bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Epstein–Barr virus‐deoxyribonucleic acid load after induction chemotherapy combined with American Joint Committee on Cancer stage determine the chemotherapy intensity of locally advanced nasopharyngeal carcinoma?
Authors: Zhang Qun , Peng Zhen‐Wei , Gu Zhuo‐Sheng , Wang Yan , He Fang , Zhao Wen‐Bin , Luo Wei , Mei Yong‐Yu
Published: June 2022

Background

Induction chemotherapy (IC) comprising docetaxel, cisplatin, and fluorouracil (TPF), combined with concurrent chemoradiotherapy (CCRT) effectively improves the survival rate of locally advanced nasopharyngeal carcinoma (LA‐NPC). Selecting patients whose risk of tumor recurrence and metastasis is high and the appropriate chemotherapy intensity is a concern. We combined tumor‐node‐metastasis staging with the load of Epstein–Barr virus (EBV) after IC to select the individualized chemotherapy strength.

Methods

The clinical data and prognostic factors of patients with stage III–IV LA‐NPC treated with TPF IC combined with CCRT were analyzed retrospectively. The conventional treatment group received the standard three cycles TPF IC combined with CCRT. For the new treatment group, the cycles of IC were determined according to whether the EBV‐DNA disappeared completely after a certain course of IC, if so, subsequent IC was stopped and the chemoradiotherapy stage was entered. Propensity score matching (PSM) was performed at a ratio of 1:1 to balance baseline characteristics. Survival outcomes and adverse events between the conventional treatment group and the new method treatment group were compared.

Results

The study included 256 patients, among whom 192 were matched successfully into 96 pairs. The patients were followed up for a median of 51 months. The proportions of patients receiving three, two, and one cycle of IC after PSM in the routine and new treatment cohorts were 93.8%, 3.1%, 3.1% versus 21.9%, 49.0%, 24.0%, respectively. However, their 3‐year distant metastasis‐free survival, local recurrence‐free survival, progression‐free survival, and overall survival did not differ significantly. The incidence of grade 3–4 neutropenia toxicity in CCRT decreased significantly in patients receiving the new treatment method compared with that in the conventional treatment group (p = 0.026).

Conclusion

Combining TNM stage and EBV‐DNA load after IC to determine the courses of IC in patients with LA‐NPC did not alter the curative effect but decreased toxicity.
Racial inequity and other social disparities in the diagnosis and management of bladder cancer
Authors: Hasan Shaakir , Lazarev Stanislav , Garg Madhur , Mehta Keyur , Press Robert H. , Chhabra Arpit , Choi J. Isabelle , Simone Charles B. , Gorovets Daniel
Published: June 2022

Background

We investigate the impact of gender, race, and socioeconomic status on the diagnosis and management of bladder cancer in the United States.

Methods

We utilized the National Cancer Database to stratify cases of urothelial cell carcinoma of the bladder as early (Tis, Ta, T1), muscle invasive (T2–T3, N0), locally advanced (T4, N1–3), and metastatic. Multivariate binomial and multinomial logistic regression analyses identified demographic characteristics associated with stage at diagnosis and receipt of cancer‐directed therapies. Odds ratios (OR) are reported with 95% confidence intervals.

Results

After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases from 2004–2016. Relative to diagnosis at early stage, the strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included Black race (OR = 1.19 [1.15–1.23], OR = 1.49 [1.40–1.59], OR = 1.66 [1.56–1.76], respectively), female gender (OR = 1.21 [1.18–1.21], OR = 1.16 [1.12–1.20], and OR = 1.34 [1.29–1.38], respectively), and uninsured status (OR = 1.22 [1.15–1.29], OR = 2.09 [1.94–2.25], OR = 2.57 [2.39–2.75], respectively). Additional demographic factors associated with delayed diagnosis included older age, treatment at an academic center, Medicaid insurance and patients from lower income/less educated/more rural areas (all p < 0.01).

Treatment at a non‐academic center, older age, women, Hispanic and Black patients, lower income and rural areas were all less likely to receive cancer‐directed therapies in early stage disease (all p < 0.01). Women, older patients, and Black patients remained less likely to receive treatment in muscle invasive, locally advanced, and metastatic disease (all p < 0.01).

Conclusion

Black race was the strongest independent predictor of delayed diagnosis and substandard treatment of bladder cancer.
Assessing social dominance orientation and system justification as psychological pathways from practicing meditation to tax evasion intentions and support for tax progressivity
Authors: De Cristofaro Valeria , Giacomantonio Mauro , Pellegrini Valerio , Salvati Marco , Leone Luigi
Published: June 2022

Recent research showed that trait mindfulness might reduce tax evasion intentions and increase support for tax progressivity. The present study proposed that these beneficial effects of being mindful can be explained theoretically by different associations with inequality‐related constructs: social dominance orientation and system justification. Specifically, we tested our predictions by comparing meditation practitioners to nonpractitioners. Results from a path analysis revealed that relative to nonpractitioners, meditation practitioners were less likely to evade taxes primarily because of associations with lower social dominance orientation. Instead, they were more likely to support a progressive taxation primarily through associations with lower system justification. These results support the beneficial role of practicing meditation for tax compliance for people who meditate regularly. Moreover, these results may shed light about the psychological pathways through which practicing meditation brings about such beneficial social consequences.
Rational Design, Synthesis, in Vitro, and in Silico Studies of Chlorophenylquinazolin‐4(3H)‐One Containing Different Aryl Acetohydrazides as Tyrosinase Inhibitors
Authors: Hajimiri Mirhamed , Khosravikia Mohammad , Khoshneviszadeh Mehdi , Pedrood Keyvan , Hosseini Seyedeh Zahra , Asgari Mohammad Sadegh , Pirhadi Somayeh , Attarroshan Mahshid , Mobaraki Koroush , Hosseini Samanesadat , Behnammanesh Hossein , Biglar Mahmood , Karimian Somayeh , Rastegar Hossein , Hamedifar Haleh , Larijani Bagher , Mahdavi Mohammad , Iraji Aida
Published: June 2022

Tyrosinase plays a pivotal role in the hyperpigmentation and enzymatic browning of fruit and vegetable. Therefore, tyrosinase inhibitors can be of interest in industries as depigmentation compounds as well as anti‐browning agents. In the present study, a series of chlorophenylquinazolin‐4(3H)‐one derivative were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H‐NMR, 13C‐NMR, and elemental analysis. Among the synthesized derivatives, compound 8l was proved to be the most potent inhibitor with an IC50 value of 25.48±1.19 μM. Furthermore, the results of the molecular docking study showed that this compound fitted well in the active site of tyrosinase with the binding score of −10.72.
Evaluation of Gene Expression Knock‐Down by Chemically and Structurally Modified Gapmer Antisense Oligonucleotides
Authors: Lisowiec‐Wąchnicka Jolanta , Danielsen Mathias B. , Nader Eugenie Abi , Jørgensen Per T. , Wengel Jesper , Pasternak Anna
Published: June 2022

We analyzed the effect of modified nucleotides within gapmer antisense oligonucleotides on RNase H mediated gene silencing. Additionally, short hairpins were introduced into antisense oligonucleotides as structural motifs, and their influence on biological and physicochemical properties of pre‐structured gapmers was investigated for the first time. The results indicate that two LNA residues in specified positions of the gap flanking regions are sufficient and favorable for efficient knock‐down of the β‐actin gene. Furthermore, the introduction of other modified nucleotides, i. e. glycyl‐amino‐LNA−T, 2′‐O‐propagyluridine, polyamine functionalized uridine, and UNA, in specified positions, also increases the inhibition of β‐actin expression. Importantly, the presence of hairpins within the gapmers improves their silencing properties.
Anaerobic ATP synthesis pathways and inorganic phosphate transport and their possible roles in encystment in Acanthamoeba castellanii
Authors: Carvalho‐Kelly Luiz Fernando , Dick Claudia Fernanda , Rocco‐Machado Nathalia , Gomes‐Vieira André Luiz , Paes‐Vieira Lisvane , Meyer‐Fernandes José Roberto
Published: June 2022

Acanthamoeba castellanii is the etiological agent of amoebic keratitis and is present in the environment in trophozoite or cyst forms. Both forms can infect the vertebrate host and colonize different tissues. The high resistance of cysts to standard drugs used in clinics contributes to the lack of effective treatments. Therefore, in this context, studies have emerged to understand cyst physiology and metabolism. Phosphate transporters are proteins responsible for the uptake of extracellular inorganic phosphate and transport to the cytosol. This work aims to verify the relationship between Pi transport and energetic metabolism in cysts of A. castellanii. The phosphate uptake ratio was higher in cysts compared with trophozoites. Recently, three sequences related to phosphate transporters have been identified in the A. castellanii genome (AcPHS1, AcPHS2, and AcPHS3); the messenger RNA expression levels of which differ depending on the amoeba life form. Pi uptake in cysts displayed peak activity at alkaline pH, whereas Pi transport in trophozoites was not affected in the same pH ranges. Cysts harbor a low‐affinity Pi transport system (K0,5 and Vmax values of 1.76 ± 0.26 mM and 104.6 ± 6.3 nmol Pi × h−1 × 106 cells) compared to the trophozoite phosphate transport system. Pi transport seems important for anaerobic adenosine triphosphate synthesis in cysts, which initially occurs through the glycolytic pathway and subsequently through the pyruvate ferredoxin oxidoreductase pathway. Altogether, these results suggest that contrary to that previously postulated, cysts are active metabolic forms, and, as noted in trophozoites, phosphate uptake is important for energetic metabolism.
Sex‐related differences in cardiogenic shock: Can we do better in women?
Authors: Thakker Ravi , Jneid Hani
Published: June 2022

Key Points

The overall incidence of cardiogenic shock (CS) increased over time in both men and women, although women had lower incidence of acute myocardial infarction (AMI)‐CS and non‐AMI‐CS across all age groups.

A favorable trend of reduction in in‐hospital mortality was seen among all age groups regardless of sex in CS patients, except in young AMI‐CS patients (20–44 years) in whom a notable uptrend was observed.

After adjustment using propensity score matching, middle‐aged women (45–64 years) with AMI‐CS had higher in‐hospital mortality compared to their male counterparts, while women with non‐AMI‐CS experienced a higher mortality across all age categories (except among elderly patients ≥85 years).
Functionalized Lignin for Fabrication of FeCoNi Nanoparticles‐Enriched 3D Carbon Hybrid: From Waste to a High‐Performance Oxygen Evolution Reaction Catalyst
Authors: Min Xiaoye , Zhang Tingzheng , Xie Mingbo , Zhang Kejing , Chai Liyuan , Lin Zhang , Ding Chunlian , Shi Yan
Published: June 2022

The application of lignin‐derived carbon materials in energy conversion is hindered by the complex molecular structure and few metal coordination sites of lignin. In this work, a simple oxidation–coordination method was developed for scalable synthesis of a FeCoNi nanoparticles‐modified nitrogen‐doped carbon hybrid (designated as O−FeCo40Ni10−C) with lignin as carbon precursor for oxygen evolution reaction (OER). Specifically, a Fenton reaction‐driven pre‐oxidation process changed the molecular structure of alkali lignin and increased functional groups, which contributes to the efficient incorporation of metal active sites into lignin‐derived carbon materials. Benefiting from abundant active sites, the synergistic effect of CoFe/NiFe compositions and interconnected porous structure, the obtained O−FeCo40Ni10−C exhibited a high OER activity. It only required an overpotential of 280 mV to drive current densities of 10 mA cm−2 in 1 M KOH solution. Moreover, the turnover frequency of O−FeCo40Ni10−C was 0.030 and 0.185 s−1 at the overpotential of 300 and 400 mV, respectively. This work provided an environmentally‐friendly strategy to synthesize lignin‐derived catalyst for OER and expanded the application of lignin in energy conversion filed.
Transcriptome sequencing reveals altered ciliogenesis under hypoxia in nasal epithelial cells from chronic rhinosinusitis with nasal polyps
Authors: Jiao Jian , Hu Puqi , Zhuang Mengyan , Li Ying , Cai Chao , Wang Xiangdong , Zhang Luo
Published: June 2022

Background

Hypoxia is considered a key factor in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific mechanism driving polypogenesis under hypoxic conditions is unclear. This study aimed to explore hypoxia‐induced alterations in the transcriptome of human nasal epithelial cells (HNECs) in vitro.

Methods

HNECs derived from the tissue of patients with CRSwNP were established as air–liquid interface (ALI) cultures. Confluent cultures were kept submerged or treated with cobalt chloride (CoCl2) to induce hypoxia. Transcriptome analysis was used to identify key mRNAs involved in this process. Real‐time PCR (RT–PCR), Western blotting, and immunofluorescence were used to observe the effects of hypoxia on ciliogenesis.

Results

Numerous genes, biological processes and pathways were altered under submerged culture conditions or after CoCl2 treatment. Analysis of the results under both hypoxic conditions revealed that the transcriptional program responsible for ciliogenesis was significantly impaired. Downregulation of cilia‐related genes and inhibition of ciliated cell differentiation under hypoxia were confirmed by RT–PCR, Western blot and immunofluorescence analyses.

Conclusion

Hypoxia impairs ciliogenesis and ciliary function in HNECs, which might play a role in the pathogenesis of CRSwNP.
Acridine‐Peptide Conjugated Nanofiber Assembly Triggers Stimuli‐Free Immobilization of Crude Oil and Read‐Out by Turn‐On Emission
Authors: Asthana Deepak , Patti Nagabhushanam , Mukhopadhyay Pritam
Published: June 2022

Nanomaterials that can perform cascading functions in the domain of rapidity and strength of self‐assembly, able to immobilize a large mass with minimum energy, and generate optical signal hold potential to contain recurring oil‐spills and remediation of land or water bodies. Herein, we report the stimuli‐free, phase‐selective immobilization of naturally occurring heavy crude oil. Molecule(s) described herein are capable of forming nanofibers with large‐area junction zones and instantaneously immobilize petroleum products (PPs), and also report the event with a turn‐on emission. The extraordinary efficiency of 0.4 kg immobilizer per ton of petrol and wide operational temperature range (up to 330–360 K) stems from the rapid creation of advanced assemblies having strength (>105 Pa) akin to the robust polymeric fibers. Thus, this new generation of intelligent nanomaterials with ingrained information to carry out multiple and complex function in tandem offers bright prospects to control and effectively detect the oil spill menace in a proficient manner.
Performance assessment of ensembles of in situ workflows under resource constraints
Authors: Do Tu Mai Anh , Pottier Loïc , Ferreira da Silva Rafael , Caíno‐Lores Silvina , Taufer Michela , Deelman Ewa
Published: June 2022

Scientific breakthroughs in biomolecular methods and improvements in hardware technology have shifted from a long‐running simulation to a large set of shorter simulations running simultaneously, called an ensemble. In an ensemble, simulations are usually coupled with analyses of data produced by the simulations. In situ methods can be used to analyze large volumes of data generated by scientific simulations at runtime (i.e., simulations and analyses are performed concurrently). In this work, we study the execution of ensemble‐based simulations paired with in situ analyses using in‐memory staging methods. Using an ensemble of molecular dynamics in situ workflows with multiple simulations and analyses, we first show that collecting traditional metrics such as makespan, instructions per cycle, memory usage, or cache miss ratio is not sufficient to characterize complex behaviors of ensembles. We propose a method to evaluate the performance of ensembles of workflows that captures multiple resource usage aspects: resource efficiency, resource allocation, and resource provisioning. Experimental results demonstrate that the proposed method can effectively distinguish the performance of different component placements in an ensemble with up to 32 ensemble members. By evaluating different co‐location scenarios, our proposed performance indicators demonstrate benefits of co‐locating simulation and coupled analyses within a compute node.
A modified Z‐source switched‐capacitor based non‐isolated high gain DC‐DC converter for photovoltaic applications
Authors: Kishor Yugal , Patel Ramnarayan
Published: June 2022

This work proposes a modified high gain DC‐DC converter integrated with two boost converter stages, based on a boost cell and a Z‐source (ZS) cell with a switched capacitor (SC). The proposed converter architecture is simple, with a continuous input current and a wide range of input voltage fluctuation handling capabilities. It also provides a high voltage gain while minimizing voltage stress on semiconductor components. Because of the aforementioned characteristics, the proposed converter is suitable for combining with low‐voltage DC‐sources to high‐voltage DC bus in a variety of applications such as solar photovoltaic (SPV), fuel‐cell, and LED lighting. The operational principles, thermal modeling, steady‐state, and dynamic performance analysis are meticulously carried out on a 400 W laboratory prototype of the proposed converter. The converter's performance is carefully compared with similar existing topologies in terms of total device count and size, the voltage stress on power semiconductors, voltage gain, and peak efficiency. Furthermore, experimental findings show that a 12 V input is boosted to 98.8 V at a duty ratio of 0.3, demonstrating the efficacy of the proposed converter over a comparable structure.
Hürthle cell‐predominant thyroid fine needle aspiration cytology: A four risk‐factor model highly accurate in excluding malignancy and predicting neoplasm
Authors: Yuan Lisi , Nasr Christian , Bena James F. , Elsheikh Tarik M.
Published: June 2022

Background

Interpretation of Hürthle cell‐predominant cytologies (HCP) is very challenging as a majority is diagnosed as indeterminate. Prior studies have reported various cytologic features to help distinguish non‐neoplastic (NN) from neoplastic and malignant lesions but had contradicting results. Our aim was to identify risk factors predictive of neoplasm and/or malignancy by correlating cytologic features with clinical and ultrasound findings.

Methods

Sixty‐nine HCP cases with surgical follow‐up were identified, including 35 NN, 20 adenomas, and 14 carcinomas. Ultrasound data were recorded utilizing Thyroid Imaging Reporting and Data System (TI‐RADS) and American Thyroid Association (ATA) scoring systems. Sixteen cytologic criteria were evaluated and semi‐quantitatively scored. Data were assessed by univariable, multivariable and stepwise logistic regression analysis; and statistical significance achieved at P‐value <0.05.

Results

On univariable analysis, significant predictors of neoplasm were high cellularity, isolated single cells, absent colloid, non‐uniform HC population (anisonucleosis), larger nodule size, and higher ATA score. Large‐cell dysplasia and transgressing blood vessels were not found to be significant factors. Multivariable analysis identified a combination of four risk factors (high cellularity, anisonucleosis, absent colloid, and size ≥2.9 cm) that was associated with neoplasm in 10/11 patients. None of 15 patients with zero or 1 out of 4 risk factors had malignancy or neoplasm on follow‐up. This model also significantly outperformed ATA and TI‐RADS scoring systems.

Conclusion

In the absence of four or three risk factors, the model excluded malignancy and neoplasm in all patients. The presence of all four factors predicted neoplasm and malignancy in 91% and 46% of cases, respectively.
Expressive language in infancy and toddlerhood: The roles of child temperament and maternal parenting behaviors
Authors: Bruce Madeleine , McFayden Tyler C. , Ollendick Thomas H. , Bell Martha Ann
Published: June 2022

Prompt, appropriate, and contingent maternal behaviors play a role in early language acquisition, as do individual differences in children's temperament. However, little work has investigated the combined influence of maternal psychosocial and child biological factors on expressive language development. The purpose of this study was to evaluate the concurrent and longitudinal contributions of responsive/intrusive parenting and child temperament to multiple expressive language outcomes at 10 and 24 months of age. Participants included 407 mothers and children (209 girls). Mothers completed questionnaires about their infant's temperament and language, and maternal parenting was coded during mother–child interaction tasks. Dependent variables included (1) gestures at 10 months, (2) vocabulary at 24 months, (3) mean length of utterance at 24 months, and (4) sentence complexity at 24 months. After controlling for child sex and maternal education, child temperament was associated with language outcomes at 10 and 24 months, whereas intrusive, but not responsive, parenting related to only 24 month language outcomes. Longitudinally, infant negative affectivity predicted sentence complexity in toddlerhood. These findings elucidate the presence of both psychological and biological predictors as they differentially influence various aspects of expressive language development across the first two postnatal years.
Plant responses to soil biota depend on precipitation history, plant diversity, and productivity
Authors: Lundell Seth , Batbaatar Amgaa , Carlyle Cameron N. , Lamb Eric G. , Otfinowski Rafael , Schellenberg Michael P. , Bennett Jonathan A.
Published: June 2022

Soil biota are critical drivers of plant growth, population dynamics, and community structure and thus have wide‐ranging effects on ecosystem function. Interactions between plants and soil biota are complex, however, and can depend on the diversity and productivity of the plant community and environmental conditions. Plant–soil biota interactions may be especially important during stressful periods, such as drought, when plants can gain great benefits from beneficial biota but may be susceptible to antagonists. How soil biota respond to drought is also important and can influence plant growth following drought and leave legacies that affect future plant responses to soil biota and further drought. To explore how drought legacies and plant community context influence plant growth responses to soil biota and further drought, we collected soils from 12 grasslands varying in plant diversity and productivity where precipitation was experimentally reduced. We used these soils as inoculum in a growth chamber experiment testing how precipitation history (ambient or reduced) and soil biota (live or sterile soil inoculum) mediate plant growth and drought responses within an experimental plant community. We also tested whether these responses differed with the diversity and productivity of the community where the soil was collected. Plant growth responses to soil biota were positive when inoculated with soils from less diverse and productive plant communities and became negative as the diversity and productivity of the conditioning community increased. At low diversity, however, positive soil biota effects on plant growth were eliminated if precipitation had been reduced in the field, suggesting that diversity loss may heighten climate change sensitivity. Differences among species within the experimental community in their responses to soil biota and drought suggest that species benefitting from less drought sensitive soil biota may be able to compensate for some of this loss of productivity. Regardless of the plant species and soil origin, further drought eliminated any effects of soil biota on plant growth. Consequently, soil biota may be unable to buffer the effects of drought on primary productivity or other ecosystem functions as extreme events increase in frequency.
Bayesian quantile forecasting via the realized hysteretic GARCH model
Authors: Chen Cathy W. S. , Lin Edward M. H. , Huang Tara F. J.
Published: June 2022

This research introduces a new model, a realized hysteretic GARCH, that is similar to a three‐regime nonlinear framework combined with daily returns and realized volatility. The setup allows the mean and volatility switching in a regime to be delayed when the hysteresis variable lies in a hysteresis zone. This nonlinear model presents explosive persistence and high volatility in Regime 1 in order to capture extreme cases. We employ the Bayesian Markov chain Monte Carlo (MCMC) procedure to estimate model parameters and to forecast volatility, value at risk (VaR), and expected shortfall (ES). A simulation study highlights the properties of the proposed MCMC methods, as well as their accuracy and satisfactory performance as quantile forecasting tools. We also consider two competing models, the realized GARCH and the realized threshold GARCH, for comparison and carry out Bayesian risk forecasting via predictive distributions on four stock markets. The out‐of‐sample period covers the recent 4 years by a rolling window approach and includes the COVID‐19 pandemic period. Among the realized models, the realized hysteretic GARCH model outperforms at the 1% level in terms of violation rates and backtests.
Reduced kidney function is associated with poorer domain‐specific cognitive performance in community‐dwelling older adults
Authors: Dyer Adam H. , Laird Eamon , Hoey Leane , Hughes Catherine F. , McNulty Helene , Ward Mary , Strain J. J. , O’Kane Maurice , Tracey Fergal , Molloy Anne M. , Cunningham Conal , Sexton Donal J. , McCarroll Kevin
Published: June 2022

Objectives

Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain‐specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults.

Methods

Participants aged >60 years from the Trinity‐Ulster‐Department of Agriculture study underwent detailed cognitive assessment using the Mini‐Mental State Examination (Mini‐Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance.

Results

In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR <45 ml/ml/1.73 m2 (Incidence Rate Ratio: 1.17; 95% CI 1.08, 1.27; p < 0.001 for MMSE; IRR: 1.13; 95% CI 1.04, 1.13; p < 0.001 for FAB; β: −3.66; 95% CI −5.64, −1.86; p < 0.001 for RBANS). Additionally, eGFR <45 ml/ml/1.73 m2 was associated with poorer performance on all five RBANS domains, with greatest effect sizes for immediate memory, delayed memory and attention. Associations were strongest in those aged 60–70, with no associations observed in those >80 years.

Conclusions

Reduced kidney function was associated with poorer global and domain‐specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m2 and in those aged 60–70 years, suggesting that this population may potentially benefit from potential multi‐domain interventions aimed at promoting optimal brain health in older adults.
Response of runoff components to climate change in the source‐region of the Yellow River on the Tibetan plateau
Authors: Zhang Ting , Li Dongfeng , Lu Xixi
Published: June 2022

Climate change will likely increase the total streamflow in most headwaters on the Tibetan Plateau in the next decades, yet the response of runoff components to climate change and permafrost thaw remain largely uncertain. Here, we investigate the changes in runoff components under a changing climate, based on a high‐resolution cryosphere‐hydrology model (Spatial Processes in Hydrology model, SPHY) and multi‐decadal streamflow observations at the upstream (Jimai) and downstream stations (Maqu and Tangnaihai) in the source‐region of the Yellow River (SYR). We find that rainfall flow dominates the runoff regime in SYR (contributions of 48%–56%), followed by snowmelt flow (contributions of 26%/23% at Maqu/Tangnaihai). Baseflow is more important at Jimai (32%) than at the the downstream stations (21%–23%). Glacier meltwater from the Anyê Maqên and Bayankala Mountains contributes negligibly to the downstream total runoff. With increasing temperature and precipitation, the increase in total runoff is smaller in the warm and wet downstream stations than in the cold and dry upstream station. This is because of a higher increase in evapotranspiration and a larger reduction in snowmelt flow in the downstream region in response to a warming climate. With temperature increase, there is less increase in rainfall flow in the downstream region due to increased water loss through evapotranspiration. Meanwhile, the decline in snowmelt flow is larger further downstream, which can negatively impact the spring irrigation for the whole Yellow River basin that supports the livelihoods of 140 million people. Importantly, we find that baseflow plays an increasingly important role in the permafrost‐dominated upstream region with atmospheric warming and permafrost thaw, accompanied by decreased surface flow. These findings improve our current understanding of how different hydrological processes respond to climate change and provide insights for optimizing hydropower and irrigation systems in the entire Yellow River basin under a rapidly changing climate.
The role of temperament and parenting on anxiety problems among toddlers: Moderating role of parenting and mediating role of attachment
Authors: Bahtiyar‐Saygan Bahar , Berument Sibel Kazak
Published: June 2022

Anxiety problems are seen as early as 1–2 years of age. Among others, parenting and child temperament are considered as the most important factors affecting anxiety in early childhood. In the current study, the unique roles of parenting (maternal overprotectiveness and warmth) and temperament (behavioral inhibition and negative emotionality), parenting‐temperament interactions, and mediating role of ambivalent attachment between behavioral inhibition and anxiety were investigated. One‐hundred mother–child (18–36‐month‐old) dyads participated in this study. Children's anxiety and temperament were measured through mother‐reported scales, attachment was measured by observation via home visits, and parenting dimensions were measured via both mother‐reported scales and observation. The results revealed that behavioral inhibition and overprotectiveness were positively associated with toddlers’ anxiety, whereas there were no significant direct associations of negative emotionality and warmth with anxiety. However, the interaction between behavioral inhibition and warmth predicted toddler's anxiety; that is, if behaviorally inhibited children had mothers who were low on warmth, those children were more likely to exhibit anxiety symptoms compared to children with low behavioral inhibition, whereas anxiety levels did not change for children of warm mothers. Ambivalent attachment mediated the relationship between behavioral inhibition and anxiety. The nature of parent‐child interactions is discussed based on toddlerhood anxiety.
Oxidative brain and cerebellum injury induced byd‐galactosamine: Protective effect ofS‐methyl methionine sulfonium chloride
Authors: Mahmarzayeva Dastagul , Bayrak Bertan Boran , Turkyilmaz Ismet Burcu , Sacan Ozlem , Yanardag Refiye
Published: June 2022

The objective of this study was to examine the protective effects ofS‐methyl methionine sulfonium chloride (MMSC) against galactosamine (GalN)‐induced brain and cerebellum injury in rats. A total of 22 female Sprague–Dawley rats were randomly divided into four groups as follows: Group I (n = 5), intact animals; Group II (n = 6), animals received 50 mg/kg/day of MMSC by gavage technique for 3 consecutive days; Group III (n = 5), animals injected with a single dose of 500 mg/kg of GalN intraperitoneally (ip); and Group IV (n = 6), animals injected with the same dose of GalN 1 h after MMSC treatment. After 6 h of the last GalN treatment (at the end of the experiments), all animals were killed under anesthesia, brain and cerebellum tissues were dissected out. Reduced glutathione, total antioxidant status levels, and antioxidant enzymes (catalase, superoxide dismutase, and glutathione‐related enzymes), aryl esterase, and carbonic anhydrase activities remarkably declined whereas advanced oxidized protein products, reactive oxygen species, total oxidant status, oxidative stress index levels, and myeloperoxidase, acetylcholinesterase, lactate dehydrogenase, and xanthine oxidase activities were significantly elevated in the GalN group compared with intact rats. In contrast, the administration of MMSC to GalN groups reversed these alterations. In conclusion, we may suggest that MMSC has protective effects against GalN‐induced brain and cerebellar toxicity in rats.
Resveratrol mitigates diclofenac‐induced hepatorenal toxicity in rats via modulation of miR‐144/Nrf2/GSH axis
Authors: Elbaz Eman M. , Ahmed Kawkab A. , Abdelmonem Maha
Published: June 2022

Despite the extensive therapeutic uses of diclofenac, it may cause several adverse effects, including hepatorenal injury. The antioxidant and anti‐inflammatory properties of resveratrol, a polyphenolic compound, make the agent effective in ameliorating a variety of drug‐induced injuries. This study investigated the potential beneficial effects of resveratrol on diclofenac‐induced hepatorenal toxicity and explored the role of miR‐144 and its relationship to oxidative stress and inflammation triggered by diclofenac. Rats were divided into four groups: control; diclofenac group received diclofenac (10 mg/kg/day, intraperitoneal [ip]) for 7 days; prevention group received resveratrol concomitantly with diclofenac for 7 days; and the treatment group received diclofenac for 7 days followed by resveratrol (20 mg/kg/day, per oral) for another 7 days. Diclofenac administration induced a significant increase in serum hepatorenal biomarkers and histopathological aberrations. In addition, diclofenac upregulated miR‐144 while reducing nuclear factor erythroid 2‐related factor 2 (Nrf2) protein levels and glutathione (GSH) content. Moreover, diclofenac induced tissue inflammation and apoptosis as evidenced by increased protein expression of nuclear factor kappa B (NF‐κB), tumor necrosis factor α (TNF‐α), and caspase‐3. Intriguingly, resveratrol prevention or treatment significantly mitigated the toxic effects of diclofenac as manifested by normalization of the hepatorenal functions and amelioration of the histopathological changes. Resveratrol also triggered miR‐144 downregulation with Nrf2 upregulation. Consequently, resveratrol showed hepatorenal antioxidant, anti‐inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF‐κB, TNF‐α, and caspase‐3 expressions. In conclusion, this study demonstrates a potential therapeutic role of resveratrol in mitigating diclofenac‐induced hepatorenal insult, possibly via modulating miR‐144/Nrf2/GSH axis.
Favorable effect of rivaroxaban against vascular dysfunction in diabetic mice by inhibiting NLRP3 inflammasome activation
Authors: Li Qing , Yang Xin‐Tong , Wei Wei , Hu Xiang‐Peng , Li Xiao‐Xue , Xu Ming
Published: June 2022

Cardiovascular disease (CVD) is the leading cause of death in various complications of type 2 diabetes mellitus (T2DM). Rivaroxaban (Xarelto; Bayer), an oral direct factor Xa (FXa) inhibitor, prevents the activation of the coagulation cascade in CVD. Considering its anticoagulant and anti‐inflammatory effects, we assessed the hypothesis that rivaroxaban treatment may attenuate the vascular lesion and dysfunction in T2DM mice. C57BL/6, BKS‐db/db, BKS‐db/+, wild‐type (WT), and NLRP3−/− mice were fed with standard chow or high‐fat diet (HFD). Biochemical indexes, vascular lesions, and protein expression were evaluated using Western blot analysis, immunofluorescent staining, and RNA interference. Rivaroxaban presented favorable protection of vascular dysfunction in T2DM mice with significantly relieved vascular tension, intima‐media thickness, and collagen deposition. Similar improvements in NLR family pyrin domain containing 3 (NLRP3) knockout groups and rivaroxaban pointed to the positive role of rivaroxaban against vascular dysfunction in diabetic mice by ameliorating NLRP3 inflammasome activation. Furthermore, the augmentation of inflammation and cell dysfunction in mice aortic endothelial cells (MAECs) and smooth muscle cells (MOVASs) induced by soluble FXa may be blocked by rivaroxaban via protease‐activated receptors (PAR‐1, PAR‐2), mitogen‐activated protein kinase (MAPK), and nuclear factor κ‐B (NF‐κB) pathway. The data indicate that the development of vascular dysfunction and inflammation in T2DM mice may be blocked by rivaroxaban in vivo and in vitro. Rivaroxaban treatment may also attenuate NLRP3 inflammasome activation via PARs, MAPK, and NF‐κB pathway. This study provides mechanistic evidence of rivaroxaban therapies for vascular complications of T2DM.
A pilot study on dasatinib in patients with Waldenström macroglobulinemia progressing on ibrutinib
Authors: Castillo Jorge J. , Sarosiek Shayna , Flynn Catherine A. , Leventoff Carly , Little Megan , White Timothy , Meid Kirsten , Treon Steven P.
Published: June 2022

The hematopoietic cell kinase (HCK) regulates BTK activation and represents a potential therapeutic target in Waldenstrom macroglobulinemia (WM). We investigated dasatinib, a potent HCK inhibitor, in patients with WM progressing on ibrutinib. Study treatment consisted of dasatinib administered at 100 mg by mouth once daily in four‐week cycles for up to 24 cycles. This study was registered under ClinicalTrials.Gov ID NCT04115059. Three participants were enrolled and received at least one cycle of dasatinib. The best response was stable disease. Two patients received 5 months and one patient received 1 month of therapy. The dose of dasatinib was decreased in one participant due to volume overload. Based on the lack of responses observed, the study was terminated. Dasatinib might not be effective in patients with WM progressing on ibrutinib.
Low and high storage temperature inhibited the coloration of mandarin fruit (Citrus unshiu Marc.) with different mechanism
Authors: Ge Xiaoxiao , Cao Tingting , Yi Lanhua , Yao Shixiang , Zeng Kaifang , Deng Lili
Published: June 2022

BACKGROUND

Peel color regulated by pigment metabolism is one of the most crucial indicators affecting the commodity values of citrus fruit. Storage temperature is a vital environmental factor that regulates the fruit pigmentation.

RESULTS

Results showed that the peel coloring process was significantly inhibited when mandarin fruit were stored at 5 and 32 °C with normal coloring at 25 °C as the control. However, the inhibitive mechanisms of 5 and 32 °C storage were different. At 5 °C, higher levels of CcNYC and CcCHL2 were detected, which indicated that 5 °C induces the circulation of chlorophyll rather than inhibits chlorophyll degradation. CcPSY2, CcCHYB, and CcZEP exhibited higher expression levels in fruit stored at 5 °C, which accelerated the accumulation of carotenoids. In fruit stored at 32 °C, CcNYC, CcPAO, and CcCHL2 exhibited lower expression levels than those fruit stored at 5 °C, and the expressions of CcPSY2, CcCHYB, and CcZEP were down regulated, implying the carotenoid synthesis was suppressed.

CONCLUSION

Storage at 5 °C inhibited the postharvest coloring of mandarin fruit mainly by activating the cycle of chlorophyll, although it promotes the accumulation of carotenoids at the same time, but chlorophyll covers the color of carotenoids. Storage at 32 °C inhibited mandarin fruit coloring mainly by inhibiting the degradation of chlorophyll. Compared with the change of individual chlorophyll or carotenoid content, the change of the ratio of chlorophyll and carotenoid had a more important role in the coloration of mandarin fruit. This research offers valuable details for understanding the effect of temperature on the coloring process of postharvest citrus fruit. © 2022 Society of Chemical Industry.
Identification of peptides of cinobufacini by gel filter chromatography and peptidomics
Authors: Li Junxian , Lv Xiang , Li Bingxv , Liu Lina , Yu Chengli , Cheng Haibo , Zhou Jing , Zhu Yuyu , Ma Hongyue
Published: June 2022

Aqueous extract of toad skin (named as Cinobufacini or Huachansu) provides plentiful sources of bioactive peptides that remain undetected and unidentified. High‐resolution mass spectrometry‐based peptidomics platforms have developed into a major approach to the discovery of natural peptides, with data‐dependent acquisition modes providing a wealth of peptide profiling information. In this study, we used a gel‐ and HLB (a solid phase extraction cartridge)‐based two‐dimensional separation and purification system and nano‐liquid chromatography‐tandem mass spectrometry‐based peptidomic studies with homology matching for the identification of peptides from Cinobufacini. We evaluated 232 multi‐charged peptides and found several specific peptides, some of which were validated by target parallel reaction monitoring mode. These peptides are the first to be identified in Cinobufacini and are completely different from ones identified in toad venom. So, this mapping provides key peptide information for the quality control of Bufo bufo gargarizans skin and its preparation.
A probabilistic Bayesian approach to recover R2*$$ {R}_{2\ast } $$ map and phase images for quantitative susceptibility mapping
Authors: Huang Shuai , Lah James J. , Allen Jason W. , Qiu Deqiang
Published: June 2022

Purpose

Undersampling is used to reduce the scan time for high‐resolution three‐dimensional magnetic resonance imaging. In order to achieve better image quality and avoid manual parameter tuning, we propose a probabilistic Bayesian approach to recover map and phase images for quantitative susceptibility mapping (QSM), while allowing automatic parameter estimation from undersampled data.

Theory

Sparse prior on the wavelet coefficients of images is interpreted from a Bayesian perspective as sparsity‐promoting distribution. A novel nonlinear approximate message passing (AMP) framework that incorporates a mono‐exponential decay model is proposed. The parameters are treated as unknown variables and jointly estimated with image wavelet coefficients.

Methods

Undersampling takes place in the y‐z plane of k‐space according to the Poisson‐disk pattern. Retrospective undersampling is performed to evaluate the performances of different reconstruction approaches, prospective undersampling is performed to demonstrate the feasibility of undersampling in practice.

Results

The proposed AMP with parameter estimation (AMP‐PE) approach successfully recovers maps and phase images for QSM across various undersampling rates. It is more computationally efficient, and performs better than the state‐of‐the‐art ‐norm regularization (L1) approach in general, except a few cases where the L1 approach performs as well as AMP‐PE.

Conclusion

AMP‐PE achieves better performance by drawing information from both the sparse prior and the mono‐exponential decay model. It does not require parameter tuning, and works with a clinical, prospective undersampling scheme where parameter tuning is often impossible or difficult due to the lack of ground‐truth image.
Retrospective study on the safety of COVID‐19 vaccination in myasthenia gravis
Authors: Urra Pincheira Alejandra , Alnajjar Sara , Katzberg Hans , Barnett Carolina , Daniyal Lubna , Rohan Ritesh , Bril Vera
Published: June 2022

Introduction/Aim

Given the lack of information on safety of coronavirus disease 2019 (COVID‐19) vaccination in myasthenia gravis (MG) patients, we aimed to review our experience after surveying patients, as part of routine clinical practice, to ensure that advice on safety is accurate.

Methods

We performed a retrospective chart review of MG patients from the Prosserman Family Neuromuscular Clinic at the Toronto General Hospital who received two injections of any COVID‐19 vaccine from February to August 2021. Demographic data were abstracted from the patient medical records. We assessed changes in the severity of MG using the virtual Myasthenia Gravis Impairment Index (vMGII), the simple single question (SSQ), and Patient Acceptable Symptom State (PASS). We also assessed adverse effects after vaccination.

Results

We included 200 patients with a mean age of 64.3 ± 13.9 y, 51.5% were men, and 82% had generalized MG. The vMGII, SSQ, and PASS scores remained stable after each vaccine dose, and at last follow‐up. Of the patients, 60% reported an adverse reaction after the first injection, and 56% after the second. The most common adverse reactions reported were local pain at the injection site, fatigue, headache, and fever.

Discussion

COVID‐19 vaccinations were well tolerated in MG patients and were not associated with worsening severity of their MG. The prevalence of vaccine‐related adverse reactions was the same as in the general population.
Gold Coast criteria expand clinical trial eligibility in amyotrophic lateral sclerosis
Authors: Jewett Gordon , Khayambashi Shahin , Frost Geoffrey S. , Beland Benjamin , Lee Angela , Hodgkinson Victoria , Korngut Lawrence , Chhibber Sameer
Published: June 2022

Introduction/Aims

Consensus criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast consensus criteria are intended to simplify use and increase sensitivity. We aimed to evaluate the potential impact of these criteria on clinical trial eligibility.

Methods

We performed a single‐center, retrospective study of people diagnosed with ALS between 2016 and 2021 to determine the numbers of those meeting Gold Coast, revised El Escorial (rEEC) criteria, and Awaji criteria. We identified the proportion of those who would have been eligible for participation in three major ALS clinical trials if Gold Coast were used in place of rEEC definite/probable criteria. (rEEC D/P).

Results

Two hundred six people with ALS were included in our study. 48.5% met Gold Coast criteria but not rEEC D/P. Using the Gold Coast criteria would result in higher rates of clinical trial eligibility after other inclusion criteria were met: 95.2% vs 42.5% (P < .001) in a phase III study of riluzole; 100% vs 31.0% (P = .002) in a phase III study of edaravone; and 95.6% vs 45.3% (P < .001) in an ongoing phase III study of sodium phenylbutyrate and taurursodiol. The sensitivity of the Gold Coast criteria (96.1%; 95% confidence interval [CI], 92.2%‐98.2%) was significantly higher than that of rEEC D/P (47.6%; 95% CI, 40.6%‐54.6%; for difference, χ2 = 117.6; P < .001).

Discussion

Until robust biomarkers are available to diagnose ALS, consensus diagnostic criteria remain necessary. Gold Coast criteria would expand research and clinical trial eligibility and improve external validity of clinical trial results.