bluuebunny/crossref_metadata_2025 huggingface dataset:
NRN1 interacts with Notch to increase oncogenic STAT3 signaling in melanoma
Authors: Devitt Lucia , Westphal Dana , Pieger Katharina , Schneider Nadja , Bosserhoff Anja Katrin , Kuphal Silke
Published: May 2024

Background

Melanoma is a highly heterogeneous cancer, in which frequent changes in activation of signaling pathways lead to a high adaptability to ever changing tumor microenvironments. The elucidation of cancer specific signaling pathways is of great importance, as demonstrated by the inhibitor of the common BrafV600E mutation PLX4032 in melanoma treatment. We therefore investigated signaling pathways that were influenced by neurotrophin NRN1, which has been shown to be upregulated in melanoma.

Methods

Using a cell culture model system with an NRN1 overexpression, we investigated the influence of NRN1 on melanoma cells’ functionality and signaling. We employed real time cell analysis and spheroid formation assays, while for investigation of molecular mechanisms we used a kinase phosphorylation kit as well as promotor activity analysis followed by mRNA and protein analysis.

Results

We revealed that NRN1 interacts directly with the cleaved intracellular domain (NICD) of Notch1 and Notch3, causing a potential retention of NICD in the cytoplasm and thereby reducing the expression of its direct downstream target Hes1. This leads to decreased sequestration of JAK and STAT3 in a Hes1-driven phosphorylation complex. Consequently, our data shows less phosphorylation of STAT3 while presenting an accumulation of total protein levels of STAT3 in association with NRN1 overexpression. The potential of the STAT3 signaling pathway to act in both a tumor suppressive and oncogenic manner led us to investigate specific downstream targets – namely Vegf A, Mdr1, cMet - which were found to be upregulated under oncogenic levels of NRN1.

Conclusions

In summary, we were able to show that NRN1 links oncogenic signaling events between Notch and STAT3 in melanoma. We also suggest that in future research more attention should be payed to cellular regulation of signaling molecules outside of the classically known phosphorylation events.

Graphical Abstract
Toward robust and high-throughput detection of seed defects in X-ray images via deep learning
Authors: Hamdy Sherif , Charrier Aurélie , Corre Laurence Le , Rasti Pejman , Rousseau David
Published: May 2024

Background

The detection of internal defects in seeds via non-destructive imaging techniques is a topic of high interest to optimize the quality of seed lots. In this context, X-ray imaging is especially suited. Recent studies have shown the feasibility of defect detection via deep learning models in 3D tomography images. We demonstrate the possibility of performing such deep learning-based analysis on 2D X-ray radiography for a faster yet robust method via the X-Robustifier pipeline proposed in this article.

Results

2D X-ray images of both defective and defect-free seeds were acquired. A deep learning model based on state-of-the-art object detection neural networks is proposed. Specific data augmentation techniques are introduced to compensate for the low ratio of defects and increase the robustness to variation of the physical parameters of the X-ray imaging systems. The seed defects were accurately detected (F1-score >90%), surpassing human performance in computation time and error rates. The robustness of these models against the principal distortions commonly found in actual agro-industrial conditions is demonstrated, in particular, the robustness to physical noise, dimensionality reduction and the presence of seed coating.

Conclusion

This work provides a full pipeline to automatically detect common defects in seeds via 2D X-ray imaging. The method is illustrated on sugar beet and faba bean and could be efficiently extended to other species via the proposed generic X-ray data processing approach (X-Robustifier). Beyond a simple proof of feasibility, this constitutes important results toward the effective use in the routine of deep learning-based automatic detection of seed defects.
The application of deep learning in abdominal trauma diagnosis by CT imaging
Authors: Shen Xinru , Zhou Yixin , Shi Xueyu , Zhang Shiyun , Ding Shengwen , Ni Liangliang , Dou Xiaobing , Chen Lin
Published: May 2024

Background

Abdominal computed tomography (CT) scan is a crucial imaging modality for creating cross-sectional images of the abdominal area, particularly in cases of abdominal trauma, which is commonly encountered in traumatic injuries. However, interpreting CT images is a challenge, especially in emergency. Therefore, we developed a novel deep learning algorithm-based detection method for the initial screening of abdominal internal organ injuries.

Methods

We utilized a dataset provided by the Kaggle competition, comprising 3,147 patients, of which 855 were diagnosed with abdominal trauma, accounting for 27.16% of the total patient population. Following image data pre-processing, we employed a 2D semantic segmentation model to segment the images and constructed a 2.5D classification model to assess the probability of injury for each organ. Subsequently, we evaluated the algorithm’s performance using 5k-fold cross-validation.

Results

With particularly noteworthy performance in detecting renal injury on abdominal CT scans, we achieved an acceptable accuracy of 0.932 (with a positive predictive value (PPV) of 0.888, negative predictive value (NPV) of 0.943, sensitivity of 0.887, and specificity of 0.944). Furthermore, the accuracy for liver injury detection was 0.873 (with PPV of 0.789, NPV of 0.895, sensitivity of 0.789, and specificity of 0.895), while for spleen injury, it was 0.771 (with PPV of 0.630, NPV of 0.814, sensitivity of 0.626, and specificity of 0.816).

Conclusions

The deep learning model demonstrated the capability to identify multiple organ injuries simultaneously on CT scans and holds potential for application in preliminary screening and adjunctive diagnosis of trauma cases beyond abdominal injuries.
Off-the-shelf CAR-T cell therapies for relapsed or refractory B-cell malignancies: latest update from ASH 2023 annual meeting
Authors: Kang Yun , Li Chenggong , Mei Heng
Published: May 2024

Currently, many off-the-shelf chimeric antigen receptor (CAR)-T cell products are under investigation for the treatment of relapsed or refractory (R/R) B-cell neoplasms. Compared with autologous CAR-T cell therapy, off-the-shelf universal CAR-T cell therapies have many potential benefits, such as immediate accessibility for patients, stable quality due to industrialized manufacturing and additional infusions of CAR-T cells with different targets. However, critical challenges, including graft-versus-host disease and CAR-T cell elimination by the host immune system, still require extensive research. The most common technological approaches involve modifying healthy donor T cells via gene editing technology and altering different types of T cells. This article summarizes some of the latest data from preclinical and clinical studies of off-the-shelf CAR-T cell therapies in the treatment of R/R B-cell malignancies from the 2023 ASH Annual Meeting (ASH 2023).
Sepsis mortality among patients with haematological malignancy admitted to intensive care 2000–2022: a binational cohort study
Authors: MacPhail Aleece , Dendle Claire , Slavin Monica , Weinkove Robert , Bailey Michael , Pilcher David , McQuilten Zoe
Published: May 2024

Background

Sepsis occurs in 12–27% of patients with haematological malignancy within a year of diagnosis. Sepsis mortality has improved in non-cancer patients in the last two decades, but longitudinal trends in patients with haematological malignancy are not well characterised. We aimed to compare outcomes, including temporal changes, in patients with and without a haematological malignancy admitted to ICU with a primary diagnosis of sepsis in Australia and New Zealand over the past two decades.

Methods

We performed a retrospective cohort study of 282,627 patients with a primary intensive care unit (ICU) admission diagnosis of sepsis including 17,313 patients with haematological malignancy, admitted to 216 intensive care units (ICUs) in Australia or New Zealand between January 2000 and December 2022. Annual crude and adjusted in-hospital mortality were reported. Risk factors for in-hospital mortality were determined using a mixed methods logistic regression model and were used to calculate annual changes in mortality.

Results

In-hospital sepsis mortality decreased in patients with haematological malignancy, from 55.6% (95% CI 46.5–64.6%) in 2000 to 23.1% (95% CI 20.8–25.5%) in 2021. In patients without haematological malignancy mortality decreased from 33.1% (95% CI 31.3–35.1%) to 14.4% (95% CI 13.8–14.8%). This decrease remained significant after adjusting for mortality predictors including age, SOFA score and comorbidities, as estimated by adjusted annual odds of in-hospital death. The reduction in odds of death was of greater magnitude in patients with haematological malignancy than those without (OR 0.954, 95% CI 0.947–0.961 vs. OR 0.968, 95% CI 0.966–0.971, p < 0.001). However, absolute risk of in-hospital mortality remained higher in patients with haematological malignancy. Older age, higher SOFA score, presence of comorbidities, and mechanical ventilation were associated with increased mortality. Leukopenia (white cell count < 1.0 × 109 cells/L) was not associated with increased mortality in patients with haematological malignancy (p = 0.60).

Conclusions

Sepsis mortality has improved in patients with haematological malignancy admitted to ICU. However, mortality remains higher in patients with haematological malignancy than those without.

Graphical abstract
PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC): protocol for an effectiveness cluster randomised controlled trial
Authors: Væringstad Anette , Dalbak Ellen Thea Gjelseth , Holle Daniela , Myhre Janne , Kirkevold Øyvind , Bergh Sverre , Lichtwarck Bjørn
Published: May 2024

Background

Demographic changes, with an increasing number and proportion of older people with multimorbidity and frailty, will put more pressure on home care services in municipalities. Frail multimorbid people receiving home care services are at high risk of developing crises, defined as critical challenges and symptoms, which demand immediate and new actions. The crises often result in adverse events, coercive measures, and acute institutionalisation. There is a lack of evidence-based interventions to prevent and resolve crises in community settings.

Methods

This is a participatory action research design (PAR) in a 6-month cluster randomised controlled trial (RCT). The trial will be conducted in 30 municipalities, including 150 frail community-dwelling participants receiving home care services judged by the services to be at risk of developing crisis. Each municipality (cluster) will be randomised to receive either the locally adapted TIME intervention (the intervention group) or care as usual (the control group). The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) is a manual-based, multicomponent programme that includes a rigorous assessment of the crisis, one or more interdisciplinary case conferences, and the testing and evaluation of customised treatment measures. PAR in combination with an RCT will enhance adaptations of the intervention to the local context and needs. The primary outcome is as follows: difference in change between the intervention and control groups in individual goal achievement to resolve or reduce the challenges of the crises between baseline and 3 months using the PRACTIC Goal Setting Interview (PGSI). Among the secondary outcomes are the difference in change in the PGSI scale at 6 months and in neuropsychiatric symptoms (NPSs), quality of life, distress perceived by professional carers and next of kin, and institutionalisation at 3 and 6 months.

Discussion

Through customised interventions that involve patients, the next of kin, the social context, and health care services, crises may be prevented and resolved. The PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC) study will enhance innovation for health professionals, management, and users in the development of new knowledge and a new adapted approach towards crises.

Trial registration

ClinicalTrials.gov identifier: NCT05651659. Registered 15.12.22.
Repellent activity of essential oils to the Lone Star tick, Amblyomma americanum
Authors: Le Mauff Anais , Norris Edmund J. , Li Andrew Y. , Swale Daniel R.
Published: May 2024

Background

The Lone Star tick, Amblyomma americanum is important to human health because of a variety of pathogenic organisms transmitted to humans during feeding events, which underscores the need to identify novel approaches to prevent tick bites. Thus, the goal of this study was to test natural and synthetic molecules for repellent activity against ticks in spatial, contact and human fingertip bioassays.

Methods

The efficacy of essential oils and naturally derived compounds as repellents to Am. americanum nymphs was compared in three different bioassays: contact, spatial and fingertip repellent bioassays.

Results

Concentration response curves after contact exposure to 1R-trans-chrysanthemic acid (TCA) indicated a 5.6 μg/cm2 concentration required to repel 50% of ticks (RC50), which was five- and sevenfold more active than DEET and nootkatone, respectively. For contact repellency, the rank order of repellency at 50 μg/cm2 for natural oils was clove > geranium > oregano > cedarwood > thyme > amyris > patchouli > citronella > juniper berry > peppermint > cassia. For spatial bioassays, TCA was approximately twofold more active than DEET and nootkatone at 50 μg/cm2 but was not significantly different at 10 μg/cm2. In spatial assays, thyme and cassia were the most active compounds tested with 100% and 80% ticks repelled within 15 min of exposure respectively and was approximately twofold more effective than DEET at the same concentration. To translate these non-host assays to efficacy when used on the human host, we quantified repellency using a finger-climbing assay. TCA, nootkatone and DEET were equally effective in the fingertip assay, and patchouli oil was the only natural oil that significantly repelled ticks.

Conclusions

The differences in repellent potency based on the assay type suggests that the ability to discover active tick repellents suitable for development may be more complicated than with other arthropod species; furthermore, the field delivery mechanism must be considered early in development to ensure translation to field efficacy. TCA, which is naturally derived, is a promising candidate for a tick repellent that has comparable repellency to commercialized tick repellents.

Graphical Abstract
Vegetation structure drives mosquito community composition in UK’s largest managed lowland wetland
Authors: Smith Daniel C. , Schäfer Stefanie M. , Golding Nick , Nunn Miles A. , White Steven M. , Callaghan Amanda , Purse Bethan V.
Published: May 2024

Purpose

The rising burden of mosquito-borne diseases in Europe extends beyond urban areas, encompassing rural and semi-urban regions near managed and natural wetlands evidenced by recent outbreaks of Usutu and West Nile viruses. While wetland management policies focus on biodiversity and ecosystem services, few studies explore the impact on mosquito vectors.

Methods

Our research addresses this gap, examining juvenile mosquito and aquatic predator communities in 67 ditch sites within a South England coastal marsh subjected to different wetland management tiers. Using joint distribution models, we analyse how mosquito communities respond to abiotic and biotic factors influenced by wetland management.

Results

Of the 12 mosquito species identified, Culiseta annulata (Usutu virus vector) and Culex pipiens (Usutu and West Nile virus vector) constitute 47% of 6825 larval mosquitoes. Abundant predators include Coleoptera (water beetles) adults, Corixidae (water boatmen) and Zygoptera (Damselfy) larvae. Models reveal that tier 3 management sites (higher winter water levels, lower agricultural intensity) associated with shade and less floating vegetation are preferred by specific mosquito species. All mosquito species except Anopheles maculipennis s.l., are negatively impacted by potential predators. Culiseta annulata shows positive associations with shaded and turbid water, contrary to preferences of Corixidae predators.

Conclusions

Tier 3 areas managed for biodiversity, characterised by higher seasonal water levels and reduced livestock grazing intensity, provide favourable habitats for key mosquito species that are known vectors of arboviruses, such as Usutu and West Nile. Our findings emphasise the impact of biodiversity-focused wetland management, altering mosquito breeding site vegetation to enhance vector suitability. Further exploration of these trade-offs is crucial for comprehending the broader implications of wetland management.
Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones of Klebsiella pneumoniae and stresses the importance to include temporal patterns for vaccine design considerations
Authors: Heinz Eva , Pearse Oliver , Zuza Allan , Bilima Sithembile , Msefula Chisomo , Musicha Patrick , Siyabu Patriciah , Tewesa Edith , Graf Fabrice E. , Lester Rebecca , Lissauer Samantha , Cornick Jennifer , Lewis Joseph M. , Kawaza Kondwani , Thomson Nicholas R. , Feasey Nicholas A.
Published: May 2024

Background

Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking.

Methods

We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates.

Results

We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development.

Conclusions

Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.
Association between retinal microvascular abnormalities and late-life brain amyloid-β deposition: the ARIC-PET study
Authors: Egle Marco , Deal Jennifer A. , Walker Keenan A. , Wong Dean F. , Sharrett A. Richey , Gottesman Rebecca F.
Published: May 2024

Background

Retinal microvascular signs are accessible measures of early alterations in microvascular dysregulation and have been associated with dementia; it is unclear if they are associated with AD (Alzheimer’s disease) pathogenesis as a potential mechanistic link. This study aimed to test the association of retinal microvascular abnormalities in mid and late life and late life cerebral amyloid.

Methods

Participants from the ARIC‐PET (Atherosclerosis Risk in Communities‐Positron Emission Tomography) study with a valid retinal measure (N = 285) were included. The associations of mid- and late-life retinal signs with late-life amyloid-β (Aβ) by florbetapir PET were tested. Two different measures of Aβ burden were included: (1) elevated amyloid (SUVR > 1.2) and (2) continuous amyloid SUVR. The retinal measures’ association with Aβ burden was assessed using logistic and robust linear regression models. A newly created retinal score, incorporating multiple markers of retinal abnormalities, was also evaluated in association with greater Aβ burden.

Results

Retinopathy in midlife (OR (95% CI) = 0.36 (0.08, 1.40)) was not significantly associated with elevated amyloid burden. In late life, retinopathy was associated with increased continuous amyloid standardized value uptake ratio (SUVR) (β (95%CI) = 0.16 (0.02, 0.32)) but not elevated amyloid burden (OR (95%CI) = 2.37 (0.66, 9.88)) when accounting for demographic, genetic and clinical risk factors. A high retinal score in late life, indicating a higher burden of retinal abnormalities, was also significantly associated with increased continuous amyloid SUVR (β (95% CI) = 0.16 (0.04, 0.32)) independent of vascular risk factors.

Conclusions

Retinopathy in late life may be an easily obtainable marker to help evaluate the mechanistic vascular pathway between retinal measures and dementia, perhaps acting via AD pathogenesis. Well-powered future studies with a greater number of retinal features and other microvascular signs are needed to test these findings.
Budget impact analysis of continuous glucose monitoring in individuals with type 2 diabetes on insulin treatment in England
Authors: Alsaif Murtada , Farhat Ali , Blumer Zoe , Barham Leela
Published: May 2024

Introduction

In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose monitoring (CGM). In this budget impact analysis, the cost impact of CGM was compared with traditional self-monitoring of blood glucose (SMBG) in adults with T2DM over 1 year from the commissioner perspective in England.

Research Design and methods

The NICE-eligible T2DM cohort was split into 4 subgroups to enable nuanced costing by insulin administration frequency: basal human insulin, premixed insulin, basal-bolus insulin and bolus insulin. The model’s cost components comprised mild and severe hypoglycaemia (SH), diabetic ketoacidosis (DKA), consumables and healthcare resource utilisation in primary and secondary care.

Results

The introduction of CGM is estimated to be cost additive by approximately £4.6 million in the basecase, driven by increased spending on the CGM device. Overall, healthcare activity was reduced by approximately 20,000 attendances, due to fewer SH and DKA episodes in the CGM arm. General Practitioner (GP) practice-based activity is expected to drop after the first year as patients requiring CGM training is reduced. The budget impact could be neutralised if the CGM sensor was discounted by 13.2% (£29.76 to £25.83).

Conclusions

CGM may result in increased spending in the NICE-eligible T2DM cohort but is expected to reduce demand on secondary care services and GP time. These findings may be of interest to local decision-makers who wish to resolve the COVID-19 backlog with transformational investment in primary care to reduce secondary care activity.
On ultrametrics, b-metrics, w-distances, metric-preserving functions, and fixed point theorems
Authors: Samphavat Suchat , Prinyasart Thanakorn
Published: May 2024

In this article, new classes of functions based on new variations of metric-preserving functions are defined. Necessary and sufficient conditions for functions to be in these classes are also provided. As a result, we can explain relations between all classes and learn that all functions in the classes are weakly separated from 0. We can extend fixed point theorems, which were originally provided by Kirk and Shahzad and were later extended by Pongsriiam and Termwuttipong, in this journal by considering all functions that are weakly separated from 0.
Decreasing the energy demand in public buildings using nature-based solutions: case studies from Novi Sad (Republic of Serbia) and Osijek (Republic of Croatia)
Authors: Savić Stevan , Krstić Hrvoje , Šećerov Ivan , Dunjić Jelena
Published: May 2024

Background

Nature-based solutions (NBS) in urban areas offer an opportunity to improve environmental conditions and to reduce CO2 emissions towards establishing climate-neutral cities in the next few decades. Furthermore, the implementation of NBSs—vertical or horizontal green infrastructures on public facilities—could in particular improve both climate, including outdoor thermal conditions on a micro-scale (especially during the summer season) and the energy demand of buildings as well as save heating energy during the winter period.

Results

On both selected buildings, extensive green roofs were implemented as an NBS intervention. The analysed data were obtained using the monitoring systems (from 2019 to 2022) installed on two public buildings in Novi Sad (Republic of Serbia) and Osijek (Republic of Croatia), with a focus on climate/bioclimate characteristics and thermal transmission capacities. Four automatic weather stations (AWS) were used for microclimate monitoring, along with the heat flow meter (HFM) method, to measure the alterations in the thermal transmittance (U value) of a flat concrete roof before and after energy refurbishment and the installation of a green roof. The outcomes of this study show that the air temperatures (Ta) and globe temperatures (Tg) near the green roof are lower by 0–3 °C for Ta and by 0–16.5 °C for Tg than the values captured by the AWSs at other locations. An even more interesting fact is that the green roof has a constant cooling potential during tropical nights, and based upon this research, the cooling value is around 2 °C for Tg (the Ta value is not distinct). The thermal transmittance results show that more savings can be achieved by applying a green roof with an 8 cm thick substrate: U values decreased by 50–69%, as measured by two different heat flux sensors.

Conclusions

Nature-based solutions, such as the implementation of an extensive green roof, have positive effects on diverse aspects of urban environments and building energy savings, which are particularly evident in extreme seasons, both summer and winter. Applying the proposed monitoring and assessment system could help local communities in their efforts to reduce carbon-based emissions. This paper provides a good example of the implementation of NBSs on a local- and a micro-scale.
Psychophysiological effects of walking in forests and urban built environments with disparate road traffic noise exposure: study protocol of a randomized controlled trial
Authors: Schaupp Julia , Hediger Karin , Wunderli Jean-Marc , Schäffer Beat , Tobias Silvia , Kolecka Natalia , Bauer Nicole
Published: May 2024

Background

Stress is a widespread phenomenon and reality of everyday life, entailing negative consequences for physical and psychological wellbeing. Previous studies have indicated that exposure to greenspaces and nature-based interventions are promising approaches to reducing stress and promoting restoration. However, an increasing percentage of the population lives in urban regions with limited opportunities to spend time in greenspaces. In addition, urban settings typically feature increased levels of noise, which represents a major environmental stressor. Although various studies have compared the effects of exposure to greenspaces versus urban built environments, evidence of the effects of noise in this context is very limited. Psychophysiological benefits of exposure to greenspaces compared to urban built environments reported in earlier studies might be less (or at least not only) due to features of the greenspaces than to additional stressors, such as road traffic noise in the urban built environment. Hence, differences in the effects attributed to greenness in previous studies may also be due to potentially detrimental noise effects in comparison settings. This paper reports the study protocol for a randomized, controlled intervention study comparing the effects of walking in forest versus urban built environments, taking road traffic noise exposure during walks in the respective settings into account.

Methods

The protocol envisages a field study employing a pretest–posttest design to compare the effects of 30-min walks in urban built environments and forests with different road traffic noise levels. Assessments will consist of self-reported measures, physiological data (salivary cortisol and skin conductance), an attention test, and noise, as well as greenness measurements. The outcomes will be restoration, stress, positive and negative affect, attention, rumination, and nature connectedness.

Discussion

The results will inform about the restorative effect of walking in general, of exposure to different types of environments, and to different noise levels in these sites. The study will provide insights into the benefits of walking and nature-based interventions, taking into account the potential detrimental effects of noise exposure. It will thus facilitate a better understanding of low-threshold interventions to prevent stress and foster wellbeing.

Trial registration

ISRCTN48943261; Registered 23.11.2023.
Validation of an elicited Imitation test as a measure of Korean language proficiency
Authors: Kim Hojung , Song Changkyung , Kim Jiyoung , Jeong Hyeyun , Park Jisoo
Published: May 2024

This study presents a modified version of the Korean Elicited Imitation (EI) test, designed to resemble natural spoken language, and validates its reliability as a measure of proficiency. The study assesses the correlation between average test scores and Test of Proficiency in Korean (TOPIK) levels, examining score distributions among beginner, intermediate, and advanced learner groups. Using item response theory (IRT), the study explores the influence of four key facets—learners, items, raters, and constructs—on performance evaluation. An explanatory item response modeling (EIRM) analysis identified linguistic factors impacting the EI test’s performance. Notably, the study uncovered a robust positive correlation between EI test scores and TOPIK levels. Significant score disparities were observed between beginner and intermediate, as well as beginner and advanced, learner cohorts. An IRT-based exploration of each facet revealed that item difficulty was comparatively lower in contrast to learners’ commendable performance, and raters exhibited a high degree of scoring consistency. The EIRM analysis underscores the significance of variables such as the number of syllables, vocabulary score, and content word density in influencing test performance.
Comprehensive analysis of the REST transcription factor regulatory networks in IDH mutant and IDH wild-type glioma cell lines and tumors
Authors: Perycz Malgorzata , Dabrowski Michal J. , Jardanowska-Kotuniak Marta , Roura Adria-Jaume , Gielniewski Bartlomiej , Stepniak Karolina , Dramiński Michał , Ciechomska Iwona A. , Kaminska Bozena , Wojtas Bartosz
Published: May 2024

The RE1-silencing transcription factor (REST) acts either as a repressor or activator of transcription depending on the genomic and cellular context. REST is a key player in brain cell differentiation by inducing chromatin modifications, including DNA methylation, in a proximity of its binding sites. Its dysfunction may contribute to oncogenesis. Mutations in IDH1/2 significantly change the epigenome contributing to blockade of cell differentiation and glioma development. We aimed at defining how REST modulates gene activation and repression in the context of the IDH mutation-related phenotype in gliomas. We studied the effects of REST knockdown, genome wide occurrence of REST binding sites, and DNA methylation of REST motifs in IDH wild type and IDH mutant gliomas. We found that REST target genes, REST binding patterns, and TF motif occurrence proximal to REST binding sites differed in IDH wild-type and mutant gliomas. Among differentially expressed REST targets were genes involved in glial cell differentiation and extracellular matrix organization, some of which were differentially methylated at promoters or gene bodies. REST knockdown differently impacted invasion of the parental or IDH1 mutant glioma cells. The canonical REST-repressed gene targets showed significant correlation with the GBM NPC-like cellular state. Interestingly, results of REST or KAISO silencing suggested the interplay between these TFs in regulation of REST-activated and repressed targets. The identified gene regulatory networks and putative REST cooperativity with other TFs, such as KAISO, show distinct REST target regulatory networks in IDH-WT and IDH-MUT gliomas, without concomitant DNA methylation changes. We conclude that REST could be an important therapeutic target in gliomas.
Reciprocal relationship between self-efficacy and achievement in mathematics among high school students
Authors: Liu Ruixue , Jong Cindy , Fan Meng
Published: May 2024

Self-efficacy or perceived ability refers to the confidence an individual has in their ability to successfully perform a specific task. Previous researchers have demonstrated the importance of self-efficacy beliefs and its impact on predicting students’ mathematics performances. Specifically, gender has been regarded as an important moderator variable in the prediction of achievement from measures of affect. To this end, using data from High School Longitudinal Study of 2009, this study utilized the multi-group analysis under the framework of structural equation modeling to examine gender differences in the reciprocal relationship between mathematics self-efficacy and mathematics achievement. The results showed that there were statistically significant differences between male students and female students in the reciprocal relationship between mathematics self-efficacy and mathematics achievement; the impact of prior mathematics achievement on later mathematics achievement was stronger than the impact of prior mathematics self-efficacy on later mathematics self-efficacy. Significance of these findings were discussed in this paper.
Rapid development and mass production of SARS-CoV-2 neutralizing chicken egg yolk antibodies with protective efficacy in hamsters
Authors: Zhao Binan , Peng Haoran , Zhang Yanjing , Zhang Jie , Kong Desheng , Cao Sai , Li Yan , Yang Dan , Sun Chuanwen , Pu Xinyi , Zhao Ping , Xu Yan , Zhao Kai , Xie Liangzhi
Published: May 2024

Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.
The effectiveness of cervical mucus electrical impedance compared to basal body temperature to determine fertility window
Authors: Tabbaa Suzanne , Hambright Sealy , Sikes Katie J. , Levy Gary , Rydfors Jan
Published: May 2024

Background

Serial serum hormone measurements and transvaginal ultrasound are reliable measures to predict ovulation. These measures are inconvenient and expensive therefore, basal body temperature charting (BBT) and urine ovulation predictor kits (OPK) for luteinizing hormone are often used to determine the 6-day fertile window. However, BBT does not clearly change until 1–2 days after ovulation. Additionally, while OPK can indicate positivity prior to ovulation, false readings are common. A novel alternative approach involves measuring electrolyte trends in cervical mucus using electrical impedance spectroscopy. Cervical mucus electrolyte measurements are associated with hormone level changes during the menstrual cycle. The purpose of this study was to compare the effectiveness of cervical mucus electrical impedance and basal body temperature. We sought to determine if cervical mucus electrolyte measurements provided improved detection of the ovulation day and therefore, improve fertility timing for women.

Methods

14 healthy women between 18 and 44 years of age with normal menstrual cycles were enrolled in the Observational Study. Participants measured BBT and cervical mucus electrical impedance daily for 3 menstrual cycles using Kegg (Lady Technologies Inc. San Francisco, California, USA). Ovulation date for each cycle was confirmed by measuring hormone levels in urine and serum, and by vaginal ultrasound.

Results

Electrical impedance was significantly different between the follicular phase versus ovulatory date (p = 0.007) and between the luteal phase versus the ovulatory date (p = 0.007). A significant difference in the rate of change of cervical impedance measurements in the pre-ovulatory follicular phase was found compared to BBT (p = 0.0225). The sensitivity (+ 7.14%), specificity (+ 20.35%), and accuracy (+ 17.59) to determine the 1-day fertility window was significantly higher using cervical mucus impedance compared to BBT.

Conclusions

BBT is considered unreliable for evaluating ovulatory function. Cervical mucus electrical impedance offers a novel measure of electrolyte changes associated with hormone levels. We report that pre-ovulatory electrical impedance patterns demonstrated higher sensitivity, specificity, and accuracy for determining the fertility window when compared to BBT. These findings suggest that changes in electrical impedance may provide an accurate method for predicting ovulation and for measuring ovulatory function.
Prospective memory instruments for the assessment of children and adolescents: a systematic review
Authors: Signori Vanessa de A. , Watanabe Tiago M. , de Pereira Ana Paula A.
Published: May 2024

Background

Prospective memory is the ability to engage in an intention to be performed in the future. The main objective of this study was to identify instruments that assess both time-based and event-based prospective memory in children and adolescents and that have the potential to be clinically applicable.

Method

Three databases (PubMed, Scopus, and PsycINFO) were searched to identify existing PM measures in original articles published until 2022. Literature searches were conducted using the following terms: (prospective memor* OR memor* for intentions) AND (neuropsychological assessment) AND (test* OR instrument* OR questionnaire* OR task*) AND (psychometric properties) AND (child* OR adolescen*). Relevant studies identified in the reference lists were also included in the review.

Results

Ten instruments were identified and classified into three categories: (a) test batteries, (b) experimental procedures, and (c) questionnaires. All the instruments identified were described concerning their content and the psychometric properties available. Some of the instruments presented empirical evidence regarding validity and reliability, but no one provided normative data.

Conclusion

Besides the recent progress regarding studies publishing the development of a variety of novel measures, there are still many limitations surrounding the assessment of PM in the youth population because of the yet incipient psychometric properties presented by the majority of the PM instruments. Recommendations for a gold-standard PM instrument for assessing children and adolescents are provided.
Reproducibility of a semiautomatic lobar lung tissue assignment technique on noncontrast CT scans: a study on swine animal model
Authors: Luu Nile , Van Nathan , Shojazadeh Alireza , Zhao Yixiao , Molloi Sabee
Published: May 2024

Background

To evaluate the reproducibility of a vessel-specific minimum cost path (MCP) technique used for lobar segmentation on noncontrast computed tomography (CT).

Methods

Sixteen Yorkshire swine (49.9 ± 4.7 kg, mean ± standard deviation) underwent a total of 46 noncontrast helical CT scans from November 2020 to May 2022 using a 320-slice scanner. A semiautomatic algorithm was employed by three readers to segment the lung tissue and pulmonary arterial tree. The centerline of the arterial tree was extracted and partitioned into six subtrees for lobar assignment. The MCP technique was implemented to assign lobar territories by assigning lung tissue voxels to the nearest arterial tree segment. MCP-derived lobar mass and volume were then compared between two acquisitions, using linear regression, root mean square error (RMSE), and paired sample t-tests. An interobserver and intraobserver analysis of the lobar measurements was also performed.

Results

The average whole lung mass and volume was 663.7 ± 103.7 g and 1,444.22 ± 309.1 mL, respectively. The lobar mass measurements from the initial (MLobe1) and subsequent (MLobe2) acquisitions were correlated by MLobe1 = 0.99 MLobe2 + 1.76 (r = 0.99, p = 0.120, RMSE = 7.99 g). The lobar volume measurements from the initial (VLobe1) and subsequent (VLobe2) acquisitions were correlated by VLobe1 = 0.98VLobe2 + 2.66 (r = 0.99, p = 0.160, RSME = 15.26 mL).

Conclusions

The lobar mass and volume measurements showed excellent reproducibility through a vessel-specific assignment technique. This technique may serve for automated lung lobar segmentation, facilitating clinical regional pulmonary analysis.

Relevance statement

Assessment of lobar mass or volume in the lung lobes using noncontrast CT may allow for efficient region-specific treatment strategies for diseases such as pulmonary embolism and chronic thromboembolic pulmonary hypertension.

Key points

• Lobar segmentation is essential for precise disease assessment and treatment planning.

• Current methods for segmentation using fissure lines are problematic.

• The minimum-cost-path technique here is proposed and a swine model showed excellent reproducibility for lobar mass measurements.

• Interobserver agreement was excellent, with intraclass correlation coefficients greater than 0.90.

Graphical Abstract
An investigation of the impact of atenolol on the risk of all-cause mortality in Asian individuals with hypertension and cardiovascular conditions
Authors: Alkattan Abdullah , Alsalameen Eman , Harmoush Alaa , Farawati Mhd Nour , Alsharif Hind , Mahmoud Nagla , Farawati Mhd Ali , Alfaleh Amjad , Kandeel Mahmoud , Radwan Nashwa
Published: May 2024

Background

Despite several justifications for utilizing beta-blockers, such as atenolol, as the initial treatment for hypertension in the presence of cardiovascular disease, some studies have demonstrated that calcium channel blockers were more effective than beta-blockers in decreasing mortality. This review intended to determine the efficacy of atenolol in reducing all-cause mortality in Asian individuals with hypertension, coronary artery disease, atrial fibrillation, and heart failure.

Main body of the abstract

Studies published before March 31, 2023, were searched using Trip, Google Scholar, Cochrane, and EMBASE databases. We only considered studies that compared atenolol with other medications in terms of all-cause mortality rates in Asian individuals diagnosed with hypertension and cardiovascular diseases. Therefore, we only considered three trials with a total of 79,603 participants. The results indicated a statistically significant higher all-cause death rate among non-atenolol users compared to atenolol users (p < 0.001). The all-cause death rate was considerably greater in individuals who consumed metoprolol tartrate compared to those who consumed atenolol (OR = 0.50, p < 0.0001). Although the included publications were deemed to have a low risk of bias, significant heterogeneity was observed (p = 0.001).

Short conclusion

Due to the limited studies included, this analysis concluded that atenolol, in comparison with non-users of atenolol or especially metoprolol tartrate, significantly reduces the overall death rate in East Asian and Southeast Asian patients with hypertension, coronary artery disease, atrial fibrillation, and heart failure. Yet, the current study cannot finalize this conclusion for other Asian ethnic groups, such as South Asians, Central Asians, and West Asians. Additional systematic reviews and meta-analyses with low heterogeneity and high-quality evidence are suggested to validate our findings and explore the efficacy of atenolol in various ethnic populations.
Quality and safety of new types of dairy products based on cow’s and mare’s milk with vegetable additives
Authors: Iztileuov Maxat , Ospanov Assan , Dikhanbayeva Fatima , Smailova Zhuldyz , Zhunussova Gulzat
Published: May 2024

The modern market of dairy products is quite developed, but the issue of compliance with the quality and safety of their production remains relevant. The purpose of this paper was to study the organoleptic, physicochemical and safety indicators of combined dairy products based on mare’s and cow’s milk using herbal supplements. In the course of the research, analytical and statistical methods of information processing were used; experimental studies of raw materials and the finished combined product, namely the determination of acidity, solids, fat and protein; energy and biological values of the product were calculated. Technological processes of combined dairy products based on cow’s and mare’s milk using a vegetable origin filler were studied. Of the three prototypes of the proposed dairy products, it was determined to recommend samples No. 2 and 3. High quality indicators are observed in them, in particular, a rich taste with a pronounced taste of additional components, a pleasant smell and appearance. Also, the finished product in samples No. 2 and 3 have high safety indicators. Pathogenic and harmful microorganisms and substances were not found, acceptable microorganisms are within the maximum permissible limits. According to the research results, new dairy products are recommended using vegetable raw materials with different fat, protein, energy value, caloric content and lactose content. In the process of writing this paper, indicators of nutritional, energy value and safety of new types of dairy products based on cow and mare’s milk with vegetable additives were determined. Taking into account the research results and the materials of previous scientific papers, authors consider it promising to develop and sell dairy products based on cow’s and mare’s milk using a filler of plant origin. The advantages of the resulting product include: consumer interest in such products, high quality indicators, product safety, the possibility of using products in functional and specialized nutrition.

Graphical Abstract