bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning-Based Approaches for Brain Tumour Segmentation and Classification
Authors: Baiju Vidya , J Akshitha , Naveen S Namasiyava
Published: September 2024

Brain tumours are caused by the abnormal growth of cells in the brain. This occurs mainly due to genetic changes or exposure to X-ray radiation. When the tumours are detected early, they can be removed via surgery. The tumour can be removed through radiotherapy and chemotherapy if the removal of the tumour through surgery affects the survival rate. There are two main classifications of tumours: malignant or cancerous and benign or non-cancerous. Deep learning techniques are considered as they require more minimal human intervention than machine learning; they are built to accommodate huge amounts of unstructured data, while machine learning uses traditional algorithms. Though deep learning takes time to set up, the results are generated instantaneously. In this review, the authors focus on the various deep learning techniques and approaches that could detect brain tumours that were analysed and compared. The different types of deep learning approaches investigated are convolutional neural network (CNN), cascaded CNN (C-CNN), fully CNN and dual multiscale dilated fusion network, fully CNN and conditional random field, U-net convolutional network, fully automatic heterogeneous segmentation using support vector machine, residual neural network, and stacked denoising autoencoder for brain tumour segmentation and classification. After reviewing the algorithms, the authors have listed them based on their best accuracy (U-net convolutional network), dice score (residual neural network), and sensitivity score (cascaded CNN).
Right Lateral Digital Rectal Examination in Men with Suspected Prostate Disease Presenting with Lower Urinary Tract Symptoms
Authors: Takure Augustine O
Published: September 2024

Background: The prostate gland is anterior to the rectum. There are different positions for digital rectal examination, and 95% of individuals are right-handed. This study aimed to determine the suitability and efficacy of right lateral digital rectal examination (RLDRE).

Methods: A prospective cross-sectional study was conducted in a tertiary hospital on men with lower urinary tract symptoms due to benign prostate enlargement or prostate cancer. The perceptions of patients, surgical trainees, and medical students during RLDRE was assessed using the Likert scale questionnaire. The age and clinical presentation were documented. The ability to appreciate abnormal prostate disease was evaluated. The data was analysed using Statistical Package for Social Sciences (SPSS) version 24 (IBM, Armonk, New York, USA). Pearson’s correlation coefficient for non-categorical variables was performed and the level of significance was p<0.001. Ethical approval was obtained.

Results: A total of 203 patients were recruited, of which surgical trainees and medical students assessed 130 and 73 patients, respectively. The patients’ mean age was 69.5±9.1 years. The main presentations were urethral catheter in situ due to acute urinary retention in 77 patients (37.9%) and moderate lower urinary tract symptoms in 62 patients (30.5%). The number of patients with the RLDRE perception of well-tolerated, less awkward, and less painful were 161 (79.7%), 121 (59.9%), and 130 (64.4%), respectively. The perceptions of surgical trainees and medical students for ease of RLDRE were 77.7% and 74%, respectively, and for detection of abnormality were 57% and 68.5%, respectively. Detection rates for prostate cancer by surgical trainees and medical students were 87.5% and 75%, respectively, and for benign prostatic hyperplasia were 87.5% and 62.5%, respectively.

Conclusion: RLDRE was well tolerated by patients. Surgical trainees and medical students were comfortable with RLDRE with reasonable detection of benign prostatic hyperplasia and prostate cancer.
The Application, Safety, and Recent Developments of Commonly Used Gadolinium-Based Contrast Agents in MRI: A Scoping Review
Authors: Islam Moh. Tawhid , Tsnobiladze Vera
Published: September 2024

Gadolinium-based contrast agents (GBCA) have played a pivotal role in enhancing the diagnostic capabilities of MRI for several decades. The application of gadolinium as a contrast agent opened new possibilities for early diagnosis with greater accuracy of a wide range of conditions, including neurologic and vascular disorders, tumours, cancers, inflammation, and more. Gadolinium is a lanthanide metal known for its strong paramagnetic properties, which produce stronger signals in MRI. The presence of GBCAs in the body alters the magnetic properties of nearby water molecules, which changes the appearance of the organs or blood vessels containing contrast when the MRI images are taken. The safety of GBCAs has been widely studied in recent years. Gadolinium is generally considered a safe and relatively non-toxic contrast agent, according to many of these studies. Many clinical studies have also shown toxic effects, allergic reactions, and gadolinium deposition in different body tissues and the brain. The rare condition of nephrogenic systemic fibrosis in adult patients with renal dysfunction has been the most popular topic of research and the main concern amongst all other risks of post-GBCA use. This review explores various research papers regarding GBCAs and focuses on providing insight into how different types of GBCAs are commonly used today in MRI scans, their properties, clinical applications, safety concerns, and recent and possible future developments in this field of medical radiology.
Sağlık Turizmi Kapsamında Medikal (Tıbbi) Turizm Potansiyelinin ve Sürdürülebilirliğinin Kayseri Örneğinde Değerlendirilmesi
Authors: Koca Ramazan
Published: September 2024

Sağlık turizmi içerisinde yer alan medikal (tıbbi) turizm günümüzde gerek kişisel bakım hizmetlerinin çeşitlenmesi gerekse farklı ve uygun tedavi seçeneklerin artması nedeniyle küresel çapta gelişimi ve yaygınlığı hızla artan bir turizm türünü oluşturmaktadır. Araştırmanın amacı Kayseri’nin medikal (tıbbi) turizm potansiyelinin ve sürdürülebilirliğinin ilgili paydaş görüşlerine göre değerlendirilmesine dayanmaktadır. Araştırma nitel araştırma yönteminde görüşme tekniğine dayalı olarak gerçekleştirilmiştir. Bu kapsamda alanda konuyla ilgili paydaşlardan oluşan 20 katılımcı ile yüz yüze derinlemesine görüşmeler gerçekleştirilmiştir. Görüşmeler Nvivo 10 nitel veri analiz programı aracılığıyla kodlar oluşturulup analiz edilmiştir. Araştırmanın sonucunda uygun tedavi imkânları, yeterli sağlık merkezleri ve alanında uzman hekimlerinin olması alanın medikal anlamda potansiyelini artırmaktadır. Bunun yanında teknolojiye dayalı tedavilerin gerçekleştirilmesi, hasta memnuniyeti, turizm etkinliklerinin tıbbi tedaviyle birleştirilip tur paketlerinin hazırlanmasının medikal turizmin sürdürülebilirliği üzerinde etkili olduğu sonucuna ulaşılmıştır. Ayrıca medikal turizmin gelişiminin ekonomik, sosyal ve kültürel gelişim ile ilişkili olduğu ve birçok sektörün gelişimini etkilemesi bakımından sürdürülebilirliğinin sağlanması gerektiği ortaya çıkmaktadır.
The Concept of Migration in Sufism
Authors:   Azerbaijan Institute of Theology, Demirzadeh Mehrab , Allahverdiyev Ibrahim
Published: September 2024

In the science of Sufism, the concept of migration is widely used, both in an external and internal sense. Hijra, or migration, is not merely a physical journey but also reflects a deeper, broader meaning. Beyond the universally understood meaning of hijra, it also encompasses concepts such as "leaving behind evils, undergoing spiritual transformation, abandoning forbidden activities, staying away from bad traits, and embarking on a spiritual journey." According to hadiths, the Prophet Muhammad (saw) defined the Muhajir (a person who has migrated) as "...the Muhajir is a person who distances themselves from what God has forbidden." Additionally, students of knowledge and Sufi sheikhs often traveled to different countries to further their education, spread the religion, and share their knowledge with others. They frequently stayed for extended periods in the places they visited. In the science of Sufism, many terms are closely related to the concept of migration. Examples include the phenomena of Isra and Miraj, as well as concepts like seiri-suluk, journey, asceticism, and riyazat. Each of these holds its own significance and wisdom in the lives of those who seek knowledge.
The Formation of a New Soviet Education System in Azerbaijan SSR
Authors:   Azerbaijan Cooperation University, Aliyeva Aynur
Published: September 2024

This paper addresses the development of the education system during the Soviet period, with particular attention given to the role of intellectuals in the growth of education. The establishment of the new Soviet education system in Azerbaijan faced significant challenges, such as the lack of qualified teaching staff. It was necessary to prepare educators, introduce new teaching materials and programs, and apply progressive teaching methods. In response, the Soviet government of Azerbaijan issued a series of decrees and orders in 1920 to guide the development of public education. These aspects are given special attention in this article. Azerbaijani intellectuals endeavored to create all possible opportunities for the advancement of education. The 20th century holds a special place as a productive period in the enrichment of Azerbaijani culture, which is an integral part of human civilization. This period of history is distinguished by its unique characteristics, historical and social conditions, all of which left a profound impact on the fields of culture and art. The 20th century is remembered as a time of social and political revolutions and changes in the history of the Azerbaijani people. Although the social, historical, and political changes had a significant impact on national culture and art, this period can generally be characterized as a productive stage of development. At the beginning of the century, the efforts of national enlightened forces in cultural development, their initiatives, and their work in organizing and forming various cultural and artistic fields provided a major impetus for the revival of culture in Azerbaijan. It was necessary to create a new system of public education, develop a wide network of cultural and educational institutions, lay the foundations of scientific knowledge, familiarize the working class with artistic resources, free women from patriarchal oppression, eliminate harmful customs and ceremonies, and pave the way for the cultural and spiritual development of individuals.
On the Paper Currency of the Central Workers' Cooperative "Gornyak" in Baku
Authors:   Bonist - researcher, Zeyniyev Habil , Pirguliyeva Ganira ,   Baku State University, Alizade Sayavush ,   Scientific-Methodological Center for Higher Qualifications at the Ministry of Culture
Published: September 2024

This article is the result of many years of research on the issuance of paper currency by the Central Workers' Cooperative "Gornyak" in Baku. For the first time, based on relevant literature and factual material (including unique, full-color illustrations of currency notes), the article provides information on the history, classification, cataloging, and complete nominal range of currency notes issued by this cooperative during 1924- 1925. Through the study of the material presented in the article, various types of additional seals and stamps used in the circulation and implementation of currency during this period have been identified. These findings have helped clarify more accurate information about the notaphily of Azerbaijan. The authors hope that their work will encourage further study and research into this interesting issuance by notaphilists and will fill the gap in this field.
Genome-wide analysis reveals the MORC3-mediated repression of PD-L1 expression in head and neck cancer
Authors: Fu Wenxuan , Chang Xiaomeng , Ye Kun , Zheng Zige , Lai Qianyi , Ge Minyang , Shi Yan
Published: September 2024

Introduction

Programmed death-ligand 1 (PD-L1) plays essential roles in the negative regulation of anti-tumor immunity. However, the regulatory mechanisms of PD-L1 expression need further exploration. MORC family CW-type zinc finger 3 (MORC3) is a transcriptional factor that regulates innate immune responses, but the expression and roles of MORC3 in cancers remain largely unknown. The present study explored the expression of MORC3 in cancers at both transcriptional and translational levels.

Methods

The target genes and pathways were analyzed using RNA interference (RNAi), RNA sequencing (RNA-seq), and quantitative real-time polymerase chain reaction (qRT-PCR) technology in head and neck cancer cells. The expression of MORC3 and its target genes were also analyzed in single cancer cells.

Results

MORC3 was significantly downregulated in multiple cancers, including head and neck cancer, and low expression of MORC3 was associated with poor overall survival. MORC3 knockdown significantly increased the expression of many immune-related genes, including interferon (IFN)-associated genes [MX dynamin like GTPase 2 (MX2), interferon induced protein with tetratricopeptide repeats 1 (IFIT1), interferon induced protein with tetratricopeptide repeats 2 (IFIT2), interferon regulatory factor 7 (IRF7), interferon regulatory factor 9 (IRF9), interferon induced protein 44 like (IFI44L), interferon induced transmembrane protein 1 (IFITM1), interferon induced transmembrane protein 3 (IFITM3), interferon induced protein 44 (IFI44), and interferon induced with helicase C domain 1 (IFIH1)]. MORC3 knockdown significantly upregulated PD-L1 and signal transducer and activator of transcription 1 (STAT1) expression. Moreover, the LINC00880 immune-related long non-coding RNA (lnc-RNA) was upregulated by MORC3 knockdown. Silencing LINC00880 attenuated PD-L1 expression. MORC3 knockdown also increased the expression of cellular proliferation-related genes and promoted cancer cell proliferation.

Conclusion

The present study demonstrated that MORC3 regulates IFN-associated pathways and is a novel repressor of PD-L1 expression and cancer cell proliferation.
Effects of four potent entomopathogenic fungal isolates on the survival and performance of Telenomus remus, an egg parasitoid of fall armyworm
Authors: Chepkemoi Junitor , Fening Ken Okwae , Ambele Felicitas Chaba , Munywoki Joseph , Akutse Komivi Senyo
Published: September 2024

Fall armyworm (FAW), Spodoptera frugiperda is a generalist pest known to feed on more than 300 plant species, including major staple crops such as rice, maize and sorghum. Biological control of FAW using a combination of a major indigenous egg parasitoid Telenomus remus and entomopathogenic fungi was explored in this study. Metarhizium anisopliae strains (ICIPE 7, ICIPE 41, and ICIPE 78) and Beauveria bassiana ICIPE 621 which demonstrated effectiveness to combat the pest, were evaluated through direct and indirect fungal infection to assess their pathogenicity and virulence against T. remus adults, S. frugiperda eggs and their effects on T. remus parasitism rates. Metarhizium anisopliae ICIPE 7 and ICIPE 78 exhibited the highest virulence against T. remus adults with LT50 values >2 days. ICIPE 7 induced the highest T. remus mortality rate (81.40 ± 4.17%) following direct infection with dry conidia. Direct fungal infection also had a significant impact on parasitoid emergence, with the highest emergence rate recorded in the M. anisopliae ICIPE 7 treatment (42.50 ± 5.55%), compared to the control ± (83.25 ± 5.94%). In the indirect infection, the highest concentration of 1 x 109 conidia ml-1 of ICIPE 78 induced the highest mortality (100 ± 0.00%) of T. remus adults, and the highest mortality (51.25%) of FAW eggs, whereas the least FAW egg mortality (15.25%) was recorded in the lowest concentration 1 x 105 conidia ml-1 of ICIPE 41. The number of parasitoids that emerged and their sex ratios were not affected by the different fungal strain concentrations except in ICIPE 7 at high dose. This study showed that potential combination of both M. anisopliae and B. bassiana with T. remus parasitoid can effectively suppress FAW populations.
Specific cell subclusters of dental pulp stem cells respond to distinct pathogens through the ROS pathway
Authors: Xu Tiansong , Liu Yangjia , Zhang Wen , Li Murong , Zhang Liqi , Li Xueying , Zhang Yifei , Yue Lin , Li Sha , Lin Ye , Zou Xiaoying , Chen Feng
Published: September 2024

Introduction

Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection.

Methods

DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed.

Results

DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a.

Conclusions

Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.
How media narratives can be used in Decision Making under Deep Uncertainty practice?
Authors: Molina-Perez Edmundo , Lempert Robert J. , Wong Jody Chin Sing
Published: September 2024

Media narratives employed in contemporary journalism, including data journalism, are critical in shaping public understanding of the complex systems that affect our lives. Depicting a chain of events in a “story” format, narratives are constructed with detailed, precise, and well-researched information based on character identification, human emotions, and real social problems. In many ways, they are indispensable intermediaries of practiced judgment and expertise that guide the public to meaningfully engage with evidence-based understanding of our world and how we can act upon it. DMDU narratives suggest that we can act to shape the future toward our liking even when we cannot predict what that future will be, that we need to simultaneously consider multiple rather than a single future, and that the quest for prediction can interfere with the task of identifying the best actions. DMDU practice relies on substantive stakeholder interaction, and it is supported by vast amounts of empirical evidence. This perspective discusses how media narratives intersect with DMDU to inform and to leverage the complexities of modern contemporary public challenges. We first explore how uncertainty might be actionable, as opposed to fearful. Next, while acknowledging limitations on transference of information during the journalistic process, we address the challenges and best strategies to distill information to the public to maintain and build trust about uncertainty. Next, we discuss how journalistic practices could be useful for disseminating more broadly findings of DMDU analyses.
Case Report: Lung cancer with rare cardiac and other multiple metastases
Authors: Chen Li , Zhang Jing , Zhang Chunquan
Published: September 2024

Metastasis to the left atrium is exceptionally uncommon, occurring at a rate of only 3.1%. The clinical manifestations of lung cancer metastasizing to the heart can vary widely. They range from paraneoplastic syndrome, dyspnea, and ST-segment elevation on an electrocardiogram to no clinically significant symptoms. Diverging from typical metastatic patterns observed in lung cancer, this case report presents a detailed description, from the perspective of the microenvironment, of a rare instance where lung cancer metastasized to the mediastinal lymph nodes, adrenal glands, brain, and notably, the left atrium, in a non-smoking female patient.
Weekend screen use of parents and children associates with child language skills
Authors: Tulviste Tiia , Tulviste Jaan
Published: September 2024

Introduction

The study examined the relationship between screen time and types of screen activities engaged in by children, mothers, and fathers on weekends, and its association with mother-reported vocabulary and grammatical skills of children aged 2;5 to 4;0.

Methods

Mothers reported the language skills of 421 children (M age = 38.18 months; SD = 5.73) by the Estonian CDI-III, and the screen use of children, mothers, and fathers by the Screen Time Inventory. We applied Latent Class Analysis (LCA) to analyze the screen time of children, mothers, and fathers, aiming to identify common family screen use profiles.

Results

The results showed that higher total screen time of children was linked to poorer vocabulary and grammatical skills. None of the screen-based activities that children, mothers, and fathers engaged in, including co-viewing of screens and socializing time, were found to positively relate to language skills. Playing video games was negatively associated with children's language skills, regardless of whether it was the child, mother, or father gaming. LCA identified 3 distinct family screen use profiles (low, moderate, and high users) which differed by parental education, screen-based activities, and children's language skills.

Discussion

The findings underscore the significance of family-based interventions when addressing screen time within the context of child language development.
Maternal immunity shapes biomarkers of germinal center development in HIV‐exposed uninfected infants
Authors: Yin Li , Venturi Guglielmo M. , Barfield Richard , Fischer Bernard M. , Kim-Chang Julie J. , Chan Cliburn , De Paris Kristina , Goodenow Maureen M. , Sleasman John W.
Published: September 2024

Introduction

HIV-exposed uninfected (HEU) infants exhibit elevated pro-inflammatory biomarkers that persist after birth. However, comprehensive assessments of bioprofiles associated with immune regulation and development in pregnant women with HIV (PWH) and HEU infants has not been performed. Maternal immunity in PWH may be imprinted on their HEU newborns, altering immune bioprofiles during early immune development.

Methods

Cryopreserved paired plasma samples from 46 HEU infants and their mothers enrolled in PACTG 316, a clinical trial to prevent perinatal HIV-1 transmission were analyzed. PWH received antiretrovirals (ARV) and had either fully suppressed or unsuppressed viral replication. Maternal blood samples obtained during labor and infant samples at birth and 6 months were measured for 21 biomarkers associated with germinal centers (GC), macrophage activation, T-cell activation, interferon gamma (IFN-γ)-inducible chemokines, and immune regulatory cytokines using Mesoscale assays. Pregnant women without HIV (PWOH) and their HIV unexposed uninfected (HUU) newborns and non-pregnant women without HIV (NPWOH) served as reference groups. Linear regression analysis fitted for comparison among groups and adjusted for covariant(s) along with principal component analysis performed to assess differences among groups.

Results

Compared with NPWOH, PWOH displayed higher levels of GC, macrophage, and regulatory biomarkers. PWH compared to PWOH displayed elevated GC, T cell activation, and IFN-γ-inducible chemokines biomarkers at delivery. Similar to their mothers, HEU infants had elevated GC, macrophage, and IFN-γ-inducible chemokines, as well as elevated anti-inflammatory cytokines, IL-10 and IL-1RA. Across all mother/newborn dyads, multiple biomarkers positively correlated, providing further evidence that maternal inflammation imprints on newborn bioprofiles. By 6 months, many HEU biomarkers normalized to levels similar to HUU infants, but some GC and inflammatory biomarkers remained perturbed. Bioprofiles in PWH and HEU infants were similar regardless of the extent of maternal viral suppression by ARV.

Conclusions

GC immune pathways are perturbed in HEU newborns, but immune regulatory responses down regulate inflammation during early infancy, indicating a transient inflammatory effect. However, several GC biomarkers that may alter immune development remain perturbed.
Whole transcriptome landscape in HAPE under the stress of environment at high altitudes: new insights into the mechanisms of hypobaric hypoxia tolerance
Authors: Li Qiong , Fang Fujin , Yang Chuanli , Yu Dong , Gong Qianhui , Shen Xiaobing
Published: September 2024

Background

High altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood.

Methods

We conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential.

Results

We observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 ‘A3SS’ events, 103 ‘A5SS’ events, 545 ‘MXE’ events, 14 ‘RI’ events, and 1,482 ‘SE’ events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses.

Conclusion

This study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.
Identification of early predictive biomarkers for severe cytokine release syndrome in pediatric patients with chimeric antigen receptor T-cell therapy
Authors: Su Meng , Chen Luoquan , Xie Li , Fleurie Aurore , Jonquieres Renaud , Cao Qing , Li Benshang , Liang Ji , Tang Yanjing
Published: September 2024

CAR-T cell therapy is a revolutionary new treatment for hematological malignancies, but it can also result in significant adverse effects, with cytokine release syndrome (CRS) being the most common and potentially life-threatening. The identification of biomarkers to predict the severity of CRS is crucial to ensure the safety and efficacy of CAR-T therapy. To achieve this goal, we characterized the expression profiles of seven cytokines, four conventional biochemical markers, and five hematological markers prior to and following CAR-T cell infusion. Our results revealed that IL-2, IFN-γ, IL-6, and IL-10 are the key cytokines for predicting severe CRS (sCRS). Notably, IL-2 levels rise at an earlier stage of sCRS and have the potential to serve as the most effective cytokine for promptly detecting the condition’s onset. Furthermore, combining these cytokine biomarkers with hematological factors such as lymphocyte counts can further enhance their predictive performance. Finally, a predictive tree model including lymphocyte counts, IL-2, and IL-6 achieved an accuracy of 85.11% (95% CI = 0.763–0.916) for early prediction of sCRS. The model was validated in an independent cohort and achieved an accuracy of 74.47% (95% CI = 0.597–0.861). This new prediction model has the potential to become an effective tool for assessing the risk of CRS in clinical practice.
Co-creation in healthcare and research to improve service delivery for young people with chronic pain
Authors: Berryman Carolyn , Starr Tegan , Ferencz Nicki , Coakley Rachael
Published: September 2024

Introduction

The process of co-creation can enable more effective, agile and integrated healthcare solutions achieving outcomes that effectively translate to healthcare delivery. Collaborative knowledge generation is particularly important in fields such as pediatric chronic pain where there is a complex interplay between biological, social, environmental, emotional, familial and school factors. The co-creation initiative described here was designed to amplify the voices of youth with chronic pain and their families and a variety of key stakeholders and generate novel approaches to the management of chronic pediatric pain in the setting of the South Australian Pediatric Chronic Pain Service.

Methods

Stakeholders who were identified as influential in this ecosystem were allocated to 6 groups. A skilled facilitator co-prepared and delivered the workshop, engaging participants in three structured activities. Firstly, the challenges to service delivery were outlined, followed by the groups discussing what is currently working. The second activity involved lateral thinking without restrictions on time, resources or system to generate solutions to the key challenges presented. Finally, stakeholders were asked to agree on a generated solution from Activity 2 and build a case for actionable implementation of this solution. Data were summarised by the workshop facilitator and reflexive thematic analysis was used for coding and generating themes.

Results

From Activity 1, six themes collectively demonstrated that stakeholders valued many of the existing strengths of the service delivery, but some areas such as pain education was undervalued. Activity 2 generated solutions from high-level ideas to more day-to- day management strategies. Each of six groups generated unique solutions to an identified challenge for Activity 3.

Discussion

Engaging a wide variety of stakeholders in collaborative knowledge generation successfully provided the South Australian Pediatric Chronic Pain Service with a variety of novel, scalable solution across the healthcare continuum. Equally important is that this initiative helped to raise awareness about the complex issues faced in pediatric chronic pain care and helped to establish new partnerships that have led to enhanced service delivery.
Association of white matter hyperintensities with cognitive decline and neurodegeneration
Authors: Li Tao-Ran , Li Bai-Le , Xu Xin-Ran , Zhong Jin , Wang Tai-Shan , Liu Feng-Qi ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2024

Background

The relationship between white matter hyperintensities (WMH) and the core features of Alzheimer’s disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain.

Methods

Herein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (Δ) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH/ΔWMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-β deposition, cognition, and WMH using mediation analysis.

Results

Higher WMH volume was associated with older age, lower CSF amyloid-β levels, hypertension, and smoking history (all p ≤ 0.001), as well as cognitive status (MCI, p < 0.001; dementia, p = 0.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-β status were associated with a greater accrual of WMH volume, and a higher ΔWMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-β and cognition.

Conclusion

WMH are non-specific lesions that are associated with amyloid-β deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.
Parkinson’s LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress
Authors: Guevara Christopher A. , Alloo Kumayl , Gupta Swati , Thomas Romario , del Valle Pamela , Magee Alexandra R. , Benson Deanna L. , Huntley George W.
Published: September 2024

Anxiety is a psychiatric non-motor symptom of Parkinson’s that can appear in the prodromal period, prior to significant loss of midbrain dopamine neurons and motor symptoms. Parkinson’s-related anxiety affects females more than males, despite the greater prevalence of Parkinson’s in males. How stress, anxiety and Parkinson’s are related and the basis for a sex-specific impact of stress in Parkinson’s are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2G2019S) and Lrrk2WT control mice. In humans, LRRK2G2019S significantly elevates the risk of late-onset Parkinson’s. To assess within-sex differences between Lrrk2G2019S and control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby Lrrk2G2019S and Lrrk2WT control mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, male Lrrk2G2019S mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on Lrrk2G2019S mice while significantly increasing latency to feed in Lrrk2WT control mice. Female Lrrk2G2019S mice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female Lrrk2G2019S mice was generally lower compared to stressed Lrrk2WT mice, except for the nucleus accumbens of male Lrrk2G2019S mice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that the Lrrk2G2019S mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in some, but not all stress-related brain regions.
Unraveling monoclonal gammopathy of renal significance: a mini review on kidney complications and clinical insights
Authors: Shankar Mythri , Yadla Manjusha
Published: September 2024

Monoclonal gammopathy of renal significance (MGRS) is where kidney injury occurs due to the accumulation or effects of abnormal monoclonal proteins. These proteins, originating from non-cancerous or pre-cancerous plasma cells or B cells, deposit in specific areas of the kidney. Mechanisms contributing to MGRS include high levels of vascular endothelial growth factor secretion, autoantibodies targeting complement components, and targeting specific receptors leading to nephropathy. Kidney lesions in monoclonal gammopathy of renal significance (MGRS) are classified based on the presence of organized or nonorganized deposits, including fibrillar, microtubular, or crystal inclusions. Kidney biopsy is essential for confirming the diagnosis of MGRS by identifying monoclonal immunoglobulin deposits. Immunofluorescence helps determine the class of light and/or heavy chain involved in MGRS. The treatment approach is clone-directed and hence it depends on the presence of B cell clone or plasma cell clone or any detectable monoclonal protein. Chemotherapy targeting plasma cell or B cell malignancies and autologous hematopoietic cell transplantation may be used to manage MGRS. Kidney outcomes in MGRS patients strongly correlate with the hematologic response to chemotherapy.
Dietary selenium intake and sarcopenia in American adults
Authors: Li Jianfen , Jiang Chaohui , Wu Lingfeng , Tian Jiangyan , Zhang Bin
Published: September 2024

Background

The relationship between dietary selenium intake and sarcopenia remains poorly understood. Therefore, this study investigates the associations between dietary selenium intake and sarcopenia among American adults.

Methods

This cross-sectional study analyzed data from 19,696 participants in the National Health and Nutrition Examination Survey (NHANES) for the periods 1999–2006 and 2011–2018. Appendicular muscle mass, assessed using dual-energy x-ray absorptiometry and adjusted for body mass index, was used as a marker for sarcopenia. Dietary selenium intake was evaluated using the 24-h dietary recall system, and the study accounted for the complex sampling methodology and incorporated dietary sample weights in the analysis.

Results

Among the 19,696 participants, the prevalence of sarcopenia was found to be 8.46%. When compared to the lowest quintile of dietary selenium intake (Q1, < 80.10 μg/day), the odds ratios for sarcopenia in the second quintile (Q2, 80.10–124.61 μg/day) and the third quintile (Q3, >124.61 μg/day) were 0.80 [95% confidence interval (CI): 0.70–0.92, p = 0.002] and 0.61 (95% CI: 0.51–0.73, p < 0.001), respectively. A negative relationship was observed between dietary selenium intake and sarcopenia (non-linear: p = 0.285). Furthermore, sensitivity analyses revealed a robust association between selenium intake and the prevalence of sarcopenia after further adjusting for blood selenium levels.

Conclusion

The results suggest an inverse association between dietary selenium intake and the prevalence of sarcopenia among American adults.
A retrospective study of irreversible electroporation for tumors adjacent to perihepatic important structure
Authors: Gong Ju , Wang Shunhong , Wang Shuting , Li Chaojie , Li Wenhua , Chen Yingjie , Xia Ning , Wang Chen , Wang Zhongmin
Published: September 2024

Background

Irreversible electroporation has been proved as a feasible and safe method against tumor in liver. However, few studies focused on tumors adjacent to perihepatic important structure like vessels, biliary system and gall bladder. These structures limit the effectiveness of conventional treatments. The aim of this article is to analyze the clinical outcomes of patients with hepatic tumors at the special sites who received IRE treatment and provide reliable evidence for broadening the scope of IRE’s clinical application.

Methods

The clinical information of patients who underwent IRE ablation for tumors adjacent to perihepatic important structure between February 2017 and December 2021 was collected and retrospectively analyzed. All patients underwent contrast-enhanced CT or MRI for further evaluation at the 1-month follow-up and every 3 months thereafter. Post-ablation complications, recurrence, progression-free survival and overall survival were evaluated to analyze the prognosis of IRE ablation adjacent to perihepatic important structure. Categorical variables are presented as numbers followed by percentages. Continuous data are presented as the mean ± deviation. The tumor size and IRE ablation size were evaluated by the maximum diameters.

Results

Thirty-two patients who underwent IRE ablation for tumor adjacent to perihepatic important structure were studied in this research. There were 39 lesions in 32 patients treated with IRE ablation. Fourteen of them (35.9%) were located adjacent to the porta hepatis, and 8 of them (20.5%) were located adjacent to the hepatocaval confluence. Subcapsular lesions accounted for 15.4% (6 of 39 lesions). The other 11 lesions were in the para gallbladder (5 of 39 lesions, 12.8%), the caudate lobe (5 of 39 lesions, 12.8%) and the colonic hepatic flexure (1 of 39 lesions, 2.6%). According to the Clavien−Dindo classification system for complications, all relative patients with cancer experienced complications below class III except one patient who developed postoperative hemorrhagic shock and improved after timely treatment. Recurrence in situ was observed in 5 of 32 (15.6%) patients. The median PFS of the patients who received IRE ablation was 384 days, and the median OS was 571 days.

Conclusion

IRE ablation is a feasible and safe treatment strategy for tumors adjacent to perihepatic important structure. With improved equipment, optimized therapeutic parameters and long-term clinical trials, IRE will play an increasingly important role in the treatment of tumors in liver.
Differentiated thyroid cancer and adverse pregnancy outcomes: a propensity score-matched retrospective cohort study
Authors: Li Xin , Mei Fang , Xiao Wu-Cai , Zhang Fan , Zhang Shanghang , Fu Peng , Chen Jing , Shan Rui , Sun Bang-Kai , Song Shi-Bing , Yuan Chunhui , Liu Zheng
Published: September 2024

Background

Differentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC.

Methods

We conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes.

Results

After the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)].

Conclusions

DTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.
State estimation for Markovian jump Hopfield neural networks with mixed time delays
Authors: Guo Lili , Huang Wanhui
Published: September 2024

Markovian jump Hopfield NNs (MJHNNs) have received considerable attention due to their potential for application in various areas. This paper deals with the issue of state estimation concerning a category of MJHNNs with discrete and distributed delays. Both time-invariant and time-variant discrete delay cases are taken into account. The objective is to design full-order state estimators such that the filtering error systems exhibit exponential stability in the mean-square sense. Two sufficient conditions on the mean-square exponential stability of MJHNNs are established utilizing augmented Lyapunov–Krasovskii functionals, the Wirtinger–based integral inequality, the Bessel-Legendre inequality, and the convex combination inequality. Then, linear matrix inequalities-based design methods for the required estimators are developed through eliminating nonlinear coupling terms. The feasibility of these linear matrix inequalities can be readily verified via available Matlab software, thus enabling numerically tractable implementation of the proposed design methods. Finally, two numerical examples with simulations are provided to demonstrate the applicability and less conservatism of the proposed stability criteria and estimators. Lastly, two numerical examples are given to demonstrate the applicability and reduced conservatism of the proposed stability criteria and estimator design methods. Future research could explore further refinement of these analysis and design results, and exporing their extention to more complex neural network models.