bluuebunny/crossref_metadata_2025 huggingface dataset:
Humanized CXCL12 antibody delays onset and modulates immune response in alopecia areata mice: insights from single-cell RNA sequencing
Authors: An Seungchan , Zheng Mei , Park In Guk , Park Sang Gyu , Noh Minsoo , Sung Jong-Hyuk
Published: October 2024

It has been demonstrated that CXCL12 inhibits hair growth via CXCR4, and its neutralizing antibody (Ab) increases hair growth in alopecia areata (AA). However, the molecular mechanisms have not been fully elucidated. In the present study, we further prepared humanized CXCL12 Ab for AA treatment and investigated underlying molecular mechanisms using single-cell RNA sequencing. Subcutaneous injection of humanized CXCL12 Ab significantly delayed AA onset in mice, and dorsal skin was analyzed. T cells and dendritic cells/macrophages were increased in the AA model, but decreased after CXCL12 Ab treatment. Pseudobulk RNA sequencing identified 153 differentially expressed genes that were upregulated in AA model and downregulated after Ab treatment. Gene ontology analysis revealed that immune cell chemotaxis and cellular response to type II interferon were upregulated in AA model but downregulated after Ab treatment. We further identified key immune cell-related genes such as Ifng, Cd8a, Ccr5, Ccl4, Ccl5, and Il21r, which were colocalized with Cxcr4 in T cells and regulated by CXCL12 Ab treatment. Notably, CD8+ T cells were significantly increased and activated via Jak/Stat pathway in the AA model but inactivated after CXCL12 Ab treatment. Collectively, these results indicate that humanized CXCL12 Ab is promising for AA treatment via immune modulatory effects.
Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age
Authors: Miao Chuanwang , Chen Yuanji , Zhang Hao , Zhao Wei , Wang Cunliang , Ma Zeliang , Zhu Shan , Hu Xudong
Published: October 2024

Background

The shaping of the tumor immune microenvironment does not only rely on tumor-infiltrating lymphocytes but on the recruitment of lymphocytes in peripheral blood. Monitoring peripheral blood lymphocyte subsets level (PBLSL) can predict treatment response and prognosis with immune checkpoint inhibitors. This study investigated the heterogeneity of PBLSL in response to chemoradiotherapy (CRT) or combined with immunotherapy (CRIT) in advanced lung cancer patients.

Methods

77 patients with advanced lung cancer receiving CRT or CRIT were divided into treatment-responsive and non-responsive groups based on efficacy. The study analyzed short-term efficacy and progression-free survival (PFS) according to baseline PBLSL and explored the impact under different stratifications, including treatment modality, pathology type, and age.

Results

In all patients, higher levels of B cells, higher CD4+/CD8+ T cell ratios, and lower CD8+ T cell levels were associated with better short-term outcomes (P = 0.0035, P = 0.044, P = 0.022). Subgroup analysis revealed that in the CRT group, higher B cell levels correlated with improved efficacy (P = 0.011) and superior PFS (P = 0.048, HR = 0.3886, 95% CI = 0.1696 to 0.8902). In the CRIT group, higher CD4+ T cell levels, lower CD8+ T cell levels, and higher CD4+/CD8+ T cell ratios were linked to better efficacy (P = 0.038, P = 0.047, P = 0.017). For adenocarcinoma patients, higher CD4+/CD8+ T cell ratios and lower CD8+ T cell levels predicted better efficacy (P = 0.0155, P = 0.0119). B cell levels were significant in squamous cell carcinoma (P = 0.0291), while no PBLSL was predictive for small cell lung cancer. Among patients under 65, higher B cell levels were linked to improved efficacy and prolonged PFS (P = 0.0036, P = 0.0332, HR = 0.4111, 95% CI = 0.1973 to 0.8563). For patients over 65, differences in CD4+ T cell levels and CD4+/CD8+ T cell ratios were significant (P = 0.0433, P = 0.0338).

Conclusion

PBLSL predicted efficacy and prognosis in various patient stratifications, suggesting PBLSL is a reliable predictor for CRT and CRIT in advanced lung cancer. Detecting different cellular subpopulations helps identify patients with significant treatment responses across different stratifications.
A novel hollow iron nanoparticle system loading PEG-Fe3O4 with C5a receptor antagonist for breast cancer treatment
Authors: Yang Hong , Li Guiqing , Zhang Ji , Zhao Jing , Zhao Yunpei , Wu Yufei , Sun Zihan , Song Shuangshuang , Zou Ying , Zou Zhihao , Han Xiao , Deng Boshao , Wang Lulu , Rao Hang , Xu Guilian , Wang Shufeng , Guo Sheng , Ding Huanyu , Shi Yan , Wu Yuzhang , Chen Jian
Published: October 2024

Breast cancer is the most diagnosed malignancy and major cause of cancer death among women population in the worldwide. Ferroptosis is a recently discovered iron-dependent regulated cell death involved in tumor progression and therapeutic response. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells like developing iron nanoparticles as a therapeutic agent. However, resistance to ferroptosis is a vital distinctive hallmark of cancer. Therefore, further investigation of the mechanism of ferroptosis resistance to enhance its tumor sensitivity is essential for ferroptosis-target breast cancer therapy. Our results revealed that the activation of C5a/C5aR pathway can drive resistance to ferroptosis and reshaping breast cancer immune microenvironment. Accordingly, loading PEG-Fe3O4 with C5aRA significantly improved the anti-tumor effect of PEG- Fe3O4 by inhibiting ferroptosis resistance and increasing macrophage polarization toward M1 phenotype. Our findings presented a novel cancer therapy strategy that combined cancer cell metal metabolism regulation and immunotherapy. The study also provided support for further evaluation of PEG- Fe3O4@C5aRA as a novel therapeutic strategy for breast cancer in clinical trials.
Mast cell MrgprB2 in neuroimmune interaction in IgE-mediated airway inflammation and its modulation by β-arrestin2
Authors: Sutradhar Sangita , Ali Hydar
Published: October 2024

Introduction

Allergic asthma has been linked to the activation of mast cells (MCs) by the neuropeptide substance P (SP), but the mechanism underlying this neuroimmune interaction is unknown. Substance P produced from cutaneous nociceptors activates MCs via Mas-related G-protein-coupled receptor B2 (MrgprB2) to enhance type 2 immune response in experimental atopic dermatitis in mice. We recently showed that the adapter protein β-arrestin2 (β-arr2) contributes to MrgprB2-mediated MC chemotaxis. The goals of this study were to determine if MrgprB2 facilitates neuroimmune interaction in IgE (FcεRI)-mediated allergic airway inflammation (AAI) and to assess if this response is modulated by β-arr2.

Methods

Wild-type (WT), MrgprB2−/− mice and mice with MC-specific deletion of β-arr2 (Cpa3Cre+/β-arr2fl/fl) were passively sensitized with anti-TNP-IgE and challenged with antigen. The generation of SP and MC recruitment in the lung were determined by immunofluorescence and toluidine blue staining, respectively. The transcripts for Tac1, MrgprB2, TNF-α, and Th2 cytokines in lung tissue were assessed by RT-PCR, and the release of selected cytokines in bronchoalveolar lavage (BAL) was determined by ELISA. Eosinophil and neutrophil recruitment in lung tissue and BAL were determined by immunofluorescence staining and flow cytometry, respectively. Goblet cell hyperplasia was determined by periodic acid–Schiff staining.

Results

Following IgE sensitization and antigen challenge in WT mice, SP generation, and MC recruitment, transcripts for Tac1, MrgprB2, TNF-α, and Th2 cytokine were upregulated when compared to the control challenge. TNF-α, Th2 cytokine production, eosinophil/neutrophil recruitment, and goblet cell hyperplasia were also increased. These responses were significantly reduced in MrgprB2−/− and Cpa3Cre+/β-arr2fl/fl mice.

Discussion

The data presented herein suggest that SP-mediated MrgprB2 activation contributes to AAI and goblet cell hyperplasia in mice. Furthermore, these responses are modulated by β-arr2, which promotes MC recruitment to facilitate their activation through FcεRI.
In vivo analysis of CRISPR-edited germinal center murine B cells
Authors: Chege Kuria Timothy , Schneider Andrea , Baraka Favoured , Wanzek Jana , Vogg Lisa , Brey Stefanie , Habenicht Katharina M. , Winkler Thomas H.
Published: October 2024

The germinal center (GC) reaction is crucial for somatic hypermutation, affinity maturation, and the selection of high-affinity B cells, all of which are hallmarks of the humoral immune response. Understanding the distinct roles of various B cell genes is essential for elucidating the selection mechanisms within the GC reaction. Traditionally, studying B cell gene function in the GC reaction involved generating knock-out mice, a highly time-consuming method that necessitates complex vectors. The advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has simplified the creation of knock-out mice. However, even with CRISPR, the generation of knock-out mice still faces challenges, including being time-consuming, costly, having low knock-out efficiency, and raising ethical concerns regarding animal use. To address these challenges, we developed an alternative method to traditional knock-out mouse generation. Our approach entails the ex vivo CRISPR editing of B cells from transgenic donor mice with different B cell receptor affinities followed by their adoptive transfer into recipient mice. We present a cost-effective, rapid, versatile, and adaptable CRISPR-Cas9 method for in vivo loss-of-function studies of individual murine B cell genes within the context of the GC reaction. This method provides a valuable tool for investigating the complex roles of different B cell genes in the GC selection process. As proof of concept, we validated our approach by examining the role of the pro-apoptotic gene Fas in the GC selection process. We adoptively transferred a mix of Fas knock-out (FasKO) low-affinity B cells, Fas wild-type (FasWT) low-affinity B cells, and FasWT high-affinity B cells into recipient mice. From our results, FasKO low-affinity B cells were still outcompeted by the FasWT high-affinity B cells for selection in the GC. An important observation was the accumulation of FasKO low-affinity GC B cells when compared to the FasWT low-affinity B cells, which suggested a role of Fas in the GC selection process.
mRNA-seq-based analysis predicts: AEG-1 is a therapeutic target and immunotherapy biomarker for pan-cancer, including OSCC
Authors: Yao Lihong , Liu Lixue , Xu Wanqiu , Xi Hualei , Lin Song , Piao Guiyan , Liu Ying , Guo Jinrong , Wang Xiumei
Published: October 2024

Background

The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed.

Methods

The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1’s effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns.

Results

Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis.

Conclusion

In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.
CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome
Authors: Pita Sara , Myers Pernille Neve , Johansen Joachim , Russel Jakob , Nielsen Mads Cort , Eklund Aron C. , Nielsen Henrik Bjørn
Published: October 2024

Introduction

Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites.

Methods

CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities.

Results

CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples.

Discussion

Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.
The potential of strigolactones to shift competitive dynamics among two Rhizophagus irregularis strains
Authors: Klein Malin , Bisot Corentin , Oyarte Gálvez Loreto , Kokkoris Vasilis , Shimizu Thomas S. , Dong Lemeng , Weedon James T. , Bouwmeester Harro , Kiers E. Toby
Published: October 2024

Strigolactones are phytohormones that influence arbuscular mycorrhizal fungal (AMF) spore germination, pre-symbiotic hyphal branching, and metabolic rates. Historically, strigolactone effects have been tested on single AMF strains. An open question is whether intraspecific variation in strigolactone effects and intraspecific interactions can influence AMF competition. Using the Rhizophagus irregularis strains A5 and C2, we tested for intraspecific variation in the response of germination and pre-symbiotic growth (i.e., hyphal length and branching) to the strigolactones GR24 and 5-deoxystrigol. We also tested if interactions between these strains modified their germination rates and pre-symbiotic growth. Spore germination rates were consistently high (> 90%) for C2 spores, regardless of treatment and the presence of the other strain. For A5 spores, germination was increased by strigolactone presence from approximately 30 to 70% but reduced when grown in mixed culture. When growing together, branching increased for both strains compared to monocultures. In mixed cultures, strigolactones increased the branching for both strains but led to an increase in hyphal length only for the strain A5. These strain-specific responses suggest that strigolactones may have the potential to shift competitive dynamics among AMF species with direct implications for the establishment of the AMF community.
Distinct lower respiratory tract microbiota profiles linked to airway mucus hypersecretion in children with Mycoplasma pneumoniae pneumonia
Authors: Wei Xiwen , Wang Wan , Cheng Hang , Huang Yin , Zhou Qixian , Yuan Xiaopeng
Published: October 2024

Background

Airway mucus hypersecretion (AMH) can occur in children with acute respiratory diseases, but its underlying mechanisms and relationship with the lower respiratory tract microbiota (LRTM) are not yet fully understood. This study investigates the characteristics of LRTM in children with Mycoplasma pneumoniae pneumonia (MPP) and its impact on AMH.

Methods

We collected bronchoalveolar lavage fluid and related clinical indicators from 202 children with MPP. 16S rRNA gene amplicon sequencing was used for detection and identification. Microbial diversity and characteristic genera were compared, and their abundance was analyzed for correlations with clinical factors.

Results

As the disease course (days from onset to bronchoscopy, grouped into T1, T2, T3) extended, α-diversity of the LRTM gradually increased, particularly in the T3 hypersecretion group. Moreover, significant differences were observed in the incidence of AMH, co-infection rates, peripheral white blood cell (WBC) count, and C-reactive protein levels. In AMH, Mycoplasmoides and Veillonella abundance and peripheral neutrophils were risk factors for increased secretions. In addition, in the T3 co-infection group, Streptococcus and Prevotella increased, replacing Stenotrophomonas as the dominant genus, possibly due to β-lactam antibiotic use. Prevotella abundance was strongly correlated with WBC.

Conclusion

The composition and structure of LRTM in children with MPP played a crucial role in AMH and disease progression.
Olig2+/NG2+/BLBP+ astrocyte progenitors: a novel component of the neurovascular unit in the developing mouse hippocampus
Authors: Omura Shoichiro , Ogawa Rina , Kawachi Tomomi , Ogawa Aya , Arai Yuuki , Takayama Natsumi , Masui Aki , Kondo Kumiko , Sugimoto Hiroki , Shinohara Hiroshi M. , Takahashi Tokiharu , Maeda Hideyuki , Ohyama Kyoji
Published: October 2024

Astrocytes are key components of the neurovascular unit. While we have recently identified Olig2+ astrocyte progenitors (ASPs) in the developing mouse dentate gyrus (DG), their molecular signature remains incompletely characterized. Here we demonstrate that Olig2+ ASPs predominantly express brain lipid-binding protein (BLBP), while only a small population of them expresses gfap-GFP. These Olig2+/BLBP+ ASPs co-express the transcription factors Sox3, Sox9 and the proteoglycan NG2 but not Sox10, a marker for oligodendrocyte progenitors (OLPs). Olig2+ ASPs appear from embryonic day 18 (E18) onwards and decline at postnatal day 14 (P14). Consistent with the proliferation of both Olig2+ and NG2+ glial cells after brain injury, intrauterine intermittent hypoxia (IH) led to an increase in Olig2+/NG2+/BLBP+ ASPs in the postnatal DG. IH also promoted both angiogenesis and vascular coupling of Olig2+/NG2+ ASPs. Our data suggest that IH-induced expression of HIF1a increases Olig2+/NG2+/BLBP+ ASPs in a cell non-autonomous manner. Our data also revealed increased vascular coupling of GFAP+ astrocytes following IH, while the number of GFAP+ astrocytes remains unchanged. Given that BLBP, Olig2 and NG2 are expressed in reactive astrocytes, our findings suggest that Olig2+/NG2+/BLBP+ ASPs represent a subtype of reactive astrocyte progenitors. Furthermore, the enhanced vascular coupling of Olig2+/NG2+/BLBP+ ASPs appears to be an adaptive response to hypoxic brain injury. This study provides new insights into the molecular characteristics of Olig2+/NG2+/BLBP+ ASPs and their potential role in the brain’s response to hypoxic injury, contributing to our understanding of neurovascular unit dynamics in both development and pathological conditions.
Molecular specializations underlying phenotypic differences in inner ear hair cells of zebrafish and mice
Authors: Giffen Kimberlee P. , Liu Huizhan , Yamane Kacey L. , Li Yi , Chen Lei , Kramer Kenneth L. , Zallocchi Marisa , He David Z.
Published: October 2024

Introduction

Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral, and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs).

Methods

To understand the genetic mechanisms underlying differences between adult zebrafish and mammalian HCs, we compared their RNA-seq-characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization.

Results

There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. For example, OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes to OHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage-dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype.

Discussion

Our analyses unveil substantial differences in gene expression patterns that may explain phenotypic specialization of zebrafish and mouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals.
Understanding emotional influences on sustained attention: a study using virtual reality and neurophysiological monitoring
Authors: Shen Yang , Zheng Huijia , Li Yu , Tian Xuetao
Published: October 2024

Introduction

Emotion and attention regulation significantly influence various aspects of human functioning and behavior. However, the interaction between emotion and attention in affecting performance remains underexplored. This study aims to investigate how individual differences in sustained attention, influenced by varying emotional states.

Methods

A total of 12 participants underwent emotion induction through Virtual Reality (VR) videos; completed an AX-CPT (continuous performance test) task to measure sustained attention, for which task performance is evaluated from two aspects, task accuracy and task reaction times; and reported their flow states. EEG and PPG data were collected throughout the sessions, as supporting evidence for sustained attention.

Results

Our findings suggest that emotional valence and arousal significantly influence task reaction times and sustained attention, when gender differences are accounted for, but do not significantly impact task accuracy. Specifically, males responded faster under high-arousal negative emotions, while females responded faster under high-arousal positive emotions. Additionally, we find that flow experience is not significantly impacted by emotions states or sustained attention.

Discussion

The study underscores the nuanced interplay between emotion, sustained attention, and task performance, suggesting that emotional states can differentially impact cognitive processes. Also, it support the use of VR, EEG, and PPG technologies in future research on related topics. Future research could expand upon this study by including larger sample sizes and a wider range of emotional inductions to generalize the findings.
Clinicopathological correlations in 38 cases of gastroenteropancreatic high-grade neuroendocrine neoplasms
Authors: Li Na , Hu Yanping , Wu Linguo , An Jianduo
Published: October 2024

Objective

Diagnosis and treatment of gastroenteropancreatic high-grade neuroendocrine neoplasms (GEP-HG-NENs), particularly G3 well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) relies on histopathological morphology, immunohistochemistry, and molecular biological markers, which are lacking especially in cases with ambiguous histomorphology. In this study to contribute to the development of more targeted treatment strategies, we examined various immunohistochemical and molecular biological markers and their association with clinicopathological features in GEP-HG-NENs.

Methods

We included 38 patients with GEP-HG-NENs in this study, with their retrospective follow-up data. The expression of tumour protein p53 (TP53), RB transcriptional corepressor 1 (RB1), somatostatin receptor 2 (SSTR2), clusterin (CLU), and marker of proliferation Ki-67 (MKI67) was immunohistochemically analysed. KRAS proto-oncogene, GTPase (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between immunohistochemical and molecular biological markers and clinicopathological characteristics were examined using a Cox risk regression model, receiver operating characteristic (ROC) curve, and Kaplan–Meier survival analyses.

Results

SSTR2, RB, TP53, and CLU expression differed between NET G3 and NECs, with variations among the NET G3 and small- and large-cell NEC (SCNEC and LCNEC, respectively) groups (p < 0.05). The median MKI67 proliferative index was approximately 40% and 70% in G3 NETs and NECs, respectively. The NET G3 group exhibited a median survival of 25 months, indicating a relatively better prognosis than that of the NECs group (median survival, 11 months). Both Kaplan–Meier survival analysis and the Cox risk regression model indicated a statistical correlation among treatment methods, CLU expression, and prognosis (p < 0.05). The BRAF V600E mutation rate was 32.4% in G3 NETs and SCNEC, demonstrating a significant difference between both types (p = 0.0086). Furthermore, ROC curve analysis highlighted the diagnostic significance of the positive expression of the immunohistochemical markers CLU, SSTR2, and RB in identifying NET G3.

Conclusion

To guide more suitable treatment strategies, it is essential to develop and apply valuable and more targeted immunohistochemical and molecular pathological markers for a comprehensive analysis.
Implementation of an automated transition readiness assessment in a pediatric rheumatology clinic
Authors: Argraves Melissa , Murray Elizabeth , Taxter Alysha , Wise Kelly , Jensen Paul T. , Goldstein-Leever Alana , Thomas Bethanne , Scott Alexa , Gallup James , Leone Ashlee , Ardoin Stacy P. , Sivaraman Vidya
Published: October 2024

Background

Failure of successful transition to adult care for adolescents and young adults with chronic rheumatic diseases negatively impacts their health and wellbeing. Transition of care is a vital and complex process within pediatric rheumatology that can be difficult to execute. Use of quality improvement (QI) and clinical informatics (CI) can help implement transition programs.

Local problem

Despite efforts to improve transition of care within our pediatric rheumatology clinic, it has been difficult to implement and sustain good transition practices including assessment of transition readiness. Using QI methodology and CI, this study aimed to improve transition readiness assessment from 12 to 30% and sustain for one year by surveying transitioning patients yearly.

Methods

A transition-focused QI team utilized methods endorsed by the Institute for Healthcare Improvement and leveraged CI to improve survey completion. Control charts of survey completion rates were tracked monthly. Descriptive statistics were used to analyze survey responses.

Interventions

Interventions focused on automation of patient surveys at regularly scheduled clinic visits.

Results

1,265 questionnaires were administered to 1,158 distinct patients. Survey completion rose from a baseline of 12% to greater than 90% and was sustained over 18 months. Identified educational needs included health insurance, scheduling appointments, obtaining care outside of rheumatology clinic business hours, Electronic Health Record messaging, and refilling medications.

Conclusions

By leveraging CI and QI methodology, we were able to assess transition readiness in more than 90% of our patients and identify gaps in self-management. Process automation can create sustainable transition practices.
Decreased TREC and KREC levels in newborns with trisomy 21
Authors: Marakhonov Andrey , Mukhina Anna , Vlasova Elena , Efimova Irina , Balinova Natalya , Rodina Yulia , Pershin Dmitry , Markova Zhanna , Minzhenkova Marina , Shilova Nadezhda , Mudaeva Dzhaina , Saydaeva Djamila , Irbaieva Taisiya , Matulevich Svetlana , Belyashova Elena , Yakubovskiy Grigoriy , Tebieva Inna , Gabisova Yulia , Ikaev Murat , Irinina Nataliya , Nurgalieva Liya , Saifullina Elena , Belyaeva Tatiana , Romanova Olga , Voronin Sergey , Zinchenko Rena , Shcherbina Anna , Kutsev Sergey
Published: October 2024

Newborn screening (NBS) for severe combined immunodeficiency (SCID) has been widely implemented to enable early detection and intervention. Trisomy 21, commonly known as Down syndrome (DS), poses unique challenges in NBS due to its frequent association with T and/or B cell lymphopenia. The pilot NBS screening program recently conducted in Russia was aimed to identify both severe T and B cell deficiencies by measuring TREC and KREC. This study aims to evaluate the incidence of DS in newborns who participated in the pilot program, assess their TREC and KREC values, and determine the proportion of DS newborns potentially identifiable through T/B lymphopenia NBS. We conducted a retrospective analysis of the data obtained during the pilot NBS program, involving 202,908 newborns from eight regions of Russia. The study identified 157 patients with trisomy 21 among the screened cohort, resulting in a DS birth prevalence of 1:1,284. Median TREC and KREC values did not significantly differ between full-term and pre-term subgroups of DS patients. TREC values in DS newborns were decreased and comparable to those of the extremely preterm newborns. DS newborns also demonstrated significant differences in KREC values as compared to the general cohort regardless of gestational age. Our data suggests abnormalities of T- and B-cell lineages development and requires further investigation. This article highlights the need for increased awareness of the intrinsic immunological defects associated with DS. The findings underscore the importance of continued follow-up and comprehensive support by healthcare teams for individuals with DS.
Algorithm for UAV path planning in high obstacle density environments: RFA-star
Authors: Zhang Weijian , Li Jian , Yu Weilin , Ding Peng , Wang Jiawei , Zhang Xuen
Published: October 2024

Path planning is one of the key elements for achieving rapid and stable flight when unmanned aerial vehicles (UAVs) are conducting monitoring and inspection tasks at ultra-low altitudes or in orchard environments. It involves finding the optimal and safe route between a given starting point and a target point. Achieving rapid and stable flight in complex environments is paramount. In environments characterized by high-density obstacles, the stability of UAVs remains a focal point in the research of path planning algorithms. This study, utilizing a feature attention mechanism, systematically identifies distinctive points on the obstacles, leading to the development of the RFA-Star (R5DOS Feature Attention A-star) path planning algorithm. In MATLAB, random maps were generated to assess the performance of the RFA-Star algorithm. The analysis focused on evaluating the effectiveness of the RFA-Star algorithm under varying obstacle density conditions and different map sizes. Additionally, comparative analyses juxtaposed the performance of the RFA-Star algorithm against three other algorithms. Experimental results indicate that the RFA-Star algorithm demonstrates the shortest computation time, approximately 84%-94% faster than the RJA-Star algorithm and 51%-96% faster than the Improved A-Star. The flight distance is comparable to the RJA-Star algorithm, with slightly more searched nodes. Considering these factors collectively, the RFA-Star algorithm exhibits a relatively superior balance between computational efficiency and path quality. It consistently demonstrates efficient and stable performance across diverse complex environments. However, for comprehensive performance enhancement, further optimization is necessary.
Effects of NH4+-N: NO3−-N ratio on growth, nutrient uptake and production of blueberry (Vaccinium spp.) under soilless culture
Authors: Anwar Ali , Zheng Junming , Chen Chunfeng , Chen Mengqing , Xue Yanxu , Wang Jinmiao , Su Wei , Chen Riyuan , Song Shiwei
Published: October 2024

Blueberry (Vaccinium corymbosum) is a small pulp shrub, which prefers to grow on a soilless culture. For soilless culture, nutritional management remains typically vital for blueberry production. However, the effect of different nutritional treatments on blueberry growth and production is largely unknown. This study was designed to investigate to formulate a specific nutritional treatment for blueberry. The results showed that NH4+-N: NO3−-N ratios significantly affected the growth, nutrient uptake, physiological characteristics, and flowering, as well as the fruiting characteristics of blueberry plants. The number of shoots and top projection area was increased considerably by 25:75 treatment. In contrast, 50:50 treatment promotes plant height, shoot length, and stem thickness, increasing chlorophyll contents, photosynthetic capacity, and P, Ca, and Mg in leaves. In contrast, 50:50 treatment promotes the flowering fruiting rate and prolongs the blueberry flowering period. The maximum soluble sugar contents were noted in 25:75, while maximum starch contents were reported in the 50:50 treatment. The treatments 100:0 and 75:25 promote early flowering and accelerate fruit set. Notably, NH4+-N: NO3−-N ratios; 50:50 treatment significantly encourages plant growth, nutrient uptake, chlorophyll contents, photosynthetic capacity, and fruit setting rate in blueberry plants. These findings suggested that NH4+-N: NO3−-N ratios 50:50 is the most appropriate treatment that significantly promotes vegetative growth and enhances production in blueberry plants. This study provides valuable information for improved blueberry production under a controlled environment.
Integratedly analyzed quantitative proteomics with transcriptomics to discover key genes via fg-1 non-heading mutant in the early heading stage of Chinese cabbage
Authors: Li Jingrui , Fan Mi , Zhang Xiaomeng , Yang Liling , Hou Guangguang , Yang Lei , Li Na , Xuan Shuxin , Zhao Jianjun
Published: October 2024

Leaf heading is an important agronomic trait of Chinese cabbage, which directly affects its yield. Leaf heading formation in Chinese cabbage is controlled by its internal genotype and external environmental factors, the underlying mechanism of which remains poorly understood. To discover the leaf heading formation mechanism more deeply, this study analyzed the correlation between proteomic and transcriptomic data in the leaf heading formation mutant fg-1 generated by EMS. iTRAQ-based quantitative proteomics techniques were performed to identify the protein expression profiles during the key periods of the early heading stage in the section of the soft leaf apical region (section a) and the whole leaf basal region (section d). We first identified 1,246 differentially expressed proteins (DEPs) in section a and 1,055 DEPs in section d. Notably, transcriptome–proteome integrated analysis revealed that 207 and 278 genes showed consistent trends at the genes’ and proteins’ expression levels in section a and section d, respectively. KEGG analyses showed that the phenylpropanoid biosynthesis pathway was enriched in both sections a and d. Furthermore, 86 TFs exhibited co-upregulation or co-downregulation, and seven out of 86 were involved in plant hormone synthesis and signal transduction pathways. This indicates that they are potentially related to the leaf heading formation in Chinese cabbage. Taken together, we have identified several key early-heading-formation-related factors via integration analysis of the transcriptomics and proteomics data. This provides sufficient gene resources to discover the molecular mechanism of leaf heading formation.
Loneliness, online learning and student outcomes in college students living with disabilities: results from the National College Health Assessment Spring 2022
Authors: Bevens William , Stoeckl Sarah E. , Schueller Stephen M. , Kim Jeongmi , Cha Biblia S. , Chwa Cindy , Stadnick Nicole A. , Best Nakia C. , Sorkin Dara H.
Published: October 2024

Background

People with disabilities face many health, economic and social disparities. Loneliness is recognized as a significant issue for this group however, its impact on students with disabilities (SWDs) remains a critically underexplored area of research. Importantly, as higher education continues its transition to the digital space, the potential to entrench social isolation and loneliness within this population has not been examined. This research seeks to explore the associations between SWDs, loneliness, online learning, and academic outcomes in a national survey of university students.

Methods

Using the National College Health Assessment from Spring 2022, this study compared multiple outcomes between different groups of SWDs and students without disabilities. Two ordinal regression models were used to estimate associations between loneliness, disability type and learning mode (online vs. in-person), as well as cumulative grade average (CGA) with disability type.

Results

All disability types included within this study were positively associated with increased odds of loneliness for those engaged in online learning compared to students without disabilities. Interactions indicate a significant effect of in-person learning compared with online learning for deaf or hard of hearing students, and those with multiple disabilities. Several disability groups reported decreased odds of higher CGA compared to students without disabilities.

Conclusion

Loneliness is a significant issue for all SWD groups reported in this study. The impact of disability on academic outcomes is reported herein; however, its impact on medium-to-long term outcomes for these individuals remains unknown. To address inequities in higher education for SWDs, universities must invest more resources to holistically support these students.
Introducing Open Dialogue as part of the WHO QualityRights Project in South Korea: experiences and opinions from an introductory workshop and 1-year pilot practice
Authors: Cho Sooni , Cho Yong Hyuk , Noh Jai Sung , Jeong Seong Kwon , Kim Shin Kwon , Kim Seongsu
Published: October 2024

This study explores the subjective experiences of participants in a 5-day Open Dialogue (OD) workshop and a 1-year pilot practice, conducted as part of the WHO QualityRights Project in South Korea. Twenty-four participants, selected through purposive sampling, completed surveys immediately after the workshop and 1 year later. Data were analyzed through both statistical and thematic approaches. A statistically significant decrease in the availability of “Flexibility and Mobility” was observed across all participants (p = 0.044) and a significant reduction in the availability of “Tolerance of Uncertainty” (p = 0.04) was noted among participants who engaged in network meetings over the course of 1 year. Qualitative analysis revealed that participants initially felt ambivalent toward OD due to systemic, cultural, and professional challenges. However, through experiential learning, their ambivalence shifted to hope, fostering solidarity and a more positive outlook for future OD practice. Participants recognized that implementing OD supported human rights, while addressing personal, organizational, and policy challenges. The findings provide important insights for developing OD training and implementation guidelines in South Korea. Recommendations include focusing on experiential learning and selecting mixed-group trainees from catchment area institutions, emphasizing the support of client rights, and considering individual, organizational, and systemic levels for successful implementation. This study represents a new case of OD dissemination through a top-down national research and development project and its integration into the WHO QualityRights service package, suggesting complementary potential between OD and global human rights-based mental health initiatives.
When end of treatment situations challenge patient-centered care: a discussion paper proposing new theoretical insights
Authors: Bonazza Federica , Lamiani Giulia , Borghi Lidia , Del Negro Silvia , Leone Daniela , Vegni Elena
Published: October 2024

Introduction

According to the Institute of Medicine patient-centered medicine is one of the six crucial dimensions of health care quality. Although the patient-centered care model is widely recognized for its ethical underpinnings and effectiveness, its practical implementation still raises challenges, especially in end-of-treatment situations. This discussion paper offers an overview of the challenges facing the physician-patient relationship in end-of-treatment situations.

Methods

We developed three clinical vignettes and made some theoretical considerations about ethical issues related to the decision-making process leading to the end of treatment.

Results

We identified two main challenges that end-of-treatment situations pose to patient-centered care: (1) when the patient’s autonomy challenges the best clinical treatment; and (2) when the proposed treatment (discontinuation of treatment) challenges the patient’s preferences.

Discussions

Patient-centered care supports personalized decision-making, in which the physician’s approach varies according to the patient’s situation and individuality. The idea of beneficence may change during care, because of acceptance of the patient’s principles or a change in the primary goal of care.
Machine learning’s effectiveness in evaluating movement in one-legged standing test for predicting high autistic trait
Authors: Ohmoto Yoshimasa , Terada Kazunori , Shimizu Hitomi , Kawahara Hiroko , Iwanaga Ryoichiro , Kumazaki Hirokazu
Published: October 2024

Introduction

Research supporting the presence of diverse motor impairments, including impaired balance coordination, in children with autism spectrum disorder (ASD) is increasing. The one-legged standing test (OLST) is a popular test of balance. Since machine learning is a powerful technique for learning predictive models from movement data, it can objectively evaluate the processes involved in OLST. This study assesses machine learning’s effectiveness in evaluating movement in OLST for predicting high autistic trait.

Methods

In this study, 64 boys and 62 girls participated. The participants were instructed to stand on one leg on a pressure sensor while facing the experimenter. The data collected in the experiment were time-series data pertaining to pressure distribution on the sole of the foot and full-body images. A model to identify the participants belonging to High autistic trait group and Low autistic trait group was developed using a support vector machine (SVM) algorithm with 16 explanatory variables. Further, classification models were built for the conventional, proposed, and combined explanatory variable categories. The probabilities of High autistic trait group were calculated using the SVM model.

Results

For proposed and combined variables, the accuracy, sensitivity, and specificity scores were 1.000. The variables shoulder, hip, and trunk are important since they explain the balance status of children with high autistic trait. Further, the total Social Responsiveness Scale score positively correlated with the probability of High autistic trait group in each category of explanatory variables.

Discussion

Results indicate the effectiveness of evaluating movement in OLST by using movies and machine learning for predicting high autistic trait. In addition, they emphasize the significance of specifically focusing on shoulder and waist movements, which facilitate the efficient predicting high autistic trait. Finally, studies incorporating a broader range of balance cues are necessary to comprehensively determine the effectiveness of utilizing balance ability in predicting high autistic trait.
Predicting COVID-19 booster intentions among college students using the health belief model: advancing health promotion strategies for uptake
Authors: Catalano Hannah Priest , Christofora Julianne , Richards Keith , Hyatt Hawkins Shaw Katherine , Kiser Kevin
Published: October 2024

Background

COVID-19 remains a significant public health threat. The primary purpose of this study was to test the health belief model (HBM) constructs in predicting COVID-19 booster intentions of college students.

Methods

A total of 285 students enrolled at large public university in the Southeastern U.S., who were 18 years and older, completed an online survey to assess COVID-19 vaccination status, prior or current COVID-19 infection, demographics, and HBM constructs.

Results

Over three quarters of the sample (81.4%, n = 232) was fully vaccinated, 2.1% (n = 6) was partially vaccinated, and 16.5% (n = 47) was unvaccinated. Furthermore, 53.4% (n = 124) of students who self-reported being fully vaccinated also reported receiving the booster vaccine. Nearly half of the sample (49.1%, n = 140) self-reported previously or currently testing positive for COVID-19. Results of the stepwise multiple regression indicated the HBM constructs of perceived benefits (β =0.596; p < 0.001) and cues to action (β =0.275; p < 0.001) were significant predictors of respondents’ behavioral intention to receive the COVID-19 booster in the next 6 months. The significant predictors at step 2 accounted for 64.6% [R2 = 0.646, F (2, 111 = 101.331, p < 0.001)] of the variance in behavioral intention to get the COVID-19 booster in the next 6 months.

Conclusion

Practitioners developing HBM-based interventions to enhance COVID-19 booster intentions among college students should tailor health promotion strategies that target perceived benefits and cues to action. Although some of the HBM constructs were not statistically significant in the prediction model, they should not be entirely discounted in health promotion practice. Instead, practitioners should focus on supplemental strategies to improve those domains in college students.