bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and validation of an immune infiltration-related risk model for predicting prognosis and immunotherapy response in low grade glioma
Authors: Li Jinna , Guo Qing , Xing Rui 
Published: August 2023

Abstract
Background
Low grade glioma (LGG) is considered a heterogeneous tumor with highly variable survival and limited efficacy of immunotherapy. To identify high-risk subsets and apply immunotherapy effectively in LGG, the status and function of immune infiltration in the glioma microenvironment must be explored.

Methods
Four independent glioma cohorts comprising 1,853 patients were enrolled for bioinformatics analysis. We used ConsensusClusterPlus to cluster patients into four different immune subtypes based on immune infiltration. The immune-infiltration signature (IIS) was constructed by LASSO regression analysis. Somatic mutation and copy number variation (CNV) analyses were performed to explore genomic and transcriptomic traits in the high- and low- risk groups. The correlation between response to programmed cell death 1 (PD-1) blockade and the IIS risk score was confirmed in an in vivo glioma model.

Results
Patients were clustered into four different immune subtypes based on immune infiltration, and the high immune infiltration subtype was associated with worse survival in LGG. The high immune infiltration subtype had stronger inflammatory response, immune response and immune cell chemotaxis. The IIS, consisting of EMP3, IQGAP2, METTL7B, SLC1A6 and TNFRSF11B, could predict LGG malignant progression, which was validated with internal clinical samples. M2 macrophage infiltration positively correlated with the IIS risk score. The high-risk group had significantly more somatic mutations and CNVs. The IIS risk score was related to immunomodulatory molecules and could predict immunotherapy clinical benefit. In vivo, immunotherapy-sensitive glioma model exhibited higher IIS risk score and more infiltration of immune cells, especially M2 macrophages. The IIS risk score was decreased in an immunotherapy-sensitive glioma model after anti-PD1 immunotherapy.

Conclusion
Different immune subtypes of LGG had unique immune cell infiltration characteristics, and the high immune infiltration subtype was associated with immunosuppressive signaling pathways. A novel IIS prognostic model based on immune infiltration status was constructed for immunophenotypic classification, risk stratification, prognostication and immunotherapy response prediction in LGG.
Large cameral coronary artery fistula in a 5 months old infant with unusual presentation and fatal outcome: -case report
Authors: Moges Tamirat , Ahmed Hayat , Gisila Azmeraw 
Published: August 2023

Abstract
Background
Congenital coronary fistulas (CAFs) are uncommon abnormalities communicating the coronary arteries with the cardiac chambers or portion of the systemic or pulmonary circulation. Over 90% of the cases drain into the right side of the heart with only 3% terminating in the left ventricle. Infants with a large CAFs may develop congestive heart failure.

Case presentation
A 5 months old female infant presented with labored breathing and worsening of bluish discoloration of the lips and extremities following a prolonged cry. She had a history of breastfeeding difficulty and noticeable bluish discoloration of the lips and extremities since birth. The infant was wasted and had a fast heart rate, bluish lips, and nail beds with clubbing of fingers and toes. A cardiac murmur was noted during her medical checkup. Chest x-ray showed cardiomegaly. Echocardiography and CT angiography showed large Cameral CAF involving the left main and left anterior descending artery draining into the left ventricle. The tricuspid valve was dysplastic, there was secundum ASD, and VSD with a right to left shunt. The patient developed episode of cyanotic spells after crying excessively following a CT angiographic procedure which culminated in respiratory arrest and her demise. She was managed as a case of hypoxic spells in the ICU before her death.

Conclusion
This report unveiled unfamiliar case of Cameral coronary artery fistula with left-to-left shunting, cyanosis, and dysplastic tricuspid valve.
Elevated leukotriene B4 and 8-isoprostane in exhaled breath condensate from preterm-born infants
Authors: Urs Rhea , Ni Chin Rubi , Hemy Naomi , Wilson Andrew C. , Pillow J. Jane , Hall Graham L. , Simpson Shannon J. 
Published: August 2023

Abstract
Background
Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12–16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.

Methods
EBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.

Results
Leukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term (mean difference [95% CI]; 1.52 [0.45, 2.59], p = 0.02; 0.77 [0.52, 1.02], p < 0.001, respectively). Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.

Conclusions
Infants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.

Trial Registration
N/A.
Assessing the coverage and timeliness of coronavirus vaccination among people experiencing homelessness in Wales, UK: a population-level data-linkage study
Authors: Thomas Ian , Mackie Peter 
Published: August 2023

Abstract
Background
People experiencing homelessness have elevated morbidity, increasing their risk of COVID-19 related complications and mortality. Achieving high vaccination coverage in a timely manner among homeless populations was therefore important during the mass vaccination programme in Wales to limit adverse outcomes. However, no systematic monitoring of vaccinations among people experiencing homelessness in Wales has been undertaken.

Methods
Retrospective cohort analysis was conducted using de-identified administrative data. Study cohort members were adults (≥ 18 years old) living in Wales on the 2 December 2020 and who had recently experienced homelessness, defined as experiencing homelessness between 1 July 2020 and 2 December 2020. The outcome of interest was first coronavirus vaccine dose. Follow-up started on 2 December 2020, and ended if the participant died, had a break in address history > 30 days, reached the end of follow up (30 November 2021), or had the outcome of interest. Median-time-to-vaccination was used as a crude measure of ‘timeliness’ of vaccine uptake. To account for competing risk of death prior to vaccination, vaccine coverage was described using cumulative incidence at 350-days, and at 50-day increments over follow-up (2 December 2020 to 17 November 2021). As a benchmark, all time-to-event measures were generated for the adult population in Wales with similar baseline individual and residential characteristics as the study cohort.

Results
1,595 people with recent experiences of homelessness were identified and included in analysis. The study cohort were disproportionately male (68.8%) and concentrated in the most deprived areas in Wales. Median time-to-vaccination for the study cohort was 196 days (95% CI.: 184–209 days), compared to 141 days (95% CI.: 141–141 days) among the matched adult population in Wales. Cumulative incidence of vaccination after 350-days of follow-up was 60.4% (95% CI.: 57.8–62.8%) among the study cohort, compared to 81.4% (95% CI.: 81.3–81.5%) among the matched adult population. Visual analysis of cumulative incidence over time suggests that vaccine inequality, i.e., difference between study cohort and matched adult population, peaked after 200-days of follow-up, and declined slightly until last follow-up at 350-days.

Conclusions
Despite being prioritised for vaccination, people experiencing homelessness in Wales appear to have been under-engaged, leading to lower vaccination coverage and greater time unvaccinated, potentially increasing their risk of COVID-19 complications and mortality.
RETRACTED ARTICLE: The effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy: a randomized, double-blinded, controlled study
Authors: Wang Jin , Cui Xulei , Zhang Yuelun , Sang Xinting , Shen Le 
Published: August 2023

Abstract
Background
We aimed to investigate the effects of intermittent bolus paravertebral block on analgesia and recovery in open hepatectomy.

Methods
Eighty 18–70 years old, American Society of Anesthesiologists level I-III patients scheduled for hepatectomy with a J-shaped subcostal incision were enrolled and randomized to receive either intermittent bolus paravertebral ropivacaine (0.5% loading, 0.2% infusion) or 0.9% saline infusion at 1:1 ratio (25 ml loading before surgery, 0.125 ml/kg/h bolus for postoperative 48 h). The primary outcome was set as postoperative 48 h cumulative intravenous morphine consumption recorded by a patient-controlled analgesic pump.

Results
Thirty-eight patients in each group completed the study. The cumulative morphine consumptions were lower in the paravertebral block than control group at postoperative 24 (difference -10.5 mg, 95%CI -16 mg to -6 mg, P < 0.001) and 48 (difference -12 mg, 95%CI -19.5 mg to -5 mg, P = 0.001) hours. The pain numerical rating scales at rest were lower in the paravertebral block than control group at postoperative 4 h (difference -2, 95%CI -3 to -1, P < 0.001). The active pain numerical rating scales were lower in the paravertebral block than control group at postoperative 12 h (difference -1, 95%CI -2 to 0, P = 0.005). Three months postoperatively, the paravertebral block group had lower rates of hypoesthesia (OR 0.28, 95%CI 0.11 to 0.75, P = 0.009) and numbness (OR 0.26, 95%CI 0.07 to 0.88, P = 0.024) than the control group.

Conclusions
Intermittent bolus paravertebral block provided an opioid-sparing effect and enhanced recovery both in hospital and after discharge in patients undergoing hepatectomy.

Trial registration
clinicaltrials.gov (NCT04304274), date: 11/03/2020.
An unusual case of linear IgA disease affecting only the oral gingiva: a case report
Authors: He Jianing , Shen Jun , Guo Wei 
Published: August 2023

Abstract
Background
We present a case report on desquamative gingivitis diagnosed as linear IgA disease (LAD), which is a rare autoimmune bullous disease exclusively affecting the oral gingiva. The oral mucosa can be impacted by various autoimmune bullous diseases, and our report focuses on this particular manifestation of LAD.

Case presentation
This patient presented with atypical symptoms, as frequent blister formation on the gingiva was the primary clinical manifestation. A combination of systemic and local treatment was administered to the patient. Following the treatment, there was a significant improvement observed in both the erythema and the bullous lesions on the gingiva.

Conclusions
A more suitable local treatment strategy should be formulated for patients presenting with oral topical lesions, which clinicians can employ effectively.
Vitamin D and vitamin D receptor polymorphism in Asian adolescents with primary dysmenorrhea
Authors: Donayeva Ainur , Amanzholkyzy Ainur , Nurgaliyeva Roza , Gubasheva Gulnara , Saparbayev Samat , Ayaganov Dinmukhamed , Kaldybayeva Aiman , Abdelazim Ibrahim A. , Farghali Mohamed M. 
Published: August 2023

Abstract
Background
The expression of vitamin D receptor in the normal endometrium and ovaries supports the role of vitamin D in local immunity and inflammatory cytokines regulation.

Objective
This study aimed to detect the relation between serum 25(OH)D and primary dysmenorrhea in Asian Adolescents.

Methods
Two hundred and five (205) adolescents complaining of primary dysmenorrhea (study group) were compared in this prospective study to matched controls (210 controls) after informed consent following the Helsinki Declaration.
After thorough evaluation, including a thorough history and pelvic ultrasound examination, blood samples were collected from the studied adolescents to measure serum 25(OH)D and for vitamin D receptor TaqI (rs731236) genotyping.
The studied adolescents’ data were analyzed using the Pearson’s correlation to detect the relation between serum 25(OH)D and primary dysmenorrhea (primary outcome). The secondary outcome measures the odds of primary dysmenorrhea in Asian adolescents with vitamin D receptor TaqI (rs731236) polymorphism.

Results
The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls (16.17 ± 7.36 versus 17.65 ± 6.36 ng/ml, respectively), (P = 0.01). The correlation analysis showed a significant negative correlation between the serum 25(OH)D and visual analogue scale of dysmenorrhea (r = -0.9003, P < 0.0001).
The studied-dysmenorrhea cases with vitamin D receptor T/t and t/t genotypes had significantly lower serum 25(OH)D (16.7 ± 8.05 and 14.4 ± 4.1 ng/ml, respectively) compared to controls (18.97 ± 6.7 and 21.4 ± 2.45 ng/ml, respectively), (P = 0.02 and 0.004, respectively).
The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea (OR 1367.2, P < 0.0001 and OR 106.2, P = 0.001, respectively).

Conclusion
The serum 25(OH)D was significantly lower in the studied-dysmenorrhea group compared to controls. The studied-dysmenorrhea cases with VDR T/t and t/t TaqI genotypes had significantly lower serum 25(OH)D compared to controls. The VDR T/t and t/t polymorphisms significantly increase the odds of primary dysmenorrhea.
Development and validation of predictive models for unplanned hospitalization in the Basque Country: analyzing the variability of non-deterministic algorithms
Authors: Olza Alexander , Millán Eduardo , Rodríguez-Álvarez María Xosé 
Published: August 2023

Abstract
Background
The progressive ageing in developed countries entails an increase in multimorbidity. Population-wide predictive models for adverse health outcomes are crucial to address these growing healthcare needs. The main objective of this study is to develop and validate a population-based prognostic model to predict the probability of unplanned hospitalization in the Basque Country, through comparing the performance of a logistic regression model and three families of machine learning models.

Methods
Using age, sex, diagnoses and drug prescriptions previously transformed by the Johns Hopkins Adjusted Clinical Groups (ACG) System, we predict the probability of unplanned hospitalization in the Basque Country (2.2 million inhabitants) using several techniques. When dealing with non-deterministic algorithms, comparing a single model per technique is not enough to choose the best approach. Thus, we conduct 40 experiments per family of models - Random Forest, Gradient Boosting Decision Trees and Multilayer Perceptrons - and compare them to Logistic Regression. Models’ performance are compared both population-wide and for the 20,000 patients with the highest predicted probabilities, as a hypothetical high-risk group to intervene on.

Results
The best-performing technique is Multilayer Perceptron, followed by Gradient Boosting Decision Trees, Logistic Regression and Random Forest. Multilayer Perceptrons also have the lowest variability, around an order of magnitude less than Random Forests. Median area under the ROC curve, average precision and positive predictive value range from 0.789 to 0.802, 0.237 to 0.257 and 0.485 to 0.511, respectively. For Brier Score the median values are 0.048 for all techniques. There is some overlap between the algorithms. For instance, Gradient Boosting Decision Trees perform better than Logistic Regression more than 75% of the time, but not always.

Conclusions
All models have good global performance. The only family that is consistently superior to Logistic Regression is Multilayer Perceptron, showing a very reliable performance with the lowest variability.
Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art
Authors: Hatami Zahra , Hashemi Zahra Sadat , Eftekhary Mohamad , Amiri Ala , Karpisheh Vahid , Nasrollahi Kaveh , Jafari Reza 
Published: August 2023

AbstractChimeric antigen receptor natural killer cells (CAR-NK) promote off-the-shelf cellular therapy for solid tumors and malignancy.However,, the development of CAR-NK is due to their immune surveillance uncertainty and cytotoxicity challenge was restricted. Natural killer cell-derived exosome (NK-Exo) combine crucial targeted cellular therapies of NK cell therapies with unique non-toxic Exo as a self-origin shuttle against cancer immunotherapy. This review study covers cytokines, adoptive (autologous and allogenic) NK immunotherapy, stimulatory and regulatory functions, and cell-free derivatives from NK cells. The future path of NK-Exo cytotoxicity and anti-tumor activity with considering non-caspase-independent/dependent apoptosis and Fas/FasL pathway in cancer immunotherapy. Finally, the significance and implication of NK-Exo therapeutics through combination therapy and the development of emerging approaches for the purification and delivery NK-Exo to severe immune and tumor cells and tissues were discussed in detail.
Genomic variants exclusively identified in children with birth defects and concurrent malignant tumors predispose to cancer development
Authors: Liu Yichuan , Qu Hui-Qi , Chang Xiao , Mentch Frank D , Qiu Haijun , Wang Xiang , Saeidian Amir Hossein , Watson Deborah , Glessner Joseph , Hakonarson Hakon 
Published: August 2023

AbstractChildren with birth defects (BD) express distinct clinical features that often have various medical consequences, one of which is predisposition to the development of cancers. Identification of the underlying genetic mechanisms related to the development of cancer in BD patients would allow for preventive measures. We performed a whole genome sequencing (WGS) study on blood-derived DNA samples from 1566 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumors, 767 cancer-free BD probands, and 345 healthy individuals. Exclusive recurrent variants were identified in BD-cancer and BD-only patients and mapped to their corresponding genomic regions. We observed statistically significant overlaps for protein-coding/ncRNA with exclusive variants in exons, introns, ncRNAs, and 3’UTR regions. Exclusive exonic variants, especially synonymous variants, tend to occur in prior exons locus in BD-cancer children. Intronic variants close to splicing site (< 500 bp from exon) have little overlaps in BD-cancer and BD-only patients. Exonic variants in non-coding RNA (ncRNA) tend to occur in different ncRNAs exons regardless of the overlaps. Notably, genes with 5’ UTR variants are almost mutually exclusive between the two phenotypes. In conclusion, we conducted the first genomic study to explore the impact of recurrent variants exclusive to the two distinguished clinical phenotypes under study, BD with or without cancer, demonstrating enrichment of selective protein-coding/ncRNAs differentially expressed between these two phenotypes, suggesting that selective genetic factors may underlie the molecular processes of pediatric cancer development in BD children.
Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis
Authors: Lee Chi-Chiu , Yu Chia-Jui , Panda Sushree Shankar , Chen Kai-Chi , Liang Kang-Hao , Huang Wan-Chen , Wang Yu-Shiuan , Ho Pei-Chin , Wu Han-Chung 
Published: August 2023

Abstract
Background
Epithelial cell adhesion molecule (EpCAM) is known to highly expression and promotes cancer progression in many cancer types, including colorectal cancer. While metastasis is one of the main causes of cancer treatment failure, the involvement of EpCAM signaling in metastatic processes is unclear. We propose the potential crosstalk of EpCAM signaling with the HGFR signaling in order to govern metastatic activity in colorectal cancer.

Methods
Immunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA), and fluorescence resonance energy transfer (FRET) was conducted to explore the extracellular domain of EpCAM (EpEX) and HGFR interaction. Western blotting was taken to determine the expression of proteins in colorectal cancer (CRC) cell lines. The functions of EpEX in CRC were investigated by proliferation, migration, and invasion analysis. The combined therapy was validated via a tail vein injection method for the metastasis and orthotopic colon cancer models.

Results
This study demonstrates that the EpEX binds to HGFR and induces downstream signaling in colon cancer cells. Moreover, EpEX and HGF cooperatively mediate HGFR signaling. Furthermore, EpEX enhances the epithelial-to-mesenchymal transition and metastatic potential of colon cancer cells by activating ERK and FAK-AKT signaling pathways, and it further stabilizes active β-catenin and Snail proteins by decreasing GSK3β activity. Finally, we show that the combined treatment of an anti-EpCAM neutralizing antibody (EpAb2-6) and an HGFR inhibitor (crizotinib) significantly inhibits tumor progression and prolongs survival in metastatic and orthotopic animal models of colon cancer.

Conclusion
Our findings illuminate the molecular mechanisms underlying EpCAM signaling promotion of colon cancer metastasis, further suggesting that the combination of EpAb2-6 and crizotinib may be an effective strategy for treating cancer patients with high EpCAM expression.