bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell RNA Sequencing to Identify an Immunogenic Cell Death-Related Prognostic Signature in Intrahepatic Cholangiocarcinoma
Authors: Sha Bowen , Tong Fei , Shu Qinghua , Wu Miao , Zhao Liang , Zhang Yufeng 
Published: December 2024

Abstract

Immunogenic cell death (ICD) is crucial for cancer development and enhances the effectiveness of immunotherapy by triggering an adaptive immune response. However, the impact of ICD-related genes (ICDRGs) on iCCA progression and patient prognosis remains unclear. iCCA samples from The Cancer Genome Atlas (TCGA) were categorized into two ICD-associated subtypes by consensus clustering, and patient prognosis in these subgroups was assessed. Single-cell RNA sequencing was conducted on viable cells from 8 iCCA patients to understand their transcriptomic profiles, heterogeneity, and immune microenvironment. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identified 13 cell subpopulations. The gene set enrichment analysis (GSEA) was used to investigate pathway heterogeneity among these subpopulations. CellChat was employed for intercellular communication analysis. Pseudotime trajectory analyses with CytoTRACE and Monocle2 were used to explore differentiation trajectories and functional differences across various states. 30485 single cells from human iCCA and normal tissues were sequenced, revealing two ICD-associated subtypes. The ICD-low subtype correlates with better clinical outcomes, whereas the ICD-high subtype is linked to increased immune cell infiltration and immune response signaling activity. Distinct biological functions and metabolic characteristics were observed in iCCA between high- and low-ICD groups. High infiltration of ICD-low subtype in iCCA is associated with poor prognosis, potentially through the ANXA-FPR pathway affecting macrophage proliferation and differentiation. Our study constructed an immunogenic cell death-related signature that can promise prognosis prediction and personalized medicine in iCCA. This finding might help guide clinicians for iCCA patients.
Untargeted Metabolomics Reveals Key Pathways in Miscarriage: Steroid, Folate, Fatty Acid &amp; Glycosaminoglycan Metabolism
Authors: Ku Chee Wai , Tan Yu Bin , Chew Kuan Yang , Ku Chee Onn , Ng Carissa , Sultana Rehena , Tan Thiam Chye , Lee Yie Hou 
Published: December 2024

Abstract

Metabolites influencing miscarriage outcomes remain understudied. We hypothesized that aberrant metabolism impacts threatened miscarriage outcomes and that understanding these pathways could offer new management strategies. This case-control study analyzed serum metabolomics from 80 women between 5-12 weeks’ gestation at KK Women’s and Children’s Hospital, Singapore, comparing three groups: women with threatened miscarriage who miscarried (TMMC), those with ongoing pregnancies (TMO), and women with normal pregnancies (NP). Using untargeted liquid chromatography-mass spectrometry and pathway analysis through MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes, 267 metabolites across 12 enriched pathways were identified. Dysregulations in steroid (AUC 0.82), folate (AUC 0.59), fatty acid (AUC 0.70), and glucosaminoglycan (AUC 0.64) pathways distinguished women who miscarried from those with ongoing pregnancies. We provide initial insights into the metabolic profile associated with miscarriage, highlighting disruptions in steroid hormone, fatty acid, folate, and glucosaminoglycan biosynthesis. Further validation may support biomarker development for prognostication.
Factors affecting intensive care length of stay in critically ill pediatric patients with burn injuries
Authors: Lerner Reut Kassif , Gibori Amit , Hubara Evyatar , Sadeh Tal , Rubinstein Marina , Paret Gidi , Pessach Itai M. 
Published: December 2024

Abstract

Background
Burns in children are often complex injuries, leading to prolonged length of stay (LOS) and significant morbidity. LOS in pediatric intensive care units (PICUs) is a key measure for evaluating illness severity, clinical outcomes, and quality of care. Accurate prediction of LOS is vital for improving care planning and resource allocation. There is limited data for predicting LOS in severely burned children in PICU. This study aims to identify significant factors associated with prolonged PICU stays and offer a simple LOS predicting model.
Methods
This historical cohort study included all patients < 18 years, admitted for severe burn injuries to Israel’s largest tertiary hospital PICU, from 2015 to 2020. Statistical analyses were conducted to identify factors linked to prolonged LOS, and a predictive model was designed.
Results
The study included 39 pediatric burn patients and identified several factors associated with longer PICU stays. Patients with "long LOS" had significantly higher %TBSA (33.11 ± 17.87% vs. 16.67 ± 7.98%, p < 0.001. During the first 24 and 48 hours, the "long LOS" group had lower minimal systolic blood pressure (SBP) (70.67 ± 17.49 mmHg vs. 84.38 ± 16.73 mmHg, p = 0.015 and 69.39 mmHg ± 16.44 vs. 81.10 mmHg ± 19.67, p = 0.018). Although serum lactate levels were higher in the "long LOS" group, the difference was not significant, and platelet counts in this group were significantly lower during the first 48 hours (184 K/µL vs. 264.5 K/µL, p = 0.003). A predictive model based on %TBSA, SBP, lactate, and platelet count was developed, demonstrating 100% specificity and positive predictive value for predicting LOS over 7 days in severely burned children.
Conclusions
Key clinical indicators at PICU admission in severely burned children were associated with LOS > 7 days. The resulting predictive model, although requiring further validation in multi-site studies, offers a promising tool for enhancing care planning in this population.
Utility of Prostate-Specific Antigen Derivatives to Minimize Unnecessary Magnetic Resonance Imaging in Patients with Prior Negative Prostate Biopsy Running title: PSAD to Minimize MRI in Prior Negative Prostate Biopsy
Authors: Lee Sangchul , Ryu Hoyoung , Song Sang Hun , Hwang Sung Il , Lee Hak Jong , Lee Hakmin , Hong Sung Kyu , Byun Seok-Soo , Song Byeongdo 
Published: December 2024

Abstract

Magnetic resonance imaging (MRI) has become an important tool for recommending prostate biopsy (PB) in prostate cancer (PCa) detection. However, the routine use of MRI in patients with previous negative PB remains debatable. This study aimed to evaluate the utility of prostate-specific antigen (PSA) derivatives to guide MRI use and reduce unnecessary scans in such cases. Receiver operating characteristic analysis identified a Prostate Imaging Reporting and Data System score ≥ 4 as the optimal threshold for predicting clinically significant PCa (Gleason score ≥ 7). A cohort of 251 patients with at least one prior negative PB who underwent serum PSA testing, free PSA, and MRI between October 2015 and June 2024 were analyzed. The optimal cutoff values for PSA, PSA density (PSAD), and free-to-total PSA ratio (%fPSA) were 11.87 ng/mL, 0.19 ng/mL2, and 18.76%, respectively (all p < 0.001). Restricting MRI to patients with PSA < 11.87 ng/mL, PSAD < 0.19 ng/mL2, or %fPSA > 18.76% could induce MRI use by 22.7% while missing only 9.1% of significant PCa cases on MRI-targeted PB.
Acupuncture for Collaborative Efficiency in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps After Nasal Surgery: A Randomized Controlled Trial Protocol
Authors: Huang Yue , Lv Zeyi , Pan Zhuo , Sui Wen , Chen Yulan , Li Qihong , Li Yu , Yin Man , Chen Xi , Yang Hao , Li Xinrong 
Published: December 2024

Abstract

Background: Eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) is a chronic inflammatory disease of the nasal and sinus mucosa dominated by eosinophil infiltration with polyp formation. both hormonal and surgical treatment face a high recurrence rate, with studies showing that when eosinophils constitute more than 27%, the recurrence rate of eCRSwNP is more than 90%. Hence, alternative therapy is needed. However, the insufficient randomized controlled trial limited the quality of evidence.
Methods: From November 2024 to April 2026, 84 acupuncture eCRSwNP patients after nasal surgery will be recruited at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Participants will be randomized 1:1 to the acupuncture and sham acupuncture groups. The visual analogue scale (VAS), nasal sinus outcome test 22 (SNOT-22), and Lund-Kennedy endoscopic mucosal morphology score are used as the main outcome measures, and the SAS anxiety self-rating scale is used as the secondary outcome measures. Assessments are performed before and at the end of each week and at the end of 1 month, a total of 6 times.
Expected Results and Conclusion: We will be able to measure the effectiveness of acupuncture in patients with eCRSwNP and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients.
The study was registered with the Chinese Clinical Trial Registry on 1 November 2024. (identifier: ChiCTR2400091693)
Antitumor activity of Gilteritinib, an inhibitor of AXL, in human solid tumor
Authors: wang liefeng , Zhang Zuxiong , Hu Ruxia , Liu Jie , Yang Xiaohan , Xiao Youban , Xu Xi , Liu Xinxin , Zeng Wen , Zhang Shuyong 
Published: December 2024

Abstract

AXL, a receptor tyrosine kinase, has recently emerged as a potential therapeutic target against various cancer types. Gilteritinib, a FDA-approved small-molecule inhibitor, is used for the treatment of patients with FLT3-mutated acute myeloid leukemia. However, the antitumor activity of Gilteritinib in solid tumors remains poorly elucidated. Here, The antitumor activity of Gilteritinib and molecular mechanisms underlying were explored in the AXL- expressing esophageal cancer (EC), ovarian cancer (OC) and gastric cancer (GC). Our data demonstrated that Gilteritinib significantly inhibited cell proliferation and spheroids formation via triggering apoptosis and cell cycle arrest in AXL-positive EC, OC and GC cells. Moreover, we found that Gilteritinib treatment repressed EC, OC and GC cell migration and invasion. Mechanistically, RNA-seq analysis revealed that Gilteritinib significantly downregulated multiple cancer-related pathways, such as apoptosis, cell cycle, mTOR pathway, AMPK pathway, p53 pathway, FOXO pathway, Hippo pathway and Wnt pathway, etc. Furthermore, Gilteritinib inhibited a unique set of E2F and MYC targets-associated genes in EC, OC and GC cells. Intriguingly, interrogation of the EC, OC and GC cohort demonstrated that these genes were overexpressed and associated with poor prognosis. Finally, Gilteritinib also displayed strong antitumor effects on AXL-positive PDX-derived explants (PDXEs) and PDX-derived organoids (PDXOs) ex vivo, and PDXs in vivo. Collectively, these findings reveals Gilteritinib as a potent therapeutic agent for the treatment of AXL-positive solid tumors.
Vessel volume decrease during early brain injury period as predictor for evolving delayed cerebral ischemia after SAH – a case-control study
Authors: Pantel Tobias , Kranawetter Beate , Sauvigny Jennifer , Ricklefs Franz L. , Drexler Richard , Thaler Christian , Malinova Vesna , Meyer Hanno S. , Czorlich Patrick , Sauvigny Thomas , Mielke Dorothee , Dührsen Lasse 
Published: December 2024

Abstract

Introduction: Delayed cerebral ischemia (DCI) secondary to aneurysmal subarachnoid hemorrhage (SAH) is a feared complication with frequent negative impact on the neurological outcome. Although early diagnosis and treatment is crucial, identifying patients at increased risk is difficult despite clinical risk stratifies such as the VASOGRADE score. Since a reduction in vessel volumes occurs regularly in this cohort and may indicate evolving DCI, the aim of this study was to investigated the reduction in vessel volume in the early brain injury (EBI) phase as an additional predictive marker for the development of DCI.
Methods: A bi-centric retrospective case-control study for the period 01/2018 to 12/2020 was conducted. Inclusion criteria were 1) angiographically confirmed aneurysmatic bleeding source and 2) cranial CT (CCT) scan with CT-angiography on admission (SAH onset) and between EBI (day 1–3). Patient-related, disease-specific and outcome parameters (modified Rankin scale (mRs)) were collected. VASOGRADE score was calculated and the volume of M1 segments of the middle cerebral arteries were measured. Subsequently, the occurrence of DCI was unblinded and the data were statistically analyzed.
Results: 80 patients met the inclusion criteria, of those 32 developed a DCI. Vessel volume was reduced in the DCI cohort at SAH onset (0.072 ± 0.027 cm3 vs. 0.108 ± 0.029 cm3, p < 0.001) and during EBI period (0.085 ± 0.028 cm3 vs. 0.121 ± 0.029 cm3, p < 0.001). ROC-analysis unveiled a volume of 0.095 cm3 AUC 0.836; p < 0.001) at SAH onset and 0.105 cm3 (AUC 0.837; p < 0.001) for the EBI period as predictive for the development of DCI. The predictive statistical markers of the volume threshold were superior to those of the VASOGRADE score.
Conclusions: Our data indicate that a reduction in vessel volume during the early brain injury (EBI) phase is a predictive marker for delayed cerebral ischemia (DCI). Furthermore, the statistical parameters associated with the volume threshold suggest that it serves as a more accurate predictor of DCI risk compared to the VASOGRADE score.
Long non-coding RNA PRKG1-AS1 Promotes Cell Proliferation and Migration in Lung Adenocarcinoma
Authors: Jiao Tong , Wen Haimei , Zeng Lizhong , Chen Yang , Shi Jie , Yang Shuanying 
Published: December 2024

Abstract

In previous studies, we have discovered a significant correlation between cGMP-dependent protein kinase I antisense RNA 1 (PRKG1-AS1) and the prognosis of lung adenocarcinoma (LUAD). Through analysis of The Cancer Genome Atlas (TCGA) database and expression data from non-small cell lung cancer tissues and cells, we found that PRKG1-AS1 is overexpressed in LUAD tissues. High expression of PRKG1-AS1 is associated with poor prognosis in LUAD patients. Cox regression analysis revealed that PRKG1-AS1 is an independent factor affecting the prognosis of LUAD. Gene Set Enrichment Analysis (GSEA) results indicated that PRKG1-AS1 might participate in various cancer-related biological processes and signaling pathways, including immune response. Furthermore, our study demonstrated that knockdown of PRKG1-AS1 expression inhibited proliferation and metastasis in LUAD. Correlation analysis between PRKG1-AS1 and protein-coding genes (PCGs) revealed a positive correlation between PRKG1-AS1 and dickkopf-1 (DKK1). Downregulation of PRKG1-AS1 led to decreased expression of DKK1, which is highly expressed in LUAD and is associated with poor prognosis. In summary, our findings suggest that PRKG1-AS1 may function as an oncogene contributing to the development of LUAD and holds significant prognostic value.
PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?
Authors: Falsaperla Raffaele , Sapuppo Annamaria , Pappalardo Xena Giada , Rizzo Roberta , Rocca Roberta , Fusto Gaia , Marino Silvia , Sortino Vincenzo , Saccuzzo Lucia , Ruggieri Martino , Fichera Marco 
Published: December 2024

Abstract

Background Emerging evidence suggesting a possible link between the PPP5C gene (Protein Phosphatase 5 Catalytic Subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PPP5C is a member of the protein phosphatase catalytic subunit family, which is involved in various signaling pathways governing cell growth, differentiation, and responses to hormonal signals or cellular stress. To date, only one case with a PPP5C variant has been reported, associated with a severe neurological phenotype, including microcephaly, failure to thrive, and early-onset seizures.Results We report a 12-year-old girl affected by epilepsy and learning disorders. At the age of five, she presented convulsive status epilepticus with respiratory failure at onset and she started anticonvulsant therapy with Levetiracetam with a significant improvement. Genetic analysis revealed a de novo heterozygous missense variant of PPP5C gene (c.202C > T: p.Arg68Cys), which had not been previously described in the literature.Conclusion This case expands the phenotypic spectrum associated with PPP5C variants, highlighting the potential role of this gene in neurological disorders. Our findings may provide some valuable insights into the spectrum of phenotypic manifestations linked to this gene less investigated in neuropediatrics.
Development of a prediction system for KRAS mutation detection via circulating tumour DNA analysis among patients with unresectable pancreatic cancer
Authors: Shimizu Hiroshi , Suzuki Rei , Asama Hiroyuki , Sugimoto Mitsuru , Sato Kentaro , Ohira Rei , Kametaka Akira , Nakamura Jun , Kato Tsunetaka , Yanagita Takumi , Hikichi Takuto , Takagi Tadayuki , Ohira Hiromasa 
Published: December 2024

Abstract

Background
Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis and limited treatment options. Advances in molecular profiling and liquid biopsy, specifically the detection of circulating tumour DNA (ctDNA), offer new avenues for personalized therapy. KRAS mutations are present in approximately 63–70% of PC patients, but detection via liquid biopsy can be influenced by disease stage, metastasis site, and ctDNA concentration. The aim of this retrospective study was to develop a prediction model for KRAS mutation detection in unresectable PC patients using clinical variables.
Methods
We analysed 32 patients who underwent ctDNA testing from 2019 to 2024, utilizing FoundationOne® Liquid CDx and Guardant360® CDx panels. Multivariate analysis of the clinical factors was performed via logistic regression with stepwise selection to elucidate independent predictors of KRAS mutation detection. According to the independent predictors of successful KRAS detection, a nomogram was plotted
Results
Multivariate analysis revealed that liver metastasis, multiple metastatic sites, and disease progression were significant predictors of successful KRAS mutation detection. A nomogram and ROC curve demonstrated high predictive accuracy, with a sensitivity of 70%, specificity of 90.9%, and AUC of 0.83.
Conclusions
Our prediction system effectively stratified patients by the likelihood of KRAS mutation detection, offering a practical tool for selecting candidates for liquid biopsy. These findings underscore the importance of personalized approaches in PC management and suggest that patients without these key clinical factors may not benefit from ctDNA testing. Future studies should validate this model in larger cohorts.
Association between remnant cholesterol levels and reversion to normoglycemia from prediabetes: a 5-year longitudinal cohort study of Chinese non-obese adults
Authors: Liu Wei , Jian Wenjing , Lin Suina , Huang Zhenhua 
Published: December 2024

Abstract

The primary objective of this study is to explore the relationship between remnant cholesterol (RC) levels and the reversion to normoglycemia in non-obese Chinese individuals with prediabetes. To achieve this goal, we conducted a retrospective cohort study involving 8,109 non-obese prediabetic participants in China, using the Cox proportional hazards regression model to analyze the correlation between RC and the likelihood of returning to normoglycemia. The results indicate a significant negative correlation between RC levels and reversion to normoglycemia (HR = 0.55, 95% CI: 0.47–0.64). Specifically, as RC quartiles increase, the probability of reverting to normoglycemia significantly decreases, with participants in the highest quartile having a 49% lower likelihood of recovery compared to those in the lowest quartile. Furthermore, we identified a nonlinear relationship between RC and the reversion to normoglycemia, with 1.47 mmol/L established as the inflection point. When RC levels are below this threshold, decreasing RC significantly increases the likelihood of recovery, whereas above this threshold, the relationship is no longer significant. To further validate the robustness of our findings, we conducted sensitivity and subgroup analyses, all of which support the reliability of the main results. In summary, there exists a significant negative and nonlinear relationship between RC levels and the reversion to normoglycemia in non-obese Chinese prediabetic patients. This suggests that lowering RC levels may play an important role in the blood glucose recovery of these patients. Aggressive interventions aimed at reducing RC levels below 1.47 mmol/L may significantly enhance the chances of prediabetic patients returning to normoglycemia.
Characteristics and prevalence of MHT use among women aged 40-65 years with low socioeconomic status: a multi-district study in Shanghai, China
Authors: Zhou Yang , Li Changbin , Sun Yixuan , Zhang Dongyao , Wang Zhijie , Wang Mei , liu Zhou , Fengyun Yang , Su Minjun , Pang Xixia , Jin Ruifu , Xu Fengyin , Chen Xuelian , Zhang Lin , Teng Yincheng , Tao Minfang 
Published: December 2024

Abstract

Background:
China faces a burgeoning demand for menopausal health care. Guidelines recommend Menopausal Hormone Therapy (MHT) as the most effective treatment for menopausal symptoms. However, the prevalence of MHT use and its influencing factors remains largely unknown in China, especially for women with minimal assurance.
Objective: This multi-center study aimed to explore the prevalence of MHT use with low socioeconomic status in shanghai and to understand its factors associated with MHT use.
Methods and design
We conducted a cross-sectional, multi-district, large-scale study of 6068 women aged 40-65 years with minimal living assurance from 10 health facilities in 7 districts of Shanghai supported by the Chinese government's public health benefit program. Data from cross-sectional survey of women between January 2023 and September 2023 were collected from comprehensive and modified questionnaires. Odds ratios (ORs) were calculated using logistic regression for characteristics related to MHT use, adjusting for sociodemographic, reproductive, health and lifestyle factors.
Discussion
This was the first largest of all similar studies to investigate the prevalence and the specific determinants of MHT use in southeast China. Our study revealed a low rate of MHT prescription among women with minimal assurance in Shanghai and MHT use was independently associated with undergoing a dual energy x-ray absorptiometry (DXA) scan, family history of osteoporosis, hospital-based sample source, regular physical activity, menopause, employment and higher educational level. It raises the need for increased awareness and strategies to help women seek menopausal health care of socioeconomic deprivation.
Trial registration: chiCTR-EPC-17011255.