native consumers.
Low‐dose versus standard‐dose four‐factor prothrombin complex concentrate for factor‐Xa inhibitor reversal in spontaneous and traumatic intracranial hemorrhage
Authors: Cascone Ava E. , Daley Mitchell J. , Pan Neil , Padilla‐Tolentino Eimeira , Milling Truman J.
Published: April 2021

Study Objectives

Current neurocritical care guidelines recommend 50 IU/kg four‐factor prothrombin complex concentrate (4PCC) for factor Xa inhibitor (FXaI) reversal in intracranial hemorrhage (ICH) based on few clinical studies conducted among non‐ICH subjects. Two recent studies suggest that low‐dose (25 IU/kg) 4PCC may be similar to 50 IU/kg in reversal of FXaI in ICH, and both 25 and 50 IU/kg doses are used in clinical practice for this indication. To our knowledge, no studies have directly compared 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH. The purpose of this study is to determine whether there is a difference in hemostatic efficacy between 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH.

Design

This multicenter, retrospective cohort study was performed in five hospitals in central Texas from November 2013 to December 2019.

Data Source

Patients were identified with a medication use report of 4PCC and were classified in the low‐ or standard‐dose group based on whether the 25 IU/kg or 50 IU/kg dose was received, respectively.

Patients

A total of 93 patients were included (25 IU/kg, n = 62; 50 IU/kg, n = 31).

Measurements and Main Results

There was no difference in hemostatic efficacy between groups (82.3% low dose vs. 83.9% standard dose, p = 0.846). No differences were identified in‐hospital mortality, length of stay, thrombotic events, or the need for surgery or additional blood products between groups.

Conclusion

For the reversal of FXaI in ICH, a 25 IU/kg dose may be an effective alternative to 50 IU/kg 4PCC dosing.
Tuning of PEDOT:PSS synthesis via multiple doping for enhanced electrical conductivity
Authors: Sakunpongpitiporn Phimchanok , Phasuksom Katesara , Sirivat Anuvat
Published: April 2021

The poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) synthesis conditions were refined to obtain extremely high electrical conductivity. PEDOT:PSS was synthesized by chemical oxidative polymerization under the effects of acid types and concentrations, EDOT:PSS weight ratio, and surfactant types and concentrations. The PEDOT:PSS synthesized with EDOT:PSS weight ratio of 0.5:5.5 in 0.1 mol L−1 HClO4 provided the highest electrical conductivity of 1.04 × 104 ± 188 S cm−1, not previously reported. The enhanced electrical conductivity can be attributed to the combinatorial primary doping by selective ions (ClO4−, PSS−, SO42−) generating a suitable PEDOT:PSS structure with high carrier number and electron mobility, as consistently verified using Fourier transform infrared spectroscopy, UV–visible spectrometry, X‐ray photoelectron spectrometry and thermogravimetric analysis. The refined synthesis opens a new route for PEDOT:PSS nanoparticles to be used in various electronic applications which require the starting nontoxic organic material to be highly conductive. © 2021 Society of Industrial Chemistry.
COVID‐19: A catalyst for change in virtual health care utilization for persons with limb loss
Authors: Hewitt Melissa A. , Smith Douglas G. , Heckman Jeffrey T. , Pasquina Paul F.
Published: April 2021

The dramatic uptake of virtual care, or telehealth, utilization because of COVID‐19 restrictions for persons with limb loss has led to a much greater understanding of this health care delivery method for this complex patient population. However, much is still unknown. Therefore, the authors provide a comprehensive literature review of existing evidence for virtual care delivery across the phases of amputation rehabilitation, as well as anecdotal evidence, to provide a platform for further discussion and development of research and innovative opportunities. Evidence reveals that virtual care serves as a complement to in‐person health care for individuals with limb loss because it allows for increased accessibility to these services. The authors conclude that continued use of telehealth beyond the COVID‐19 restrictions to optimize outcomes across the continuum of care for persons with limb loss is warranted.
Large difference between Enghoff and Bohr dead space in ventilated infants with hypoxemic respiratory failure
Authors: Zuiki Masashi , Kume Rika , Matsuura Amane , Mitsuno Kohei , Kitamura Kazumasa , Kanayama Takuyo , Komatsu Hiroshi
Published: April 2021

Background

Ventilated neonates with hypoxemic respiratory failure (HRF) may show a ventilation‐perfusion (V/Q) mismatch.

Objective

To evaluate the difference between the Bohr (Vd, Bohr) and Enghoff (Vd, Enghoff) dead spaces in infants by using volumetric capnography based on ventilator graphics and capnograms.

Methods

This study enrolled 46 ventilated infants (mean birth weight, 2239 ± 640 g; mean gestational age, 35.5 ± 3.3 weeks). We performed volumetric capnography and calculated Vd, Bohr and Vd, Enghoff when arterial blood sampling was necessary for treatment. According to the oxygenation index (OI) based on the Montreux definition of neonatal acute respiratory distress syndrome, each measurement was classified into the HRF (OI ≥ 4) or control (OI < 4) group. Then, a regression analysis was performed to evaluate the correlation between the OI and the difference between Vd, Enghoff and Vd, Bohr.

Results

The median Vd, Enghoff/tidal volume (VT) was significantly higher in the HRF group (0.55 [interquartile range, 0.47–0.68]) than in the control group (0.46 [0.37–0.57]). The HRF group showed a larger difference between Vd, Enghoff/VT and Vd, Bohr/VT than the control group (median, 0.22 [0.15–0.29] vs. 0.10 [0.06–0.14], respectively). Moreover, the regression analysis of the relationship between OI and Vd, Enghoff/VT − Vd, Bohr/VT showed a positive correlation (r = .60, p < .001).

Conclusion

Ventilated neonates with hypoxemic respiratory failure showed a large difference between Vd, Enghoff and Vd, Bohr, possibly reflecting a low V/Q mismatch and right‐to‐left shunting.
Differential Levels of Fatty Acid‐Amino Acid Conjugates in the Oral Secretions of Lepidopteran Larvae Account for the Different Profiles of Volatiles
Authors: Ling Xiaoyu , Gu Shimin , Tian Caihong , Guo Huijuan , Degen Thomas , Turlings Ted C J , Ge Feng , Sun Yucheng
Published: April 2021

BACKGROUND

Plants have evolved sophisticated defense responses to insect herbivore attack, which often involve elicitors in the insects' oral secretions. The major eliciting compounds in insect oral secretions across different species and their potency in inducing volatile emissions have not yet been fully characterized and compared.

RESULTS

Seven lepidopteran insects with variable duration of association with maize were selected, five species known as pests for a long time (Ostrinia furnacalis, Spodoptera exigua, Spodoptera litura, Mythimna separata, and Helicoverpa armigera) and two newly emerging pests (Athetis lepigone and Athetis dissimilis). Oral secretions of the newly emerging pests have the highest total contents of Fatty Acid‐Amino Acid Conjugates (FACs), and their relative composition was well separated from that of the other five species in principal compound analysis. Redundancy analyses suggested that higher quantity of FACs was mainly responsible for the increases in maize volatiles, of which (E)‐3,8‐dimethyl‐1,4,7‐nonatriene (DMNT) and (E, E)‐4,8,12‐trimethyltrideca‐1,3,7,11‐tetraene (TMTT) were the most strongly inducible compounds. Adding FACs to the oral secretion of S. litura larvae significantly increased the emissions of TMTT and DMNT, confirming the key role of FACs in inducing volatile emissions in maize plants. Additional experiments with artificial diet spiked with linolenic acid suggested that variation in FACs is due to differences in internal FAC degradation and fatty acid excretion.

CONCLUSION

Compared with two newly emerging pests A. lepigone and A. dissimilis, the long‐term pests could diminish the volatile emission by maize through reducing the FAC content in their oral secretions, which may lower the risk of attracting natural enemies.
Computing the polytomous discrimination index
Authors: Dover Douglas C. , Islam Sunjidatul , Westerhout Cynthia M. , Moore Linn E. , Kaul Padma , Savu Anamaria
Published: April 2021

Polytomous regression models generalize logistic models for the case of a categorical outcome variable with more than two distinct categories. These models are currently used in clinical research, and it is essential to measure their abilities to distinguish between the categories of the outcome. In 2012, van Calster et al proposed the polytomous discrimination index (PDI) as an extension of the binary discrimination c‐statistic to unordered polytomous regression. The PDI is a summary of the simultaneous discrimination between all outcome categories. Previous implementations of the PDI are not capable of running on “big data.” This article shows that the PDI formula can be manipulated to depend only on the distributions of the predicted probabilities evaluated for each outcome category and within each observed level of the outcome, which substantially improves the computation time. We present a SAS macro and R function that can rapidly evaluate the PDI and its components. The routines are evaluated on several simulated datasets after varying the number of categories of the outcome and size of the data and two real‐world large administrative health datasets. We compare PDI with two other discrimination indices: M‐index and hypervolume under the manifold (HUM) on simulated examples. We describe situations where the PDI and HUM, indices based on multiple comparisons, are superior to the M‐index, an index based on pairwise comparisons, to detect predictions that are no different than random selection or erroneous due to incorrect ranking.
Correction to: Robotic‑arm assisted total knee arthroplasty is associated with improved accuracy and patient reported outcomes: a systematic review and meta‑analysis
Authors: Zhang Junren , Ndou Wofhatwa Solomon , Ng Nathan , Gaston Paul , Simpson Philip M. , Macpherson Gavin J. , Patton James T. , Clement Nicholas D.
Published: April 2021

A correction to this paper has been published: https://doi.org/10.1007/s00167-021-06522-x
Two-step solvable SKT shears
Authors: Freibert Marco , Swann Andrew
Published: April 2021

We use the shear construction to construct and classify a wide range of two-step solvable Lie groups admitting a left-invariant SKT structure. We reduce this to a specification of SKT shear data on Abelian Lie algebras, and which then is studied more deeply in different cases. We obtain classifications and structure results for $$\mathfrak {g}$$
g
almost Abelian, for derived algebra $$\mathfrak {g}'$$

g

′

of codimension 2 and not J-invariant, for $$\mathfrak {g}'$$

g

′

totally real, and for $$\mathfrak {g}'$$

g

′

of dimension at most 2. This leads to a large part of the full classification for two-step solvable SKT algebras of dimension six.