bluuebunny/crossref_metadata_2025 huggingface dataset:
Book review: Govind Kelkar and Dev Nathan. Witch Hunts: Culture Patriarchy and Structural Transformation
Authors: Jassal Smita Tewari
Published: January 2023

Govind Kelkar and Dev Nathan. Witch Hunts: Culture Patriarchy and Structural Transformation (Cambridge University Press, 2020), 272 pages, ₹699. ISBN 9781108490511 (Hardback).
Clinical Image: A Case of Edwards’ Syndrome
Authors: Muppa Vikas , Kar Shrutiprajna , Sahoo Tanushree , Sahoo Sanjukta
Published: January 2023

Edwards’ syndrome (trisomy 18) is a rare autosomal inherited disorder arising from the presence of an extra copy on chromosome 18. It is the second most common polymalformative genetic syndrome following Down syndrome. The most common characteristic features include dysmorphic gestalt, microcephaly, fixed flexion deformity of limbs with overlapping digits, rockerbottom feet, genitourinary and gastrointestinal abnomalities. About 90% of these children have underlying cardiac defects. Intellectual disability is almost always an accompanying feature. The presence and extent of associated anomalies govern the subsequent survival and quality of life. Only 5% of such cases survive beyond childhood.
Examining recent initiatives to ensure labour rights for platform workers in the European Union to tackle the problem of domination
Authors: Buendia Esteban Ricardo M
Published: January 2023

This article discusses how recent European Commission and European Parliament initiatives have taken two paths to protect platform workers from the domination of platforms and norms: clarifying who should have access to labour rights and removing the applicability of EU competition law. It will become clear that all the initiatives of both kinds face significant challenges, hampering their effectiveness in ensuring freedom from domination for platform workers. This article concludes by arguing that the best way to tackle domination of platform workers in the EU would be to put the idea of inequality of bargaining power at the centre of the analysis, making policy initiatives less dependent on elusive definitions and expanding the reach of labour law.
Immunohistochemical analysis of expression of VEGFR2, KIT, PDGFR-β, and CDK4 in canine urothelial carcinoma
Authors: Setyo Laura C. , Donahoe Shannon L. , Shearer Patrick L. , Wang Penghao , Krockenberger Mark B.
Published: January 2023

Urothelial carcinomas (UCs), also known as transitional cell carcinomas, are the most common canine urinary tract neoplasms. Tyrosine kinases (TKs) are enzymes that tightly regulate cell growth and differentiation through phosphorylation. Receptor TK (RTK) inhibitors are currently used to treat UCs. Toceranib phosphate (Palladia; Pfizer) is an RTK inhibitor that blocks the activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor–alpha and –beta (PDGFR-α, -β), FMS-like tyrosine kinase 3, stem cell factor receptor (KIT, kinase inhibitor targeting), and colony stimulating factor receptor. To better understand UCs and validate treatment targets, we performed immunohistochemical staining for RTKs, as well as a novel target, cyclin-dependent kinase 4 (CDK4, a central regulator of the mammalian cell cycle), on formalin-fixed, paraffin-embedded tissues from bladder biopsies from 17 dogs with UCs, 17 dogs with cystitis (diseased controls), and 8 normal dogs (negative controls). Although immunohistochemical scores could not be extrapolated to prognostic value, response to treatment, and outcome of patients with UC, we demonstrated expression of PDGFR-β and VEGFR2 in UCs; all UC samples staining positively for VEGFR2. Minimal positive staining for KIT was noted in the tumor samples. CDK4 staining intensity was significantly weaker in UCs compared with normal and cystitis bladder samples. The intense staining of VEGFR2 in UC cells suggested that VEGFR2 may be of prognostic and/or therapeutic value in dogs with UC. Overexpression of VEGFR2 in UC cells validates this receptor as a treatment target in UC.
Prevalence of Breast Cancer Subtypes Among Different Ethnicities and Bangladeshi Women: Demographic, Clinicopathological, and Integrated Cancer Informatics Analysis
Authors: Islam Diganta , Islam Md. Shihabul , Dorin Sanjida Islam , Jesmin
Published: January 2023

Background:

The molecular subtyping of breast cancer is related to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The present study aimed to systematically analyze the expression, function, and prognostic value of ER, PR, HER2, and their prevalence in different ethnic groups and among Bangladeshi breast cancer (BC) patients.

Method:

This study included 25 BC patients and 25 healthy controls, aged between 25 and 70 years. The study characteristics were compared using the ANOVA and Chi-square tests. Also, the multi-Omics dataset of 775 BC patients from TCGA was analyzed for ER, PR, and HER2 in breast cancer subtypes and compared among different ethnicities.

Results:

For most BD breast cancer cases, the age at diagnosis was ⩾40 years, had only a histopathological diagnosis ( P-value .004), and no history of mammography or other pathological tests. For treatment, had only chemotherapy ( P-value .004) and no hormone therapy ( P-value <.001). The majority of patients (>60%) were of stage-II cancer and TNBC (40%) subtype. The BC ethnicity-stratified data of ER, PR, and HER2 indicated a strong correlation across all ethnicities ( P-value 4.99e−35; P-value 3.79e−18). The subtypes stratified data indicated a higher percentage of Luminal A (58.3%) in Caucasians whereas Luminal B (24.3%) and HER2 (25.2%) subtypes were found higher in Asians and TNBC (36.0%) were found in Africans. However, a significantly higher frequency of TNBC (52.2%) compared to Asians (14.8%) was found in BD patients ( P-value <.001). The overall survival analysis of BC subtypes demonstrated that Luminal B ( P-value .005) and HER2 enriched ( P-value .015) were significantly more aggressive and were dominant in the Asian population.

Conclusion:

A significant association was found between BC subtypes with different ethnicities and Bangladeshi women and these findings might aid in the prevention, management, and raising of awareness against risk factors in the near future.
Antioxidant and Anti-inflammatory Activity of Sea Cucumber (Holothuria scabra) Active Compounds against KEAP1 and iNOS Protein
Authors: Wargasetia Teresa Liliana , Ratnawati Hana , Widodo Nashi , Widyananda Muhammad Hermawan
Published: January 2023

Oxidative stress and inflammation have a role in the development of various diseases. Oxidative stress and inflammation are associated with many proteins, including Kelch ECH associating protein 1 (KEAP1) and inducible nitric oxide synthase (iNOS) proteins. The active compounds contained in Holothuria scabra have antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidant and anti-inflammatory activity of sea cucumber’s active compounds by targeting KEAP1 and iNOS proteins. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activity of H. scabra extract were measured spectrophotometrically. The 3-dimensional (3D) structures of sea cucumber’s active compounds and proteins were obtained from the PubChem and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) databases. Molecular docking was performed using AutoDock Vina software. Molecular dynamics simulations were carried out using Yet Another Scientific Artificial Reality Application (YASARA) software with environmental parameters according to the cell’s physiological conditions. The membrane permeability test was performed using the PerMM web server. The methanol extract of H. scabra had a weak antioxidant activity against DPPH and strong activity against NO radical. Scabraside and holothurinoside G had the most negative binding affinity values when interacting with the active site of KEAP1 and iNOS proteins. Molecular dynamics simulations also showed that both compounds were stable when interacting with KEAP1 and iNOS. However, scabraside and holothurinoside G were difficult to penetrate the cell plasma membrane, which is seen from the high energy transfer value in the lipid acyl chain region of phospholipids. Scabraside and holothurinoside G are predicted to act as antioxidants and anti-inflammations, but in their implementation to in vitro and in vivo study, it is necessary to have liposomes or nanoparticles, or other delivery methods to help these 2 compounds enter the cell.
Hydrological Components and Sediment Yield Response to Land Use Land Cover Change in The Ajora-Woybo Watershed of Omo-Gibe Basin, Ethiopia
Authors: Toma Meseret Bekele , Belete Mulugeta Dadi , Ulsido Mihret Dananto
Published: January 2023

Understanding how watersheds respond to ecological changes and how LULC alteration affects watershed hydrology is crucial for water and soil resource management. LULC changes in the Ajora-Woybo watershed, Ethiopia, have momentously affected the water and soil resources. The researchers aimed to see how LULC changes affect hydrological components (HCs) and sediment yield (SED) in the watershed, both historically and in the future. The Soil and Water Assessment Tool (SWAT2012) and Partial Least Squares Regression (PLSR) models were used to investigate the contribution of each of the LULC classes to achieve the goal. The findings revealed a continual growth of cultivated land, built-up areas, and bare land, and a retreat of shrub land and forest land during the 2000 to 2020 periods, which is expected to continue in the 2035 and 2050 periods. Changes in LULC that happened over the historical era increased yearly surface runoff (23.5%), water yield (5.7%), and sediment yield (23.5%). On the other hand, the observed modifications have reduced lateral flow (12.8%) and groundwater flow (10.9%). Except for the 2020 LULC period, evapotranspiration decreased during the studied years. The future impacts of LULC states are predicted to increase in line with the historical trend. The PLSR results showed that cultivated land and built-up areas had a positive association with surface runoff and sediment yield, but shrub land and forest land had a negative correlation. This highlights the importance of controlling the LULC change as soon as possible to maintain long-term watershed stability.
Investigations of thickness effects on the acoustic characteristics of symmetric and asymmetric airfoils
Authors: Kumar Sujit , Mishra Priyanshu , Narayanan S
Published: January 2023

The present paper provides a detailed acoustic characterization of symmetric and asymmetric NACA airfoils for various thickness ratios to determine the best thickness ratio and geometry which provide lower acoustic radiations with respect to the standard NACA0010 airfoil. The studies are conducted for various t/c values of 0.12, 0.15 and 0.21, where t is the airfoil thickness and c is the airfoil chord. The far-field acoustic emissions are observed to decrease with increase in t/c ratios for both the symmetric and asymmetric airfoils. For all the t/c values and jet velocities studied, the asymmetric airfoils show higher noise reductions from mid to high frequencies as compared to the symmetric ones, which might be due to the reduced transverse velocity fluctuations as a result of the large distortions imparted to oncoming turbulent gust by the formation of the larger stagnation pressure zone. The symmetric airfoils show a maximum reduction up to 3 dB from mid to high frequencies while asymmetric ones show a reduction up to about 5 dB. An empirical expression is developed for the ΔOAPWL as a function of t/c only for both the symmetric and asymmetric airfoils, where ΔOAPWL is the overall sound power reduction level in dB. It reveals that the ΔOAPWL follow a second order polynomial for both the symmetric and asymmetric airfoils at all jet velocities studied. It is observed that thicker (i.e., t/c = 0.21) symmetric and asymmetric airfoils show lower acoustic radiations as compared to the thinner ones for all the emission angles. In general, it is observed that the thinner airfoils show higher directivity as compared thicker ones, albeit they show a common trait of downstream directivity. Further the highest directivity is seen at an emission angle of 67.5° for both the symmetric and asymmetric airfoils. Thus, the present study clearly demonstrates that the airfoils with higher t/c ratios could be considered as the best passive means for achieving substantial reductions of airfoil broadband noise over a wide range of frequencies.
A Statistical Shape Model of Infrarenal Aortic Necks in Patients With and Without Late Type Ia Endoleak After Endovascular Aneurysm Repair
Authors: van Veldhuizen Willemina A. , Schuurmann Richte C. L. , Zuidema Roy , Geraedts Anna C. M. , IJpma Frank F. A. , Kropman Rogier H. J. , Antoniou George A. , van Sambeek Marc R. H. M. , Balm Ron , Wolterink Jelmer M. , de Vries Jean-Paul P. M.
Published: January 2023

Purpose:

Hostile aortic neck characteristics, including short length, severe suprarenal and infrarenal angulation, conicity, and large diameter, have been associated with increased risk for type Ia endoleak (T1aEL) after endovascular aneurysm repair (EVAR). This study investigates the mid-term discriminative ability of a statistical shape model (SSM) of the infrarenal aortic neck morphology compared with or in combination with conventional measurements in patients who developed T1aEL post-EVAR.

Materials and Methods:

The dataset composed of EVAR patients who developed a T1aEL during follow-up and a control group without T1aEL. Principal component (PC) analysis was performed using a parametrization to create an SSM. Three logistic regression models were created. To discriminate between patients with and without T1aEL, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were calculated.

Results:

In total, 126 patients (84% male) were included. Median follow-up time in T1aEl group and control group was 52 (31, 78.5) and 51 (40, 62.5) months, respectively. Median follow-up time was not statistically different between the groups (p=0.72). A statistically significant difference between the median PC scores of the T1aEL and control groups was found for the first, eighth, and ninth PC. Sensitivity, specificity, and AUC values for the SSM-based versus the conventional measurements–based logistic regression models were 79%, 70%, and 0.82 versus 74%, 73%, and 0.85, respectively. The model of the SSM and conventional measurements combined resulted in sensitivity, specificity, and AUC of 81%, 81%, and 0.92.

Conclusion:

An SSM of the infrarenal aortic neck determines its 3-dimensional geometry. The SSM is a potential valuable tool for risk stratification and T1aEL prediction in EVAR. The SSM complements the conventional measurements of the individual preoperative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleak after standard EVAR.

Clinical Impact

A statistical shape model (SSM) determines the 3-dimensional geometry of the infrarenal aortic neck. The SSM complements the conventional measurements of the individual pre-operative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleaks post-EVAR. The SSM is a potential valuable tool for risk stratification and late T1aEL prediction in EVAR and it is a first step toward implementation of a treatment planning support tool in daily clinical practice.
Now is the time to fix the evidence generation system
Authors: Califf Robert M
Published: January 2023

Despite enormous advances in biomedical science, corresponding improvements in health outcomes lag significantly. This is particularly true in the United States, where life expectancy trails far behind that of other high-income countries. In addition, substantial disparities in life expectancy and other health outcomes exist as a function of race, ethnicity, wealth, education, and geographic location. A major reformation of our national system for generating medical evidence—the clinical research enterprise—is needed to facilitate the translation of biomedical research into useful products and interventions. Currently, premarket systems for generating and evaluating evidence work reasonably well, but the postmarket phase is disaggregated and often fails to answer essential questions that must be addressed to provide optimal clinical care and public health interventions for all Americans. Solving these problems will require a focus on three key domains: (1) improving the integration of and access to high-quality data from traditional clinical trials, electronic health records, and personal devices and wearable sensors; (2) restructuring clinical research operations to support and incentivize the involvement of patients and frontline clinicians; and (3) articulating ethical constructs that enable responsible data sharing to support improved implementation. Finally, we must also address the systemic tendency to optimize individual components of the clinical research enterprise without considering the effects on the system as a whole. Overcoming suboptimization by creating incentives for integration and sharing will be essential to achieve more timely and equitable improvement in health outcomes.
Upper limb prostheses: bridging the sensory gap
Authors: Roche Aidan D. , Bailey Zachary K. , Gonzalez Michael , Vu Philip P. , Chestek Cynthia A. , Gates Deanna H. , Kemp Stephen W. P. , Cederna Paul S. , Ortiz-Catalan Max , Aszmann Oskar C.
Published: January 2023

Replacing human hand function with prostheses goes far beyond only recreating muscle movement with feedforward motor control. Natural sensory feedback is pivotal for fine dexterous control and finding both engineering and surgical solutions to replace this complex biological function is imperative to achieve prosthetic hand function that matches the human hand. This review outlines the nature of the problems underlying sensory restitution, the engineering methods that attempt to address this deficit and the surgical techniques that have been developed to integrate advanced neural interfaces with biological systems. Currently, there is no single solution to restore sensory feedback. Rather, encouraging animal models and early human studies have demonstrated that some elements of sensation can be restored to improve prosthetic control. However, these techniques are limited to highly specialized institutions and much further work is required to reproduce the results achieved, with the goal of increasing availability of advanced closed loop prostheses that allow sensory feedback to inform more precise feedforward control movements and increase functionality.
Disappearance of a small unruptured intracranial aneurysm: A case report and brief literature review
Authors: Begley Sabrina L , White Timothy G , Khilji Hamza , Katz Jeffrey , Dehdashti Amir R
Published: January 2023

Disappearing intracranial aneurysms are rare and have not been extensively reported in the literature. They are often small or partially thrombosed and carry a significant risk of recurrence. We discuss a unique case of a 65-year-old woman who presented in 2006 with a subarachnoid hemorrhage and was found to have a ruptured posterior communicating artery and an unruptured P1 aneurysm. Follow-up angiography and imaging showed no changes in the size of a left P1 aneurysm for 11 years (2006–2017). However, in 2021, 15 years after initial presentation, no aneurysm was seen on magnetic resonance angiography, and subsequent digital subtraction angiography in 2022 showed almost complete disappearance of the unruptured P1 aneurysm. Literature review reveals only six reported cases during which a small, unruptured anterior circulation aneurysm disappeared, or regressed on follow-up imaging and no reported cases in the posterior circulation.
Towards an intersectional postcapitalism
Authors: Sutherland Callum
Published: January 2023

In this reply, I reflect on the various ways in which the ‘Fisherian’ spatial imaginaries I develop in the original article can engage conceptually with my respondents’ constructive criticism, as well as posing a range of questions to their variegated postcapitalist concerns. Particular attention is paid to the ways in which Fisher's spatial imaginaries and politics must be brought into closer conversation with intersectional imaginaries of communist futures.
The San Francisco Estuary, USA as a reference section for the Anthropocene series
Authors: Himson Stephen , Williams Mark , Zalasiewicz Jan , Waters Colin N , McGann Mary , England Richard , Jaffe Bruce E , Boom Arnoud , Holmes Rachael , Sampson Sue , Pye Cerin , Berrio Juan Carlos , Tyrrell Genevieve , Wilkinson Ian P , Rose Neil , Gaca Pawel , Cundy Andrew
Published: January 2023

A San Francisco Estuary core was analysed at high resolution to assess its component stratigraphic signatures of the Anthropocene in the form of non-native species, Hg, spheroidal carbonaceous particles, δ13Corg, δ15N, radiogenic materials, and heavy metals. Time series analysis of the core using Ti data provides a chronology to depth 167 cm into the 1960s. Below this, to depth 230 cm, the lowermost part of the core may extend to the 1950s or potentially a little earlier. The earliest anthropogenic marker recorded in the core is the excursion in Hg (beginning at 190 cm) which may denote the early 1960s and is the closest stratigraphic marker in the core to the proposed mid-20th century timing for the onset of the Anthropocene. Biostratigraphical signatures of non-native species arriving in the 1970s–1980s are widespread key markers and are significant tools for the correlation of Anthropocene deposits across the estuary. The absence of signals that indicate pre-1950s deposits precludes the use of the core to mark the Holocene–Anthropocene boundary. However, the core provides an important reference section to demonstrate the palaeontological distinctiveness of Anthropocene series deposits.
The Effect of Social Capital on Outcomes of Global Citizenship among Taiwanese Young Adults: The Mediating Role of Political Self-efficacy
Authors: Liu Chao-Lung , Chung Ming-Lun , Hui Bryant Pui Hung , Li Ho Ching
Published: January 2023

The purpose of this article is to examine the level of social capital and global citizenship in Taiwan. In this study, we argue that high social capital and political self-efficacy promote the outcomes of global citizenship. We review the development of global citizenship education policy and its association with social capital and political self-efficacy. Based on the nationwide survey dataset collected from Taiwanese universitiy students, we carefully examine the relations between social capital, political self-efficacy, and global citizenship. We adopt a multiple mediation analysis with a bootstrapped method to validate our conceptual research model. The results show that there are significant positive relationships between the nine observed variables (i.e., social trust, social proactivity, political self-efficacy and six global citizenship outcomes). In addition, our findings of mediation analysis reveal that social capital, indicated by social trust and social proactivity, indirectly affects the five outcomes of global citizenship through political self-efficacy, except for the outcome of global environmental sustainability. In light of the empirical results, this article also discusses the implications of global citizenship education policy and the formation of sustainable global citizenship.
Antecedents and Consequences of Misinformation Sharing Behavior among Adults on Social Media during COVID-19
Authors: Malik Ammara , Bashir Faiza , Mahmood Khalid
Published: January 2023

Misinformation has been existed for centuries, though emerge as a severe concern in the age of social media, and particularly during COVID-19 global pandemic. As the pandemic approached, a massive influx of mixed quality data appeared on social media, which had adverse effects on society. This study highlights the possible factors contributing to the sharing and spreading misinformation through social media during the crisis. Preferred Reporting Items and Meta-Analysis guidelines were used for systematic review. Anxiety or risk perception associated with COVID-19 was one of the significant motivators for misinformation sharing, followed by entertainment, information seeking, sociability, social tie strength, self-promotion, trust in science, self-efficacy, and altruism. WhatsApp and Facebook were the most used platforms for spreading rumors and misinformation. The results indicated five significant factors associated with COVID-19 misinformation sharing on social media, including socio-demographic characteristics, financial considerations, political affiliation or interest, conspiracy ideation, and religious factors. Misinformation sharing could have profound consequences for individual and society and impeding the efforts of government and health institutions to manage the crisis. This SLR focuses solely on quantitative studies, hence, studies are overlooked from a qualitative standpoint. Furthermore, this study only looked at the predictors of misinformation sharing behavior during COVID-19. It did not look into the factors that could curb the sharing of misinformation on social media platforms as a whole. The study’s findings will help the public, in general, to be cautious about sharing misinformation, and the health care workers, and institutions, in particular, for devising strategies and measures to reduce the flow of misinformation by releasing credible information through concerned official social media accounts. The findings will be valuable for health professionals and government agencies to devise strategies for handling misinformation during public health emergencies.
Land and Water in Rural São Paulo: Case Study of Environmental Inequalities in Brazil
Authors: Martins Rodrigo Constante
Published: January 2023

The governance of environmental resources in rural territories is an issue that has received special attention in recent studies. This article presents research on conflicts in the management of water policies in rural territories in the state of São Paulo, Brazil. The study addresses a case of tensions and conflicts in water governance promoted by River Basin Committees. The case study, carried out in the municipality of Barra Bonita between 2000 and 2010, used qualitative social research techniques, focusing on semistructured interviews, utilizing oral reports, and documentary survey. Based on the results of this research, this article discusses how different agrarian and agricultural contexts reproduce specific forms of inequalities in access to water, thus compromising the promotion of lasting standards of environmental justice at the local level.
A Qualitative Study Exploring Rehabilitant and Informal Caregiver Perspectives of a Challenging Rehabilitation Environment for Geriatric Rehabilitation
Authors: Tijsen Lian M J , Derksen Els W C , Achterberg Wilco P , Buijck Bianca I
Published: January 2023

There is a trend toward formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment in rehabilitation wards. So far, literature about the principles of CRE is scarce. This study aims to explore the opinions of rehabilitants and informal caregivers regarding CRE, through a qualitative study between 2019 and 2020. Three telephone interviews were conducted with informal caregivers, and also 3 focus groups with 15 rehabilitants and 3 informal caregivers, all with recent experience in rehabilitation. Nine themes emerged regarding the rehabilitation process: (1) rehabilitant (attention for resilience, motivation, cognitive and emotional aspects), (2) rehabilitant centered (goal setting, physical and cognitive functioning and coping), (3) informal caregivers (involving and attention for resilience and relation), (4) communication (aligning the rehabilitation process), (5) exercise (increasing intensity by using task-oriented exercise, patient-regulated exercise, and group training), (6) peer support (learning experiences and recognition), (7) daily schedule (influence on the planning and activities outside therapy), (8) nutrition (energy for rehabilitation), and (9) eHealth (makes rehabilitation more challenging and fun). Regarding organizational processes, 4 themes were identified: (1) environmental aspects (single bedrooms, shared room for activities and therapy options on the ward), (2) staff aspects (small team with an emphatic supportive and motivating attitude), (3) organizational aspects (organized in an efficient way), and (4) return home (the discharge process should be well prepared for instance with home visits). Organizing excellent rehabilitation care requires a thorough understanding of the concept of CRE, as it is a complex and comprehensive concept that concerns the whole rehabilitation process. Its effectiveness and efficiency should be researched in prospective studies.
Comparing ability and norm-referenced scores as clinical trial outcomes for neurodevelopmental disabilities: a simulation study
Authors: Farmer Cristan , Thurm Audrey , Troy Jesse D. , Kaat Aaron J.
Published: January 2023

Background

For genetic conditions associated with neurodevelopmental disorder (GCAND), developmental domains such as motor ability, thinking and learning, social abilities, and communication are potential intervention targets. Performance on measures of developmental concepts can be expressed using several types of scores. Norm-referenced scores are intended for the diagnostic context, allowing for the identification of impairment relative to age-based expectations, and can exhibit dramatic floor effects when used in individuals with more significant limitations. Person ability scores, which are derived via Rasch analysis or item response theory, are available on many standardized tests and are intended to measure within-person change. However, they have not been used or evaluated as primary endpoints in GCAND clinical trials. In this study, we simulated a series of parallel-arm clinical trials under several chronological age and impairment conditions, to compare empirically the power and type I error rate of operationalizing test performance using ability scores rather than norm-referenced scores.

Results

Using the Vineland Adaptive Behavior Scales as the example, we demonstrated an advantage in statistical power of ability scores over norm-referenced scores at extreme levels of impairment. This advantage was at least partially driven by floor effects in norm-referenced scores. For simulated conditions where impairment was less severe, ability scores outperformed norm-referenced scores, but they were more similar. The type I error rate closely approximated the nominal type I error rate of 5% for both scores.

Conclusion

The results of this simulation demonstrate a substantial power and interpretative advantage of ability scores over norm-referenced scores for studies of GCAND that will enroll participants with high levels of impairment. These results are expected to generalize to studies of developmental concepts, regardless of the etiology or specific test. However, the relative advantage of ability scores is expected to be even greater for tests with a higher floor than the Vineland.
Artificially Selected Grain Shape Gene Combinations in Guangdong Simiao Varieties of Rice (Oryza sativa L.)
Authors: Yang Tifeng , Gu Haiyong , Yang Wu , Liu Bin , Liang Shihu , Zhao Junliang
Published: January 2023

Background

Grain shape is a key trait in rice breeding. Although many QTLs and genes of grain shape have been identified, how different combinations of alleles of these genes affect grain shape is largely unknown. It is important to understand the effects of grain shape gene combinations for breeding by design. In the present study, we performed genetic dissection of the grain shapes in Guangdong Simiao varieties, a popular kind of rice in South China, to identify the effective alleles and their combination for breeding.

Results

We selected two hundred nineteen indica accessions with diverse grain shapes and fifty-two Guangdong Simiao varieties with long and slender grain shapes for genome-wide selection analysis. The results showed that four (GS3, GS5, GW5 and GL7) of the twenty grain shape genes fall into the regions selected for in Guangdong Simiao varieties. Allele analysis and frequency distribution of these four genes showed that GS3allele3 and GW5allele2 accounted for 96.2%, and GL7allele2 and GS5allele2 accounted for 76.9% and 74.5% of the Simiao varieties, respectively. Further analysis of the allelic combinations showed that 30 allelic combinations were identified in the whole panel, with 28 allelic combinations found in the international indica accessions and 6 allelic combinations found in Guangdong Simiao varieties. There were mainly three combinations (combinations 17, 18 and 19) in the Guangdong Simiao varieties, with combination 19 (GS3allele3 + GW5allele2 + GL7allele2 + GS5allele2) having the highest percentage (51.9%). All three combinations carried GS3allele3 + GW5allele2, while combinations 17 (GL7allele1) and 19 (GL7allele2) showed significant differences in both grain length and length/width ratio due to differences in GL7 alleles. Pedigree analysis of Guang8B, the maintainer of the first released Simiao male sterile line Guang8A, showed that the parent lines and Guang8B carried GS3allele3 + GW5allele2 + GS5allele2, while the GL7 allele differed, resulting in significant differences in grain size.

Conclusion

The results suggest that specific alleles of GS3, GS5, GW5 and GL7 are the key grain shape genes used in the Guangdong Simiao varieties and selected for grain shape improvement. Combination 19 is the predominant allelic combination in the Guangdong Simiao varieties. Our current study is the first to dissect the genetics of grain shape in Guangdong Simiao varieties, and the results will facilitate molecular breeding of Guangdong Simiao varieties.
PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response
Authors: Wang Min , Zhang Ming , Qiu Jiayong , Liu Chenyang , Lou Yao , Wang Tongsheng , Zhang Yingmin , Mao Yimin
Published: January 2023

Background

Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear.

Methods

In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1β, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection.

Results

The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1β, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1β, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels.

Conclusions

Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.
Biochar and biofertilizer reduced nitrogen input and increased soybean yield in the maize soybean relay strip intercropping system
Authors: Luo Kai , Xie Chen , Yuan Xiaoting , Liu Shanshan , Chen Ping , Du Qing , Zheng Benchuan , Fu Zhidan , Wang Xiaochun , Yong Taiwen , Yang Wenyu
Published: January 2023

Applying Biochar (BC) or biofertilizers (BF) are potential approaches to reduce the nitrogen input and mitigate soil degradation in the maize soybean relay strip intercropping system (IS). In 2019 and 2020, a two-factor experiment was carried out to examine the effects of BC and BF on soil productivity and yield production in IS. 4 N input levels (8.4, 22.5, 45 kg, and 67.5 kg ha − 1) referred to as N0, N1, N2, and N3 were paired with various organic treatments, including BC (150 kg ha − 1), BF (300 kg ha − 1), and without organic amendments (CK). The results demonstrated that, despite BF decreasing the biomass and N distribution into grains, BF performed better on improved soybean yield (5.2–8.5%) by increasing the accumulation of soybean biomass (7.2 ~ 11.6%) and N (7.7%). Even though BC and BF have a detrimental effect on soybean nitrogen fixation by reducing nodule number and weight, the values of soybean nitrogenase activity and nitrogen fixation potential in BF were higher than those in BC. Additionally, BF performs better at boosting the soil’s nitrogen content and nitrate reductase and urease activity. BF increased the concentration of total N, soil organic matter, Olsen-phosphorus, and alkaline hydrolyzable N in the soil by 13.0, 17.1, 22.0, and 7.4%, respectively, compared to CK. Above all, applying BF combination with N2 (45 kg ha − 1 N) is a feasible strategy to raise crop grain output and keep soil productivity over the long term in IS.
The risk factors of thrombus formation and the effect of catheter ablation on repetitive thrombus formation in patients with atrial fibrillation: a single center retrospective study in China
Authors: Liu Huiyu , Lin Mingjie , Han Wenqiang , Ge Junye , Maduray Kellina , Zhong Jingquan
Published: January 2023

Background

Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus.

Methods

(1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA.

Results

The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806–5.500;p < 0.001). Twenty-seven patients agreed to undergo TEE during follow-up, no clinical ischemic stroke events were recorded, no recurrent intracardiac thrombus formation was detected in patients, 15 patients maintained sinus rhythm (55.6%) during follow-up; successful CA significantly increased LAAFV (difference between latest evaluation prior to CA 17.46 ± 14.81 cm/s,p < 0.001).

Conclusions

Persistent AF is the only independent risk factor for thrombus formation. Successful CA may improve the LAAFV and thereby decrease the risk of intracardiac thrombus formation.
3-Year outcomes after left atrial appendage closure in patients with nonvalvular atrial fibrillation: cardiomyopathy related with increased death and stroke rate
Authors: Chen Chunyu , Chen Yuyi , Qu Lulu , Su Xi , Chen Yanhong
Published: January 2023

Introduction

Left atrial appendage closure (LAAC) is a novel treatment for stroke prevention in high-risk patients with non-valvular atrial fibrillation (NVAF). However, the long-term outcomes after LAAC in Chinese NVAF patients are still lacking.

Methods

This was a single-center, bidirectional, nonrandomized registered study. Patients who underwent LAAC implantation from May 2014 to April 2021 in a large Chinese center were enrolled. The primary endpoint was combined all-cause death and stroke.

Results

From May 2014 to April 2021, a total of 673 NVAF patients were enrolled. The overall successful implantation rate was 97.62% (657 of 673). The rate of perioperative adverse events was 1.19% (8 of 673), including 3 cardiac tamponades, 2 ischemic strokes, one device-related thrombus (DRT) and 2 device dislocations. 604 (92.24%) patients completed the follow-up, the median follow-up period was 36.9 months (IQR 24.8–56.5 months). 16 stroke events occurred in 15 patients (one patient suffered from both hemorrhagic and ischemic strokes). 13 patients (2.15%) had ischemic stroke, and the fatal rate was 0.33% (2 of 604). 3 patients (0.15%) suffered from hemorrhagic stroke, and the fatal rate was 0.17% (1 of 604). The overall stroke rate was 0.74% per-year. The combined death and stroke rate was 1.93% per-year. In the multivariate Cox regression analysis, age ≥ 75 (hazard ratio 2.264, 95% CI 1.074–4.772, P = 0.032) and ventricular cardiomyopathy (hazard ratio 2.738, 95% CI 1.060–7.071, P = 0.037) were independent predictors of combined mortality and stroke.

Conclusion

The overall successful implantation rate of LAAC was 97.62% and the rate of perioperative adverse events was 1.19% in this study, and the stroke rate was 0.74% per year during the long-term follow-up. Age ≥ 75 years and ventricular cardiomyopathy were independent predictors of the primary endpoint.

Trial registration This study was retrospectively registered.
Comparing g-computation, propensity score-based weighting, and targeted maximum likelihood estimation for analyzing externally controlled trials with both measured and unmeasured confounders: a simulation study
Authors: Ren Jinma , Cislo Paul , Cappelleri Joseph C. , Hlavacek Patrick , DiBonaventura Marco
Published: January 2023

Objectives

To have confidence in one's interpretation of treatment effects assessed by comparing trial results to external controls, minimizing bias is a critical step. We sought to investigate different methods for causal inference in simulated data sets with measured and unmeasured confounders.

Methods

The simulated data included three types of outcomes (continuous, binary, and time-to-event), treatment assignment, two measured baseline confounders, and one unmeasured confounding factor. Three scenarios were set to create different intensities of confounding effect (e.g., small and blocked confounding paths, medium and blocked confounding paths, and one large unblocked confounding path for scenario 1 to 3, respectively) caused by the unmeasured confounder. The methods of g-computation (GC), inverse probability of treatment weighting (IPTW), overlap weighting (OW), standardized mortality/morbidity ratio (SMR), and targeted maximum likelihood estimation (TMLE) were used to estimate average treatment effects and reduce potential biases.

Results

The results with the greatest extent of biases were from the raw model that ignored all the potential confounders. In scenario 2, the unmeasured factor indirectly influenced the treatment assignment through a measured controlling factor and led to medium confounding. The methods of GC, IPTW, OW, SMR, and TMLE removed most of bias observed in average treatment effects for all three types of outcomes from the raw model. Similar results were found in scenario 1, but the results tended to be biased in scenario 3. GC had the best performance followed by OW.

Conclusions

The aforesaid methods can be used for causal inference in externally controlled studies when there is no large, unblockable confounding path for an unmeasured confounder. GC and OW are the preferable approaches.
The effect of peer-to-peer education on health literacy, knowledge, and adherence to COVID-19 protocols in vulnerable adolescents
Authors: Shoghli Alireza , Maleki Azam , Masjedi Mohammad Reza , Hessari Mohammadreza Bahrami , Khodaei Siavash
Published: January 2023

Background

The study was done to examine the effectiveness of peer-to-peer education on increasing health literacy, knowledge s, and observance of coronavirus disease (COVID-19) health prevention protocols in vulnerable adolescents.

Method

The study was a one-group intervention (before and after the intervention) that was performed on 1200 vulnerable adolescents living in varamin. The educational intervention was presented to adolescents in a face-to-face session. In the next step, the adolescents were taught the information received by three members of their families. Data were evaluated using a self-designed questionnaire before, and three months after the intervention. The paired t-test was used to compare scores of health literacy, compliance, and knowledge before and after the intervention at a 0.05 confidence level. The Multiple linear regression model was used to determine the predictive factors of observance of COVID-19 preventive behaviors.

Results

The most of adolescents were in the age group of 14 to 18 years (60%) and most of them were girls (61.5%). The most important source of information about COVID-19 disease was radio and television (59.6%). The results showed that the effectiveness of the intervention in increasing the adolescents’ health literacy, knowledge, and adherence to preventive behaviors were 40%, 30%, and 23%, respectively. The effectiveness of the intervention in increasing their families’ health literacy and adherence to the protocols were 11% and 20%, respectively (p = 0.001).

Discussion

Involving volunteer adolescents as health ambassadors and transmitting messages and methods of promoting personal protection against COVID-19 epidemics to family members had a significant effect on increasing the knowledge and adherence to the health procedures.
Does acute kidney injury alerting improve patient outcomes?
Authors: Atia Jolene , Evison Felicity , Gallier Suzy , Hewins Peter , Ball Simon , Gavin Joseph , Coleman Jamie , Garrick Mark , Pankhurst Tanya
Published: January 2023

Background

Electronic alerts (e-alerts) for Acute Kidney Injury (AKI) have been implemented into a variety of different Electronic Health Records (EHR) systems worldwide in order to improve recognition and encourage early appropriate management of AKI. We were interested in the impact on patient safety, specialist referral and clinical management.

Methods

All patients admitted to our institution with AKI were included in the study. We studied AKI progression, dialysis dependency, length of hospital stay, emergency readmission, ICU readmission, and death, before and after the introduction of electronic alerts. The impact on prescription of high risk drugs, fluid administration, and referral to renal services was also analysed.

Results

After the introduction of the e-alert, progression to higher AKI stage, emergency readmission to hospital and death during admission were significantly reduced. More prescriptions were stopped for drugs that adversely affect renal function in AKI and there was a significant increase in the ICU admissions and in the number of patients having dialysis, especially in earlier stages. Longer term mortality, renal referrals, and fluid alteration did not change significantly after the AKI e-alert introduction.

Conclusions

AKI e-alerts can improve clinical outcomes in hospitalised patients.