bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a molecular inflammatory predictive model with histone modification-related genes and identification of CAMK2D as a potential response signature to infliximab in ulcerative colitis
Authors: Ye Shuyu , Lyu Yongqing , Chen Libin , Wang Yiwei , He Yue , Li Quansi , Tian Li , Liu Fen , Wang Xiaoyan , Ai Feiyan 
Published: January 2024

BackgroundUlcerative colitis (UC) is a lifelong inflammatory disease affecting the rectum and colon with numerous treatment options that require an individualized treatment plan. Histone modifications regulate chromosome structure and gene expression, resulting in effects on inflammatory and immune responses. However, the relationship between histone modification-related genes and UC remains unclear.MethodsTranscriptomic data from GSE59071 and GSE66407 were obtained from the Gene Expression Omnibus (GEO), encompassing colonic biopsy expression profiles of UC patients in inflamed and non-inflamed status. Differentially expressed gene (DEG) analyses, functional enrichment analyses, weighted gene co-expression network analysis (WGCNA), and random forest were performed to identify histone modification-related core genes associated with UC inflammation. Features were screened through the least absolute shrinkage and selection operator (LASSO) and support vector machine‐recursive feature elimination (SVM‐RFE), establishing a molecular inflammatory predictive model using logistic regression. The model was validated in the GSE107499 dataset, and the performance of the features was assessed using receiver operating characteristic (ROC) and calibration curves. Immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with infliximab was used to further confirm the clinical application value. Univariate logistic regression on GSE14580 highlighted features linked to infliximab response.ResultsA total of 253 histone modification-related DEGs were identified between inflammatory and non-inflammatory patients with UC. Seven key genes (IL-1β, MSL3, HDAC7, IRF4, CAMK2D, AUTS2, and PADI2) were selected using WGCNA and random forest. Through univariate logistic regression, three core genes (CAMK2D, AUTS2, and IL-1β) were further incorporated to construct the molecular inflammatory predictive model. The area under the curve (AUC) of the model was 0.943 in the independent validation dataset. A significant association between CAMK2D protein expression and infliximab response was observed, which was validated in another independent verification set of GSE14580 from the GEO database.ConclusionThe molecular inflammatory predictive model based on CAMK2D, AUTS2, and IL-1β could reliably distinguish the mucosal inflammatory status of UC patients. We further revealed that CAMK2D was a predictive marker of infliximab response. These findings are expected to provide a new evidence base for personalized treatment and management strategies for UC patients.
DARTS: an open-source Python pipeline for Ca2+ microdomain analysis in live cell imaging data
Authors: Woelk Lena-Marie , Kovacevic Dejan , Husseini Hümeyra , Förster Fritz , Gerlach Fynn , Möckl Franziska , Altfeld Marcus , Guse Andreas H. , Diercks Björn-Philipp , Werner René 
Published: January 2024

Ca2+ microdomains play a key role in intracellular signaling processes. For instance, they mediate the activation of T cells and, thus, the initial adaptive immune system. They are, however, also of utmost importance for activation of other cells, and a detailed understanding of the dynamics of these spatially localized Ca2+ signals is crucial for a better understanding of the underlying signaling processes. A typical approach to analyze Ca2+ microdomain dynamics is live cell fluorescence microscopy imaging. Experiments usually involve imaging a larger number of cells of different groups (for instance, wild type and knockout cells), followed by a time consuming image and data analysis. With DARTS, we present a modular Python pipeline for efficient Ca2+ microdomain analysis in live cell imaging data. DARTS (Deconvolution, Analysis, Registration, Tracking, and Shape normalization) provides state-of-the-art image postprocessing options like deep learning-based cell detection and tracking, spatio-temporal image deconvolution, and bleaching correction. An integrated automated Ca2+ microdomain detection offers direct access to global statistics like the number of microdomains for cell groups, corresponding signal intensity levels, and the temporal evolution of the measures. With a focus on bead stimulation experiments, DARTS provides a so-called dartboard projection analysis and visualization approach. A dartboard projection covers spatio-temporal normalization of the bead contact areas and cell shape normalization onto a circular template that enables aggregation of the spatiotemporal information of the microdomain detection results for the individual cells of the cell groups of interest. The dartboard visualization allows intuitive interpretation of the spatio-temporal microdomain dynamics at the group level. The application of DARTS is illustrated by three use cases in the context of the formation of initial Ca2+ microdomains after cell stimulation. DARTS is provided as an open-source solution and will be continuously extended upon the feedback of the community.Code available at:10.5281/zenodo.10459243.
Minimal residual disease guided radical chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy followed by adjuvant immunotherapy for esophageal squamous cell cancer (ECMRD-001): a study protocol for a prospective cohort study
Authors: Wang Hesong , Zhang Xueyuan , Zhao Xiaohan , Song Chunyang , Deng Wenzhao , Shen Wenbin 
Published: January 2024

IntroductionFor locally advanced, inoperable esophageal cancer, concurrent chemoradiotherapy (CCRT) becomes the norm. Combining immunotherapy with radiotherapy has been shown to improve efficacy. Circulating tumor DNA (ctDNA) is a strong predictor of effectiveness and tumor recurrence and is indicative of minimal residual disease (MRD). Patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC) are enrolled in the ECMRD-001 trial to evaluate changes in MRD status before and after CCRT combined with immunotherapy and adjuvant immunotherapy following neoadjuvant immunochemotherapy.Methods and analysisThe ECMRD-001 trial is a prospective cohort study. Eligible patients will receive radical concurrent chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy, followed by adjuvant immunotherapy for at least one year. Follow-up will be up to three years. MRD-related blood and tissue samples and T-cell immunohistobank related blood and tissue samples collected before, during and after treatment and follow-up will be grouped into sample collection time points. The relationship between MRD status at different time points and treatment efficacy is the primary outcome. Correlation between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence are the secondary outcomes. Examination of ctDNA mutations is the exploratory outcome.DiscussionctDNA-based MRD may be a potential predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients. Elevated ctDNA-MRD may predict tumor recurrence earlier than imaging. ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment should be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC.Trial registrationThe ECMRD-001 study has been registered at ClinicalTrials.gov as NCT05952661 (July 19, 2023), https://classic.clinicaltrials.gov/ct2/show/NCT05952661.
Morphological and functional parameters in X-linked retinoschisis patients–A multicentre retrospective cohort study
Authors: Kiraly Peter , Seitz Immanuel P. , Abdalla Elsayed Maram E. A. , Downes Susan M. , Patel Chetan K. , Charbel Issa Peter , Birtel Johannes , Mautone Luca , Dulz Simon , Atiskova Yevgeniya , Herrmann Philipp , Vrabič Nika , Jarc-Vidmar Martina , Hawlina Marko , Fischer M. Dominik 
Published: January 2024

IntroductionX-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.MethodsIn this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI).ResultsInter-eye symmetry revealed strong correlation in CRT (r = 0.77; p &lt; 0.0001) and moderate correlations in MV (r = 0.51, p &lt; 0.0001) and BCVA (r = 0.49; p &lt; 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34).DiscussionThe XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn’t influence both morphological and functional outcomes.
Microbial transformation of soil organic matter under varying agricultural management systems in Ukraine
Authors: Symochko Lyudmyla , Demyanyuk Olena , Crisan Vlad , Dinca Lucian 
Published: January 2024

IntroductionThis paper presents comparative studies on the content and structure of organic matter (OM) and the activity of microbiological cellulose destruction in three types of Ukrainian soils intensively used in agricultural production.MethodsThe highest content of humus in the arable layer (4.9%), OM (410 t ha−1), and total carbon (30.9 mg C g−1 soil) was determined in chernic phaeozems, which is 2.2–2.5 times higher than in albic retisols. The soil of natural ecosystems is characterised by a high content of microbial carbon (Cmic) in the carbon fraction of organic soil compounds.Results and discussionIn arable soils, the content and reserves of humus and soil organic matter (SOM) have decreased by an average of 1.5–2 times. The most considerable loss of humus reserves in the soil profile was identified in albic retisols (1.96–1.44 times) and the smallest in chernic phaeozems (1.27–1.81 times). During the long-term systematic application of mineral fertilisers, the Corg content decreased by 8-21% in chernic phaeozems, 12-33% in greyzemic phaeozems, and 6–38% in albic retisols. A significant difference of 2.1–8.0 times was determined regarding the number of aerobic cellulolytic microorganisms and 1.3–3.3 times in the potential cellulolytic activity of the studied soils. The high number of cellulose-destroying microorganisms is characteristic of chernic phaeozems with a high content of OM in the soil; the advantage over other types of studied soils was 1.4 times and 7.8 times for greyzemic phaeozems and albic retisols, respectively. Among the studied soil types, high values of CO2 emissions were identified in chernic phaeozems. Intensive agricultural practices in Ukrainian soils have significantly altered the content and composition of organic matter, leading to reduced humus and soil organic matter reserves. The study also underscores the importance of considering the abundance of cellulose-destroying microorganisms and their potential activity in assessing soil health and sustainability.
The analysis of low-dose glucocorticoid maintenance therapy in patients with primary nephrotic syndrome suffering from COVID-19
Authors: Li Yong-Qi , Wu Min , Wang Yu-Jia , Zhang Yu-Xia , Lu Jing , Zhao Yi-Nan , Ji Bo-Fan , Chen Zhi-Qing , Tang Ri-Ning , Liu Bi-Cheng 
Published: January 2024

Objectives: This study aimed to describe the effects of low-dose (prednisolone acetate 2.5–7.5 mg/day) glucocorticoids (GCs) maintenance therapy in patients with primary nephrotic syndrome (NS) suffering from coronavirus disease 2019 (COVID-19).Methods: A single-center retrospective study of NS patients with COVID-19 infection in Zhongda Hospital Affiliated to Southeast University from 1 February 2022 to 31 March 2023 was conducted. All enrolled patients underwent renal biopsy for the pathological diagnosis and reached complete remission (CR) or near-CR before COVID-19 infection. According to the maintained therapy regimen, patients were divided into low-dose GCs group and non-GCs group.Results: A total of 125 patients were enrolled in the study. Their median age was 46.0 ± 15.6 years, and the median value of 24-h urine protein was 0.77 g. The majority of these patients received treatment for more than 6 months, with a significant portion achieving CR (29.6%) or near-CR (43.2%). The leading cause of NS was membranous nephropathy (52%). There were no significant differences in the baseline characteristics between low-dose GCs and non-GCs group. As compared to those in the non-GCs group, patients receiving low-dose GCs treatment showed less fatigue or muscle weakness, smell disorder, palpitations, decreased appetite, taste disorder, dizziness, sore throat or difficult to swallow and fever (p &lt; 0.05). Moreover, patients in the low-dose GCs group were with higher median quality of life scores (85.0) than in the non-GCs group (p = 0.001). Further serum inflammatory factor analysis indicated that interleukin-6 (IL-6) levels in the non-GCs group were significantly higher than that in the low-dose GCs group (p &lt; 0.05).Conclusion: Patients with NS in low-dose GCs maintenance therapy stage showed milder symptom, higher quality of life and decreased serum IL-6 levels compared to those, who were not on GCs maintenance therapy. These results suggest the beneficial effect of low-dose GCs therapy in NS patients with CR/near-CR suffering from COVID-19 infection.
Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss
Authors: Zeng Chaojun , Gu Xi , Chen Yuqing , Lin Yanchun , Chen Junying , Chen Zhifeng , Chen Chenyu , Yao Guangnan , Lin Chang 
Published: January 2024

ObjectiveTo reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.MethodsBioinformatics were used to analyze the hub genes and molecular mechanism of ferroptosis in the aging cochleae. Senescence β-galactosidase staining, iron content detection, and micro malondialdehyde (MDA) assay kits were used to measure β-galactosidase activity, and expression of Fe2+ and MDA, respectively. Fluorescence microscope was used for immunofluorescence assay of hub genes. Western blot was used to verify the expression of hub genes in HEI-OC1 cells, cochlear explants, and cochleae of C57BL/6J mice. Data were expressed as mean ± SD of at least three independent experiments.ResultsThe analysis of bioinformatics confirmed that lactotransferrin (LTF) is the hub gene and CEBPA-miR-130b-LTF network is the molecular mechanism for cochlear ferroptosis. Compared with the control group, the experiments proved that the indicators of ferroptosis, including Fe2+, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.ConclusionThese results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.
Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder
Authors: Skolariki Konstantina , Vlamos Panagiotis 
Published: January 2024

IntroductionPost-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after experiencing traumatic events. The aim of this work is to explore the role of genes and genetic variations in the development and progression of PTSD.MethodsThrough three methodological approaches, 122 genes and 184 Single Nucleotide Polymorphisms (SNPs) associated with PTSD were compiled into a single gene repository for PTSD. Using PharmGKB and DrugTargetor, 323 drug candidates were identified to target these 122 genes. The top 17 drug candidates were selected based on the statistical significance of the genetic associations, and their promiscuity (number of associated genestargets) and were further assessed for their suitability in terms of bioavailability and drug-like characteristics. Through functional analysis, insights were gained into the biological processes, cellular components, and molecular functions involved in PTSD. This formed the foundation for the next aspect of this study which was to propose an efficient treatment for PTSD by exploring drug repurposing methods.ResultsThe main aim was to identify the drugs with the most favorable profile that can be used as a pharmacological approach for PTSD treatment. More in particular, according to the genetic variations present in each individual, the relevant biological pathway can be identified, and the drug candidate proposed will specifically target said pathway, accounting for the personalized aspect of this work. The results showed that the drugs used as off-label treatment for PTSD have favorable pharmacokinetic profiles and the potential drug candidates that arose from DrugTargetor were not very promising. Clozapine showed a promising pharmacokinetic profile and has been linked with decreased psychiatric symptoms. Ambrucin also showed a promising pharmacokinetic profile but has been mostly linked with cancer treatment.
Association between red blood cell distribution width-to-albumin ratio and the prognosis in patients with autoimmune encephalitis: a retrospective cohort study
Authors: Li Dan , Yang Ali , Xia Mingrong , Ma Kai , Zhang Jiewen , Guo Yang , Zang Weizhou 
Published: January 2024

AimRed blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported.MethodsThis was a retrospective cohort study, and data were collected from the Henan Provincial People’s Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98–16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574–0.746).ConclusionThis study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.
Synonymous variants in the ATP6AP2 gene may lead to developmental and epileptic encephalopathy
Authors: Liang Yan , Wan Lin , Yan Huimin , Liu Xinting , Zhang Jing , Zhu Gang , Yang Guang 
Published: January 2024

ObjectiveTo the literature, variants in the ATP6AP2 gene may cause abnormal nervous system development and associated neurological symptoms.MethodsWe report a patient with developmental and epileptic encephalopathy (DEE) carrying an ATP6AP2 c.858G &gt; A (p.Ala286=) synonymous variant. In addition, an overview of reported patients with the same variant were collected and summarized to compare our findings.ResultsThe patient started experiencing tonic seizures at 3.5 months of age, and magnetic resonance imaging (MRI) indicated impaired brain white matter development and reduced left hippocampal volume. Furthermore, electroencephalography showed multifocal interictal epileptiform discharges. Treatment with various anti-seizure medications yielded unsatisfactory results, and the disorder eventually developed into epileptic spasms. An in vitro splicing assay for the ATP6AP2 gene mRNA revealed that the variant caused a deletion in exon 8 and a corresponding protein truncation. A review of previously reported ATP6AP2-related DEE patients found that synonymous variants in the ATP6AP2 gene can cause early DEE onset, progressive changes in early-life MRI, and exon skipping in all ATP6AP2-related DEE patients.SignificanceWe found that synonymous variants in ATP6AP2 may have significant pathogenicity and are highly correlated with DEE. Due to increased isoform production, ATP6AP2 synonymous variants may cause nervous system developmental disorders by competitively reducing the generation of full-length transcripts, resulting in defects in ATP6AP2-related physiological processes.
The Third Hand of Neurosurgeons – a novel intraoperative malleable adjustable continuous suction tube
Authors: Zhang Jibo , Nie Pan , Wei Zixuan , Xu Chengshi , Li Xiang , Chen Jincao 
Published: January 2024

ObjectiveWe designed a novel intraoperative malleable adjustable continuous suction tube to obtain clear surgical fields, reduce intracranial pressure, and lower the temperature of the surgical area.MethodsThis device consists of six parts: continuous suction tube head and cotton patty, suction tube, fixed wire position, fixed clip, spiral plastic pressure regulating valve, and tail. It can continuously extract blood, cerebrospinal fluid, and rinsing solution from surgical fields, with minimal contact and trauma to tissues, nerves, and blood vessels, while also having a negligible impact on the surgeon’s focus and procedure.ResultThe excellent and safe performance (simple, malleable, adjustable, space-saving, inexpensive, safe, and effective) of this device in clearing the operating field has been proven in more than 2000 neurosurgical operative procedures. We encountered no complications associated with this device, such as cerebral hematoma, postoperative low intracranial pressure, or vascular and nerve injuries.ConclusionThe newly innovated intraoperative malleable adjustable continuous suction tube is effective and safe for microneurosurgery.