bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreasing urgent repeat cesarean sections by offering complimentary ultrasounds and consultation in rural Burundi: The zigama mama project
Authors: McLaughlin Eric , Nagy Matthew , Magorwa Jean-Bosco , Kibinakanwa Gilbert , McLaughlin Rachel 
Published: March 2023

ObjectiveRepeat urgent cesarean sections (CS) carry an increased risk of severe maternal outcomes. As CS increase in sub-Saharan Africa, creative strategies are necessary to reduce the rate of urgent repeat CS. The Zigama-Mama Project in rural Burundi uses complimentary ultrasounds to create a clinical touchpoint to counsel women with a prior CS for a hospital-based delivery.MethodsFrom July 2019 to June 2020, complimentary ultrasounds were offered to all antenatal patients with prior CS, along with counseling for monitored trial of labor after cesarean (TOLAC) or scheduled repeat CS. Community engagement and feedback from district health centers were evaluated.ResultsIn total, 500 women with a prior CS presented for a complimentary ultrasound. During the intervention year, a relative and absolute reduction in urgent repeat CS (baseline: n = 114 {70.8%}, intervention: n = 97{49.7%}, p &lt; 0.001) was observed, with no significant change in maternal mortality or ruptured uteri. All health center personnel agreed the project improved their confidence in referring women with prior CS.ConclusionOffering complimentary ultrasounds as a clinical touchpoint for scheduling a monitored delivery or CS for women at high risk for delivery complication may be an affordable and creative strategy to care for women with previous CS during subsequent deliveries.
Safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of WBP216, a novel IL-6 monoclonal antibody, in patients with rheumatoid arthritis: A phase Ia randomized placebo-controlled study
Authors: Leng Xiaomei , Tang Xiange , Hu Pei , Guan Xiaoduo , Li Qian , Huang Cipo , Zhang Qiang , Chen Rui , Zeng Xiaofeng 
Published: March 2023

BackgroundWBP216 is a novel human immunoglobulin G1 (IgG1) monoclonal antibody for interleukin (IL)-6. We aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single ascending dose (SAD) of WBP216 in patients with rheumatoid arthritis (RA).MethodsIn this double-blind, placebo-controlled, SAD, phase Ia study, patients with RA were randomized in a 3:1 (Group A1, 10 mg) and 6:2 (Group A2, 30 mg; Group A3, 75 mg; Group A4, 150 mg; Group A5, 300 mg) ratios to receive either ascending doses of WBP216 or placebo subcutaneously. The primary endpoint was the incidence of adverse events (AEs), while the secondary endpoints were characterization of PK, PD, and immunogenicity of WBP216 and the exploratory endpoints included improvements in RA clinical metrics. All statistical analyses were performed using SAS® version 9.2.ResultsA total of 41 subjects (34 females and 7 males) were enrolled in the study. WBP216 was well tolerated in all doses (10-300 mg). Most treatment-emergent AEs (TEAEs; 97.6%) were of grade 1 severity and resolved without any treatment. No subjects experienced TEAEs leading to withdrawal or death during the study. An increase in serum concentration and total IL-6 from baseline was observed, while a substantial decrease in high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) was observed in all the WBP216 groups. Anti-drug antibodies were detected in only one subject after dosing, indicating an acceptable immunogenicity profile. Limited ACR20 and ACR50 response was observed in the WBP216 groups and no response in the placebo group.ConclusionWBP216 demonstrated a good safety profile and evidence of potential efficacy in the treatment of patients with RA.Clinical trial registrationhttp://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20170306.
PD-L1 expression as biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in metastatic triple negative breast cancer: A systematic review and meta-analysis
Authors: Khan Muhammad , Du Kunpeng , Ai Meiling , Wang Baiyao , Lin Jie , Ren Anbang , Chen Chengcong , Huang Zhong , Qiu Wenze , Yuan Yawei , Tian Yunhong 
Published: March 2023

BackgroundInhibitors of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PD-L1) checkpoint have been approved for metastatic triple negative breast cancer (mTNBC) in patients positive for PD-L1 expression. Negative results from the recent phase III trials (IMPassion131 and IMPassion132) have raises questions on the efficacy of PD-1/PD-L1 checkpoint inhibitors and the predictive value of PD-L1 expression. Here we attempt to systematically analyze the biomarker value of PD-L1 expression for predicting the response of PD-1/PD-L1 checkpoint inhibitors in mTNBC.Materials and methodsPubMed database was searched until Dec 2021 for studies evaluating PD-1/PD-L1 checkpoint inhibitors plus/minus chemotherapy in mTNBC. Outcome of interest included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Review Manager (RevMan) version 5.4. was used for data-analysis.ResultsIn total, 20 clinical trials comprising 3962 mTNBC patients (ICT: 2665 (67%); CT: 1297 (33%) were included in this study. Overall ORR was 22% (95%CI, 14-30%) and significant improvement was observed for PD-L1+ patients (ORR 1.78 [95%CI, 1.45-2.19], p&lt;0.00001) as compared to PD-L1- cohort. Pooled outcome also indicated a significant 1-year PFS and 2-year OS advantage for patients with PD-L1 expression (1-year PFS: ORR 1.39 [95%CI, 1.04-1.85], p=0.02; I2 = 0%; 2-year OS: (ORR 2.47 [95%CI, 1.30-4.69], p=0.006; I2 = 63%). Subgroup analysis indicated that PD-L1 expression can successfully predict tumor response and 2-year OS benefit in mTNBC patients regardless of the type of investigating agent, line of treatment administration, and to some extent the type of treatment. Biomarker ability of PD-L1 expression to predict 1-year PFS was slightly better with pembrolizumab (p=0.09) than atezolizumab (p=0.18), and significantly better when treatment was administered in the first-line setting (OR 1.38 [95%CI, 1.02-1.87], p=0.04) and chemotherapy was added (OR 1.38 [95%CI, 1.02-1.86], p=0.03). Immune-related toxicity of any grade and grade≥3 was 39% (95%CI, 26%-52%) and 10% (95%CI, 8%-13%), respectively.ConclusionsPD-L1 expression can predict objective response rate and 2-year OS in mTNBC patients receiving PD-1/PD-L1 checkpoint inhibitors. One-year PFS is also predicted in selected patients. PD-L1 expression can be a useful biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in mTNBC.
Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy
Authors: Hu Wei-Ting , Zhang Qiurui , Zhang Ze , He Xuan , Zhou Min , Guo Yi , Wang Xiaofei 
Published: March 2023

ObjectivesImmune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice.MethodsWe retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for &gt;1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs).ResultsA total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1–2 of irAEs vs. grades 3–4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; p = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); p = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), p = 0.02) were found to be predictive for irAEs.ConclusionEOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.
Construction and validation of chemoresistance-associated tumor- infiltrating exhausted-like CD8+ T cell signature in breast cancer: cr-TILCD8TSig
Authors: Cai DQ. , Cai Diankui , Zou Yiping , Chen Xumeng , Jian Zhixiang , Shi Mude , Lin Ye , Chen Jueming 
Published: March 2023

BackgroundAccumulating evidence has revealed that CD8+ T cell exhaustion (Tex) results in worse immunotherapy outcomes. However, the molecular functions and mechanisms of action of Tex in chemoresistance needed to be elucidated.MethodsThe populations of tumor-infiltrating CD8+ T cells (TILCD8Ts) in chemoresistant and chemosensitive groups of the GSE25066 dataset were calculated using CIBERSORT. Differentially expressed genes (DEGs) between TILCD8Ts and other immune cells were explored by integrating 16 immune cell datasets downloaded from the gene expression omnibus (GEO) database. Gene ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression of TILCD8T-specific upregulated genes were used to construct a chemoresistant TILCD8T signature (cr-TILCD8TSig). Clinical prognostic data, genomic alterations, chemotherapy response, and immunotherapy response were compared between the different cr-TILCD8TSig subgroups in the GSE25066 and the cancer genome atlas breast cancer (TCGA-BRCA) cohorts.ResultsA cr-TILCD8TSig with exhausted features was identified, consisting of seven genes (TCF7, RARRES3, ARL4C, ITK, CDH3, GZMB, and KLRD1), which were identified from 104 TILCD8Ts-specific DEGs. Our results showed that compared to the cr-TILCD8TSig-low subgroup, the -high subgroup had a poorer distant relapse-free survival (DRFS) in the GSE25066 cohort and worse progression-free survival (PFS) in the TCGA-BRCA cohort. Univariate and multivariate Cox regression analyses also demonstrated that cr-TILCD8TSig was an independent prognostic factor in the two independent cohorts. Furthermore, cr-TILCD8TSig-low patients benefited more from chemotherapy and immunotherapy than cr-TILCD8TSig-high patients. Besides, we found cell transmembrane signal transduction and the ECM may provide the molecular basis for resistance to antitumor agents in the cr-TILCD8Sig-high subgroup. For genomic alterations, we revealed that mutations in PIK3CA, DMD, and APOB were more common in the cr-TILCD8Sig-high subgroup than in the cr-TILCD8Sig-low subgroup. A nomogram was finally constructed with good discrimination and calibration.Conclusionscr-TILCD8TSig is a useful tool to independently predict prognosis, chemotherapy response, and immunotherapy outcomes in patients with breast cancer.
Spectral EEG correlations from the different phases of general anesthesia
Authors: Sun Christophe , Longrois Dan , Holcman David 
Published: March 2023

IntroductionElectroencephalography (EEG) signals contain transient oscillation patterns commonly used to classify brain states in responses to action, sleep, coma or anesthesia.MethodsUsing a time-frequency analysis of the EEG, we search for possible causal correlations between the successive phases of general anesthesia. We hypothesize that it could be possible to anticipate recovery patterns from the induction or maintenance phases. For that goal, we track the maximum power of the α−band and follow its time course.Results and discussionWe quantify the frequency shift of the α−band during the recovery phase and the associated duration. Using Pearson coefficient and Bayes factor, we report non-significant linear correlation between the α−band frequency and duration shifts during recovery and the presence of the δ or the α rhythms during the maintenance phase. We also found no correlations between the α−band emergence trajectory and the total duration of the flat EEG epochs (iso-electric suppressions) induced by a propofol bolus injected during induction. Finally, we quantify the instability of the α−band using the mathematical total variation that measures possible deviations from a flat line. To conclude, the present correlative analysis shows that EEG dynamics extracted from the initial and maintenance phases of general anesthesia cannot anticipate both the emergence trajectory and the extubation time.
An adenovirus-vectored RVF vaccine confers complete protection against lethal RVFV challenge in A129 mice
Authors: Hao Meng , Bian Ting , Fu Guangcheng , Chen Yi , Fang Ting , Zhao Chuanyi , Liu Shuling , Yu Changming , Li Jianmin , Chen Wei 
Published: March 2023

Instruction: Rift valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that causes severe disease in animals and humans. Nevertheless, there are no vaccines applied to prevent RVFV infection for human at present. Therefore, it is necessary to develop a safe and effective RVFV vaccine.Methods: We generated Ad5-GnGcopt, a replication-deficient recombinant Ad5 vector (human adenovirus serotype 5) expressing codon-optimized RVFV glycoproteins Gn and Gc, and evaluated its immunogenicity and protective efficacy in mice.Results and Discussion: Intramuscular immunization of Ad5-GnGcopt in mice induces strong and durable antibody production and robust cellular immune responses. Additionally, a single vaccination with Ad5-GnGcopt vaccination can completely protect interferon-α/β receptor-deficient A129 mice from lethal RVFV infection. Our work indicates that Ad5-GnGcopt might represent a potential vaccine candidate against RVFV. However, further research is needed, first to confirm its efficacy in a natural animal host, and ultimately escalate as a potential vaccine candidate for humans.
Understory vegetation diversity, soil properties and microbial community response to different thinning intensities in Cryptomeria japonica var. sinensis plantations
Authors: Liu Kai-Li , Chen Bo-Yao , Zhang Bin , Wang Rui-Hui , Wang Chun-Sheng 
Published: March 2023

IntroductionSoil microorganisms are the key factors in elucidating the effects of thinning on tree growth performance, but the effects of vegetation and soil on the species composition and function of soil microorganisms after thinning are still not well elaborated.MethodsThe effects of thinning on understory vegetation diversity, soil physicochemical properties and soil microbial community composition were investigated in a thinning trial plantation ofCryptomeria japonicavar.sinensis, including four thinning intensities (control: 0%, LIT: 20%, MIT: 30% and HIT: 40%), and the relationships of the microbial community structure with the understory vegetation diversity and soil properties were assessed.ResultsThe results showed that thinning had a greater effect on the diversity of the shrub layer than the herb layer. The soil bulk density and the contents of soil organic matter, total potassium and nitrogen increased with increasing thinning intensities. The Shannon and Chao indices of soil bacteria and fungi were significantly lower in the LIT, MIT and HIT treatments than in the control. Thinning can significantly increase the abundance ofProteobacteriaandActinobacteria, and higher thinning intensities led to a higher relative abundance ofAscomycotaand a lower relative abundance ofBasidiomycota,Rozellomycota, andMortierellomycota. Redundancy analysis indicated that soil physicochemical properties rather than understory vegetation diversity were the main drivers of microbial communities, and fungi were more sensitive to soil properties than bacteria. Functional prediction showed that thinning significantly reduced the potential risk of human diseases and plant pathogens, and the nitrogen fixation capacity of bacteria was the highest in the HIT treatment. Thinning significantly increased the relative abundance of cellulolysis and soil saprotrophs in bacteria and fungi.ConclusionThe findings provide important insights into the effects of thinning onC. japonicavar.sinensisplantation ecosystems, which is essential for developing thinning strategies to promote their ecological and economic benefits.
Antisense lncRNA CHROMR is linked to glioma patient survival
Authors: Širvinskas Dovydas , Steponaitis Giedrius , Stakaitis Rytis , Tamašauskas Arimantas , Vaitkienė Paulina , Skiriutė Daina 
Published: March 2023

Background: Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA CHROMR (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene PRKRA (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked CHROMR effect on the survival of glioma patients.Methods: We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for CHROMR and PRKRA genes. These data were validated using the TCGA and GTEx gene expression databases.Results: The gene expression level of ncNAT lncRNA CHROMR in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding PRKRA mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA PRKRA/lncRNA CHROMR gene expression ratio compared to high ratio showing a link between lncRNA CHROMR and glioma patient survival prognosis.Conclusion: Here we show that elevated levels of lncRNA CHROMR (i.e., low ratio of mRNA PRKRA/lncRNA CHROMR) is associated with poor prognosis for glioma patients.
Are tai chi and qigong effective in the treatment of TBI? A systematic review protocol
Authors: Laskosky Nicole Alexandra , Huston Patricia , Lam Wai Ching , Anderson Charlotte , Zheng Ya , Zhong Linda L. D. 
Published: March 2023

BackgroundTraumatic brain injury (TBI) adversely affects both young and old and is a growing public health issue. A number of recent trends in managing TBI, such as recommending sub-threshold aerobic activity, tailoring multi-modal treatment strategies, and studying the possible role of low-grade inflammation in those with persistent symptoms, all suggest that the physical and cognitive exercise of tai chi/qigong could have benefit.MethodDesigned in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the following databases will be searched: MEDLINE, CINAHL, Cochrane Library, Embase, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. All clinical trials on mild, moderate and/or severe TBI with tai chi and/or qigong as the treatment group and any comparison group, in any setting will be included. Four reviewers will independently select studies; two reviewers for the English and two for the Chinese databases. Cochrane-based risk of bias assessments will be conducted on all included studies. An analysis will then be conducted with the grading of recommendation, assessment, development, and evaluation (GRADE) instrument.ResultsThis review will summarize the clinical trial evidence on tai chi/qigong for TBI including type of TBI, age/sex of participants, type and length of intervention and comparator, outcome measures, and any adverse events. The risk of bias will be considered, and the strengths and weaknesses of each trial will be analyzed.DiscussionThe results of this review will be considered with respect to whether there is enough evidence of benefit to merit a more definitive randomized controlled trial.Systematic Review Registration: PROSPERO [CRD42022364385].
Prognostic analysis in children with focal cortical dysplasia II undergoing epilepsy surgery: Clinical and radiological factors
Authors: Zhang Siqi , Luo Yi , Zhao Yilin , Zhu Fengjun , Jiang Xianping , Wang Xiaoyu , Mo Tong , Zeng Hongwu 
Published: March 2023

ObjectiveThe aim of this study was to investigate the value of clinical profiles and radiological findings in assessing postsurgical outcomes in children with focal cortical dysplasia (FCD) II while exploring prognostic predictors of this disease.MethodsWe retrospectively reviewed 50 patients with postoperative pathologically confirmed FCD II from January 2016 to June 2021. The clinical profiles and preoperative radiological findings were measured and analyzed. The patients were classified into four classes based on the Engel Class Outcome System at the last follow-up. For the analysis, the patients were divided into two categories based on Engel I and Engel II–IV, namely, seizure-free and non-seizure-free groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics. Receiver operating characteristic (ROC) curves were used to identify the predictors of prognosis in children with FCD II.ResultsThirty-seven patients (74%) had Engel class I outcomes. The minimum postsurgical follow-up was 1 year. At the epilepsy onset, patients who attained seizure freedom were older and less likely to have no apparent lesions on the preoperative MRI (“MRI-negative”). The non-seizure-free group exhibited a higher gray matter signal intensity ratio (GR) on 3D T1-MPRAGE images (p = 0.006), with a lower GR on T2WI images (p = 0.003) and FLAIR images (p = 0.032). The ROC curve indicated that the model that combined the GR value of all MRI sequences (AUC, 0.87; 95% CI, 0.77–0.97; p &lt; 0.001; 86% sensitivity, 85% specificity) was able to predict prognosis accurately.ConclusionA lower age at the onset or the MRI-negative finding of FCD lesions suggests a poor prognosis for children with FCD II. The model consisting of GR values from three MRI sequences facilitates the prognostic assessment of FCD II patients with subtle MRI abnormalities to prevent worse outcomes.