bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab
Authors: Lee Jaejun , Yoo Jae-Sung , Kim Ji Hoon , Lee Dong Yeup , Yang Keungmo , Kim Bohyun , Choi Joon-Il , Jang Jeong Won , Choi Jong Young , Yoon Seung Kew , Han Ji Won , Sung Pil Soo 
Published: December 2024

BackgroundProgrammed death-ligand 1 (PD-L1) expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells.MethodsThis study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023. PD-L1 expression on tumor tissues was assessed using the combined positive score (CPS) with cutoff values of 1 and 10, utilizing antibody clone 22C3 (Dako).ResultsThe distribution of PD-L1 CPS included 24 patients with CPS &lt;1, 33 patients with CPS 1–10, and 15 patients with CPS ≥10. Significant differences in overall survival (OS) were observed across the three groups, with CPS ≥10 showing the highest survival rates (p = 0.010). Patients with CPS ≥10 had better OS than those with CPS &lt;10 (median OS 14.8 vs. 8.3 months, P = 0.046), and CPS ≥1 had better OS than CPS &lt;1 (P = 0.021). For progression-free survival (mPFS), the CPS ≥10 group had the highest median PFS of 11.0 months among the three groups (P = 0.044). Objective response rates (ORR) were higher in the PD-L1 CPS ≥10 group than in the 1-10 and &lt;1 group (53.3%, 27.3%, and 16.7%, respectively; P = .047). Multivariate analysis identified that PD-L1 expression ≥10 and ≥1 were associated with favorable outcomes regarding OS (hazard ratio [HR] 0.283, P = .027 and HR 0.303, P = .006, respectively).ConclusionsCombined analysis of PD-L1 expression in malignant and tumor-infiltrating cells can be a promising biomarker for the prognosis of HCC patients treated with AB.
Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes
Authors: Campione Elena , Cosio Terenzio , Pistoia Enrico Salvatore , Artosi Fabio , Shumack Ruslana Gaeta , Borselli Cristiana , Rivieccio Antonia , Caputo Valerio , Favaro Marco , Sorge Roberto , Pica Francesca , Bianchi Luca , Gaziano Roberta 
Published: December 2024

IntroductionFungi, including Candida, may be a trigger or exacerbate psoriasis, especially in difficult to treat (DTT) areas, through the activation of IL-17/23 axis.MethodsIn this study, seventy patients with DDT psoriasis were enrolled to evaluate Candida species and/or other opportunistic fungi colonization rate at baseline (T0) and the impact of apremilast on fungal load, clinical outcome, serum cytokine levels and biochemical serum profile of patients after 16, 24 and 52 weeks of treatment.ResultsIn our population, 33 (47%) patients were colonized by Candida spp. at baseline. In 24 (34%) individuals Candida was detected in the oral cavity while in the remaining 9 (13%) individuals the fungus was isolated from stool samples. Twenty subjects were colonized by only the species C. albicans, whereas in the remaining 13 a combination of two or more species (C. albicans plus non-albicans strains) was found in the oral cavity. Moreover, 27 (39%) patients were affected by onychomycosis. At 52 weeks, apremilast treatment induced a full recovery from Candida colonization in 83% of patients colonized with a single species of Candida (C. albicans); while in those co-infected by two or more Candida spp. induced a significant reduction (colony counts &gt;10 CFU/mL) in fungal load was observed in comparison to baseline. Among patients with onychomycosis, 78% (21/27) of them presented a complete clinical resolution of nail psoriasis and concomitant nail infections. Finally, improvements in clinical scores i.e., PASI, NAPSI, DLQI, itch VAS, PAIN VAS, scPGA and sPGA-G and biochemical serum profile, as well as a significant decrease in serum IL-17A, TGF-β 1 and IL-10 levels (from 8.51 to 4.16 pg/mL; from 66.10 to 48.70 ng/mL and from 20.05 to 14 pg/mL, respectively) were observed in all patients.ConclusionsFungi may play a role in the psoriasis pathogenesis. Apremilast has been shown to ameliorate psoriasis signs and symptoms and counteract fungal overgrowth, probably by dampening inflammation, triggered by the fungal infections themselves. Thus, apremilast may represent an effective therapeutic approach in the treatment of DTT psoriasis and modulate the fungal colonization.
Decoding the prognostic landscape of LUAD: the interplay between N6-methyladenosine modification and immune microenvironment
Authors: Chen Quan , Wan Weijun , Zhao Qing , Li Juan , Xiong Yanli , Yuan Yuchuan , Tang Lu , Wu Xiaofeng , Xing Wei , Guo Wei , Lu Di , Ao Luoquan , Xu Xiang , Ao Xiang 
Published: December 2024

BackgroundTo determine the role of N6-methyladenosine (m6A) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).MethodsConsensus clustering was performed to identify the subgroups with distinct immune or m6A modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays. For experimental validation, the regulation of METTL3/m6A axis in the expression of candidate genes by RIP-qPCR assay in A549 and H460 cell lines. Co-culture experiments with human T cells were performed to evaluate the impact of METTL3 on the enhancement of anti-tumor immunity through in vitro experiments.ResultsWe identified 282 m6A regulator genes and 955 immune-related genes, selecting seven key genes (SFTPC, CYP24A1, KRT6A, PTTG1, S100P, FAM83A, and ANLN) to develop a risk score model using Lasso regression. High-risk patients, determined by this model, exhibited poorer prognosis, increased immune infiltration, higher tumor mutational burden, more neoantigens, and elevated PD-L1 expression. These findings were validated by two independent databases and LUAD tissue microarrays. METTL3 was found to impact the mRNA expression of these genes, with METTL3 deficiency abolishing these interactions. Inhibition of METTL3 enhanced anti-tumor immunity, T cell activation, exhaustion, and infiltration in vitro.ConclusionThis risk score system shows promise for prognostic prediction and the development of personalized treatment strategies for LUAD patients.
Predictors of breakthrough invasive fungal infections (BIFI) in pediatric acute leukemia: a retrospective analysis and predictive model development
Authors: Li Yan , Qu Lijun , Wang Jian , Chen Pingtian , Jiang Aoshuang , Liu Hongjun 
Published: December 2024

ObjectiveThis study aims to identify key risk factors associated with the development of breakthrough invasive fungal infections (BIFI) in pediatric acute leukemia patients to improve early detection and intervention strategies.MethodA retrospective analysis was conducted on 160 pediatric patients with acute leukemia admitted to Anhui Provincial Children's Hospital between October 2018 and June 2022. The study evaluated the impact of various clinical parameters on BIFI risk using univariate and multivariable analyses, with data including patient demographics, treatment regimens, and infection outcomes. The predictive model was assessed using receiver operating characteristic (ROC) curve analysis, calibration plots, and decision curve analysis (DCA).ResultAmong the 160 pediatric acute leukemia patients, 34 (22.22%) developed BIFI. Univariate analysis identified longer durations of neutrophil deficiency (P &lt; 0.001), broad-spectrum antibiotic use (P &lt; 0.001), higher volumes of red blood cell transfusions (P = 0.001), and elevated C-reactive protein (CRP) levels (P &lt; 0.001) as significant factors associated with BIFI. Multivariable analysis confirmed these as significant predictors, with odds ratios for neutrophil deficiency (OR = 1.38, 95% CI [1.15, 1.69]), antibiotic use (OR = 1.41, 95% CI [1.10, 1.84]), transfusions (OR = 2.54, 95% CI [1.39, 5.13]), and CRP levels (OR = 1.10, 95% CI [1.04, 1.17]). The model validation showed strong predictive performance with an AUC of 0.890 (95% CI: 0.828–0.952), good calibration (Brier score = 0.099), and demonstrated clinical utility across a range of risk thresholds.ConclusionThe study highlights the importance of considering these key predictors in the management of pediatric acute leukemia patients to mitigate the risk of BIFI. Incorporating these factors into personalized treatment strategies could enhance early intervention, reduce infection rates, and improve overall patient outcomes.
Effect of carbonated water on cerebral blood flow in the frontal region: a study using near-infrared spectroscopy
Authors: Kosugi Wataru , Sumali Brian , Hamada Nozomu , Mitsukura Yasue 
Published: December 2024

IntroductionCarbonated water (CarbW) affects the swallowing function associated with the action of the brainstem. In addition, CarbW ingestion promotes mean blood flow in the middle cerebral artery, which is associated with blood flow to the frontal and temporal lobes. In this milieu, studies regarding the effect of drinking CarbW on brain activity are of significance. In the present study, we compared the changes in cerebral blood flow in the frontal region before and after the ingestion of CarbW or uncarbonated water (SW).MethodsNear-infrared spectroscopy was used to continuously measure the cerebral blood flow at 22 channels in the frontal region of 13 healthy young adults for 10 min before and after the ingestion of CarbW or SW. We statistically compared the changes in oxyhemoglobin concentration before and after the ingestion of CarbW or SW.ResultsCompared with that before CarbW ingestion, the oxyhemoglobin concentration in the left frontal region increased after CarbW ingestion. In particular, a significant increase (p &lt; 0.05) was observed in the ch21 region. On the contrary, no marked increase or decrease in cerebral blood flow was observed after SW ingestion compared with that before ingestion.DiscussionThe activated part of the frontal region (ch21) corresponds to the vicinity of the orbitofrontal cortex, which is reportedly activated by rewarding stimuli. In addition, as the orbitofrontal cortex is located at the terminal end of the reward pathway of the mesocortical system, CarbW ingestion might have acted on the dopaminergic reward pathway of the mesocortical system.
Characteristics of peripheral immune response induced by large-vessel occlusion in patients with acute ischemic stroke
Authors: Ma Ling , Sun Bin , Fan Chenliu , Xiao Juan , Geng Maomao , Liu Jie , Jiang Runze , Jiang Yang , Liu Dianwei 
Published: December 2024

IntroductionDespite improvements in the treatment of acute ischemic stroke (AIS), some patients still suffer from functional impairments, indicating the poor understanding of pathophysiologic process of AIS. Inflammation plays an important role in the pathophysiology of AIS. The purpose of the study was to investigate the peripheral inflammation in different subtypes of AIS.MethodsHere, retrospective data from AIS with large vessel occlusion (LVO) and small vessel occlusion (SVO), and healthy controls, were initially analyzed. Then, flow cytometry was performed to evaluate the levels of peripheral naïve and memory T-cells. Finally, we characterized the T cell receptors (TCR) repertoire using high-throughput sequencing.ResultsElevated levels of leukocytes, neutrophils, and neutrophil-to-lymphocyte ratio (NLR), and decreased levels of lymphocytes were found in LVO group than that in SVO group, which were correlated with the severity of LVO. In addition, higher percentages of both effector memory (Tem) and central memory (Tcm) T cells, and lower percentage of naïve T cells in CD4+ and CD8+ T cells, were found in LVO group than that in SVO and healthy groups. Moreover, impaired TCR diversity, and different abundances of V-J gene combinations and amino acid sequences, were found in LVO as compared with healthy group, which would be potential biomarkers for LVO diagnosis.DiscussionIn conclusion, AIS with LVO can rapidly induce peripheral immune response, which provides new insight into the understanding of pathophysiology of AIS.
Clinical feasibility of Ethos auto-segmentation for adaptive whole-breast cancer treatment
Authors: Prunaretty Jessica , Mekki Fatima , Laurent Pierre-Ivan , Morel Aurelie , Hinault Pauline , Bourgier Celine , Azria David , Fenoglietto Pascal 
Published: December 2024

IntroductionFollowing a preliminary work validating the technological feasibility of an adaptive workflow with Ethos for whole-breast cancer, this study aims to clinically evaluate the automatic segmentation generated by Ethos.Material and methodsTwenty patients initially treated on a TrueBeam accelerator for different breast cancer indications (right/left, lumpectomy/mastectomy) were replanned using the Ethos® emulator. The adaptive workflow was performed using 5 randomly selected extended CBCTs per patient. The contours generated by artificial intelligence (AI) included both breasts, the heart, and the lungs. The target volumes, specifically the tumor bed (CTV_Boost), internal mammary chain (CTV_IMC), and clavicular nodes (CTV_Nodes), were generated through rigid propagation. The CTV_Breast corresponds to the ipsilateral breast, excluding 5mm from the skin. Two radiation oncologists independently repeated the workflow and qualitatively assessed the accuracy of the contours using a scoring system from 3 (contour to be redone) to 0 (no correction needed). Quantitative evaluation was carried out using the Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), surface Dice (sDSC) and the Added Path Length (APL). The interobserver variability (IOV) between the two observers was also assessed and served as a reference. Lastly, the dosimetric impact of contour correction was evaluated. The physician-validated contours were transferred onto the plans automatically generated by Ethos in adaptive mode. The dose prescription was 52.2Gy in 18 fractions for the boost, 42.3Gy for the breast, IMC, and nodes. The CTV/PTV margin was 2mm for all volumes, except for the IMC (5mm). Dose coverage (D98%) was assessed for the CTVs, while specific parameters for organs at risk (OAR) were evaluated: mean dose and V17Gy (relative volume receiving at least 17Gy) for the ipsilateral lung, mean dose and D2cc (dose received by 2cc volume) for the heart, the contralateral lung and breast.ResultsThe qualitative analysis showed that no correction or only minor corrections were needed for 98.6% of AI-generated contours and 86.7% of the target volumes. Regarding the quantitative analysis, Ethos’ contour generation outperformed inter-observer variability for all structures in terms of DSC, HD, sDSC and APL. Target volume coverage was achieved for 97.9%, 96.3%, 94.2% and 68.8% of the breast, IMC, nodes and boost CTVs, respectively. As for OARs, no significant differences in dosimetric parameters were observed.ConclusionThis study shows high accuracy of segmentation performed by Ethos for breast cancer, except for the CTV_Boost. Contouring practices for adaptive sessions were revised following this study to improve outcomes.
Prophylactic ondansetron for preventing intraoperative shivering, nausea and vomiting during spinal anesthesia for cesarean section: a randomized controlled trial
Authors: Zhang Yuan , Xia Fen , Zhang Wangping , Lv Anqing 
Published: December 2024

BackgroundShivering, nausea and vomiting are common complications in cesarean section during neuraxial anesthesia. The aim of this study was to investigate the effects of prophylactic use of ondansetron on intraoperative shivering, nausea and vomiting in women undergoing cesarean section.MethodsA total of 80 full-term parturients were randomly divided into the ondansetron group and the control group. The ondansetron group received 0.075 mg/kg of ondansetron 15 min before anesthesia, the control group were given the same volume of saline solution. The incidence of shivering, nausea and vomiting was noted. The occurrence and severity of shivering and other outcomes, such as hypotension, bradycardia and dizziness were recorded during the surgery. Umbilical arterial blood was analyzed, and the neonatal Apgar scores were assessed.ResultsThe incidence of grade ≥1 shivering was lower in ondansetron group. The incidence of shivering, nausea and vomiting was significantly lower in ondansetron group than the control group (2.5% vs. 22.3%, P = 0.007, 2.5% vs. 40%, P = 0.001, respectively). No significant differences were observed in the incidence of hypotension, bradycardia, headache and dizziness between the 2 groups (P &gt; 0.05). The umbilical artery pH and neonatal Apgar score were similar between the 2 groups (P &gt; 0.05).ConclusionProphylactic use of ondansetron could prevent intra-operative shivering and reduce the incidence of nausea and vomiting in cesarean section under spinal anesthesia without increasing the incidence of maternal and infant adverse events.Clinical Trial Registrationhttps://www.chictr.org.cn, identifier ChiCTR2100042453
Genome-wide identification and characterization of BASIC PENTACYSTEINE transcription factors and their binding motifs in coconut palm
Authors: Lao Zifen , Mao Jiali , Chen Runan , Xu Ran , Yang Zhuang , Wang Ying , Zhou Junjie , Mu Zhihua , Xu Hang , Li Fengmei , Huang Dongyi , Xiao Yong , Luo Jie , Xia Wei 
Published: December 2024

IntroductionBASIC PENTACYSTEINE (BPC) is a small transcription factor family known for its role in various developmental processes in plants, particularly in binding GA motifs and regulating flower and seed development. However, research on the functional characteristics and target genes of BPCs in coconut (Cocos nucifera) is limited.MethodsIn this study, we systematically characterized the gene structure, conserved protein domains, gene expansion, and target genes of CnBPCs in the coconut genome. We conducted yeast one-hybrid (Y1H) and dual-luciferase assay to explore gene interactions. We identified genes with the GA motif in their promoter regions and combined this information with a weighted gene co-expression network to identify the target genes of CnBPCs.ResultsEight CnBPCs were identified, including three Class I CnBPCs from triplication, four Class II CnBPCs (with CnBPC6A and CnBPC6B resulting from segmental duplication), and one Class III CnBPC (CnBPC7). Three conserved DNA-binding motifs were detected, exhibiting variation in certain sites. Widespread BPC gene expansion was detected in coconut and other plant species, while only three BPCs were found in the most basal extant flowering plant. Notably, 92% of protein-coding genes contained at least one GA motif, with the (GA)3 motif being most prevalent. Genes containing the GA motif that exhibit a high expression correlation with CnBPCs, tend to interact strongly with the corresponding CnBPCs. Additionally, promoters rich in the GA motif tend to interact with all members of CnBPC. The dual-luciferase assay showed that CnBPCs could activate or repress the transcriptional activities of promoters containing either (GA)3 or (GA)11 motif but with a bias toward certain genes. Furthermore, we constructed co-expressed networks identifying 426 genes with GA motifs as potential CnBPC targets.DiscussionOur findings suggest that CnBPCs may play significant roles in seed germination, flower development, and mesocarp development by interacting with genes such as CnAG1, CnAG2, CnSTK, CnMFT, and CnCS. This study characterized CnBPCs’ binding motif and possible target genes, laying a theoretical foundation to reveal CnBPCs’ function in flower and seed development.
The relationship between perfectionism and marital outcomes: a systematic review and meta-analysis
Authors: Hadian Hamedani Kiana , Majzoobi Mohammad Reza , Forstmeier Simon 
Published: December 2024

IntroductionPerfectionism, as a transdiagnostic variable, can influence both the intrapersonal and interpersonal domains, one of the most significant of them is thought to be marital relationship. Given that perfectionism within a couple can negatively affect their intimate relationship and potentially lead to destructive outcomes, reviewing studies conducted in this area seems to be essential to gain a clearer understanding. Therefore, the present systematic review aims to examine the association between perfectionism and marital outcomes in married individuals.MethodsA comprehensive search was conducted across major scientific databases, including APA PsycArticles, PubMed, and Web of Science, using specific keywords and Boolean operators. Included were the English-Language studies published between 1980 and 2023 that investigated the relationship between perfectionism and marital outcomes in heterosexual couples. Out of the studies identified, 23 met the inclusion criteria for this review, of which 16 studies met the criteria for meta-analysis.ResultsThe meta-analysis indicated a small-to-moderate effect size for the association between perfectionism and marital outcomes (r = 0.26). Given the importance of marital relationship, such effect sizes for variables which may influence marital relationship bears significant value.DiscussionTherefore, the findings may encourage researchers to conduct various studies to examine specific details, moderators, and mediators in the relationship between perfectionism and marital outcomes and may also prompt couple therapists to address perfectionism as a destructive factor and integrate strategies into their protocols to reduce its impact in intimate relationships.