bluuebunny/crossref_metadata_2025 huggingface dataset:
Sponge abundance and diversity patterns in the shallow and mesophotic reefs of the northern Red Sea
Authors: Raijman-Nagar Lilach , Goren Liron , Shefer Sigal , Ilan Micha
Published: April 2024

Accumulating data on the increasing degradation of coral reefs worldwide has led to a focus on the unique mesophotic coral ecosystem (MCE) as a potential refuge for threatened shallow-water species (i.e., the deep reef refugia hypothesis: DRRH). Sponges play a crucial role in coral-reef functioning but are often overlooked in benthic surveys. This knowledge gap is especially true for the Red Sea, where data on sponge abundance, coverage and species composition are scarce. Furthermore, to date, no study has examined mesophotic sponges in the Red Sea. Here we compared sponge abundance and diversity metrics between shallow and mesophotic reefs at two sites in the Gulf of Aqaba, northern Red Sea. We also examined the role of biotic and abiotic parameters in determining sponge variability between sites and depths. Sponge diversity metrics significantly varied with increasing depth and between sites. Sponge species composition also differed significantly between depth and sites. However, parameters measured in the water column, that is, Total Organic Carbon (TOC), Particulate Organic Carbon (POC), NOx, etc., did not differ between depths and sites, except for Synechococcus and Prochlorococcus concentration, which did. The findings indicated that site characteristics and biotic interactions may play an essential role in determining sponge diversity and community composition. Between-site differences in sponge fauna revealed in the study highlight the importance of considering the variability in the benthic communities and the factors controlling it when designing management tools for coral reefs, particularly for the northern Red Sea.
Genomic surveillance and serological profile of SARS-CoV-2 variants circulating in Macaé and nearby cities, southeastern Brazil
Authors: da Silva Amanda Cristina Veiga Fernandes , Silva Carina Azevedo Oliveira , de Sousa Graziele Fonseca , Coelho Viktoria Aparecida Gomes Silva , da Cunha Lucas Tavares , Paes Artur Nunes , Pozzobon Allan Pierre Bonetti , das Graças dos Santos Daniele , Carpes Raphael Mello , Costa Evenilton Pessoa , Monteiro-de-Barros Cintia , Nepomuceno-Silva José Luciano , de Souza Gestinari Raquel , Mury Flávia Borges
Published: April 2024

Introduction

A characteristic of the COVID-19 pandemic has been the sequential emergence and global dissemination of SARS-CoV-2 variants, noted for their enhanced transmission efficiency. These variants with mutations in the Spike glycoprotein (S-glycoprotein), which interacts with ACE2 receptors in human cells is critical for infection, affects the transmissibility of the virus, which is a matter of great concern for public health.

Objective

This research analyses the effects these variants on a cohort of vaccinated and naturally infected individuals from the cities of Macaé-RJ, Rio das Ostras-RJ, and Campos dos Goytacazes-RJ, Brazil, from March 2021 to March 2023.

Methods

This investigation encompasses the Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2, B.1.671.3), and Omicron (BQ.1, BQ.1.1 sublines, and BF.7) variants, focusing on their genomic surveillance and implications for the disease’s epidemiology. The experimental analysis included a control group (vaccinated and uninfected subjects), and an infected group (post-vaccinated subjects). Samples from nasopharyngeal swabs underwent viral detection via RT-qPCR for diagnosis confirmation. RNase H-dependent RT-qPCR (rhAmp-PCR) and third-generation sequencing were used to detect SARS-CoV-2 variants. Anti-S-glycoprotein immunoglobulins were also evaluated for vaccinated infected and noninfected volunteers. Symptoms from infected individuals were compiled in order to reveal patterns of clinical signs associated with viral infection.

Results

The study included 289 participants, with infections identified by Gamma (n = 44), Delta (n = 189), and Omicron (n = 56) variants. The prevalent symptoms among the naturally infected participants were cough, fever, sore throat, headache, and runny nose. For Omicron, cognitive symptoms such as memory loss and concentration issues were reported. Interestingly, the infected vaccinated group had higher anti-S-glycoprotein IgM production (n = 28, 0.2833 ± 0.09768 OD) compared to the uninfected vaccinated group (n = 14, 0.1035 ± 0.03625 OD). Conversely, anti-S-glycoprotein IgG production was higher in the control group (n = 12, 1.770 ± 0.1393 OD) than in the infected vaccinated group (n = 26, 1.391 ± 0.1563 OD).

Conclusion

This comprehensive study enables monitoring of predominant variants and their correlation with clinical cases, providing valuable insights for public health. Our research group continues to survey circulating variants, contributing to the global understanding of the pandemic.
Dynamics and thermal stability of the bypass polymerase, DinB homolog (Dbh)
Authors: Soto Jenaro , Moro Sean L. , Cocco Melanie J.
Published: April 2024

The DinB homolog polymerase (Dbh) is a member of the Y-family of translesion DNA polymerases that can synthesize using a damaged DNA template. Since Dbh comes from the thermophilic archaeon Sulfolobus acidocaldarius, it is capable of functioning over a wide range of temperatures. Existing X-ray structures were determined at temperatures where the protein is least active. Here we use NMR and circular dichroism to understand how the structure and dynamics of Dbh are affected by temperature (2°C–65°C) and metal ion binding in solution. We measured hydrogen exchange protection factors, temperature coefficients, and chemical shift perturbations with and without magnesium and manganese. We report on regions of the protein that become more dynamic as the temperature is increased toward the functional temperature. Hydrogen exchange protection factors and temperature coefficients reveal that both the thumb and finger domains are very dynamic relative to the palm and little-finger (LF) domains. These trends remain true at high temperature with dynamics increasing as temperatures increase from 35°C to 50°C. Notably, NMR spectra show that the Dbh tertiary structure cold denatures beginning at 25°C and increases in denaturation as the temperature is lowered to 5°C with little change observed by CD. Above 35°C, chemical shift perturbation analysis in the presence and absence of magnesium and manganese reveals three ion binding sites, without DNA bound. In contrast, these bound metals are not apparent in any Dbh crystal structures of the protein without DNA. Two ion binding sites are confirmed to be near the active site, as reported in other Y-family polymerases, and we report a novel ion binding site in the LF domain. Thus, the solution-state structure of the Dbh polymerase is distinct from that of the solid-state structures and shows an unusually high cold denaturation temperature.
Multimodal cognitive and behavioral interventions for patients with MCI: a systematic review and meta-analysis on cognition and mood
Authors: Ying Gelan , Perez-Lao Ambar , Marsiske Michael , Levy Shellie-Anne , Smith Glenn E.
Published: April 2024

Background

Research has increasingly suggested a benefit to combining multiple cognitive or behavioral strategies in a single treatment program for cognitively impaired older adults. Therefore, this systematic review and meta-analysis aimed to summarize results on the effects of multimodal cognitive and behavioral interventions versus control conditions on changes in cognition and mood in patients with mild cognitive impairment (pwMCI).

Methods

The review followed a general PRISMA guideline for systematic literature review with a format consisting of participants, interventions, comparators, and outcomes (PICO). Multilevel meta-analyses of aggregated efficacy were performed to assess the pooled effect sizes for cognitive and mood outcomes. Risk-of-bias, heterogeneity across studies, and publication bias were assessed for each outcome.

Results

After primary and reference searches, 18 studies with low or some concerns of risk of bias were included. Low heterogeneity was found for mood and cognition. Funnel plots did not indicate publication bias. All the studies assessed changes in cognition (n = 1,555) while seven studies with mood outcomes (n = 343) were included. Multilevel meta-analyses demonstrated moderate effect (Hedge’s g = 0.44, 95% CI = [0.21–0.67]) in cognitive outcomes and large effect in mood (g = 0.65, 95% CI = [0.37–0.93]). Subdomain analyses found low-moderate effects in global cognition, verbal and non-verbal memory, executive function, visuospatial abilities, and semantic fluency (0.20 < g < 0.50).

Conclusion

These findings showed comparable to larger effects of multimodal cognitive and behavioral interventions on cognition than pharmacological treatment. Future studies should focus on the longitudinal effects of multimodal interventions in delaying dementia.

Systematic review registration: PROSEPRO, CRD42022349297.
Research status and global trends of late-life depression from 2004 to 2023: bibliometric analysis
Authors: Du Ruonan , Yang Kebing , Li Wei , Wang Zhiren , Cai Haipeng
Published: April 2024

Background

Global research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear.

Objectives

This study profiled the current state of global research on LLD and predicted future research trends in the field.

Methods

Literature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages.

Results

In total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The International Journal of Geriatric Psychiatry was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots.

Conclusion

Late-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.
Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed pericyte culture
Authors: Ucar Ege Anil , Ozkan Esra , Shomalizadeh Narges , Sekerdağ-Kilic Emine , Akpunar Fatmanur , Sapanci Selin , Kesibi Judy , Ozler Ceyda , Bilgez Alara Su , Gursoy-Ozdemir Yasemin
Published: April 2024

Introduction

Multiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX).

Methods

PLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated.

Results

In the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture.

Discussion

The study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.
Return to work after aneurysmal subarachnoid hemorrhage
Authors: Sorteberg Angelika , Lashkarivand Aslan , Western Elin
Published: April 2024

Introduction

Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often recover without severe physical or cognitive deficits. However, strikingly low levels of engagement in productive employment have also been reported in aSAH patients with good or excellent outcomes. Knowledge about return to work (RTW) after aSAH and predictors of no RTW remain limited and controversial. The study aimed to delineate the return to maximum work capacity up to 5 years after the ictus in a larger number of consecutive aSAH patients from the entire aSAH severity spectrum and to identify demographic and medical predictors of no RTW.

Methods

Data were acquired from a prospective institutional database. We included all 500 aSAH survivors aged > 18 years who were treated between January 2012 and March 2018. In addition to gathering data on work status and the type of work at ictus, we retrieved demographical data and assessed aSAH severity based on the quantification of subarachnoid, intraventricular, and intraparenchymal blood (ICH), as well as the World Federation of Neurological Societies (WFNS) grade. We registered the mode of aneurysm repair (endovascular or surgical) and recorded complications such as vasospasm, newly acquired cerebral infarctions, and chronic hydrocephalus.

Results

Furthermore, work status and the grade of fatigue at follow-up were registered. RTW was assessed among 299 patients who were employed at ictus. Among them, 63.2% were women, and their age was 51.3 ± 9.4 (20–71) years. Return to gainful employment was 51.2%, with complete RTW accounting for 32.4%. The independent predictors of no RTW at ictus were age, the WFNS grade 3, and active smoking. The strongest independent predictor was the presence of clinically significant fatigue, which increased the risk of not returning to work by 5-fold. The chance to return to gainful employment significantly increased with the individual's years of education prior to their hemorrhage. The mode of aneurysm repair was not relevant with regard to RTW. Patients in the WFNS grades 1–2 more often returned to work than those in the WFNS grades 3–5, but our results indicate that neurological motor deficits are linked closer to no RTW than aSAH severity per se.

Conclusion

Fatigue needs to be addressed as an important element on the path to return to work integration.
Defining the concept of reserve in the motor domain: a systematic review
Authors: Giustiniani Andreina , Quartarone Angelo
Published: April 2024

A reserve in the motor domain may underlie the capacity exhibited by some patients to maintain motor functionality in the face of a certain level of disease. This form of “motor reserve” (MR) could include cortical, cerebellar, and muscular processes. However, a systematic definition has not been provided yet. Clarifying this concept in healthy individuals and patients would be crucial for implementing prevention strategies and rehabilitation protocols. Due to its wide application in the assessment of motor system functioning, non-invasive brain stimulation (NIBS) may support such definition. Here, studies focusing on reserve in the motor domain and studies using NIBS were revised. Current literature highlights the ability of the motor system to create a reserve and a possible role for NIBS. MR could include several mechanisms occurring in the brain, cerebellum, and muscles, and NIBS may support the understanding of such mechanisms.
Assessment of nutritional status and health behaviors in yoga-trained women versus exercisers
Authors: Gogojewicz Anna , Pilaczyńska-Szcześniak Łucja , Popierz-Rydlewska Natalia , León-Guereño Patxi , Malchrowicz-Mośko Ewa
Published: April 2024

Introduction

Recreational physical activity is becoming more popular due to the increased public awareness about the beneficial effects on health status and quality of life. The aim of the study was to assess the nutritional status and health behaviors of women who regularly practice yoga as a form of physical recreation and to compare them with those who had not practiced before and had just signed up for yoga classes. A total of 143 women took part in this study.

Methods

The nutritional status was assessed based on the obtained anthropometric measurements. The following indicators were calculated: Body Mass Index (BMI) and waist-to-hip ratio (WHR), determining the visceral accumulation of fat tissue. Health behaviors were assessed using a standardized five-point scale Health Behavior Inventory (HBI).

Results

There were significant differences in the value of the general health behavior index, the sten scale, and the subscale regarding proper eating habits in the study groups compared to women who had not practiced yoga before (control group). Health behaviors indicators, particularly proper eating habits, are significantly higher in women participating regularly in yoga exercises, indicating a higher awareness among yoga practitioners.

Conclusion

It can be suggested that yoga participation as a recreational physical activity can be an appropriate option for pursuing healthy habits.
Sociodemographic characteristics help predict Canadian urbanites’ acceptability of restaurant food environment policies
Authors: Lambert-De Francesch Jessica , Saint-Onge Kadia , Muhajarine Nazeem , Gauvin Lise
Published: April 2024

Introduction

Public acceptability of policies aiming to improve the healthfulness of the restaurant food environment is key to their successful implementation. Yet, the acceptability of these policies remains ambiguous, especially across diverse population groups. This study aims to examine associations between sociodemographic characteristics and acceptability levels of three restaurant food environment policies of varying degrees of intrusiveness across 17 urban Canadian jurisdictions.

Methods

Data was extracted from the THEPA survey, one of the largest and most jurisdictionally comprehensive surveys on intervention acceptability (N = 27,162). To account for potential jurisdictional differences in acceptability, for each policy, multilevel logistic regression models were developed.

Results

Results indicated that, on average, those in complete agreement with the implementation of the targeted policies represented 20.3%–26.9% of participants, depending on the policy. Acceptability varied according to policy intrusiveness, jurisdiction, and participants’ sociodemographic characteristics. Women, individuals with household incomes of <$40,000/year, immigrants from a high-income country other than Canada, and Indigenous peoples were more likely to express complete agreement with all policies, versus men, participants with household incomes of $40,000–$79,999/year, Canadian-born individuals, and non-Indigenous individuals. A lower likelihood of expressing complete agreement with all policies was observed for those with a $80,000–$119,999/year household income, versus those with a $40,000–$79,999/year household income. For selected policies and models, other sociodemographic characteristics (i.e., age, education, and being born in a low-or middle-income country) predicted acceptability. The examined sociodemographic characteristics did not explain jurisdictional differences in acceptability.

Discussion

Understanding jurisdictional differences in acceptability merits further research. Policy implications involve engaging diverse sociodemographic groups in conversations about acceptable ways in which their restaurant food environment could be rendered more healthful.
Specifically formulated ketogenic, low carbohydrate, and carnivore diets can prevent migraine: a perspective
Authors: Stanton Angela A.
Published: April 2024

This article presents a hypothesis explaining the cause of migraines, suggesting that electrolyte imbalance, specifically a lack of sufficient sodium in the extracellular space of sensory neurons, leads to failed action potentials. The author argues that migraines are triggered when sodium channels fail to initiate action potentials, preventing communication between neurons. The article discusses the evolutionary perspective of the migraine brain, stating that migraineurs have a hypersensitive brain with more sensory neuronal connections, making them more reactive to environmental stimuli and in need of more minerals for the increased sensory neuronal communication. Since glucose is often used to reduce serum hypernatremia, it follows that a high carbohydrate diet reduces sodium availability for use in the brain, causing an electrolyte imbalance. Low carbohydrate diets, such as ketogenic, low carb-high fat (LCHF), and carnivore (all animal products), can be beneficial for migraineurs by reducing/eliminating carbohydrate intake, thereby increasing sodium availability. In support, many research papers and some anecdotal evidences are referred to. The article concludes by proposing lifestyle modifications, such as dietary changes and sodium intake management. These will provide migraineurs with a long-term healthy metabolic foundation helping them to maintain strong nutritional adherence and with that aiding continued proper neuronal functioning and migraine free life.
A Mendelian randomization study to examine the causal associations of circulating micronutrient levels with frailty risk
Authors: Kuribanjiang Kaidiriyan , Min Yiping , Yan Shikang , Chen Simin , Aiheti Nuerbiyamu , Wupuer Abudunaibi , Wang Jie , Peng Xing , Li Yihan , Li Huilong , Dong Yiran , Fan Yuanlin , Yang Lei , Zhao Jianping
Published: April 2024

Background

Observational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach.

Methods

We gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty.

Results

Our study found, no causal relationship between genetically predicted vitamin D (β = −0.059, p = 0.35), vitamin B6 (β = 0.006, p = 0.80), vitamin E (β = −0.011, p = 0.79), vitamin C (β = −0.044, p = 0.06), vitamin B12 (β = −0.027, p = 0.37), and folate (β = 0.029, p = 0.17), with frailty.

Conclusion

This study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.
MAMILNet: advancing precision oncology with multi-scale attentional multi-instance learning for whole slide image analysis
Authors: Wang Qinqing , Bi Qiu , Qu Linhao , Deng Yuchen , Wang Xianhong , Zheng Yijun , Li Chenrong , Meng Qingyin , Miao Kun
Published: April 2024

Background

Whole Slide Image (WSI) analysis, driven by deep learning algorithms, has the potential to revolutionize tumor detection, classification, and treatment response prediction. However, challenges persist, such as limited model generalizability across various cancer types, the labor-intensive nature of patch-level annotation, and the necessity of integrating multi-magnification information to attain a comprehensive understanding of pathological patterns.

Methods

In response to these challenges, we introduce MAMILNet, an innovative multi-scale attentional multi-instance learning framework for WSI analysis. The incorporation of attention mechanisms into MAMILNet contributes to its exceptional generalizability across diverse cancer types and prediction tasks. This model considers whole slides as “bags” and individual patches as “instances.” By adopting this approach, MAMILNet effectively eliminates the requirement for intricate patch-level labeling, significantly reducing the manual workload for pathologists. To enhance prediction accuracy, the model employs a multi-scale “consultation” strategy, facilitating the aggregation of test outcomes from various magnifications.

Results

Our assessment of MAMILNet encompasses 1171 cases encompassing a wide range of cancer types, showcasing its effectiveness in predicting complex tasks. Remarkably, MAMILNet achieved impressive results in distinct domains: for breast cancer tumor detection, the Area Under the Curve (AUC) was 0.8872, with an Accuracy of 0.8760. In the realm of lung cancer typing diagnosis, it achieved an AUC of 0.9551 and an Accuracy of 0.9095. Furthermore, in predicting drug therapy responses for ovarian cancer, MAMILNet achieved an AUC of 0.7358 and an Accuracy of 0.7341.

Conclusion

The outcomes of this study underscore the potential of MAMILNet in driving the advancement of precision medicine and individualized treatment planning within the field of oncology. By effectively addressing challenges related to model generalization, annotation workload, and multi-magnification integration, MAMILNet shows promise in enhancing healthcare outcomes for cancer patients. The framework’s success in accurately detecting breast tumors, diagnosing lung cancer types, and predicting ovarian cancer therapy responses highlights its significant contribution to the field and paves the way for improved patient care.
A hybrid deep learning scheme for MRI-based preliminary multiclassification diagnosis of primary brain tumors
Authors: Wang Zhichao , He Chuchu , Hu Yan , Luo Haifeng , Li Chao , Wu Xiandong , Zhang Yang , Li Jingjing , Cai Jun
Published: April 2024

Objectives

The diagnosis and treatment of brain tumors have greatly benefited from extensive research in traditional radiomics, leading to improved efficiency for clinicians. With the rapid development of cutting-edge technologies, especially deep learning, further improvements in accuracy and automation are expected. In this study, we explored a hybrid deep learning scheme that integrates several advanced techniques to achieve reliable diagnosis of primary brain tumors with enhanced classification performance and interpretability.

Methods

This study retrospectively included 230 patients with primary brain tumors, including 97 meningiomas, 66 gliomas and 67 pituitary tumors, from the First Affiliated Hospital of Yangtze University. The effectiveness of the proposed scheme was validated by the included data and a commonly used data. Based on super-resolution reconstruction and dynamic learning rate annealing strategies, we compared the classification results of several deep learning models. The multi-classification performance was further improved by combining feature transfer and machine learning. Classification performance metrics included accuracy (ACC), area under the curve (AUC), sensitivity (SEN), and specificity (SPE).

Results

In the deep learning tests conducted on two datasets, the DenseNet121 model achieved the highest classification performance, with five-test accuracies of 0.989 ± 0.006 and 0.967 ± 0.013, and AUCs of 0.999 ± 0.001 and 0.994 ± 0.005, respectively. In the hybrid deep learning tests, LightGBM, a promising classifier, achieved accuracies of 0.989 and 0.984, which were improved from the original deep learning scheme of 0.987 and 0.965. Sensitivities for both datasets were 0.985, specificities were 0.988 and 0.984, respectively, and relatively desirable receiver operating characteristic (ROC) curves were obtained. In addition, model visualization studies further verified the reliability and interpretability of the results.

Conclusions

These results illustrated that deep learning models combining several advanced technologies can reliably improve the performance, automation, and interpretability of primary brain tumor diagnosis, which is crucial for further brain tumor diagnostic research and individualized treatment.
Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response
Authors: Cosma Andrei Alexandru , Fenesan Mihaela Pasca , Nesiu Alexandru , Melnic Eugen , Ferician Adela Maria , Ferician Ovidiu Catalin , Ceban Emil , Sarb Simona , Cimpean Anca Maria
Published: April 2024

Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney’s blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.
The treatment process of a giant phyllodes tumor of the breast: a case report and review of the literature
Authors: Tong Yujun , Liu Siyu , Zhao Lijuan , Zhang Zhen , Hu Haiyan , Jing Yu , Liang Tiantian
Published: April 2024

Giant phyllodes tumors are rare fibroepithelial tumors that are usually larger than 10 cm in diameter, have rapid tumor growth, and are easily recurrent. They are frequently accompanied by skin necrosis and infection, particularly in malignant phyllodes tumors. This case report presents a 50-year-old woman who presented to the hospital with a huge left breast mass that was ruptured and infected. The patient received anti-infective treatment and underwent mastectomy and skin grafting, which indicated a malignant phyllodes tumor. The tumor was completely excised after a local recurrence in the chest wall 6 months post-surgery. Unfortunately, one year later, the patient pass away due to multiple organ failure. Giant phyllodes tumor management presents challenges to the surgeon. This case is being presented to enhance understanding and treatment of phyllodes tumors, specifically giant malignant phyllodes tumors, with the aim of improving patients’ quality of life.
MK591 (Quiflapon), a 5-lipoxygenase inhibitor, kills pancreatic cancer cells via downregulation of protein kinase C-epsilon
Authors: Monga Jitender , Ghosh Ritisha , Guddeti Rohith , Chitale Dhananjay , Khan Gazala , Ghosh Jagadananda
Published: April 2024

Introduction

Pancreatic tumors and cell lines derived from them exhibit elevated expression of 5-lipoxygenase (5-Lox), whereas non-tumor glands or normal cells do not exhibit this overexpression. Arachidonic acid stimulates pancreatic cancer cell growth via metabolic conversion through the 5-Lox pathway, and inhibition of 5-Lox activity decreases the viability of pancreatic cancer cells. However, the downstream signaling mechanisms through which 5-Lox exerts its effects on the survival of pancreatic cancer cells remain to be elucidated.

Methods

The effects of 5-Lox inhibition on cell proliferation, apoptosis, and invasive potential were investigated in pancreatic cancer cells. The protein expression was analyzed by Western blot. Apoptosis was analyzed by Annexin-V binding assay and by detecting the degradation of chromatin-DNA to nucleosomal fragments. The protein kinase C-epsilon (PKCε) activity was measured by an immunoprecipitation-kinase assay. The in vivo effects of MK591 were evaluated in pancreatic tumor xenograft model.

Results

MK591, a specific inhibitor of 5-Lox activity, killed pancreatic cancer cells via induction of apoptosis, involving externalization of phosphatidylserine, cleavage of PARP (poly-ADP ribose polymerase) and degradation of chromatin DNA to nucleosomes. MK591 effectively blocked in vitro invasion and soft-agar colony formation by pancreatic cancer cells and decreased pancreatic tumor growth in nude mice xenografts. Furthermore, inhibition of 5-Lox downregulated K-Ras and inhibited phosphorylation of c-Raf and ERKs. Interestingly, 5-Lox inhibition induced apoptosis in pancreatic cancer cells without the inhibition of Akt but the protein level of PKCε was dramatically downregulated. Furthermore, inhibition of 5-Lox decreased the phosphorylation of Stat3 at Serine-727. Pre-treatment of pancreatic cancer cells with peptide activators of PKCε prevented apoptosis induced by 5-Lox inhibition, suggesting that the mechanism by which 5-Lox inhibition causes cell death in pancreatic cancer involves downregulation of PKCε. The combination of low doses of MK591 and gemcitabine synergistically reduced the oncogenic phenotype and killed pancreatic cancer cells by inducing apoptosis.

Discussion

These findings indicate that inhibition of 5-Lox interrupts an Akt-independent, PKCε-dependent survival mechanism in pancreatic cancer cells and suggest that metabolism of arachidonic acid through the 5-Lox pathway plays an integral part in the survival of pancreatic cancer cells via signaling through PKCε, an oncogenic, pro-survival serine/threonine kinase.
Diagnostic testing for chest pain in a pediatric emergency department and rates of cardiac disease before and during the COVID-19 pandemic: a retrospective study
Authors: Atmanli Ayhan , Yen Kenneth , Zhou Amy Z.
Published: April 2024

Objectives

Chest pain is a common chief complaint in pediatric emergency departments (EDs). Coronavirus disease-2019 (COVID-19) has been shown to increase the risk of cardiac disease. It remains unclear how COVID-19 changed how pediatric emergency clinicians approach patients presenting with chest pain. The goal of this study was to characterize the diagnostic testing for chest pain in a pediatric ED before and during the COVID-19 pandemic.

Methods

This was a retrospective study of children between the ages of 2–17 years presenting to a pediatric ED from 1/1/2018–2/29/2020 (Pre-COVID-19) and 3/1/2020–4/30/2022 (COVID-19) with chest pain. We excluded patients with a previous history of cardiac disease.

Results

Of the 10,721 encounters during the study period, 5,692 occurred before and 5,029 during COVID-19. Patient demographics showed minor differences by age, weight, race and ethnicity. ED encounters for chest pain consisted of an average of 18% more imaging studies during COVID-19, including 14% more EKGs and 11% more chest x-rays, with no difference in the number of echocardiograms. Compared to Pre-COVID-19, 100% more diagnostic tests were ordered during COVID-19, including cardiac markers Troponin I (p < 0.001) and BNP (p < 0.001). During COVID-19, 1.1% of patients had a cardiac etiology of chest pain compared with 0.7% before COVID-19 (p = 0.03).

Conclusions

During COVID-19, pediatric patients with chest pain underwent more diagnostic testing compared to Pre-COVID-19. This may be due to higher patient acuity, emergence of multisystem inflammatory syndrome in children (MIS-C) that necessitated more extensive testing and possible changes in ED clinician behavior during COVID-19.
Cognitive performance in children and adolescents with primary hypertension and the role of body mass
Authors: Azukaitis Karolis , Puteikis Kristijonas , Kinciniene Odeta , Mikucionyte Dovile , Mameniskiene Ruta , Jankauskiene Augustina
Published: April 2024

Objective

Primary hypertension has been shown to affect cognitive functions in adults but evidence in the pediatric population remain scarce and equivocal. We aimed to compare cognitive functioning between children diagnosed with primary hypertension and normotensive controls, with a focus on the role of different blood pressure (BP) parameters and body mass.

Methods

We conducted a single-center, prospective, cross-sectional study of children and adolescents (6–17 years old) with primary hypertension and age- and sex-matched normotensive controls. All participants underwent office BP, ambulatory BP monitoring (ABPM), and central BP measurements using an oscillometric device. Neurocognitive assessment consisted of evaluation of (i) intelligence quotient (IQ), (ii) categorical and phonemic fluency, (iii) verbal memory (verbal-logical story recall), and (iv) non-verbal computerized cognitive assessment.

Results

The study included a total of 59 patients with primary hypertension (14 ± 3 years) and 37 normotensive controls (14 ± 3 years). Participants in the primary hypertension group had a significantly higher body mass index z-score (BMIz: 2.1 ± 1.4 vs. 0.7 ± 0.9, p < 0.001), and 85% received antihypertensive therapy. Participants with primary hypertension showed worse performance in the domains of reaction speed, attention and processing speed, visual memory, new learning, and phonemic fluency. After adjusting for BMIz, only the differences in the reaction speed tasks remained significant. None of the BP parameters was associated with cognitive outcomes after adjustment for age, sex, and BMIz. BMIz associated with tasks of visual memory, new learning, spatial planning, and working memory, independent of age and sex.

Conclusion

Children and adolescents diagnosed with primary hypertension exhibit worse performance in the cognitive domains of reaction speed, attention, processing speed, visual memory, and new learning. These differences to healthy controls can be partially attributed to accompanying increase of body mass.
Past and future of an IMI-PharmaTrain (IMI-PhT)-initiated multinational pharmaceutical medicine course at the Semmelweis University in Hungary
Authors: Kerpel-Fronius S. , Gottwald M. , Arányi P. , Renczes G. , Görbe A. , Papp R. , Ferdinandy P.
Published: April 2024

The pharmaceutical medicine course at the Semmelweis University of Budapest, Hungary, was initiated as part of the Innovative Medicines Initiative (IMI is the main program, IMI-PharmaTrain is one of the IMI projects) Pharmaceutical Medicine Training Programs (16 IMI Call 2008/1/16). The aim was to extend training in the development of pharmaceutical medicine to those EU member states where no such education was present. The final program envisaged the development of a cooperative education supported by universities located in Central and Eastern Europe. It was considered to be the economically and scientifically most viable approach to combine the expertise from these countries to form a united teaching staff and provide education jointly for young professionals of the region. Semmelweis University was selected to manage this coordinated program. In this report, we describe the organization and functioning of this international university-based pharmaceutical medicine education project called the Cooperative European Medicines Development Course (CEMDC) and evaluate its successes and shortcomings. During the pandemic, the educational course was interrupted. The follow-on program is reorganized as a postgraduate MSc course named “Semmelweis Pharma MBA” and will be started in 2025. It will continue the established PharmaTrain educational tradition. However, it will deal in more detail with the transition from basic pharmacological to industrial research, as well as biopharmaceutical formulation and manufacturing and marketing aspects of medicines development.
Predicting the suitable cultivation areas of breadfruit crops Artocarpus altilis (Moraceae) under future climate scenarios in Central Java, Indonesia
Authors: Utomo Suyud Warno , Lestari Fatma , Adiwibowo Andrio , Fatmah  , Fisher Micah R. , Qadriina Hafizha Ilma
Published: April 2024

Artocarpus altilis, commonly known as breadfruit, is a potential crop adapted to a wide variety of climates and widely spread, including in Indonesia. However, information on how this species can adapt to climate change, in particular in Central Java, is still limited. In Indonesia, Central Java is the center for cultivation areas for many crop species to support the 145 million people living on Java Island. One of the potential crops being developed in Central Java is breadfruit. To assess the suitable cultivation areas for breadfruit, species distribution modeling (SDM) was used to predict the current and future (2050–2070) distribution of breadfruit. Two climate change scenarios, including optimistic RCP2.6 and pessimistic RCP8.5 models, were considered to represent future climate change impacts. Based on the results for both optimistic and pessimistic scenarios, the breadfruit’s suitable cultivation areas will expand eastward. Implementing a mitigation climate change scenario and limiting the temperature increase to only 1°C under RCP2.6 will provide 270.967 km2 more of suitable cultivation areas for breadfruit in 2050 and 133.296 km2 in 2070. To conclude, this study provides important information on the status and potential cultivation areas for breadfruit, mainly in the Southeast Asia region. The identification of suitable areas will guide land conservation for breadfruit to support food security in this region.
The fungicide pyraclostrobin affects gene expression by altering the DNA methylation pattern in Magnaporthe oryzae
Authors: Fang Shumei , Wang Hanxin , Qiu Kaihua , Pang Yuanyuan , Li Chen , Liang Xilong
Published: April 2024

Introduction

Rice blast disease caused by Magnaporthe oryzae has long been the main cause of rice (Oryza sativa L.) yield reduction worldwide. The quinone external inhibitor pyraclostrobin is widely used as a fungicide to effectively control the spread of pathogenic fungi, including M. oryzae. However, M. oryzae can develop resistance through multiple levels of mutation, such as target protein cytb mutation G143A/S, leading to a decrease in the effectiveness of the biocide after a period of application. Therefore, uncovering the possible mutational mechanisms from multiple perspectives will further provide feasible targets for drug development.

Methods

In this work, we determined the gene expression changes in M. oryzae in response to pyraclostrobin stress and their relationship with DNA methylation by transcriptome and methylome.

Results

The results showed that under pyraclostrobin treatment, endoplasmic reticulum (ER)-associated and ubiquitin-mediated proteolysis were enhanced, suggesting that more aberrant proteins may be generated that need to be cleared. DNA replication and repair processes were inhibited. Glutathione metabolism was enhanced, while lipid metabolism was impaired. The number of alternative splicing events increased. These changes may be related to the elevated methylation levels of cytosine and adenine in gene bodies. Both hypermethylation and hypomethylation of differentially methylated genes (DMGs) mainly occurred in exons and promoters. Some DMGs and differentially expressed genes (DEGs) were annotated to the same pathways by GO and KEGG, including protein processing in the ER, ubiquitin-mediated proteolysis, RNA transport and glutathione metabolism, suggesting that pyraclostrobin may affect gene expression by altering the methylation patterns of cytosine and adenine.

Discussion

Our results revealed that 5mC and 6mA in the gene body are associated with gene expression and contribute to adversity adaptation in M. oryzae. This enriched the understanding for potential mechanism of quinone inhibitor resistance, which will facilitate the development of feasible strategies for maintaining the high efficacy of this kind of fungicide.
Alterity-space: national spatiality in Lasnamäe, Estonia
Authors: Shaharyar Nawal
Published: April 2024

This research investigates the relationship between the city and the state in framing the national belonging of space as arenas of inclusion and difference within the nation. It is argued that bringing Isin and Lefebvre into dialogue allows for a genealogical analysis of space as a social product imbued in and constituted by narratives of national inclusion (or exclusion). This research develops the concept of alterity-space as a distinct spatial category in which the constitution of citizenship is inscribed on socially produced space. This alterity-space refers to categories of difference as an internal other of space at odds with the space of the nation. Alterity-space as a concept invites reflection on how state engagement, competing symbolisms, narratives, and interactions produce spatiality and create mechanisms of othering that obscure other articulations of national belonging in space. This approach is illustrated through a genealogical examination of Lasnamäe, an urban district at the heart of Estonia’s capital. In the constitution of national, ecological, digital, and European identities, Lasnamäe is positioned as an alterity-space to Tallinn and Estonia. This positioning reflects how space itself becomes imbued as an immediate other at odds with Estonia’s past and future of national belonging.