bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose‐escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF‐mutant solid tumors
Authors: Mooradian Meghan J. , Cleary James M. , Giobbie‐Hurder Anita , Darville Lancia N. F. , Parikh Aparna , Buchbinder Elizabeth I. , Cohen Justine V. , Lawrence Donald P. , Shapiro Geoffrey I. , Keer Harold , Chen Helen X. , Ivy Susan Percy , Smalley Keiran S. M. , Koomen John M. , Sullivan Ryan J.
Published: April 2023

Background

Combination BRAF and MEK inhibitor therapy is an active regimen in patients who have BRAF V600E‐mutated tumors; however, the clinical efficacy of this therapy is limited by resistance. Preclinically, the addition of heat shock protein 90 (HSP90) inhibition improves the efficacy of BRAF inhibitor therapy in both BRAF inhibitor–sensitive and BRAF inhibitor–resistant mutant cell lines.

Methods

Cancer Therapy Evaluation Program study 9557 (ClinicalTrials.gov identifier NCT02097225) is a phase 1 study that was designed to assess the safety and efficacy of the small‐molecule HSP90 inhibitor, AT13387, in combination with dabrafenib and trametinib in BRAF V600E/K–mutant solid tumors. Correlative analyses evaluated the expression of HSP90 client proteins and chaperones.

Results

Twenty‐two patients with metastatic, BRAF V600E–mutant solid tumors were enrolled using a 3 + 3 design at four dose levels, and 21 patients were evaluable for efficacy assessment. The most common tumor type was colorectal cancer (N = 12). Dose‐limiting toxicities occurred in one patient at dose level 3 and in one patient at dose level 4; specifically, myelosuppression and fatigue, respectively. The maximum tolerated dose was oral dabafenib 150 mg twice daily, oral trametinib 2 mg once daily, and intravenous AT13387 260 mg/m2 on days 1, 8, and 15. The best response was a partial response in two patients and stable disease in eight patients, with an overall response rate of 9.5% (90% exact confidence interval [CI], 2%–27%), a disease control rate of 47.6% (90% CI, 29%–67%), and a median overall survival of 5.1 months (90% CI, 3.4–7.6 months). There were no consistent proteomic changes associated with response or resistance, although responders did have reductions in BRAF expression, and epidermal growth factor receptor downregulation using HSP90 inhibition was observed in one patient who had colorectal cancer.

Conclusions

HSP90 inhibition combined with BRAF/MEK inhibition was safe and produced evidence of modest disease control in a heavily pretreated population. Additional translational work may identify tumor types and resistance mechanisms that are most sensitive to this approach.
Temperature Ramp Strategy for Regulating Oxygen Vacancies in NiCo2O4 Nanoneedles Towards Enhanced Electrocatalytic Water Splitting
Authors: Rashid Bushra , Mala Kanchan , Ali Mubashir , Rafiq Umer , Quereshi Mehroosa , Ahmad Parvaz , Dar Mudasir , Wahid Malik
Published: April 2023

Oxide‐based systems often suffer from higher overpotentials compared to transition metal sulfides and phosphides for the electrochemical hydrogen evolution reaction (HER). Interestingly, the generation of oxygen vacancy/defect has been seen as the strategy for further activating transition metal oxides (NiCo2O4 as a model system) for an electrochemical water‐splitting process. Herein, we employ the temperature ramp strategy (ambient air calcination) for the generation of oxygen vacancies in NiCo2O4 (NCO) towards the tuning of electrocatalytic enhancements. The NiCo2O4 synthesized at temperature ramp rates of 2 °C/min (NCO‐2), 5 °C/min (NCO‐5), and 10 °C/ min (NCO‐10) depicts contrasting structural features and varying Ni : Co : O surface composition. The decrease in the crystallite size and converse trend in the particle strain were observed from NCO‐2 to NCO‐10. Interestingly, the surface Ni : Co : O ratios of 1 : 0.78 : 3.6, 1 : 0.81 : 3.3, and 1 : 0.69 : 2.8 for NCO‐2, NCO‐5, and NCO‐10, respectively, were observed. The reduced relative oxygen ratio in the latter implies the generation of an ample amount of oxygen vacancy defects. HER performance depicts a consistent trend with enhanced oxygen defect concentration with the overpotential requirement of 700, 647, and 597 mV for NCO‐2, NCO‐5, and NCO‐10, respectively, for the generation of a cathodic current of 25 mA cm−2. The same trend in an electrocatalytic enhancement is observed for other cathodic currents.
Formate Over‐Oxidation Limits Industrialization of Glycerol Oxidation Paired with Carbon Dioxide Reduction to Formate
Authors: van den Bosch Bart , Rawls Brian , Brands Maria B. , Koopman Christel , Phillips Matthew F. , Figueiredo Marta C. , Gruter Gert‐Jan M.
Published: April 2023

Electrocatalytic CO2 reduction processes are generally coupled with the oxidation of water. Process economics can greatly improve by replacing the water oxidation with a more valuable oxidation reaction, a process called paired electrolysis. Here we report the feasibility of pairing CO2 reduction with the oxidation of glycerol on Ni3S2/NF anodes to produce formate at both anode and cathode. Initially we optimized the oxidation of glycerol to maximize the Faraday efficiency to formate by using design of experiments. In flow cell electrolysis, excellent selectivity (up to 90 % Faraday efficiency) was achieved at high current density (150 mA/cm2 of geometric surface area). Then we successfully paired the reduction of CO2 with the oxidation of glycerol. A prerequisite for industrial application is to obtain reaction mixtures with a high concentration of formate to enable efficient downstream separation. We show that the anodic process is limited in formate concentration, as Faraday efficiency to formate greatly decreases when operating at 2.5 M formate (∼10 w%) in the reaction mixture due to over‐oxidation of formate. We identify this as a major bottleneck for the industrial feasibility of this paired electrolysis process.
Electrochemically Activated Expanded Graphite with Tailor‐Made Pores for Magnesium–Organocation Hybrid Batteries
Authors: Mohanty Sangram Keshari , Cao Lei , Choi Byeong Kil , Ryu Ji Heon , Park Jin Kyoon , Yoo Hyun Deog
Published: April 2023

Persisting limitations of lithium‐ion batteries (LIBs) in terms of safety, energy and power density, natural resources, and the price call for expeditious research to develop the “beyond Li‐ion” technologies. In this regard, magnesium–organocation hybrid batteries (MOHB) hold the potential to address the above issues associated with LIBs by utilizing abundant and inexpensive elements of magnesium and carbon for the anode and cathode, respectively. Moreover, magnesium metal anode is highly energy‐dense yet less susceptible to the dendrite formation, enabling safer operation compared to lithium metal anodes. In this study, we targeted to increase the capacity and rate capability of porous carbon cathode of MOHB by generating tailor‐made pores, which were provided by the interlayer accommodation of solvated organic cations with controlled sizes during the electrochemical activation of expanded graphite. Our electrochemically activated expanded graphite can be used as an efficient cathode in MOHB with enhanced kinetics, specific capacitance, and cycle life.
Heterostructural Ni‐Ni0.2Mo0.8N Interface Engineering Boosts Alkaline Hydrogen Electrocatalysis
Authors: An LuLu , Yang Junhao , Zhu Jiang , Yang Chang , Zhao Xu , Wang Deli
Published: April 2023

Exploring efficient and low‐cost bifunctional catalysts for hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) is highly desirable for the achievement of unitized regenerative fuel cells. Herein, a facile method to prepare hetero‐interfacial Ni‐Ni0.2Mo0.8N nanosheets with tailoredd‐band for efficient alkaline hydrogen electrocatalysis is presented. Mechanism studies indicate that interface engineering can downshift thed‐band center of Ni‐Ni0.2Mo0.8N nanosheets due to the electron transfer from Ni to Ni0.2Mo0.8N, which weakens the binding strength of reaction intermediates, thereby boosting the catalytic performance. Relative to pure Ni, Ni‐Ni0.2Mo0.8N nanosheets show a lower overpotential of 83 mV at −10 mA cm−2and good stability during 2,000 cycles for HER. Meanwhile, Ni‐Ni0.2Mo0.8N nanosheets exhibit an improved exchange current density for HOR with a 10.2‐fold enhancement in comparison with that of pure Ni. This work provides valuable insight into the reasonable design of efficient energy‐related electrocatalysts based on the tailoring ofd‐band center by interface engineering.
Acne and its association with internalizing problems
Authors: Hammill Charlotte , Vaillancourt Tracy
Published: April 2023

Acne vulgaris or “acne” is a prevalent and burdensome cutaneous condition that has been linked with unique mental health implications. Clinical (i.e., general and social anxiety, and major depression) and subclinical indicators (e.g., excessive worry, social self‐consciousness, and low self‐esteem) of internalizing disorders have been associated with acne across demographics (e.g., age groups and cultures). Considering the persistent burden of disease associated with these mental health outcomes, our primary aim was to concretely synthesize the relation between acne and internalizing symptoms. A secondary aim was to address the role that combined oral contraceptives and isotretinoin (e.g., Accutane), widely prescribed medical treatments for acne, may play in this relation as both have been linked to depression and anxiety. We discuss practical implications that may strengthen the effective biopsychosocial management of acne for suffering individuals. This review actively upholds and amplifies the call for longitudinal research that integrates the developmental psychology and dermatology literature to effectively treat acne in its entirety, including mental health.
The impact of dopamine receptor D4, temperamental negativity, and household chaos on young twins’ externalizing behaviors
Authors: Jamnik Matthew R. , DiLalla Lisabeth Fisher
Published: April 2023

Biological and genetic factors, as well as contextual influences, contribute to the etiology of externalizing behaviors in children and adolescents. The current project used a longitudinal design to examine how individual vulnerability for externalizing behavior is influenced by the interplay among biological/genetic and environmental factors, and how this occurs across development. We investigated the influence of dopamine receptor D4 genotype (DRD4), child temperament, and household chaos on children's externalizing behaviors using a sample of twins/triplets tested at the ages of 4 and 5 years (n = 229), including a subset of these who were tested again in middle childhood (ages 7–13 years; n = 174). Multilevel linear regression modeling demonstrated that the DRD4‐7repeat genotype, 4‐year‐old negative affectivity, and household chaos at the age of 4 years were related to 5‐year‐old externalizing behaviors. Stability in externalizing behaviors from the age of 5 years to middle childhood was demonstrated. A significant interaction between DRD4 and household chaos showed that children with no 7‐repeat DRD4 alleles had significantly higher levels of externalizing in homes with extremely low levels of parent‐reported chaos, suggesting a “goodness‐of‐fit” pattern of gene–environment interaction. These findings suggest that risk for childhood externalizing behaviors is likely multifaceted and differs across developmental periods.
Loss of myocardial Hey2/Hrt2 function disrupts rightward shift of atrioventricular cushion tissue and causes tricuspid atresia
Authors: Okumura Kazuki , Ioka Tomoko , Sakabe Masahide
Published: April 2023

Background

Endocardial cushion tissue is primordia of the valves and septa of the adult heart, and its malformation causes various congenital heart diseases (CHDs). Tricuspid atresia (TA) is defined as congenital absence or agenesis of the tricuspid valve caused by endocardial cushion defects. However, little is known about what type of endocardial cushion defect causes TA.

Results

Using three‐dimensional volume rendering image analysis, we demonstrated morphological changes of endocardial cushion tissue in developing Hey2/Hrt2 KO mouse embryos that showed malformation of the tricuspid valve, which resembled human TA at neonatal period. In control embryos, atrioventricular (AV) endocardial cushion tissues showed rightward shift to form a tricuspid valve. However, the rightward shift of endocardial cushion tissue was disrupted in Hey2/Hrt2 KO embryos, leading to the misalignment of AV cushions. We also found that muscular tissue filled up the space between the right atrium and ventricle, resulting in the absence of the tricuspid valve. Moreover, analysis using tissue‐specific conditional KO mice showed that HEY2/HRT2‐expressing myocardium may physically regulate the AV shift.

Conclusion

Disruption of rightward cushion movement is an initial cue of TA phenotype, and myocardial HEY2/HRT2 is necessary for the regulation of proper alignment of AV endocardial cushion tissue.
Negative outcomes of novel trophic interactions along mangrove range edges
Authors: Goeke Janelle A. , Foster Emelie M. , Armitage Anna R.
Published: April 2023

Tropicalization is a phenomenon that is changing the structure of ecosystems around the world. Mangrove encroachment is a particular form of tropicalization that may have cascading consequences for resident fauna in subtropical coastal wetlands. There is a knowledge gap regarding the extent of interactions between basal consumers and mangroves along mangrove range edges and the consequences of these novel interactions for consumers. This study focuses on the key coastal wetland consumers, Littoraria irrorata (marsh periwinkle) and Uca rapax (mudflat fiddler crabs), and their interactions with encroaching Avicennia germinans (black mangrove) in the Gulf of Mexico, USA. In food preference assays, Littoraria avoided consuming Avicennia and selectively ingested leaf tissue from a common marsh grass, Spartina alterniflora (smooth cordgrass), a preference that was also previously documented in Uca. The quality of Avicennia as a food source was determined by measuring the energy storage of consumers that had interacted with either Avicennia or marsh plants in the lab and the field. Littoraria and Uca both stored ~10% less energy when interacting with Avicennia, despite their different feeding behaviors and physiologies. The negative consequences of mangrove encroachment for these species at the individual level suggest that there may be negative population‐level effects as encroachment continues. Many studies have documented shifts in floral and faunal communities following mangrove replacement of salt marsh vegetation, but this study is the first to identify physiological responses that may be contributing to these shifts.
A Mechanistic Perspective on the Mechanochemical Method To Reduce Carbonyl Groups with Stainless Steel and Water
Authors: Mokhtar Mennatullah M. , Andersen Joel M. , Kister Ethan A. , Hopkins Jordan X. , Estier Tom , Hamilton Fiona , Guan Hairong , Mack James , Haley Rebecca A.
Published: April 2023

Mechanochemistry through high‐speed ball milling has become an increasingly popular method for performing organic transformations. This newfound interest in high‐speed ball milling is in part driven by the benefit of performing reactions in the absence of solvent. Mechanochemical reactions are often conducted in stainless‐steel vials with stainless‐steel balls. Since stainless steel is made of several readily oxidizable metals (Fe, Cr, and Ni), reduction reactions using water as a hydrogen source were explored using a temperature‐controlled mixer mill. Mechanistic studies suggest that the reduction proceeds via a single electron transfer (SET) pathway, with iron and nickel being essential components for the reaction.
Genotoxicity evaluation of orally administered styrene monomer in mice using comet, micronucleus, and Pig‐a endpoints
Authors: Gollapudi B. Bhaskar
Published: April 2023

Male B6C3F1 mice were administered styrene monomer by oral gavage for 29 consecutive days at dose levels of 0, 75, 150, or 300 mg/kg/day. The highest dose level represented the maximum tolerated dose based on findings in a 28‐day dose range‐finding study, in which the bioavailability of orally administered styrene was also confirmed. The positive control group received ethyl nitrosourea (ENU; 51.7 mg/kg/day) on Study Days 1–3 and ethyl methanesulfonate (EMS; 150 mg/kg/day) on Study Days 27–29 by oral gavage. Approximately 3 h following the final dose, blood was collected to assess erythrocyte Pig‐a mutant and micronucleus frequencies. DNA strand breakage was assessed in glandular stomach, duodenum, kidney, liver, and lung tissues using the alkaline comet assay. The %tail DNA for stomach, liver, lung, and kidney in the comet assay among the styrene‐treated groups was neither significantly different from the respective vehicle controls nor was there any dose‐related increasing trend in any of the tissues; results for duodenum were interpreted to be inconclusive because of technical issues. The Pig‐a and micronucleus frequencies among styrene‐treated groups also did not show significant increases relative to the vehicle controls and there was also no evidence for a dose‐related increasing trend. Thus, orally administered styrene did not induce DNA damage, mutagenesis, or clastogenesis/aneugenesis in these Organization of Economic Co‐operation and Development test guideline‐compliant genotoxicity studies. Data from these studies can contribute to the overall assessment of genotoxic hazard and risk posed to humans potentially exposed to styrene.
Analysis of the operating characteristics of hydrogen PEM fuel cell and battery onelectric vehicle in different driving cycles
Authors: Gürbüz Hüseyin
Published: April 2023

Battery cost, short‐range, and long charging time problems await effective solutions in electric vehicles, where the fight against pollutant emissions from vehicles comes to the fore. In order to solve these issues effectively, vehicles should be equipped with a compatible fuel cell. Therefore, in this study, a hydrogen‐powered PEM fuel cell (PEMFC) and a battery‐powered electric vehicle model were created with GT Suite simulation software. This simulation model vehicle was operated under FTP75, NEDC, and WLTC class 3 driving cycle conditions, and the performance analysis of the PEM fuel cell and the battery was conducted. Along with the contribution of PEMFC, an increase of 113% was calculated for the potential range of Fuel Cell Battery Electric Vehicle (FCBEV) on a single charge. Although the battery provides energy quickly at sudden vehicle accelerations, the fuel cell supplied the necessary energy with a delay. With the PEMFC, a total of 4224.23, 19386.9, and 13596.9 kW of energy were stored by charging the battery, and 0.885, 0.449, and 0.878 kg of hydrogen were consumed in the FTP 75, NEDC, and WLTC tests, respectively. Accordingly, NEDC is the driving cycle that stores the most energy and consumes the least hydrogen.
Determinants of access to clean fuels and technologies for cooking in Africa: A panel autoregressive distributed lag approach
Authors: Onyeneke Robert Ugochukwu , Chidiebere‐Mark Nneka Maris , Ankrah Daniel Adu , Onyeneke Louis Uchenna
Published: April 2023

Clean cooking fuels and technologies remain essential in addressing the climate crises, environmental degradation, deforestation, air pollution, health complications, and poverty. Nevertheless, many countries in Africa lack access to clean fuels and technologies for cooking. The extant literature remains scarce on the determinants of clean cooking fuels and technologies using macroeconomic indicators covering many African countries in a single study. This article addresses this gap using panel data from 38 African countries. The paper shows that rural population, particulate matter emission, and natural resources depletion significantly decreased access to clean cooking fuels and technologies in the long run while the gross domestic product (GDP) per capita significantly increased access to clean cooking fuels and technologies in the long run in Africa. The results show a bi‐causal relationship between clean cooking fuels and technologies and rural population, GDP per capita, natural resource depletion, and particulate emissions damage. Understanding the determinants of clean cooking fuels and technologies will expand insights into addressing challenges associated with particulate emission damages. Governments in Africa should target improvements in GDP per capita, promote advocacies, and advocate for investments to address the limited access to clean cooking fuels and technologies, particularly for the rural poor.
Cannabidiol in the acute phase of febrile infection‐related epilepsy syndrome (FIRES)
Authors: Fetta Anna , Crotti Elisa , Campostrini Elena , Bergonzini Luca , Cesaroni Carlo Alberto , Conti Francesca , Di Pisa Veronica , Gentile Valentina , Mondardini Maria Cristina , Vezzoli Cesare , Giordano Lucio , Cordelli Duccio Maria
Published: April 2023

Febrile infection‐related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long‐term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure‐free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add‐on treatment in the acute phase of FIRES.
High Sensitivity of the Antarctic Rotifer Adineta editae to Metals and Ecological Relevance in Contaminated Site Risk Assessments
Authors: Brown Kathryn E. , Koppel Darren J. , Price Gwilym A. V. , King Catherine K. , Adams Merrin S. , Jolley Dianne F.
Published: April 2023

Anthropogenic activities in Antarctica have led to contamination of terrestrial sites, and soils in ice-free areas have elevated concentrations of metals, particularly around current and historic research stations. Effective management of Antarctic contaminated sites depends on the assessment of risks to a representative range of native terrestrial species. Bdelloid rotifers are an abundant and biodiverse component of Antarctic limnoterrestrial communities and play a key role in nutrient cycling in Antarctic ecosystems. The present study investigates the toxicity of five metals (cadmium, copper, nickel, lead, and zinc) to the endemic bdelloid rotifer Adineta editae, both singly and in metal mixtures. Based on the concentrations tested, zinc was the most toxic metal to survival with a 7-day median lethal concentration (LC50) of 344 µg Zn/L, followed by cadmium with a 7-day LC50 of 1542 µg Cd/L. Rotifers showed high sensitivity using cryptobiosis (chemobiosis) as a sublethal behavioral endpoint. Chemobiosis was triggered in A. editae at low metal concentrations (e.g., 6 µg/L Pb) and is likely a protective mechanism and survival strategy to minimize exposure to stressful conditions. Lead and copper were most toxic to rotifer behavior, with 4-day median effect concentrations (EC50s) of 18 and 27 µg/L, respectively, followed by zinc and cadmium (4-day EC50 values of 52 and 245 µg/L, respectively). The response of rotifers to the metal mixtures was antagonistic, with less toxicity observed than was predicted by the model developed from the single-metal exposure data. The present study provides evidence that this bdelloid rotifer represents a relatively sensitive microinvertebrate species to metals and is recommended for use in contaminant risk assessments in Antarctica. Environ Toxicol Chem 2023;42:1409–1419. © 2023 SETAC
Pleistocene freshwater ostracods from the Homo erectus site at Bilzingsleben, Germany—Review of historic collection and unpublished manuscript material for palaeoenvironmental reconstruction
Authors: Daniel Thomas , Frenzel Peter
Published: April 2023

We provide a review of micropalaeontological research on Ostracoda from the Middle Pleistocene (MIS 11, Holstein interglacial) hominin site Bilzingsleben in Thuringia in Central Germany from 1963 to the 1990s. Samples from four sections inside and six search pits outside the excavation area were investigated and, in total, 49 ostracod species were identified. The ostracod assemblages of the sections mirror the complex and small‐scale palaeoenvironmental evolution of the site from a seeping‐spring to fluviatile, lacustrine and finally seeping‐spring habitat in which a massive tufa layer formed and prevented erosion of the sediments beneath. Pleistocene index fossils are represented by Ilyocypris quinculminata from search pit 3/sample 9933 and Scottia browniana from section 70. Both species indicate the age dating of MIS 11 for the tufa deposit. The results of this study facilitate new insights into site formation processes, enable refinement of the interpretation of the archaeological record and shed light on the question: Does the find‐bearing layer at the Bilzingsleben site contain in situ remains of a camp site of Homo erectus or not? Our results suggest that the site is not unaffected at least.
Willingness to receive COVID‐19 booster dose and its associated factors in Ghana: A cross‐sectional study
Authors: Storph Rebecca Peniel , Essuman Mainprice Akuoko , Duku‐Takyi Ruth , Akotua Albert , Asante Samuel , Armah Richard , Donkoh Irene Esi , Addo Prince Anim
Published: April 2023

Background and Aim

The COVID‐19 booster dose has been cited as an important supplement for the control of the COVID‐19 pandemic due to reports of waning immunity among fully vaccinated persons. Determining factors that would affect its acceptability is necessary for initiating successful vaccination programs. In this study, we aimed to evaluate the factors associated with the acceptability of the COVID‐19 booster dose in Ghana.

Methods

We conducted an online cross‐sectional survey among the public. A self‐administered questionnaire was used to collect information on demographic characteristics, willingness to vaccinate, perceptions toward COVID‐19 vaccines, and trust in the government. Participants provided reasons and sources of advice that may affect their willingness to accept a booster dose. Using IBM SPSS and R Statistic; descriptive, univariate, and multivariate analyses were performed.

Results

Out of 812 respondents, 375 (46.2%) intended to accept the booster dose. Individuals who were males (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.07−2.48), had previously received other forms of vaccination twice (aOR 1.96, 95% CI 1.07−3.57) or in most years (aOR 2.51, 95% CI 1.38−4.57), tested positive for COVID‐19 (aOR 3.46, 95% CI 1.23−10.52), have high trust in government (aOR=1.77, 95% CI: 1.15‐2.74) and had positive perceptions regarding COVID‐19 vaccines (OR = 14.24, 95% CI: 9.28−22.44) were more likely to accept a booster dose. Experiencing side effects from the primer dose (aOR 0.12, 95% CI 0.08−0.18) was associated with reduced acceptance. Concerns about vaccine safety and efficacy were the common reasons impeding willingness, while advice from health professionals would be the most considered.

Conclusion

Low intention to accept the booster dose which is associated with a range of factors including the perception of vaccines and trust in the government, is a cause for concern. Thus, more effort would have to be taken through education and policy interventions to increase booster vaccine acceptability.
Dynamics of Brownian motion and flux conditions on naturally unsteady thermophoretic flow with variable fluid properties
Authors: Kumar Poshala Vijay , Sivakumar Narsu , Shukla Pankaj , Prakash Putta , Durgaprasad Putta , Krishna Chekolu Murali , Raju Chakravarthula Siva Krishnam , Reddy Gottam Viswanatha
Published: April 2023

This work examines the boundary flow difficulties of the past and the heat transfer properties of Blasius and Sakiadis flows under prescribed concentration flux and prescribed heat flux. The nanofluid is also taken into account in this model, along with impacts from Brownian motion and thermophoresis. The modified system governing partial differential equations is numerically solved by using the R‐K method along with the shooting technique. Various values of physical quantities like thermophoresis parameter, Brownian motion parameter, Eckert number, thermal radiation parameter, heat source parameter, and magnetic field parameter along with the were calculated using the temperature, concentration, and velocity profiles. Finally, we demonstrated how the Brownian motion, radiation, and thermophoresis parameters can significantly increase the temperature distributions. The concentration distributions were decelerated with an increase in Brownian motion parameters for both Blasius and Sakiadis cases.
‘The system is unfair’: Uncontrollable attributions for inequality predict more equitable giving in adolescents
Authors: Gonzalez Antonya M. , Koepf Isabella , McLean Kate C.
Published: April 2023

Socioeconomic position is often determined by uncontrollable, structural factors, yet people from the United States tend to attribute wealth and poverty to individual control. However, information about behavioural correlates of such beliefs across development is relatively lacking. Thus, we examined adolescents' reasoning about the causes of inequality in a sample of 599 adolescents from a socioeconomically, ethnically, and racially diverse middle school (grades 6–8). Additionally, early adolescents were presented with two novel groups with an unexplained wealth disparity and given a task in which they could perpetuate or rectify inequality. We found that while adolescents tended to give equitably and rectify the inequality, this outcome was predicted by the type of explanation they gave for societal inequality. Furthermore, participants' socioeconomic status and sexual identity predicted their inequality explanations. These results add to our knowledge of adolescent reasoning about inequality by demonstrating a potential link between attributions for inequality and giving behaviour.
Phonological–semantic flexibility and its role in reading for Chinese kindergarten children
Authors: Fong Cathy Yui‐Chi
Published: April 2023

The present study aimed to examine the role of phonological–semantic flexibility (PSF) in learning to read Chinese. PSF refers to a specific flexibility applied to process the dual linguistic dimensions of words (i.e., sound and meaning). A correlational study (Study 1) was conducted to determine the unique contribution of PSF to three aspects of early reading abilities, including word reading accuracy, word reading fluency and reading comprehension. A total of 190 Chinese kindergarten children were tested on a PSF task and a range of cognitive, linguistic and reading tasks. Results of hierarchical regressions showed that PSF uniquely and significantly contributed to the reading abilities beyond the effects of established cognitive factors (IQ, working memory, inhibition control, and cognitive flexibility) and linguistic factors (syllable skills, morphological skill and vocabulary skill). In the second part, an intervention study (Study 2) was conducted in which two groups of kindergarten children received explicit training on PSF (27 children) and colour–shape flexibility (26 children) respectively. Children in the PSF group showed significantly more improvement in PSF and word reading fluency than the control group. Overall, the present study demonstrated the theoretical and practical importance of PSF for learning to read Chinese.
The comparison of clinical, laboratory, and radiological findings in immunocompromised and immunocompetent patients with COVID‐19: A case‐control study
Authors: Abasian Ladan , Jafari Fatemeh , SeyedAlinaghi SeyedAhmad , Ayoobi Yazdi Niloofar , Daraei Morteza , Ahmadinejad Nasrin , Ghiasvand Fereshteh , Khalili Hosein , Seifi Arash , Meidani Mohsen , Behnezhad Farzane , Ahmadinejad Zahra
Published: April 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19) with significant morbidity and mortality. We reported and compared the clinical and para‐clinical findings of immunocompromised and immunocompetent COVID‐19 patients in a case‐control study at the Imam Khomeini hospital in Tehran, Iran.

Methods

In this study, 107 immunocompromised COVID‐19 patients were recruited as the case group, and 107 immunocompetent COVID‐19 patients as the control group. The participants were matched based on age and sex. The patients' information was retrieved from the hospital records in an information sheet. Associations between clinical and para‐clinical findings with the immune status were assessed using bivariate and multivariate analyses.

Results

The initial pulse rate and recovery time were significantly higher in immunocompromised patients (p < .05). Myalgia, nausea/vomiting, loss of appetite, headache, and dizziness were more frequently reported by the control group (p < .05). Regarding the prescribed medications' duration, Sofosbovir was used longer in the case group, while Ribavirin was used longer in the control groups (p < .05). The most common complication in the case group was acute respiratory distress syndrome, although no major complications were observed in the control group. According to the multivariate analysis, recovery time and Lopinavir/Ritonavir (Kaletra) prescription were significantly higher in the immunocompromised compared to the immunocompetent group.

Conclusion

Recovery time was significantly longer in the immunocompromised compared to the immunocompetent group, which emphasizes the necessity of prolonged care in these high‐risk patients. Also, it is recommended to investigate the effect of novel therapeutic interventions to reduce the recovery time in addition to improving the prognosis of immunodeficient patients with COVID‐19.
Role of adenosine A2a receptor in cancers and autoimmune diseases
Authors: Ye Hongling , Zhao Junqi , Xu Xuejing , Zhang Dagan , Shen Han , Wang Sen
Published: April 2023

Adenosine receptors are P1 class of purinergic receptors that belong to G protein‐coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.
Determining Reliability Requirements and Testing Costs in the Early Stages of Single Use Medical Product Design
Authors: Eubanks Fritz
Published: April 2023

The production of single use medical devices, particularly for home use by patients, continues to grow, and the reliability of these devices is a primary concern for manufacturers and end‐users. The systems engineer tasked with the device development needs methods and tools to establish reliability requirements and provide cost estimates for the testing necessary to show compliance with those requirements. This paper examines methods for determining reliability requirements, the cost of reliability testing for single use medical devices in the design input phase of product development, and how the costs of testing and potential errors can be used to perform trade‐off analysis between reliability tolerance and confidence level.
Verification and Validation of SysML Models
Authors: Hecht Myron , Chen Jaron
Published: April 2023

Model‐based systems engineering depends on correct models. However, thus far, relatively little attention has been paid to ensuring their correctness. This paper describes a methodology for performing verification and validation on models written in SysML. The methodology relies on a catalog of candidate requirements that can be tailored for a specific project. Both manual and automated methods are used to verify and validate these requirements. Manual methods are necessary where knowledge of the domain and other extrinsic characteristics are necessary. Automated methods can be used where the requirements cover the use of SysML. Examples from a public domain SysML model of a satellite are presented to demonstrate application of automated requirements verification.
Framework for Formal Verification of Machine Learning Based Complex System‐of‐Systems
Authors: Raman Ramakrishnan , Gupta Nikhil , Jeppu Yogananda
Published: April 2023

A complex system is characterized by emergence of global properties which are very difficult, if not impossible, to anticipate just from complete knowledge of component behaviors. Emergence, hierarchical organization, and numerosity are some of the characteristics of complex systems. Recently, there has been an exponential increase on the adoption of various neural network‐based machine learning models to govern the functionality and behavior of systems. With this increasing system complexity, achieving confidence in systems becomes even more difficult. Further, ease of interconnectivity among systems is permeating numerous system‐of‐systems, wherein multiple independent systems are expected to interact and collaborate to achieve unparalleled levels of functionality. Traditional verification and validation approaches are often inadequate to bring in the nuances of potential emergent behavior in a system‐of‐systems, which may be positive or negative. This paper describes a novel approach towards application of machine learning based classifiers and formal methods for analyzing and evaluating emergent behavior of complex system‐of‐systems that comprise a hybrid of constituent systems governed by conventional models and machine learning models. The proposed approach involves developing a machine learning classifier model that learns on potential negative and positive emergent behaviors, and predicts the behavior exhibited. A formal verification model is then developed to assert negative emergent behavior. The approach is illustrated through the case of a swarm of autonomous UAVs flying in a formation, and dynamically changing the shape of the formation, to support varying mission scenarios. The effectiveness and performance of the approach are quantified.
Microchip encapsulation andmicroRNA‐7 overexpression of trabecular meshwork mesenchymal stem/stromal cells improve motor function after spinal cord injury
Authors: Mohammadi Parvin , Nadri Samad , Abdanipour Alireza , Mortazavi Yousef
Published: April 2023

Manipulation of stem cells and microencapsulation through microfluidic chips has shown more promising results in treating complex conditions, such as spinal cord injury (SCI), than traditional treatments. This study aimed to investigate the potency of neural differentiation and its therapeutic role in SCI animal model of trabecular meshwork mesenchymal stem/stromal cells (TMMSCs) via miR‐7 overexpression and microchip‐encapsulated. TMMSCs are transduced with miR‐7 via a lentiviral vector (TMMSCs‐miR‐7[+]) and encapsulated in alginate‐reduced graphene oxide (alginate‐rGO) hydrogel via a microfluidic chip. Neuronal differentiation of transduced cells in hydrogel (3D) and tissue cultures plate (2D) was assessed by expressing specific mRNAs and proteins. Further evaluation is being carried out through 3D and 2D TMMSCs‐miR‐7(+ and −) transplantation into the rat contusion SCI model. TMMSCs‐miR‐7(+) encapsulated in the microfluidic chip (miR‐7‐3D) increased nestin, β‐tubulin III, and MAP‐2 expression compared with 2D culture. Moreover, miR‐7‐3D could improve locomotor behavior in contusion SCI rats, decrease cavity size, and increase myelination. Our results revealed that miR‐7 and alginate‐rGO hydrogel were involved in the neuronal differentiation of TMMSCs in a time‐dependent manner. In addition, the microfluidic‐encapsulated miR‐7 overexpression TMMSCs represented a better survival and integration of the transplanted cells and the repair of SCI. Collectively, the combination of miR‐7 overexpression and encapsulation of TMMSCs in hydrogels may represent a promising new treatment for SCI.
Triumphs and challenges in exploiting poly(ADP‐ribose) polymerase inhibition to combat triple‐negative breast cancer
Authors: Wooten Jonathan , Mavingire Nicole , Damar Katherine , Loaiza‐Perez Andrea , Brantley Eileen
Published: April 2023

Poly(ADP‐ribose) polymerase 1 (PARP1) regulates a myriad of DNA repair mechanisms to preserve genomic integrity following DNA damage. PARP inhibitors (PARPi) confer synthetic lethality in malignancies with a deficiency in the homologous recombination (HR) pathway. Patients with triple‐negative breast cancer (TNBC) fail to respond to most targeted therapies because their tumors lack expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Certain patients with TNBC harbor mutations in HR mediators such as breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2), enabling them to respond to PARPi. PARPi exploits the synthetic lethality of BRCA‐mutant cells. However, de novo and acquired PARPi resistance frequently ensue. In this review, we discuss the roles of PARP in mediating DNA repair processes in breast epithelial cells, mechanisms of PARPi resistance in TNBC, and recent advances in the development of agents designed to overcome PARPi resistance in TNBC.
The relationship between having a usual source of primary care and COVID‐19 parental vaccine hesitancy: A nationwide survey among Japanese mothers
Authors: Ie Kenya , Kushibuchi Mio , Tsuchida Tomoya , Motohashi Iori , Hirose Masanori , Albert Steven M. , Kimura Miyako
Published: April 2023

Background

Studies have shown that a usual source of care increases the receipt of child preventive care; however, the relationship between having a usual source of primary care and COVID‐19 parental vaccine hesitancy has not been fully investigated. The aims of this study were to elucidate the characteristics of mothers with a primary care physician, and to explore the relationship between having a usual source of primary care and COVID‐19 parental vaccine hesitancy among mothers in Japan.

Method

This cross‐sectional survey‐based study included 4516 mothers. Using a chi‐square test, the characteristics of mothers with and without a primary care physician were compared. Poisson regression was applied to evaluate the relationship between having a usual source of primary care and parental COVID‐19 vaccine hesitancy.

Results

Mothers with a usual source of primary care had higher education, lower mental distress, had younger children, and were less hesitant toward the child's COVID‐19 vaccination. Vaccine hesitancy was observed in 39.8% of mothers with a usual source of primary care and 45.5% of those without. Poisson regression analysis showed that mothers with a primary care physician were less vaccine‐hesitant (IRR = 0.90, 95% CI = 0.84–0.96) after adjusting for potential confounders.

Conclusion

This study suggested that having a usual source of primary care may contribute to lower parental COVID‐19 vaccine hesitancy. However, the high vaccine hesitancy rate, even among mothers with a usual source of primary care, warrants healthcare providers to be equipped to help parents make informed decisions about vaccination through the continuity of care.
Show, don't tell: Education and physical exposure effects in remanufactured product markets
Authors: Abdulla Huseyn , Abbey James D. , Atalay A. Selin , Meloy Margaret G.
Published: April 2023

We study the effectiveness of two theoretically and practically relevant interventions designed to increase familiarity with and thereby stimulate the appeal of and willingness to pay (WTP) for remanufactured (refurbished) consumer products that are often found repulsive by consumers: (1) educating consumers about the remanufacturing process, (2) providing physical exposure to remanufactured products. We find that education does not cause an increase in the appeal of and WTP for remanufactured consumer products. Providing physical exposure to remanufactured products, relative to text and text‐plus picture or video modalities, significantly increases both the appeal and WTP as a result of increasing perceived quality and decreasing disgust. Sellers can benefit from marketing remanufactured consumer products through physical channels (i.e., brick‐and‐mortar, outlet, showroom stores) as opposed to solely through online channels, which is the common practice among many sellers.
Citation tracking for systematic literature searching: A scoping review
Authors: Hirt Julian , Nordhausen Thomas , Appenzeller‐Herzog Christian , Ewald Hannah
Published: April 2023

Citation tracking (CT) collects references with citation relationships to pertinent references that are already known. This scoping review maps the benefit of and the tools and terminology used for CT in health‐related systematic literature searching. We included methodological studies on evidence retrieval by CT in health‐related literature searching without restrictions on study design, language, or publication date. We searched MEDLINE/Ovid, Web of Science Core Collection, CINAHL/EBSCOhost, LLISFT/EBSCOhost, LISTA/EBSCOhost, conducted web searching via Google Scholar, backward/forward CT of included studies and pertinent reviews, and contacting of experts. Two reviewers independently assessed eligibility. Data extraction and analysis were performed by one reviewer and checked by another. We screened 11,861 references and included 47 studies published between 1985 and 2021. Most studies (96%) assessed the benefit of CT either as supplementary or primary/stand‐alone search method. Added value of CT for evidence retrieval was found by 96% of them. Science Citation Index and Social Sciences Citation Index were the most common citation indexes used. Application of multiple citation indexes in parallel, co‐citing or co‐cited references, CT iterations, or software tools was rare. CT terminology was heterogeneous and frequently ambiguous. The use of CT showed an added value in most of the identified studies; however, the benefit of CT in health‐related systematic literature searching likely depends on multiple factors that could not be assessed with certainty. Application, terminology, and reporting are heterogeneous. Based on our results, we plan a Delphi study to develop recommendations for the use and reporting of CT.