bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive immunophenotypic study of acute myeloid leukemia with KMT2A (MLL) rearrangement in adults: A single‐institution experience
Authors: Konoplev Sergej , Wang Xiaoqiong , Tang Guilin , Li Shaoying , Wang Wei , Xu Jie , Pierce Sherry A. , Jia Fuli , Jorgensen Jeffrey L. , Ravandi Farhad , Issa Ghayas C. , Medeiros L. Jeffrey , Wang Sa A.
Published: December 2021

Background

Acute myeloid leukemia (AML) with KMT2A (MLL) rearrangement is known for monocytic or myelomonocytic differentiation, but the full immunophenotypic spectrum and dynamic changes of the immunophenotype in this genetically defined disease have not been systematically studied.

Methods

We reviewed the immunophenotype, karyotype, and mutations at the time of initial diagnosis and relapse of adults with AML with KMT2A rearrangement in our institution between 2007 and 2020.

Results

We identified 102 patients: 44 men and 58 women with a median age of 52 years (range, 18–87). Forty‐three patients were considered to be therapy‐related. Twenty‐four out of 64 patients relapsed from complete remission after induction therapy, 34 had persistent/progressive disease, and 58 patients died with a median overall survival of 17 months.

We detected five immunophenotypes: immature monocytic (38%); myelomonocytic (22%); myeloblastic (22%); mature monocytic (10%); and acute promyelocytic (APL)‐like (8%). By chromosomal breakpoints, we presumed 11 different partners; t(9;11) (p22;q23)/MLLT3‐KMT2A was the most common rearrangement (n = 56, 55%), followed by t(6;11) (q27;q23)/AFDN‐KMT2A (n = 13,13%). Patients with t(6;11) (q27;q23)/AFDN‐KMT2A preferentially showed a myeloblastic phenotype (p = 0.026). Mutations were detected in 39/64 (61%) cases, and RAS pathway (NRAS/KRAS/PTPN11) was involved in 26/64 (41%) cases. None of the APL‐like cases had mutations detected. At the time of disease relapse, 10/24 (42%) showed major immunophenotypic change, and 7/10 cases gained additional cytogenetic and/or molecular alterations.

Conclusion

The immunophenotype of AML with KMT2A rearrangement is more diverse than previously recognized, with a substantial subset showing no evidence of monocytic differentiation. Major immunophenotype change is common at the time of relapse.
Power efficient Space Division Multiplexing–Wavelength Division Multiplexing system using multimode EDFA with elevated refractive index profile
Authors: Arunachalam Muthukumar , Raju Sumathy
Published: December 2021

Space division multiplexing (SDM) is an endowment technology to increase the collective bandwidth of multimode transmission in wavelength division multiplexing (WDM) system. In this paper, four wavelength signals from 229.6 to 232.6 THz are transmitted. For each wavelength, three linearly polarized (LP) modes are multiplexed using SDM. These 12 LP modes are transmitted through four parallel Multimode Step Index (MSI) fibers and received by four optical network units (ONUs). A multimode erbium doped fiber amplifier (MMEDFA) with elevated refractive index profile (ERIP) is used as preamplifier to this SDM–WDM system. This ERIP is complying with ITU‐T G.651.1 standard fiber in dispersion performance. The pumping power of 10 mW is adequate for this MMEDFA which is very low and cost effective. LP modes are transmitted, and performance of proposed transmission system is evaluated in terms of spatial electric fields, pumping power requirement, output optical power, and bit error rate (BER).
Design of highly‐directive Night‐flowering Jasmine‐shaped printed radiator based array for Ku‐band applications†
Authors: Sundar Kola Kalyan , Chatterjee Anirban , Jagannath Ravi Prasad K.
Published: December 2021

This article presents a four‐elements linear array of highly directive radiators for Ku‐band satellite applications. The antenna array's sole element is a newly introduced nature‐inspired Night‐flowering Jasmine‐shaped radiator. The proposed single element gives an appreciably decent gain and shallow cross‐polarization (x‐pol.) level along its main beam direction. The array's corporate feed network is designed in a precise manner to achieve a low level of loss and better bandwidth response. The fabricated sole antenna resonates at 17.95 GHz and offers a peak‐gain and return‐loss bandwidth of 11.54 dBi and 537 MHz, respectively. Similarly, 16.69 dBi absolute gain and 756‐MHz bandwidth have been achieved from the array geometry at 17.96 GHz resonating frequency. The prototypes' electromagnetic compatibility (EMC) is validated by their computed correction factor (CF) values, and those are becoming 43.73 and 38.57 dB/m, respectively. The measured cross‐pol. of both prototypes, along the entire HPBW region, is below −35 dB. The prototypes offer a reasonably good radiation efficiency of 92.09% and 97.25%, respectively. Both the prototype's measured results make an excellent agreement with the simulated outcomes.
The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID‐19 patients. A systematic review, meta‐analysis and meta‐regression
Authors: Tentolouris Nikolaos , Samakidou Georgia , Eleftheriadou Ioanna , Tentolouris Anastasios , Jude Edward B.
Published: December 2021

Aims

The aim of this systematic review and meta‐analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID‐19 patients.

Methods

A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID‐19 was conducted on 26 March 2021. Comprehensive Meta‐Analysis software was used for the quantitative assessment of data and random‐effects model was applied. To investigate the association between the dose of vitamin D and the outcomes of interest, meta‐regression analysis was performed.

Results

Two thousand and seventy‐eight patients from nine studies with data on mortality were included (583 received vitamin D supplementation, while 1495 did not). Sixty‐one (10.46%) individuals in the treated group died, compared to 386 (25.81%) in the non‐treated group (odds ratio [OR]: 0.597; 95% CI: 0.318–1.121; p = 0.109). Eight hundred and sixty patients from six studies with data on ICU admission were included (369 received vitamin D supplementation, while 491 did not). Forty‐five (12.19%) individuals in the treated group were admitted to ICU, compared to 129 (26.27%) in the non‐treated group (OR: 0.326; 95% CI: 0.149–0.712; p = 0.005). No significant linear relationship between vitamin D dose and log OR of mortality or log OR of ICU admission was observed.

Conclusion

This meta‐analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID‐19 patients. Further research is urgently needed to understand the benefit of vitamin D in COVID‐19.
Assessing environmental DNA metabarcoding and camera trap surveys as complementary tools for biomonitoring of remote desert water bodies
Authors: Mas‐Carrió Eduard , Schneider Judith , Nasanbat Battogtokh , Ravchig Samiya , Buxton Mmabaledi , Nyamukondiwa Casper , Stoffel Céline , Augugliaro Claudio , Ceacero Francisco , Taberlet Pierre , Glaizot Olivier , Christe Philippe , Fumagalli Luca
Published: December 2021

Biodiversity assessments are indispensable tools for planning and monitoring conservation strategies. Camera traps (CT) are widely used to monitor wildlife and have proven their usefulness. Environmental DNA (eDNA)‐based approaches are increasingly implemented for biomonitoring, combining sensitivity, high taxonomic coverage and resolution, non‐invasiveness and easiness of sampling, but remain challenging for terrestrial fauna. However, in remote desert areas where scattered water bodies attract terrestrial species, which release their DNA into the water, this method presents a unique opportunity for their detection. In order to identify the most efficient method for a given study system, comparative studies are needed. Here, we compare CT and DNA metabarcoding of water samples collected from two desert ecosystems, the Trans‐Altai Gobi in Mongolia and the Kalahari in Botswana. We recorded with CT the visiting patterns of wildlife and studied the correlation with the biodiversity captured with the eDNA approach. The aim of the present study was threefold: (a) to investigate how well waterborne eDNA captures signals of terrestrial fauna in remote desert environments, which have been so far neglected in terms of biomonitoring efforts; (b) to compare two distinct approaches for biomonitoring in such environments; and (c) to draw recommendations for future eDNA‐based biomonitoring. We found significant correlations between the two methodologies and describe a detectability score based on variables extracted from CT data and the visiting patterns of wildlife. This supports the use of eDNA‐based biomonitoring in these ecosystems and encourages further research to integrate the methodology in the planning and monitoring of conservation strategies.
Defusing environmental activism through scientific greening: Government framing strategy and its effects in China
Authors: Du Juan , Han Rongbin , Lv Weixia
Published: December 2021

Using a mixed‐method approach, we explore how the Chinese government frames environmentally controversial projects as well as how citizens may react to the government's framing strategy. Through content analysis of state‐run media reports on paraxylene (a chemical product with many industrial implications, also known as PX) and waste incineration plants, we identify the government's most salient framing tactic asscientific greening—positively depicting such projects as technologically advanced, reliable, and green, often citing experts and scientific sources. Through a survey experiment among 280 college students, we test the effects of such positive frames as well as the negative frames that highlight environmental risks and the comprehensive frames that present both positive and negative information. We find that although the positive scientific‐greening frames can increase one's tolerance of proposed projects in general, they may also enhance their not‐in‐my‐backyard inclination as compared with the control group. Importantly, both the positive scientific‐greening frames and the negative frames reduce citizens' intent to engage in environmental protests. We also find that the negative frames are particularly influential for respondents who have low trust in government. Our findings contribute to the understanding of how framing affects environmental activism in China and elsewhere.
Exacerbated post‐infarct pathological myocardial remodelling in diabetes is associated with impaired autophagy and aggravated NLRP3 inflammasome activation
Authors: Mao Shuai , Chen Peipei , Pan Wenjun , Gao Lei , Zhang Minzhou
Published: December 2021

Background

Diabetes mellitus (DM) patients surviving myocardial infarction (MI) have substantially higher mortality due to the more frequent development of subsequent pathological myocardial remodelling and concomitant functional deterioration. This study investigates the molecular pathways underlying accelerated cardiac remodelling in a well‐established mouse model of diabetes exposed to MI.

Methods and results

Myocardial infarction in DM mice was established by ligating the left anterior descending coronary artery. Cardiac function was assessed by echocardiography. Myocardial hypertrophy and cardiac fibrosis were determined histologically 6 weeks post‐MI or sham operation. Autophagy, the NLRP3 inflammasome, and caspase‐1 were evaluated by western blotting or immunofluorescence. Echocardiographic imaging revealed significantly increased left ventricular dilation in parallel with increased mortality after MI in DM mice (53.33%) compared with control mice (26.67%, P < 0.05). Immunoblotting, electron microscopy, and immunofluorescence staining for LC3 and p62 indicated impaired autophagy in DM + MI mice compared with control mice (P < 0.05). Furthermore, defective autophagy was associated with increased NLRP3 inflammasome and caspase‐1 hyperactivation in DM + MI mouse cardiomyocytes (P < 0.05). Consistent with NLRP3 inflammasome and caspase‐I hyperactivation, cardiomyocyte death and IL‐1β and IL‐18 secretion were increased in DM + MI mice (P < 0.05). Importantly, the autophagy inducer and the NLRP3 inhibitor attenuated the cardiac remodelling of DM mice after MI.

Conclusion

In summary, our results indicate that DM aggravates cardiac remodelling after MI through defective autophagy and associated exaggerated NLRP3 inflammasome activation, proinflammatory cytokine secretion, suggesting that restoring autophagy and inhibiting NLRP3 inflammasome activation may serve as novel targets for the prevention and treatment of post‐infarct remodelling in DM.
Determinants of left ventricular function improvement for cardiac resynchronization therapy candidates
Authors: Hong Jung Ae , Lee Sang Eun , Kim Seon‐Ok , Kim Min‐Seok , Lee Hae‐Young , Cho Hyun‐Jai , Choi Jin Oh. , Jeon Eun‐Seok , Hwang Kyung‐Kuk , Chae Shung Chull , Baek Sang Hong , Kang Seok‐Min , Choi Dong‐Ju , Yoo Byung‐Su , Kim Kye Hun , Cho Myeong‐Chan , Oh Byung‐Hee , Kim Jae‐Joong
Published: December 2021

Aims

A waiting period of more than 3 months is recommended for patients before undergoing cardiac resynchronization therapy (CRT). However, due to an anticipated high mortality rate, early implementation of CRT might be beneficial for some patients. We aimed to evaluate the rate and the probability of left ventricular (LV) function improvement and their predictors in patients with heart failure (HF) with indications for CRT.

Methods and results

From March 2011 to February 2014, a total of 5625 hospitalized patients for acute HF were consecutively enrolled in 10 tertiary hospitals. Among them, we analysed 1792 patients (mean age 63.96 ± 15.42 years, female 63.1%) with left ventricular ejection fraction (LVEF) ≤ 35% at the baseline echocardiography and divided them into three groups: 144 with left bundle branch block (LBBB), 136 with wide QRS complexes without LBBB, and 1512 not having these findings (control). We compared and analysed these three groups for improvement of LV function at follow‐up echocardiography. In patients who met CRT indications (patients with LBBB or wide QRS complexes without LBBB), logistic regression was performed to identify risk factors for no improvement of LV. No improvement of LV was defined as LVEF ≤ 35% at follow‐up echocardiography or the composite adverse outcomes: death, heart transplantation, extracorporeal membrane oxygenation, or use of a ventricular assist device before follow‐up echocardiography. A classification tree was established using the binary recursive partitioning method to predict the outcome of patients who met CRT indications. In a median follow‐up of 11 months, LVEF improvement was observed in 24.3%, 15.4%, and 40.5% of patients with LBBB, wide QRS complexes without LBBB, and control, respectively. Patients meeting CRT indications had higher 3 month mortality rates than the control (24.6% vs. 17.7%, P = 0.002). Multivariable logistic regression analysis revealed that large LV end‐systolic dimension [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.05–1.15, P < 0.001], low LVEF (OR 0.92, 95% CI 0.87–0.98, P = 0.006), diabetes requiring insulin (OR 6.49, 95% CI 2.53–19.33, P < 0.001), and suboptimal medical therapy (OR 6.85, 95% CI 3.21–15.87, P < 0.001) were significant factors predictive of no improvement. A decision tree analysis was consistent with these results.

Conclusions

Patients with CRT indications had higher mortality during their follow‐up compared with control. LV function improvement was rare in this population, especially when they had some risk factors. These results suggest that the uniform waiting period before CRT implantation could be reconsidered and individualized.
Lanthanide Complexes with 4,4′‐Bis(2‐sulfonatostyryl)‐biphenyl: Crystal Structures and Luminescence Properties
Authors: Mikhalyova Elena A. , Zeller Matthias , Goreshnik Evgeny A. , Jasinski Jerry P. , Butcher Raymond J. , Nelyubina Yulia V. , Hunter Jordan L. , Sedykh Alexander E. , Shishkina Svitlana V. , Müller‐Buschbaum Klaus , Eremenko Igor L. , Addison Anthony W. , Pavlishchuk Vitaly V.
Published: December 2021

A series of new tris(pyrazolyl)borate (Tp−) and tris(2‐pyridylpyrazolyl)borate (TpPy−) Eu3+, Gd3+, Tb3+ and Dy3+ complexes with the dianionic ligand 4,4′‐bis(2‐sulfonatostyryl)biphenyl (Ssp2−, a widely used fluorescent whitener) were synthesized and their luminescence properties were studied. The Gd3+, Tb3+ and Dy3+ compounds possess only ligand‐centered emission, arising from the Ssp2− ligand, with quantum yields of up to 60 %. While the emission centers in these complexes are similar, the positions of the luminescence maxima, the emission quantum yields, and the lifetimes change in the order [(Tp2Ln)2Ssp]<[(TpPyLnSsp)2]<[Ln2Ssp3]n. Among the complexes studied, Eu3+‐centered emission was observed for only [(Tp2Eu)2Ssp]. In this compound, Tp− plays the role of an antenna ligand for Eu3+‐radiation, though the quantum yield is only 5 %.
Gold‐Catalyzed Cascade and Divergent Synthesis of Indolobenzazepines and Indoloquinolines from Nitrogen‐Tethered 1,8‐Diynes
Authors: Ito Mamoru , Onoda Hideaki , Takaki Asahi , Shibata Takanori
Published: December 2021

We describe the divergent construction of two nitrogen‐containing polycyclic systems by gold‐catalyzed cycloisomerizations. The gold‐catalyzed cascade hydroamination and 7‐endo‐dig‐selective cycloisomerization of nitrogen‐tethered 1,8‐diynes yielded indolo[1,7‐ab]benzazepines in one pot. In contrast, when Johnphos‐coordinated gold catalyst was used, the same 1,8‐diynes were transformed into indolo[1,2‐a]quinolines by 6‐endo‐dig‐selective cycloisomerization along with rearrangement of the substituent on one of the alkynes. The reaction of a naphthalene‐tethered substrate provided a helically chiral aza[6]helicene.
Solid‐Phase Synthesis of Macrocyclic Peptides via Side‐Chain Anchoring of the Ornithine δ‐Amine
Authors: Peterse Evert , Meeuwenoord Nico , van den Elst Hans , van der Marel Gijsbert A. , Overkleeft Hermen S. , Filippov Dmitri V.
Published: December 2021

Cyclic peptides represent a popular class of macrocyclic drug candidates and therefore their solid phase synthesis has attracted much attention. In this contribution we present an efficient method of side‐chain anchoring for ornithine and lysine residues to be used in the standard Fmoc‐based synthesis of cyclic peptides via on‐resin cyclization. We demonstrate that the side chain of ornithine and lysine protected with N‐Boc‐group can efficiently be converted to the isocyanate which is then immobilized on Wang‐type resin in almost quantitative yield. We further show the synthesis of four biologically active cyclic peptides employing the side chain ornithine anchoring. Our method is at least on a par with the previously reported methodologies in terms of yield and the purity of the final products and is arguably operationally more straightforward.
Cobalt‐Mediated Decarboxylative/Desilylative C−H Activation/Annulation Reaction: An Efficient Approach to Natural Alkaloids and New Structural Analogues
Authors: Chen Kang , Lv Shan , Lai Ruizhi , Yang Zhongzhen , Hai Li , Nie Ruifang , Wu Yong
Published: December 2021

A Co(II)‐mediated decarboxylative/desilylative C−H activation/annulation reaction for the efficient synthesis of 3‐arylisoquinolines has been developed. Using alkynyl carboxylic acid and alkynyl silane as terminal alkyne precursors, providing straightforward routes for the synthesis of natural alkaloids and novel structural analogues.
Use of transcutaneous electrical nerve stimulation along with functional tasks for immediate pain relief in individuals with knee osteoarthritis
Authors: Lawson Daryl , Degani Adriana M. , Lee Kevin , Beer Emily I. , Gohlke Katelyn E. , Hamidi Kevin N. , Coler Mitchell A. , Tews Nolan M.
Published: December 2021

Background

Knee pain is the major complaint in individuals with knee osteoarthritis (OA), and the effects of transcutaneous electrical nerve stimulation (TENS) on knee pain are controversial. The present study applied TENS along with functional tests to investigate its effect on pain level in individuals with mild‐to‐moderate knee OA.

Methods

Twenty volunteers with knee OA classification of graded 2–3 performed four functional tests (stair climb test [SCT], timed up and go test [TUG], 6‐minute walk test [6‐MWT], knee extensor strength test [KES], and 2‐step test from the locomotive syndrome risk test [LSR_2ST]) while wearing either an active or inactive TENS. Knee pain level before and after each test was self‐accessed by the Visual Analogue Scale (VAS). The effect of TENS (active vs. inactive) on pain level was submitted to statistical analyses.

Results

Knee pain during SCT, TUG, and LSR_2ST tests was significantly lower when subjects used the active TENS, compared with using the inactive unit. The effect of the active TENS on pain level was also more significant in subjects with no anxiety or depression.

Conclusions

The results provided evidence of immediate pain relief in individuals with mild‐to‐moderate knee OA when TENS is applied along with functional activities, that usually induced pain in people with knee OA.

Significance

The use of transcutaneous electrical nerve stimulation (TENS) in pain management is still unclear. In this study, the analgesic effects of TENS in people with knee osteoarthritis (OA) were found effective when applied along with functional activities. Therefore, study findings provided clinical evidence for the use of TENS during functional activities as a conservative approach to reduce knee OA pain.
Inverted Perovskite Solar Cells: The Emergence of a Highly Stable and Efficient Architecture
Authors: Príncipe Joana , Duarte Vera C. M. , Andrade Luísa
Published: December 2021

Perovskite solar cells (PSCs) have experienced a rapid development during the past decade. For regular PSCs, device efficiency has reached already a power conversion efficiency (PCE) of 25.5%. Inverted PSCs have been attracting increasing attention owing to their easy fabrication, cost‐effectiveness, and suppressed hysteresis characteristics. A maximum PCE of 23.72% for these types of devices is already achieved and some recent progresses in their performance suggest that inverted PSCs are still far from being fully optimized. Great opportunities for reaching simultaneously high stability and efficiency are forecast. Within this work, the most recent developments concerning solar device structure, fabrication of perovskite films, hole and electron transport materials, and electrode contacts in inverted PSCs are overviewed. This work also focuses on stability issues, fabrication methods for large‐area inverted PSCs, encapsulation techniques, economic assessment, and environmental opportunities for hastening inverted PSCs for commercialization.
Insight into energy dissipation behavior of a SDOF structure controlled by the pounding tuned mass damper system
Authors: Zhang Jingcai , Zhang Chunwei , Xue Qichao
Published: December 2021

The purpose of this paper is to present an innovative insight into the behavior and energy dissipation mechanism of a single‐degree‐of‐freedom (SDOF) structure controlled by pounding tuned mass damper (PTMD). In this study, a shake table test was conducted to investigate energy response of the SDOF structure incorporated with PTMD and subjected to seismic excitations. Moreover, SDOF structure and the updated analytical structural pounding force model based on viscoelasticity of materials have been investigated for parametric studies, including dynamic parameters of the primary structure, properties of PTMD, and characteristics of the earthquake records. The influence of these parameters has been discussed in details in this paper. The results showed that energy can be dissipated by PTMD as well as via the three traditional ways of TMD. The energy dissipated by PTMD keeps increasing during excitation, which is similar to the process of energy dissipated by damping mechanism. Furthermore, energy dissipated by damping and PTMD are nearly equal, and the two types of energy dissipation predominate the behavior of the system. Hysteretic, recoverable elastic strain and kinetic energy of the controlled structure diminish to very low level during earthquakes.
New apatite‐type oxide ion conductors Ce9.33+xSi6O26+δ: Structures, phase stabilities, electrical properties, and conducting mechanisms
Authors: Wei Tianjie , Xu Jungu , Zhu Wenfeng
Published: December 2021

Apatite‐type rare earth silicate with high oxygen ion conductivity are attractive materials for their wide potential applications, such as being used in solid oxide fuel cells as electrolytes. Herein, a series of new apatite‐type oxide ion conductors Ce9.33+xSi6O26+δ (x = 0.43, 0.67, 1.03) have been prepared, with their phases, stabilities, electrical properties, and conducting mechanisms been thoroughly studied. The results reveal that these materials are stable under inert or reducing atmospheres, but decomposed under an oxidizing environment at elevated temperatures. The combined alternative current and directive current techniques reveal dominating oxide ion conductions and minor electronic conductions in them. The bond‐valence‐based method is applied to investigate the possible oxide ion migration pathways and disclose the main contribution from interstitial oxygens, which locate between two neighboring tetrahedral SiO4 units and enable the oxide ion transporting among them along the c‐axis direction, whereas the intrinsic channel oxygens show an inferior responsibility for the oxide ion conductivities.
Multi- and Trans-Generational Effects on Daphnia Magna of Chlorpyrifos Exposures
Authors: Maggio Stephanie A. , Jenkins Jeffrey J.
Published: December 2021

Chlorpyrifos, a broad-spectrum neurotoxic organophosphate insecticide, is subject to atmospheric and hydrolytic transport from application sites to aquatic ecosystems. Across the landscape, concentrations in surface water can vary spatially and temporally according to seasonal use practices. Standardized bioassays can provide a screening-level understanding of aquatic receptor acute and chronic toxicity. However, these bioassays do not address ecologically relevant exposure patterns that may impact fitness and survival within and across generations. The aim of the present study was to evaluate the utility of a second-tier, screening-level methodology employing Daphnia magna multi- and transgenerational bioassays spanning four generations to investigate the effect of variable chronic chlorpyrifos exposure. The multigenerational assay consisted of continuous chlorpyrifos exposure across four consecutive 21-day bioassays using progeny from the previous assay for each successive generation. In the transgenerational assay, only the parent (F0) generation was exposed. For both assays, survival and reproduction were assessed across treatments and generations. Results indicated that (1) following continuous chlorpyrifos exposure at ecologically relevant concentrations to four generations of D. magna, the highest treatment showed an apparent tolerance response for both survival and reproductive success in the F3 generation, and (2) chlorpyrifos exposure to the F0 generation did not result in treatment effects in the unexposed F1, F2, and F3 generations in the apical endpoints of survival and reproduction. Employing a suite of acute and chronic bioassays, including chronic exposures spanning multiple generations, allows for a more robust screening-level evaluation of the potential impact of chlorpyrifos on aquatic receptors for variable periods of exposure. Environ Toxicol Chem 2022;41:1054–1065. © 2021 SETAC
A dynamic scenario‐driven technique for stock price prediction and trading
Authors: Thesia Yash , Oza Vidhey , Thakkar Priyank
Published: December 2021

It has always been a challenge to accurately forecast the behavior of a stock market due to its extremely nonlinear and dynamic nature. Numerous studies have shown that technical indicators describing stocks in conjunction with machine learning models can serve as useful tools for forecasting in the stock market. There are various challenges, and one of them is the choice of the right technical indicators and prediction models. It is believed that there is no optimal set of technical indicators that work well in all market scenarios in a dynamic environment such as the stock market. The statement also applies to different prediction models. There is no definite winner, and different settings can emerge as winners in different market scenarios. On this premise, we propose DSdT: a dynamic scenario‐driven technique for stock price prediction and trading strategy enhancement. The proposed novel technique uses the scenario recognition and integration module to identify and integrate the current market scenario into the forecasting pipeline, resulting in a scenario‐driven stock price prediction. We use a large set of technical indicators and a shallow neural network equipped with a gating mechanism to capture and integrate the current market scenario in the prediction process. Experiments are performed on 11 stocks of the Indian Stock Market. The proposed approach yields mean absolute percentage error (MAPE) of 1.67%compared with 2.4%of its closest nonscenario‐driven counterpart for the next day's stock price prediction task. A trading strategy is also devised using the proposed technique, and the returns are compared with different baselines. Results show that the devised trading strategy yields an approximate average return of 54%compared with 25%of the return obtained by the nearest benchmark.
Are option traders more informed than Twitter users? A PVAR analysis
Authors: Frino Alex , Xu Caihong , Zhou Z. Ivy
Published: December 2021

Prior research has examined whether Twitter information predicts stock returns and volatility. We study the causality between Twitter information, stock‐realized volatility, and option‐implied volatility using a panel vector autoregressive model. Using panel data on S&P/ASX 200 stocks, we reveal a bidirectional causality between realized volatility and Twitter activity and divergence of opinion. We also find strong evidence of causality from implied idiosyncratic volatility to Twitter activity, sentiment, and divergence of opinion. Our results highlight the role of the options market in predicting Twitter information and monitoring social media flows to prevent the spread of fake news.
Influence of ramped pressure gradient on transient flow formation in a horizontal porous channel
Authors: Jha Basant K. , Yunus Zainab Sa'id
Published: December 2021

The transient flow formation in a horizontal porous channel assuming a ramped pressure gradient is presented. The equation governing the flow is modeled into a partial differential equation (PDE) which is solved by employing the Laplace transformation technique to transform the PDE to an ordinary differential equation (ODE). The obtained ODE is solved by employing the method of undetermined coefficients to obtain the velocity profile in the Laplace domain. The Riemann sum approximation technique is then adopted to change the obtained solution from the Laplace domain into the time domain. For accuracy checks, the numerical results of the obtained equation are reckoned with previously published work, and an excellent agreement is found. For a clearer understanding of the impact of various flow parameters entering the solutions obtained, graphical and tabular representations are offered using MATLAB software. We noticed that the velocity is slower with ramped pressure gradient compared to a constant pressure gradient. This is because the motion of the fluid occurs gradually with ramped pressure gradient.
Cyanidin‐3‐glucoside protects against high glucose‐induced injury in human nucleus pulposus cells by regulating the Nrf2/HO‐1 signaling
Authors: Bai Xiaoliang , Lian Yong , Hu Changqing , Yang Shuai , Pei Bo , Yao Mingyan , Zhu Xiaojuan , Shang Lin , Li Zhihong
Published: December 2021

Cyanidin‐3‐glucoside (C3G) is a well‐known natural anthocyanin with antioxidant and anti‐inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)‐induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK‐8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl‐caspase‐3, caspase‐3, Bax, Bim, collagen II, aggrecan, MMP‐3, MMP‐13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH‐DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si‐Nrf2 or pcDNA3.0‐Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG‐induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl‐caspase‐3/caspase‐3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP‐3, MMP‐13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N‐acetylcysteine (NAC) reversed HG‐induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO‐1 in HG‐induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS‐mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO‐1 signaling pathway.
Effect of m6A methyltransferase METTL3 ‐mediated MALAT1/E2F1/AGR2 axis on adriamycin resistance in breast cancer
Authors: Li Sumei , Jiang Fengru , Chen Feiyu , Deng Yingzhao , Pan Xiaoping
Published: December 2021

N6‐methyladenosine (m6A) methyltransferase METTL3 has been implicated in carcinogenesis, which may be associated the overexpression of MALAT1. However, the downstream mechanics actions remain largely unknown. This study intends to probe the downstream mechanism of the N6‐methyladenosine (m6A) methyltransferase METTL3 and MALAT1 in adriamycin resistance in breast cancer. Through Bioinformatics databases lncMAP, TCGA and GTEx, we predicted the downstream transcription factors E2F1 and AGR2 of MALAT1 in breast cancer. The Cancer Genome Atlas and Genotype‐Tissue Expression (GTEx) databases were used to screen the downstream target genes of MALAT1. MeRIP‐qPCR was used to detect the m6A level of MALAT1 in cells. RIP was used to detect the binding between MALAT1 and E2F1, and chromatin immunoprecipitation (ChIP) for the binding of E2F1 to AGR2 promoter. Cell Counting Kit‐8 and colony formation assays were used to detect cell viability. Transwell was used to detect cell invasion. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and western blot were used to detect the expression of related genes and proteins. A nude mouse xenograft tumor model was established to observe the effect of METTL3 on adriamycin resistance of breast cancer. The total survival of mice after exogenous gene silencing was analyzed by the Kaplan–Meier method. METTL3 was highly expressed in adriamycin‐resistant breast cancer cells. METTL3 promotes adriamycin resistance in breast cancer cells. METTL3 mediates the expression of MALAT1 in adriamycin‐resistant breast cancer through m6A. MALAT1 increases adriamycin resistance in breast cancer cells by recruiting E2F1 to activate AGR2 transcription. METTL3 can regulate the expression of MALAT1 through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer. METTL3 may modify MALAT1 protein through m6A, recruit E2F1 and activate downstream AGR2 expression, thus promoting adriamycin resistance in breast cancer.
Selenium and silver nanoparticles: A new approach for treatment of bacterial and viral hepatic infections via modulating oxidative stress and DNA fragmentation
Authors: Gad Sameh S. , Abdelrahim Dina S. , Ismail Sameh H. , Ibrahim Sherine M.
Published: December 2021

Nanoparticles are recently playing a potential role in improving drug uptake and the treatment of diseases. A variety of nanoparticles, such as selenium nanoparticles (SeNPs) and silver nanoparticles (AgNPs) have been used as drug carriers in various ways for treatment of cancers and liver diseases. Our aim in this study is to investigate the ability of AgNPs and SeNPs to target and treat the viral and bacterial infection of the liver in rats and cell lines. For assessment of antioxidant activity of AgNPs in rats with induced liver bacterial infection, six adult male albino rats were included in this study, liver slices were taken and assigned to 6 groups. Markers of hepatic functions, oxidative stress, and inflammation in liver slices are carried out. Although for assessment of antiviral activity of SeNPs, hepatitis B virus transfected (HBV)‐replicating human cell line HepG2 and normal hepatocyte cells were used, hepatic and inflammatory alterations are determined through quantitative polymerase chain reaction and comet assay techniques. The effect of AgNPs on interleukin‐6 and tumor necrosis factor levels were reduced in different treated groups with AgNPs compared with the control and diseased groups. On the other hand, SeNPs revealed significant alterations in the inflammatory markers as well as DNA damage in the treated HBV‐human cell line HepG2 compared to the diseased ones. AgNPs have the ability for producing various hepatic alterations and can inhibit the proliferation of hepatic stellate cells (HSCs) in a dose and size‐dependent manner. On the other hand, SeNPs showed excellent selectivity towards viral cells in the HepG2 cell lines. Both AgNPs and SeNPs might be promising drug designs for treating viral and bacterial liver diseases.
Efficacy of N‐acetyl‐l‐cysteine against glyphosate induced oxidative stress and apoptosis in testicular germ cells preventing infertility
Authors: Bhardwaj Jitender K. , Kumar Vijay , Saraf Priyanka , Panchal Harish , Rathee Vishavjeet , Sachdeva Som N.
Published: December 2021

The present era's demand for continuous pesticides' use to increase the agriculture outcome, has caused numerous health effects among which mammalian infertility, owing to reproductive toxicity, is serious. Thus, the present study emphasizes upon glyphosate (GLY) induced toxicity and mitigating effects of N‐acetyl cysteine (NAC) in testicular cells of caprine by using various cytotoxic and biochemical parameters. GLY was found to induce several apoptotic attributes such as pyknotic nuclei, tubular degeneration, increased vacuolization, and so on, in testicular cells. GLY also decreased the cell viability and increased the incidence of apoptosis in testicular cells in a dose‐ and time‐dependent manner as revealed by MTT assay and Fluorescence (ethidium bromide/acridine orange) assay, respectively. It also increased the level of oxidative stress as evident with an increase in lipid peroxidation and decline in antioxidant power along with the decreased enzymatic activity of different antioxidant enzymes (SOD, CAT, and GST). However, NAC supplementation showed antagonistic results in GLY‐treated testicular tissues with maximum amelioration at the highest dose, thereby decreasing GLY‐mediated apoptosis rate and oxidative stress. Maximum amelioration was reported at 10 mM NAC concentration. Reduced GLY toxicity due to NAC will prove NAC to be an excellent approach for dealing with male reproductive toxicity at the cellular level, benefiting the mammalian reproductive status.
Association of Type 1 diabetes with ulcerative colitis in BALB/c mice: Investigations on sex‐specific differences
Authors: Singla Shivani , Sahu Chittaranjan , Jena Gopabandhu
Published: December 2021

Diabetes comorbidity in ulcerative colitis (UC) has relevant clinical and therapeutic implications. The link between hyperglycemia and intestinal barrier function with respect to infection and inflammation consequences exists in diabetes. The present study was designed to decipher the molecular mechanisms associated with Type 1 Diabetes mellitus and the UC in both male and female BALB/c mice. Dextran sulfate sodium (DSS; 2.5%w/v) dissolved in drinking water was given for three cycles (each cycle; 7 days) with 7 days recovery period in‐between to both male and female BALB/c mice. At the first recovery period, Streptozotocin (40 mg/kg; i.p.) was administered for 5 consecutive days in the case of male BALB/c mice; whereas the same procedure was repeated at the beginning of each recovery period in female animals. In the DSS + DB group of male animals, disease activity index, myeloperoxidase activity, nitrite level, plasma lipopolysaccharides, interleukin‐1β, histological score, % fibrotic area, % TUNEL positive cells were significantly increased. Furthermore, protein expression of phosphorylated nuclear factor kappa light chain enhancer of activated B cells (pNFκB65), proliferating cell nuclear antigen, interleukin‐6, apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain, and cysteine‐containing aspartate‐specific proteases‐1 (caspase‐1) significantly increased in the DSS + DB group of male animals as compared to female. The present study findings proved that hyperglycemic conditions exacerbated the pathological conditions in UC of male animals; whereas milder conditions developed in females.
Population Pharmacokinetics and Exposure‐Response Relationships of Astegolimab in Patients With Severe Asthma
Authors: Kotani Naoki , Dolton Michael , Svensson Robin J. , Ribbing Jakob , Friberg Lena E. , Vadhavkar Shweta , Cheung Dorothy , Staton Tracy , Sperinde Gizette , Jin Jin , Putnam Wendy S. , Quartino Angelica
Published: December 2021

Astegolimab is a fully human immunoglobulin G2 monoclonal antibody that binds to the ST2 receptor and blocks the interleukin‐33 signaling. It was evaluated in patients with uncontrolled severe asthma in the phase 2b study (Zenyatta) at doses of 70, 210, and 490 mg subcutaneously every 4 weeks for 52 weeks. This work aimed to characterize astegolimab pharmacokinetics, identify influential covariates contributing to its interindividual variability, and make a descriptive assessment of the exposure‐response relationships. A population pharmacokinetic model was developed using data from 368 patients in the Zenyatta study. Predicted average steady‐state concentration was used in the subsequent exposure‐response analyses, which evaluated efficacy (asthma exacerbation rate) and biomarker end points including forced expiratory volume in 1 second, fraction exhaled nitric oxide, blood eosinophils, and soluble ST2. A 2‐compartment disposition model with first‐order elimination and first‐order absorption best described the astegolimab pharmacokinetics. The relative bioavailability for the 70‐mg dose was 15.3% lower. Baseline body weight, estimated glomerular filtration rate, and eosinophils were statistically correlated with pharmacokinetic parameters, but only body weight had a clinically meaningful influence on the steady‐state exposure (ratios exceeding 0.8‐1.25). The exposure‐response of efficacy and biomarkers were generally flat with a weak trend in favor of the highest dose/exposure. This study characterized astegolimab pharmacokinetics in patients with asthma and showed typical pharmacokinetic behavior as a monoclonal antibody–based drug. The exposure‐response analyses suggested the highest dose tested in the Zenyatta study (490 mg every 4 weeks) performed close to the maximum effect, and no additional response may be expected above it.
Analysis of high intensity focused ultrasound in treatment of uterine fibroids on ovarian function and pregnancy outcome
Authors: Ji Jingjing , Liu Jun , Chen Yingzhen , Liu Xi , Hao Lihong
Published: December 2021

Aim

To investigate the ovarian function and pregnancy outcome of patients with uterine fibroids and the influencing factors after high intensity focused ultrasound (HIFU) ablation treatment.

Methods

A total of 80 patients were recruited. All patients were divided into the pregnancy group (64 cases) and the non‐pregnancy group (16 cases). The pregnancy group was categorized into the good pregnancy outcome (GOP) group (46 cases) and adverse pregnancy outcome (APO) group (18 cases). The general data of all study subjects were collected. The changes of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), inhibin B (INHB), and antral follicle count (AFC) before HIFU and 3, 6, and 12 months after HIFU were compared. The related factors affecting pregnancy and pregnancy outcomes were analyzed.

Results

There were no significant differences in AMH, FSH, INHB levels, and AFC at 6 and 12 months after HIFU compared with those before HIFU in pregnancy and non‐pregnancy groups (p > 0.05). This study demonstrated that patients with prior history of pregnancy, younger age, lower body mass index (BMI), and smaller fibroids volume had a higher pregnancy rate (p < 0.05). Besides, younger age and smaller fibroids volume were associated with better pregnancy outcomes (p < 0.05).

Conclusions

HIFU in the treatment of uterine fibroids has little effect on ovarian function and does not increase the risk of infertility and adverse pregnancy. The prior history of pregnancy, age, BMI, and fibroids volume are essential factors affecting the postoperative pregnancy.
Transgender patients’ perspectives on their cancer genetic counseling experiences
Authors: Rolle Lathel , Zayhowski Kimberly , Koeller Diane , Chiluiza Dee , Carmichael Nikkola
Published: December 2021

Transgender (trans) individuals face many forms of discrimination in accessing health care, including lack of provider knowledge and denial of services. Barriers specific to the cancer setting include limited availability of information concerning cancer management and its potential impact on gender affirmation therapies and minimal training for providers regarding inclusive practices for the trans population. The limited research about the experiences of cancer genetic counseling for trans patients has investigated exclusively the perspective of the provider, not the patient. This constructivist grounded theory study sought to fill this gap in the literature by interviewing trans individuals who had undergone cancer genetic counseling. Participants were recruited through social media platforms, LGBTQ+ advocacy and cancer support groups, and the National Society of Genetic Counselors’ list serv. Six semi‐structured interviews were conducted with participants focusing on their expectations and goals prior to the genetic counseling session, concerns during the session, and reflections on inclusive practices. Transcripts were coded and analyzed using a constant comparative approach and five themes emerged: (a) Anxiety for the consult, (b) Disruptions of familial relationships and emotional support systems, (c) Use of inclusive language during session, (d) Impact on gender affirmation journey, and (e) Lack of appropriate cancer risk information for trans patients. The results from this pilot study suggest that trans patients experience anticipatory anxiety before the genetic counseling appointment, particularly about the potential of a physical examination. They may be more likely to experience disrupted family relationships that impact access to family history information and support. Genetic counselors should utilize inclusive language both when referring to the patient and when discussing cancer risk. Finally, additional research is needed to provide more accurate cancer risk predictions for trans individuals.