bluuebunny/crossref_metadata_2025 huggingface dataset:
Tillage and manure effects on runoff nitrogen and phosphorus losses from frozen soils
Authors: Prasad Laxmi R. , Thompson Anita M. , Arriaga Francisco J. , Vadas Peter A.
Published: September 2022

In cold regions, nutrient losses from dairy agroecosystems are a longstanding and recurring problem, especially when manure is applied during winter over snow‐covered frozen soils. This study evaluated two tillage (fall chisel tillage [CT] and no‐tillage [NT]) and three manure‐type management treatments (unmanured control, liquid manure [<5% solids], and solid manure [>20% solids]). The liquid and solid manure used in this study were from the same animal species (Bos taurus) and facility. The six management treatments were field tested in south‐central Wisconsin during the winters (November–April) of 2017–2018 and 2018–2019 with a complete factorial design. Seasonal runoff losses were significantly lower from fall CT compared with NT during both seasons. Manure applications (both liquid and solid) on top of snow significantly increased most of the nutrients (NH4+, dissolved reactive phosphorus, total Kjeldahl nitrogen, and total phosphorus) in runoff compared with unmanured control. Irrespective of tillage and multiple runoff events, solid manure was present on the surface for longer periods, potentially releasing nutrients each time it interacted with runoff. In contrast, liquid manure infiltrated the snowpack and was partly lost with snowmelt and infiltrated soil depending upon soil frost and surface conditions. Overall, results indicate that wintertime manure applications over snow‐covered frozen soils pose a risk of nutrient loss irrespective of tillage and manure type, but in unavoidable situations, prioritizing tillage × manure type combination can help reduce losses.
The combined effects of salinity and ammonia on the growth behavior, stress‐related markers, and hepato‐renal function of common carp (Cyprinus carpio)
Authors: Dawood Mahmoud A. O. , Sewilam Hani
Published: September 2022

One of the most critical factors affecting aquaculture efficiency is the capability of releasing ammonia from the water. By applying a high salinity strategy, this study provides a prompt approach for removing high ammonia levels and relieving its adverse impacts on common carp. The study investigated five groups with triplicates where the control was kept with fresh water, and the remaining four groups stressed with different salinity levels (5, 10, 15, and 20 ppt) for 8 weeks. Then fish were exposed to unionized ammonia (NH3) stress (0.5 ppm) for 6 h. The final weight (FBW) and weight gain (WG) showed lower values in fish stressed with 15 and 20 ppt salinity levels than fish reared in 0 and 5 ppt salinity levels (p < 0.05). The lowest FBW and WG and the highest feed conversion ratio were shown in fish grown in 20 ppt (p < 0.05). The survival rate was markedly lowered by 15 and 20 ppt salinity levels (p < 0.05), while no significant differences were observed among 0, 5, and 10 ppt salinity levels (p > 0.05). Liver condition‐related indices (alanine aminotransferase, aspartate aminotransferase, and alanine aminotransferase) were markedly increased in fish grown in 15 and 20 ppt before or after ammonia stress (p < 0.05). The results showed higher creatinine levels in fish raised in 15 and 20 ppt than the remaining salinity levels, with the highest value in fish of 20 ppt salinity before and after ammonia stress (p < 0.05). Markedly the blood glucose and cortisol levels were upraised in fish reared in 10, 15, and 20 ppt before and after ammonia stress (p < 0.05). The glucose level was not significantly different in fish reared in 5 ppt than 0 and 10 ppt salinity levels (p < 0.05). Generally, the blood glucose and cortisol levels were decreased markedly after ammonia stress than before ammonia stress (p < 0.05). Interestingly, total protein, albumin, and globulin levels were increased in common carp reared in different salinity levels after ammonia stress (p < 0.05). In conclusion, ammonia toxicity combined with high salinity resulted in a regulatory effect on the hepato‐renal function and stress‐related markers in common carp.
Evaluation of the usefulness of costovertebral angle tenderness in patients with suspected ureteral stone
Authors: Higuchi Hiroyasu , Harada Taku , Hiroshige Juichi
Published: September 2022

Background

The usefulness of costovertebral angle (CVA) tenderness for the diagnosis of a suspected ureteral stone remains controversial.

Methods

This single‐center, retrospective, observational study included patients aged 16–64 years with acute‐onset unilateral lower back pain or abdominal pain. The diagnostic accuracy of CVA tenderness was investigated.

Results

In total, 132 patients met the criteria; 80 were diagnosed with ureteral stones. The sensitivity and specificity of CVA tenderness were 0.65 and 0.50, respectively; positive and negative likelihood ratios were 1.3 and 0.7, respectively.

Conclusions

CVA tenderness cannot be used as a single diagnostic indicator to confirm or exclude ureteral stone diagnosis.
Arylpyrazole as selective anti‐enterococci; synthesis and biological evaluation of novel derivatives for their antimicrobial efficacy
Authors: Sayed Ahmed M. , Abutaleb Nader S. , Kotb Ahmed , Ezzat Hany G. , Seleem Mohamed N. , Mayhoub Abdelrahman S. , Elsebaie Mohamed M.
Published: September 2022

Exploring the structure–activity relationships (SAR) of a new set of phenylpyrazoles unveiled a potential anti‐enterococcus lead compound 12. The benzofuran moiety linked to the phenylpyrazole 12 was 32 times better than vancomycin against Enterococcus faecalis ATCC 51299. Besides, compound 12 is expected to have an excellent oral bioavailability according to the in silico studies. Of SAR analysis, we found that the benzofuran side chain was essential for the activity. Changing the benzofuran with either benzothiophene, phenyl, pyridinyl, tolyl, or naphthyl reduces/nullifies the pharmacological action. Besides the anti‐enterococcal activity, derivatives 4 and 6 can be used to develop new broad‐spectrum antibiotics as they exhibited activity against the wild‐type highly virulent Escherichia coli isolate. Moreover, compound 13 was proved to show antifungal activity (MIC = 4 μg/ml) against the Candida albicans SS5314 (wild type). Finally, the in silico analysis showed that those compounds have good profiles regarding the absorption, distribution, metabolism, and excretion studies, drug‐likeness and pharmacokinetics properties.
Co‐operative visible‐light and Cu/Cu2O@g‐C3N4 catalysis towards Hantzsch/Biginelli synthesis of dihydro‐pyridine/pyrimidine
Authors: Singh Puneet K. , Khuntey Bhushashi , Bhardiya Smita R. , Singh Manorama , Rai Vijai K. , Rai Ankita
Published: September 2022

Herein, Cu/Cu2O@g‐C3N4 catalyzed direct Hantzsch and Biginelli protocols are reported for the synthesis of 1,4‐dihydropyridines and 1,4‐dihydropyrimidines, respectively. The reactions were carried out in the presence of visible light at room temperature via sequential activation of 1,3‐diketones and cyclodehydration steps to afford the target products in good to excellent yield (84–97%). Salient features of the developed methodology are operational simplicity, mild reaction conditions, low catalyst loading, no use of column chromatography, and reusability of catalyst up to five times with no significant loss of catalytic activity.
Perspectives of healthcare providers on implementation of long‐acting cabotegravir plus rilpivirine in US healthcare settings from a Hybrid III Implementation‐effectiveness study (CUSTOMIZE)
Authors: Czarnogorski Maggie , Garris Cindy P. , Dalessandro Marybeth , D'Amico Ronald , Nwafor Toyin , Williams Will , Merrill Deanna , Wang YuanYuan , Stassek Larissa , Wohlfeiler Michael B. , Sinclair Gary I. , Mena Leandro A. , Thedinger Blair , Flamm Jason A. , Benson Paul , Spreen William R.
Published: September 2022

Introduction

CUSTOMIZE evaluated the implementation of long‐acting (LA) cabotegravir + rilpivirine, a novel healthcare provider–administered injectable antiretroviral therapy regimen, in diverse US healthcare settings. Findings from staff‐study participants (SSPs) through 12 months of implementation are reported.

Methods

CUSTOMIZE was a phase IIIb, 12‐month, single‐arm, hybrid III implementation‐effectiveness study conducted from July 2019 to October 2020 at eight US clinics of five clinic types: private practice (n = 2), federally qualified health centre (n = 2), university (n = 2), AIDS Healthcare Foundation (n = 2) and health maintenance organization (n = 1). Eligible patient participants received monthly cabotegravir + rilpivirine LA injections after a 1‐month oral lead‐in. At baseline, month 4 and month 12, SSPs (n = 3 each per clinic), including physicians, nurses or injectors, and administrators, completed quantitative surveys and semi‐structured interviews to assess implementation outcomes (acceptability, appropriateness and feasibility of intervention measures), programme sustainability and SSP perceptions of, attitudes towards, and expectations for cabotegravir + rilpivirine LA. Month 12 data collection occurred during the COVID‐19 pandemic.

Results

In surveys, SSPs reported high mean total scores for acceptability, appropriateness and feasibility of cabotegravir + rilpivirine LA implementation at baseline (4.43, 4.52 and 4.38 of 5, respectively) and month 12 (4.45, 4.61 and 4.46 of 5, respectively), regardless of clinic type. At month 12, SSPs were positive about the implementation sustainability (mean Program Sustainability Assessment Tool score, 5.83 out of 7). At baseline, SSPs’ top concern was patients’ ability to maintain monthly appointments (81%); at month 12, 39% had this concern. The proportion of SSPs reporting patient injection pain or soreness as a barrier was consistent at month 12 versus baseline (48% vs. 46%). Most (78%) SSPs reported optimal implementation of cabotegravir + rilpivirine LA in their clinics was achieved in 1–3 months. In interviews, SSP‐reported strategies for successful implementation included teamwork, using a web‐based treatment planner and having a designated person to track appointment scheduling. In month 12 interviews, SSP‐reported structural changes needed for implementation included changing clinic hours and purchasing refrigerators.

Conclusions

In CUSTOMIZE, cabotegravir + rilpivirine LA was successfully implemented across a range of US healthcare settings. Barriers were mitigated with minor process adjustments.
Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency
Authors: Rybova Jitka , Kuchar Ladislav , Sikora Jakub , McKillop William M. , Medin Jeffrey A.
Published: September 2022

Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. Acid ceramidase deficiency results in lipid accumulation in many tissues and leads to the development of Farber disease (FD). Typical manifestations of classical FD include formation of subcutaneous nodules and joint contractures as well as the development of a hoarse voice. Healthy skin depends on a unique lipid profile to form a barrier that confers protection from pathogens, prevents excessive water loss, and mediates cell–cell communication. Ceramides comprise ~50% of total epidermis lipids and regulate cutaneous homeostasis and inflammation. Abnormal skin development including visual skin lesions has been reported in FD patients, but a detailed study of FD skin has not been performed. We conducted a pathophysiological study of the skin in our mouse model of FD. We observed altered lipid composition in FD skin dominated by accumulation of all studied ceramide species and buildup of abnormal storage structures affecting mainly the dermis. A deficiency of acid ceramidase activity also led to the activation of inflammatory IL‐6/JAK/signal transducer and activator of transcription 3 and noncanonical NF‐κB signaling pathways. Last, we report reduced proliferation of FD mouse fibroblasts and adipose‐derived stem/stromal cells (ASC) along with impaired differentiation of ASCs into mature adipocytes.
Development of a multi‐recombinase polymerase amplification assay for rapid identification of COVID‐19, influenza A and B
Authors: Liang Li‐Guo , Zhu Miao‐jin , He Rui , Shi Dan‐Rong , Luo Rui , Ji Jia , Cheng Lin‐Fang , Lu Xiang‐Yun , Lu Wei , Liu Fu‐Ming , Wu Zhi‐Gang , Wu Nan‐Ping , Chen Hang , Chen Zhe , Yao Hang‐Ping
Published: September 2022

The coronavirus disease 2019 (COVID‐19) pandemic caused extensive loss of life worldwide. Further, the COVID‐19 and influenza mix‐infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real‐time reverse‐transcription PCR (RT‐PCR) assay for early diagnosis of COVID‐19 was developed, but detection was time‐consuming (4–6 h). To improve the diagnosis of COVID‐19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), the causative agent of COVID‐19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA‐dependent‐RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS‐CoV‐2 were selected, and specific primers were designed. We validated our method using SARS‐CoV‐2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID‐19 and Influenza A/B (RT‐PCR‐verified) positive patients. The method could detect SARS‐CoV‐2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID‐19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS‐CoV‐2, H1N1, H3N2 and influenza B, and adapted for point‐of‐care (POC) detection of a broad range of infectious pathogens in resource‐limited settings.
Regional winds over the Iberian Peninsula (Cierzo, Levante and Poniente) from high‐resolution COSMO‐REA6 reanalysis
Authors: Ortega María , Sánchez Enrique , Gutiérrez Claudia , Molina María Ofelia , López‐Franca Noelia
Published: September 2022

Cierzo in the Ebro Valley and Levante and Poniente in the Strait of Gibraltar are three of the main winds over the Iberian Peninsula. However, their study is difficult due to the limited amount of observational data and available literature. In addition, current reanalysis products do not usually have sufficient resolution, generally greater than 10 km, to capture the orographic characteristics of these winds. In this study we explore the ability of high‐resolution COSMO‐REA6 reanalysis (6 km, 0.055°) to describe Cierzo, Levante and Poniente using HadISD observational data validation whenever it was possible. A numerical definition according to the characteristics of these winds is proposed through speed and directional range thresholds. Regional winds statistics, annual cycles, wind roses and covered areas are calculated. The results show a reasonable agreement between reanalysis and observations, with an annual average of 95 Cierzo days, and around 80 Levante and Poniente days for the whole period. These windy days typically extend around 21,000 km2 (or 600 reanalysis cells). Both extension and number of days present strong annual cycles and interannual variability. Several weather regimes associated to those regional wind days are obtained, in agreement with other comparable studies. Therefore, the study shows the capability of the high‐resolution COSMO‐REA6 reanalysis to capture and describe regional winds such as Cierzo, Levante and Poniente.
Assessment of hot weather seasonal temperatures over India using Monsoon Mission Coupled Forecasting System hindcasts
Authors: Rohini P. , Rajeevan M. , Rao Suryachandra A. , Pillai Prasanth A.
Published: September 2022

The present study evaluates the skill of seasonal forecasts of temperatures over India during April to June using the Monsoon Mission Coupled Forecasting System (MMCFS) model hindcasts, which are initialized with February initial conditions. Model hindcast data of 1981–2017 period have been used for the analysis. The India Meteorological Department (IMD) gridded temperature dataset has been used for model verifications. The MMCFS model captures the annual cycle of temperatures reasonably well, but with a higher mean and smaller variability compared to observations. The model hindcasts show a significant skill for seasonal forecasts of temperatures over most of northwest and central India. Empirical Orthogonal Function (EOF) analysis suggests that the model captures temporal and spatial characteristics of different modes of maximum temperatures but with less accuracy. The model teleconnections of maximum temperatures with Indian Ocean sea surface temperatures (SSTs) and El Niño–Southern Oscillation (ENSO) are weakly represented. The model is also found capable of predicting the spatial distribution of heat wave characteristics such as heat wave frequency (HWF) and heat wave duration (HWD) reasonably well. The present study suggests that the MMCFS Model can be used to generate a useful outlook of hot weather seasonal temperatures and heat waves over India.
Study of the efficiency of technical grade nonionic surfactants
Authors: Cattelaens Frederike , Myrdek Thomas
Published: September 2022

Parameters concerning the microemulsion phase behavior of nonionic surfactants of the alkyl polyglycol ether type have extensively been investigated in the last years. By studying these, essential parameters for future applications can be determined. Especially in the field of enhanced oil recovery, lubricants, and cosmetic applications these parameters are of special interest. In this work, the influence of technical grade nonionic surfactants on the phase behavior and the resulting surfactant efficiency has been studied. For this, the alkyl chain length, the degree, type, and order of alkoxylation of the surfactant have been varied. The investigation of these parameters has been conducted by measuring the phase behavior via the Kahlweit fish diagram. It has been found that varying the C‐chain length has a great impact on the efficiency, whereas the influence of the ethoxylation degree is minor. By the introduction of propylene oxide, the efficiency has been improved significantly. Additionally, it is important to have the right order of alkoxylation. If the fatty alcohol is first ethoxylated and afterwards propoxylated the efficiency is significantly decreased.
Quantification of 16 cephalosporins in the aquatic environment by liquid chromatography‐tandem mass spectrometry
Authors: Kaddah Mohamed M. Y. , Al‐Dokhmaisy Emad H. , Mansour Basem , Daabees Hoda G. , Kamal Miranda F.
Published: September 2022

Antimicrobial agents are essential to protect human and animal health. During the coronavirus disease 2019 pandemic, antimicrobials such as cephalosporins were widely used as prophylactics and to prevent bacterial co‐infection. Undoubtedly, the prevalence of antibiotics in the aquatic environment will ultimately affect the degree of resistance against these bacteria in animals and the environmental systems. In order to monitor 16 cephalosporins in the aquatic environment, we developed a new liquid chromatography‐tandem mass spectrometry method that functioned simultaneously under positive and negative electrospray ionization switching modes. The chromatographic separation has been implemented using a pentafluorophenyl propyl column kept at 40°C. The limits of detection and quantitation for the studied cephalosporins ranged from (8 × 10−4) to (7.11 × 10−2) ng/ml and from (2.61 × 10−3) to (2.37 × 10−1) ng/ml, respectively. The percent extraction efficiency (apparent recovery) and relative standard deviations for the analyzed cephalosporins ranged from 61.69% to 167.67% and 2.45% to 13.48%, respectively. The overall findings showed that the effluent from the wastewater treatment plants that receive wastewater from pharmaceutical factories had a higher detected amount of cephalosporins than that of domestic sewage. Moreover, seven cephalosporins, including cefuroxime, ceftazidime, cefradine, cefprozil, cefixime, cefalexin, and cefadroxil (0.68–105.45 ng/L) were determined in the aquatic environment.
Adjusted dose regimens in dupilumab treatment for atopic dermatitis: Daily practice experiences
Authors: Olydam Jill I. , de Wijs Linde E. M. , Nijsten Tamar E. C. , van Rosmalen Joost , Hijnen Dirk Jan
Published: September 2022

Background

Clinical trials with dupilumab in atopic dermatitis (AD) patients showed a trend towards better effectiveness with a weekly or biweekly dosing interval, compared with extended dosing intervals. However, literature about adjusted dose regimens in daily practice is lacking.

Objectives

To evaluate adjusted dosing intervals of dupilumab for AD in daily practice.

Methods

An observational, longitudinal cohort study was conducted in AD patients who started dupilumab treatment in daily practice. Dosing intervals were adjusted upon shared decision making between physicians and patients in daily practice, without strict criteria. Disease courses of patients with shortened or extended dosing intervals were illustrated using spaghetti plots. In addition, data of patients who were treated with standard or extended dosing intervals were analysed using linear mixed effect (LME) models to determine the estimated effectiveness of extended dosing regimens.

Results

In total, 180 AD consecutive patients treated with dupilumab in daily practice were included in our study. Patients with an extended dosing interval (n = 28) had relatively low Eczema Area and Severity Index (EASI) scores at the time of interval adjustment (range: 0−7) and the majority of patients showed continuous effectiveness after adjustment. In patients with a shortened dosing interval (n = 26), the scores at the time of adjustment were more widespread (range: 0−34) and follow‐up showed variable disease courses. Based on the LME model, we found an overall continuous improvement of EASI scores in time, in patients with a regular and extended interval.

Conclusions

Patients with extended dosing intervals showed sustained effectiveness, similar to patients with standard dosing intervals. The effects of shortened intervals on disease severity could not be adequately analysed due to methodological limitations in this retrospective study.
Transformation of dissolved organic matter by two Indo‐Pacific sponges
Authors: Hildebrand Tabea , Osterholz Helena , Bunse Carina , Grotheer Hendrik , Dittmar Thorsten , Schupp Peter J.
Published: September 2022

Dissolved organic matter (DOM) is the largest organic carbon reservoir in the ocean and an integral component of biogeochemical cycles. The role of free‐living microbes in DOM transformation has been studied thoroughly, whereas little attention has been directed towards the influence of benthic organisms. Sponges are efficient filter feeders and common inhabitants of many benthic communities circumglobally. Here, we investigated how two tropical coral reef sponges shape marine DOM. We compared bacterial abundance, inorganic and organic nutrients in off reef, sponge inhalant, and sponge exhalant water of Melophlus sarasinorum and Rhabdastrella globostellata. DOM and bacterial cells were taken up, and dissolved inorganic nitrogen was released by the two Indo‐Pacific sponges. Both sponge species utilized a common set of 142 of a total of 3040 compounds detected in DOM on a molecular formula level via ultrahigh‐resolution mass spectrometry. In addition, species‐specific uptake was observed, likely due to differences in their associated microbial communities. Overall, the sponges removed presumably semi‐labile and semi‐refractory compounds from the water column, thereby competing with pelagic bacteria. Within minutes, sponge holobionts altered the molecular composition of surface water DOM (inhalant) into a composition similar to deep‐sea DOM (exhalent). The apparent radiocarbon age of DOM increased consistently from off reef and inhalant to exhalant by about 900 14C years for M. sarasinorum. In the pelagic, similar transformations require decades to centuries. Our results stress the dependence of DOM lability definition on the respective environment and illustrate that sponges are hotspots of DOM transformation in the ocean.
R&D investment under incomplete markets
Authors: Hu Fan , Wu Yaoyao
Published: September 2022

Entrepreneurs often face undiversifiable idiosyncratic risks from their R&D investments. We extend the real options model of R&D to an incomplete markets environment. We find the effect of market incompleteness on R&D investment is ambiguous. With low technological uncertainty, the agent under incomplete markets over‐investment in R&D. However, market incompleteness leads to under‐investment in R&D when the technological uncertainty is high.
Mathematical analysis of impulsive fractional differential inclusion of pantograph type
Authors: Agarwal Ravi P. , Rahman Ghaus Ur , Muhsina
Published: September 2022

In this article, we formulate fractional differential inclusion of pantograph type (IFDIP), incorporating impulsive behavior of the solution. The boundary conditions taken into account are nonlocal in nature. We will consider the convex problem and prove the Filippov–Wazewski‐type theorem. Moreover, existence of solution, uniqueness of a solution, and the topological properties of the solution's set will be examined for the problem under consideration. In the second part, the study will be confined to the second‐order impulsive fractional differential equation of pantograph type. For certain geometric characteristics of the solution's set, Aronszajn–Browder–Gupta‐type results will be explored for the newly introduced differential equation. Also, it will prove the existence of solution for the first‐order fractional differential equation of pantograph type having impulsive behavior of the solution.
Pre‐treatment analysis of non‐rigid variations can assist robust intensity‐modulated proton therapy plan selection for head and neck patients
Authors: Zhang Ying , Alshaikhi Jailan , Amos Richard A. , Tan Wenyong , Anaya Virginia Marin , Pang Yaru , Royle Gary , Bär Esther
Published: September 2022

Purpose

To incorporate small non‐rigid variations of head and neck patients into the robust evaluation of intensity‐modulated proton therapy (IMPT) for the selection of robust treatment plans.

Methods

A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone‐beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non‐rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3‐field to 5‐field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT.

Results

Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D) of parotid 11.87 Gy, increase in max dose (D) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D by 4.88 Gy, increase in brainstem D by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low‐risk CTV.

Conclusion

This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.
Motion resilience of the balanced steady‐state free precession geometric solution
Authors: Hoff Michael N. , Xiang Qing‐San , Cross Nathan M. , Hippe Daniel , Andre Jalal B.
Published: September 2022

Purpose

Many MRI sequences are sensitive to motion and its associated artifacts. The linearized geometric solution (LGS), a balanced steady‐state free precession (bSSFP) off‐resonance signal demodulation technique, is evaluated with respect to motion artifact resilience.

Theory and Methods

The mechanism and extent of LGS motion artifact resilience is examined in simulated, flow phantom, and in vivo clinical imaging. Motion artifact correction capabilities are decoupled from susceptibility artifact correction when feasible to permit controlled analysis of motion artifact correction when comparing the LGS with standard and phase‐cycle‐averaged (complex sum) bSSFP imaging.

Results

Simulations reveal that the LGS demonstrates motion artifact reduction capabilities similar to standard clinical bSSFP imaging techniques, with slightly greater resilience in high SNR regions and for shorter‐duration motion. Flow phantom experiments assert that the LGS reduces shorter‐duration motion artifact error by ∼24%–65% relative to the complex sum, whereas reconstructions exhibit similar error reduction for constant motion. In vivo analysis demonstrates that in the internal auditory canal/orbits, the LGS was deemed to have less artifact in 24%/49% and similar artifact in 76%/51% of radiological assessments relative to the complex sum, and the LGS had less artifact in 97%/81% and similar artifact in 3%/16% of assessments relative to standard bSSFP. Only 2 of 63 assessments deemed the LGS inferior to either complex sum or standard bSSFP in terms of artifact reduction.

Conclusion

The LGS provides sufficient bSSFP motion artifact resilience to permit robust elimination of susceptibility artifacts, inspiring its use in a wide variety of applications.
Accelerated two‐dimensional phase‐contrast for cardiovascular MRI using deep learning‐based reconstruction with complex difference estimation
Authors: Oscanoa Julio A. , Middione Matthew J. , Syed Ali B. , Sandino Christopher M. , Vasanawala Shreyas S. , Ennis Daniel B.
Published: September 2022

Purpose

To develop and validate a deep learning‐based reconstruction framework for highly accelerated two‐dimensional (2D) phase contrast (PC‐MRI) data with accurate and precise quantitative measurements.

Methods

We propose a modified DL‐ESPIRiT reconstruction framework for 2D PC‐MRI, comprised of an unrolled neural network architecture with a Complex Difference estimation (CD‐DL). CD‐DL was trained on 155 fully sampled 2D PC‐MRI pediatric clinical datasets. The fully sampled data () was retrospectively undersampled (6–11) and reconstructed using CD‐DL and a parallel imaging and compressed sensing method (PICS). Measurements of peak velocity and total flow were compared to determine the highest acceleration rate that provided accuracy and precision within . Feasibility of CD‐DL was demonstrated on prospectively undersampled datasets acquired in pediatric clinical patients () and compared to traditional parallel imaging (PI) and PICS.

Results

The retrospective evaluation showed that 9 accelerated 2D PC‐MRI images reconstructed with CD‐DL provided accuracy and precision (bias, [95 confidence intervals]) within . CD‐DL showed higher accuracy and precision compared to PICS for measurements of peak velocity (2.8 [, 4.5] vs. 3.9 [, 4.9]) and total flow (1.8 [, 3.4] vs. 2.9 [, 6.9]). The prospective feasibility study showed that CD‐DL provided higher accuracy and precision than PICS for measurements of peak velocity and total flow.

Conclusion

In a retrospective evaluation, CD‐DL produced quantitative measurements of 2D PC‐MRI peak velocity and total flow with error in both accuracy and precision for up to 9 acceleration. Clinical feasibility was demonstrated using a prospective clinical deployment of our 8 undersampled acquisition and CD‐DL reconstruction in a cohort of pediatric patients.
Improving infectious adverse event reporting for children and adolescents enrolled in clinical trials for acute lymphoblastic leukemia: A report from the Children's Oncology Group
Authors: Elgarten Caitlin W. , Thompson Joel C. , Angiolillo Anne , Chen Zhiguo , Conway Susan , Devidas Meenakshi , Gupta Sumit , Kairalla John A. , McNeer Jennifer L. , O'Brien Maureen M. , Rabin Karen R. , Rau Rachel E. , Rheingold Susan R. , Wang Cindy , Wood Charlotte , Raetz Elizabeth A. , Loh Mignon L. , Alexander Sarah , Miller Tamara P.
Published: September 2022

Infections cause substantial morbidity for children with acute lymphoblastic leukemia (ALL). Therefore, accurate characterization of infectious adverse events (AEs) reported on clinical trials is imperative to defining, comparing, and managing safety and toxicity. Here, we describe key processes implemented to improve reporting of infectious AEs on two active phase III Children's Oncology Group (COG) ALL trials. Processes include: (a) identifying infections as a targeted toxicity, (b) incorporation of infection‐specific case report form questions, and (c) physician review of AEs with real‐time data cleaning. Preliminary assessment of these processes suggests improved reporting, as well as opportunities for further improvement.
Closed‐loop recycling of thermoset composites from electric motor assembly process into flexible polyurethane foams
Authors: Couvreur Rachel , Tamrakar Sandeep , Savich Pauline , Mielewski Deborah , Kiziltas Alper
Published: September 2022

Polyurethane foams (PU) are used in many automotive applications due to their durability and sound absorption properties. This paper examines the effects of reusing predominantly silica‐filled thermoset composites as a reinforcing agent when ground to a particle size less than 106 μm (0%, 2.5%, 5%, 7.5% by wt%) on mechanical, physical, thermal, and sound absorption properties of PU foam. Young's modulus improved by 27%, and tensile strength increased by 18% with 7.5% reinforcement. Compression stress improved at 25%, 50%, and 65% strain by 37%, 41%, and 44%, respectively, with the 7.5% filler. Compression modulus increased by 66% with 7.5% filler. The addition of the filler did not impact tensile extension or tear resistance. TGA showed increased thermal stability, and the sound absorption coefficient increased over a spectrum of frequencies. This research demonstrates a promising recycling opportunity for thermoset materials and how Ford Motor Company can create a closed‐loop recycling process from an assembly aid material into another vehicle application.
An artificial neural network and Taguchi prediction on wear characteristics ofKenaf–Kevlarfabric reinforced hybrid polyester composites
Authors: Thimmaiah Sreenivas Huligere , Narayanappa Krishnamurthy , Thyavihalli Girijappa Yashas , Gulihonenahali Rajakumara Arpitha , Hemath Mohit , Thiagamani Senthil Muthu Kumar , Verma Akarsh
Published: September 2022

Fiber‐reinforced composites have found their prominent place in various applications, including aerospace, automobile and marine manufacturing industries, because of outstanding properties obtained during composite preparation. One such aspect of improving the composite property is hybridization, where natural fibers (or both natural and synthetic fibers) are combined to obtain different composite structures for diverse applications. This research aims to hybridize the composite considering Kenaf fabric and Kevlar fabric reinforced in an unsaturated polyester matrix with different proportions. Three different laminate sequences (L1, L2, and L3) were developed by considering the fabric's stacking sequence, weave pattern, and orientation. The composite laminates prepared were tested where Taguchi's method (L9 orthogonal array) and artificial neural network were used to study influencing parameters for tribological behavior of the composite. From the practical information, a prediction model from the artificial neural network is applied to forecast the wear rate of the laminates at a broader range of operating factors beyond and within the test phase. The microstructures of the worn surfaces were investigated from a scanning electron microscope to confirm the wear principle of the laminates under different cases.
Preferences for a non‐invasive prenatal test as first‐line screening for Down Syndrome: A discrete choice experiment
Authors: Sim Wen Shan , Yeo Seow Heong , Choi Christina , Yeo Tai Wai , Lee Jia Jia , Huynh Vinh Anh , Finkelstein Eric Andrew , Ozdemir Semra
Published: September 2022

Objective

To investigate preferences of pregnant women for the characteristics of prenatal testing, and to quantify their willingness‐to‐pay (WTP) for non‐invasive prenatal testing (NIPT) as first‐line screening for Down Syndrome.

Method

A cross‐sectional discrete choice experiment survey including five testing attributes was administered to 192 pregnant women (≤14 weeks' gestation) who were aged ≥21 years in Singapore. We calculated marginal WTP for improvements in testing characteristics and NIPT.

Results

We identified two groups of women with distinct preferences for prenatal testing. Women aged ≥35 years, with at least a university education, and with intention to terminate pregnancy of an affected fetus were more likely to be in the group with higher WTP for improvements in test characteristics. While participants valued increased detection rate and lower screen positive rate associated with NIPT, they also valued no risk of test failure and ability to test for birth defects using standard testing. The participants, on average, were not willing to pay for NIPT over the standard testing as a first‐line screening test.

Conclusions

As a first‐line screening, NIPT was not preferred over standard testing. The prenatal consultations should focus on each testing characteristic equally as our findings show diverse preferences for testing characteristics.
Medicine use in children aged under 12 years—Population survey in Finland
Authors: Kesti Joonas , Saastamoinen Leena , Lavikainen Piia , Sepponen Kati
Published: September 2022

Purpose

To study the prevalence of prescribed and over‐the‐counter (OTC) medicine use in children under 12 years of age in Finland and to examine factors associated with the medicine use.

Methods

A nationwide population survey was carried out in Finland in spring 2018 with a random sample of children under 12 years (n = 8000). A response rate of 24% (n = 1921) was attained. The questionnaire was sent to the child's primary guardian. Current use of prescribed medicines and the use of OTC medicines in the preceding 2 days were the main outcome measures.

Results

Of all the children 19% had used prescribed medicines, 15% OTC medicines, and 31% either prescription or OTC medicines during the preceding 22 days. Children's health related factors were positively associated with prescribed medicine use including fairly good to poor health status, symptoms experienced, and illnesses diagnosed by a physician. The guardian's healthcare education and use of prescribed medicines were also associated with children's prescribed medicine use. Symptoms of illnesses and fairly good health status were found to be associated with childrens' use of OTC medicines.

Conclusions

The use of medicines in children under 12 years of age is quite common in Finland. As expected, children's health‐related factors were associated with medicine use. Also, guardians' healthcare education and the use of prescribed medicines were associated with children's prescription medicine use. Children's medicine use should be continuously monitored and investigated further to identify the reasons leading to appropriate and inappropriate medicine use in children.
SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer
Authors: Lin Rui , Yang Yiping , Wu Eran , Zhou Menghan , Wang Shan , Zhang Qingyun
Published: September 2022

Background

Prostate cancer (PCa) is an age‐related malignancy with a high incidence and mortality rate due to lack of efficacy drugs for its therapy in late castration‐resistant stage. Sirtuin 2 (SIRT2), a NAD+‐dependent protein deacetylase, is associated with age‐related diseases. However, SIRT2 roles in PCa are unclear yet.

Methods

Data of SIRT2 expression were extracted from TCGA cohort and GSE54460 cohort. Realtime quantitative PCR and immunohistochemistry were employed to analyze the expression of SIRT2 in PCa tissues. Cell counting Kit‐8 assay, lentiviral transduction, flow cytometry, transwell experiments, western blot and metabolomic analysis were performed to explore the functions of SIRT2.

Results

SIRT2 exhibited increased expression in castration‐resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Overexpression of SIRT2 promoted cell proliferation, the proportion of S phase, migration and invasion, and reduced apoptosis rate. The increased phosphorylated ERK1/2 indicated the regulation of SIRT2 to cell proliferation, migration and invasion through activation of ERK1/2 pathway. Furthermore, SIRT2 affected cell metabolic profile and induces lactosylceramide production through upregulation of B4GALT5, which further contributes cell migration and invasion.

Conclusions

Our data suggested that SIRT2 is overexpressed in CRPC and NEPC and could promote cell growth and migration through activating ERK1/2 pathway and inducing lactosylceramide production, indicating that SIRT2 has the potential to be a new target for the treatment of PCa.
Berberine ameliorates depression‐like behavior in CUMS mice by activating TPH1 and inhibiting IDO1‐associated with tryptophan metabolism
Authors: Ge Ping‐Yuan , Qu Shu‐Yue , Ni Sai‐jia , Yao Zeng‐Ying , Qi Yi‐Yu , Zhao Xin , Guo Rui , Yang Nian‐Yun , Zhang Qi‐Chun , Zhu Hua‐Xu
Published: September 2022

Berberine, which is a potential antidepressant, exhibits definite efficiency in modulating the gut microbiota. Depressive behaviors in mice induced using chronic unpredictable mild stress (CUMS) stimulation were evaluated by behavioral experiments. The markers of neurons and synapses were measured using immunohistochemical staining. An enzyme‐linked immunosorbent assay was adopted to analyze serum inflammatory cytokines levels and neurotransmitters were evaluated by LC–MS/MS. Untargeted metabolomics of tryptophan metabolism was further performed using LC–MS/MS. The target enzymes of berberine involved in tryptophan metabolism were assayed using AutoDock and GRMACS softwares. Then, antibiotics was utilized to induce intestinal flora disturbance. Berberine improved the depressive behaviors of mice in a microbiota‐dependent manner. Increased neurons and synaptic plasticity were observed following berberine treatment. Meanwhile, berberine decreased serum levels of TNF‐α, IL‐1β, and IL‐4 and increased levels of IL‐10. Moreover, berberine induced retraction of the abnormal neurotransmitters and metabolomics assays revealed that berberine promoted tryptophan biotransformation into serotonin and inhibited the kynurenine metabolism pathway, which was attributed to the potential agonist of tryptophan 5‐hydroxylase 1 (TPH1) and inhibitor of indoleamine 2,3‐dioxygenase 1 (IDO1). In conclusion, berberine improves depressive symptoms in CUMS‐stimulated mice by targeting both TPH1 and IDO1, which are involved in tryptophan metabolism.
NIR‐II Ratiometric Chemiluminescent/Fluorescent Reporters for Real‐Time Monitoring and Evaluating Cancer Photodynamic Therapy Efficacy
Authors: Su Lichao , Chen Yiming , Huo Hongqi , Liao Naishun , Wu Ying , Ge Xiaoguang , Guo Zhiyong , Chen Zhongxiang , Zhang Xuan , Song Jibin
Published: September 2022

The development of probes for early monitoring tumor therapy response may greatly benefit the promotion of photodynamic therapy (PDT) efficacy. Singlet oxygen (1O2) generation is a typical indicator for evaluating PDT efficacy in cancer. However, most existing probes cannot quantitatively detect 1O2 in vivo due to the high reactivity and transient state, and thus have a poor correlation with PDT response. Herein, a 1O2‐responsive theranostic platform comprising thiophene‐based small molecule (2SeFT‐PEG) and photosensitizer Chlorin e6 (Ce6) micelles for real‐time monitoring PDT efficacy is developed. After laser irradiation, the Ce6‐produced 1O2 could simultaneously kill cancer and trigger 2SeFT‐PEG to produce increased chemiluminescence (CL) and decreased fluorescence (FL) signals variation at 1050 nm in the second near‐infrared (NIR‐II, 950–1700 nm) window. Significantly, the ratiometric NIR‐II CL/FL imaging at 1050 nm could effectively quantify and monitor the concentration of 1O2 and O2 consumption or recovery, so as to evaluate the therapeutic efficacy of PDT in vivo. Hence, this 1O2 activated NIR‐II CL/FL probe provides an efficient ratiometric optical imaging platform for real‐time evaluating PDT effect and precisely guiding the PDT process in vivo.
Tuning Electronic Structure and Composition of FeNi Nanoalloys for Enhanced Oxygen Evolution Electrocatalysis via a General Synthesis Strategy
Authors: Wang Yong , Nong Wei , Gong Na , Salim Teddy , Luo Mingchuan , Tan Teck Leong , Hippalgaonkar Kedar , Liu Zheng , Huang Yizhong
Published: September 2022

Developing low‐cost and efficient oxygen evolution electrocatalysts is key to decarbonization. A facile, surfactant‐free, and gram‐level biomass‐assisted fast heating and cooling synthesis method is reported for synthesizing a series of carbon‐encapsulated dense and uniform FeNi nanoalloys with a single‐phase face‐centered‐cubic solid‐solution crystalline structure and an average particle size of sub‐5 nm. This method also enables precise control of both size and composition. Electrochemical measurements show that among FexNi(1−x) nanoalloys, Fe0.5Ni0.5 has the best performance. Density functional theory calculations support the experimental findings and reveal that the optimally positioned d‐band center of O‐covered Fe0.5Ni0.5 renders a half‐filled antibonding state, resulting in moderate binding energies of key reaction intermediates. By increasing the total metal content from 25 to 60 wt%, the 60% Fe0.5Ni0.5/40% C shows an extraordinarily low overpotential of 219 mV at 10 mA cm−2 with a small Tafel slope of 23.2 mV dec−1 for the oxygen evolution reaction, which are much lower than most other FeNi‐based electrocatalysts and even the state‐of‐the‐art RuO2. It also shows robust durability in an alkaline environment for at least 50 h. The gram‐level fast heating and cooling synthesis method is extendable to a wide range of binary, ternary, quaternary nanoalloys, as well as quinary and denary high‐entropy‐alloy nanoparticles.