bluuebunny/crossref_metadata_2025_split huggingface dataset:
A machine learning-based predictive model for biliary stricture attributable to malignant tumors: a dual-center retrospective study
Authors: Yang Qifan , Nie Lu , Xu Jian , Li Hua , Zhu Xin , Wei Mingwei , Yao Jun 
Published: July 2024

BackgroundBiliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes.MethodologyThrough a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People’s Hospital affiliated with Jiangsu University and the Second People’s Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model’s accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model’s predictions.ResultsRF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor.ConclusionThe model’s effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.
Tumor-informed ctDNA assessment as a valuable prognostic and predictive biomarker in diffuse large B-cell lymphoma
Authors: Narkhede Mayur , Tomassetti Sarah , Iqbal Madiha , Tin Antony , Rivero-Hinojosa Samuel , George Giby V. , Widden Hayley , Benrud Ryan , Malhotra Meenakshi , Rodriguez Angel , Liu Minetta C. 
Published: July 2024

BackgroundA novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.MethodsA personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification.ResultsIn total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy.ConclusionctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.
Case report: Durable response of ensartinib targeting EML4-ALK fusion in osimertinib-resistant non-small cell lung cancer
Authors: Guo Yongkuan , Zhang Ran , Meng Yiran , Wang Li , Zheng Liuqing , You Jian 
Published: July 2024

BackgroundDespite significant benefits from targeted therapy in patients with driver mutations, inevitable drug resistance usually occurred in non-small cell lung cancer, highlighting the necessity for sequential treatments to prolong overall survival. Unfortunately, durable drug response has not been reported in posterior-line therapy of cases with acquired EML4-ALK fusion after resistance to osimertinib, urging the need of referable decision-making in clinical management.Case presentationWe present a case of a 71-year-old Chinese female, never smoker, diagnosed with invasive adenocarcinoma in the left inferior lobe of her lung, with metastases in regional lymph nodes. She received erlotinib treatment after the detection of coexistent EGFR L858R/G719S and BRAF V600E via next-generation sequencing of resected tumor tissue. Routine imaging revealed disease progression approximately 14 months after starting erlotinib treatment, followed by the detection of EGFR L858R through non-invasive liquid biopsy. Subsequently, osimertinib was administered, showing clinical activities for nearly 19 months until the emergence of an EML4-ALK fusion. Given the EML4-ALK fusion, a relatively rare resistance mechanism to osimertinib, she received third-line ensartinib treatment. One month later, alleviated tumor lesions plus normal serum marker levels demonstrated the effectiveness of ensartinib in overcoming resistance to osimertinib. Of note, the clinical response to ensartinib persisted for more than 14 months, superior to the previously reported efficacy of aletinib and crizotinib in osimertinib-failure cases. As of the last follow-up in July 2022, the patient showed no signs of recurrence and maintained a good life quality.ConclusionWe reported a third-line ensartinib therapy in a patient with lung adenocarcinoma who developed an acquired EML4-ALK fusion after sequential treatment with erlotinib and osimertinib. Given the rarity of the EML4-ALK fusion as a resistance mechanism to osimertinib, ensartinib emerges as a promising treatment option for this specific clinical challenge, offering superior efficacy and good safety.
Potential mechanism of Luoshi Neiyi prescription in endometriosis based on serum pharmacochemistry and network pharmacology
Authors: Wu Lizheng , Lin Shuhong , Hu Yongjun , Jing Shangwen , Sun Bowen , Chen Xiaoxin , Jia Jinjin , Zeng Cheng , Pei Fangli 
Published: July 2024

IntroductionEndometriosis (EMs) is characterized by ectopic growth of active endometrial tissue outside the uterus. The Luoshi Neiyi prescription (LSNYP) has been extensively used for treating EMs in China. However, data on the active chemical components of LSNYP are insufficient, and its pharmacological mechanism in EMs treatment remains unclear. This study aimed to explore the potential mechanism of LSNYP for EMs through network pharmacology based on the components absorbed into the blood.MethodsUltra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze blood components, and a series of network pharmacology strategies were utilized to predict targets of these components and EMs. Protein–protein interaction (PPI) network analysis, component–target–disease network construction, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Additionally, molecular docking, molecular dynamics simulations, and in vitro and in vivo experiments were conducted to validate the HIF1A/EZH2/ANTXR2 pathway associated with hypoxic pathology in EMs.ResultsThirty-four absorbed components suitable for network pharmacology analysis were identified, and core targets, such as interleukin 6, EGFR, HIF1A, and EZH2, were founded. Enrichment results indicated that treatment of EMs with LSNYP may involve the regulation of hypoxia and inflammatory-related signaling pathways and response to oxidative stress and transcription factor activity. Experimental results demonstrated that LSNYP could decrease the expression of HIF1A, ANTXR2, YAP1, CD44, and β-catenin, and increased EZH2 expression in ectopic endometrial stromal cells and endometriotic tissues. Molecular docking and molecular dynamics simulations manifested that there was stable combinatorial activity between core components and key targets of the HIF1A/EZH2/ANTXR2 pathway.ConclusionLSNYP may exert pharmacological effects on EMs via the HIF1A/EZH2/ANTXR2 pathway; hence, it is a natural herb-related therapy for EMs.
Genetic variability in the glucocorticoid pathway and treatment outcomes in hospitalized patients with COVID-19: a pilot study
Authors: Štampar Patricija , Blagus Tanja , Goričar Katja , Bogovič Petra , Turel Gabriele , Strle Franc , Dolžan Vita 
Published: July 2024

Introduction: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19. Genetic polymorphisms of the glucocorticoid receptor, metabolizing enzymes, or transporters may affect treatment response to dexamethasone. This study aimed to evaluate the association of the glucocorticoid pathway polymorphisms with the treatment response and short-term outcomes in patients with severe COVID-19.Methods: Our pilot study included 107 hospitalized patients with COVID-19 treated with dexamethasone and/or methylprednisolone, genotyped for 14 polymorphisms in the glucocorticoid pathway.Results: In total, 83% of patients had severe disease, 15.1% had critical disease and only 1.9% had moderate disease. CYP3A4 rs35599367 was the major genetic determinant of COVID-19 severity as carriers of this polymorphism had higher risk of critical disease (OR = 6.538; 95% confidence interval = 1.19–35.914: p = 0.031) and needed intensive care unit treatment more frequently (OR = 10; 95% CI = 1.754–57.021: p = 0.01). This polymorphism was also associated with worse disease outcomes, as those patients had to switch from dexamethasone to methylprednisolone more often (OR = 6.609; 95% CI = 1.137–38.424: p = 0.036), had longer hospitalization (p = 0.022) and needed longer oxygen supplementation (p = 0.040). Carriers of NR3C1 rs6198 polymorphic allele required shorter dexamethasone treatment (p = 0.043), but had higher odds for switching therapy with methylprednisolone (OR = 2.711; 95% CI = 1.018–7.22: p = 0.046). Furthermore, rs6198 was also associated with longer duration of hospitalization (p = 0.001) and longer oxygen supplementation (p = 0.001). NR3C1 rs33388 polymorphic allele was associated with shorter hospitalization (p = 0.025) and lower odds for ICU treatment (OR = 0.144; 95% CI = 0.027–0.769: p = 0.023). GSTP1 rs1695 was associated with duration of hospitalization (p = 0.015), oxygen supplementation and (p = 0.047) dexamethasone treatment (p = 0.022).Conclusion: Our pathway-based approach enabled us to identify novel candidate polymorphisms that can be used as predictive biomarkers associated with response to glucocorticoid treatment in COVID-19. This could contribute to the patient’s stratification and personalized treatment approach.
Sex differences in the associations between right heart structure and peak exercise capacity parameters in amateur cyclists
Authors: Pytka Michał Jakub , Domin Remigiusz Andrzej , Żołyński Mikołaj Stanisław , Niziński Jan , Krauze Tomasz , Wykrętowicz Andrzej , Guzik Przemysław 
Published: July 2024

Introduction: Right heart changes and their association with exercise capacity, including sex differences, are still being investigated. We analysed right heart structure and its relationship with exercise capacity parameters in amateur cyclists.Materials and methods: A cross-sectional study involving 215 consecutive adult amateur cyclists, who underwent resting transthoracic echocardiography and a cardiopulmonary exercise test (CPET) to exhaustion was performed.Results: The median age of participants was 29 years (IQR 24–37), 71% of them were men. The mean training time was 6 h/week, and 90% participated in vigorous or moderate physical activity. Men had larger right ventricular diameters (basal - RVD1, mid-cavity - RVD2 and longitudinal - RVD3) compared to women (40.9 vs. 37.6 mm, p = 0.0005, 28.7 vs. 26.3 mm, p = 0.03, 92.2 vs. 81.9 mm, p &lt; 0.0001). Indexing for body surface area revealed comparable right atrial volume (RAVI) between sexes (24.1 vs. 22.7 mL/m2). Men achieved higher peak exercise capacity parameters [O2 pulse, oxygen consumption (VO2) and workload] in CPET. Multivariate linear regression models revealed a positive association between peak VO2, workload and O2 pulse with RAVI in women but not with RVD1 or RVD3. Conversely, these parameters showed a positive association with RVD3 and RVD1 but not with RAVI in men.Conclusion: Sex differences exist in the relationship between right heart structural parameters and peak exercise capacity descriptors in amateur cyclists. Better exercise capacity during CPET to exhaustion is associated with greater RAVI in women but a greater RVD1 and RVD3 in men. These findings suggest different mechanisms of right heart adaptation to training in men and women.
Ontogenic stage-associated SA response contributes to leaf age-dependent resistance in Arabidopsis and cotton
Authors: Hu Lanxi , Mijatovic Jovana , Kong Feng , Kvitko Brian , Yang Li 
Published: July 2024

IntroductionAs leaves grow, they transition from a low-microbe environment embedded in shoot apex to a more complex one exposed to phyllosphere microbiomes. Such change requires a coordinated reprogramming of cellular responses to biotic stresses. It remains unclear how plants shift from fast growth to robust resistance during organ development.ResultsHere, we reported that salicylic acid (SA) accumulation and response were temporarily increased during leaf maturation in herbaceous annual Arabidopsis. Leaf primordia undergoing active cell division were insensitive to the elicitor-induced SA response. This age-dependent increase in SA response was not due to prolonged exposure to environmental microbes. Autoimmune mutants with elevated SA levels did not alter the temporal pattern dependent on ontogenic stage. Young Arabidopsis leaves were more susceptible than mature leaves to Pseudomonas syringae pv. tomato (Pto) DC3000 cor− infection. Finally, we showed a broadly similar pattern in cotton, a woody perennial, where young leaves with reduced SA signaling were preferentially invaded by a Xanthomonas pathogen after leaf surface infection.DiscussionThrough this work, we provided insights in the SA-mediated ontogenic resistance in Arabidopsis and tomato.
Bodily-tactile early intervention: a pilot study of the role of maternal touch and emotional availability in interactions between three children with visual impairment and additional disabilities and their mothers
Authors: Peltokorpi Sini , Salo Saara , Nafstad Anne , Hart Paul , Biringen Zeynep , Laakso Minna 
Published: July 2024

BackgroundChildren with visual impairment and additional disabilities (VIAD) have difficulty accessing the visual information related to their parents’ facial expressions and gestures. Similarly, it may be hard for parents to detect their children’s subtle expressions. These challenges in accessibility may compromise emotional availability (EA) in parent–child interactions. The systematic use of the bodily-tactile modality for expressive and receptive communicative functions may function as a strategy to compensate for a child’s lack of vision. This multiple-case study explored the effects of a bodily-tactile early intervention for three mothers and their one-year-old children with VIAD.MethodsVideo data from baseline, intervention, and follow-up sessions were analyzed using a bodily-tactile coding procedure and EA Scales.ResultsDuring the intervention, all mothers began to use a more bodily-tactile modality in early play routines and in different communicative functions. They increased their use of anticipatory cues, noticing responses, and tactile signs. Moreover, the children were more emotionally available to their mothers during the intervention and follow-up compared to the baseline.ConclusionThe results indicated that, during a short intervention, mothers could adopt a systematic use of the bodily-tactile modality in interactions with their children with VIAD. The results also suggest that, when mothers increased flexibility in communication channels, it was positively linked to their children’s EA.
The interaction between mental resilience and insomnia disorder on negative emotions in nurses in Guangdong Province, China
Authors: Zhan Ningjing , Xu Yixuan , Pu Jiangfeng , Wang Waner , Xie Zhanghao , Huang Huigen 
Published: July 2024

ObjectiveTo investigate the current status of psychological resilience, insomnia and negative emotions among nurses in Guangdong Province, China. And to explore the effects of the interaction between psychological resilience and insomnia on negative emotions.MethodsA cross-sectional survey method was used to select 1874 nurses in Guangdong Province from February 2023 to April 2023 for the survey. The Chinese version of the Psychological Resilience Scale (PRS), Insomnia Severity Index (ISI), Depression Anxiety and Stress Scale-21(DASS-21)were used in this study. We use SPSS 26.0 for statistical analysis. A simple effect analysis was established to analyze the association between psychological resilience, insomnia and negative emotions by using psychological resilience, insomnia and the interaction term.ResultsThe overall PRS and ISI scores were (59.79 ± 17.29) and (9.83 ± 5.97). The scores of DASS-21 each dimension were (8.19 ± 9.02) for depression emotion,(7.93 ± 7.66) for anxiety emotion and (10.58 ± 9.77) for stress emotion. The results of the interaction effect analysis indicated that psychological resilience and insomnia exhibited statistically significant differences in the between-subjects effect test for depression emotion (r2 = 0.136, P&lt;0.01), anxiety emotion (r2 = 0.127, P&lt;0.01), and stress emotion (r2 = 0.142, P&lt;0.01).ConclusionThe nurses exhibited moderate levels of psychological resilience. Most of them have varying degrees of insomnia, with majority being classified as mild insomnia. Additionally, they demonstrated varying degrees of negative emotions. There was a negative correlation between psychological resilience and insomnia. Psychological resilience was negatively correlated with depression, anxiety and stress emotions. Insomnia was positively correlated with depression, anxiety and stress emotions. Furthermore, the interaction between psychological resilience and insomnia had an effect on all three dimensions of negative emotions. Consequently, hospital administrators may implement efficacious intervention strategies such as cognitive behavioral therapy and improving workplace climate in a timely manner according to the different psychological tolerance and severity of insomnia of nurses in order to reduce the occurrence of negative emotions among nurses and improve their mental health.
Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study
Authors: Jácome-Ferrer Pablo , Costas Javier 
Published: July 2024

BackgroundEpidemiological studies have linked low birth weight to psychiatric disorders, including substance use disorders. Genomic analyses suggest a role of placental physiology on psychiatric risk. We investigated whether this association is causally related to impaired trophoblast function.MethodsWe conducted a two-sample summary-data Mendelian randomization study using as instrumental variables those genetic variants strongly associated with birth weight, whose effect is exerted through the fetal genome, and are located near genes with differential expression in trophoblasts. Eight psychiatric and substance use disorders with &gt;10,000 samples were included as outcomes. The inverse variance weighted method was used as the main analysis and several sensitivity analyses were performed for those significant results.ResultsThe inverse variance weighted estimate, based on 14 instrumental variables, revealed an association, after correction for multiple tests, between birth weight and broadly defined depression (β = −0.165, 95% CI = −0.282 to −0.047, P = 0.0059). Sensitivity analyses revealed the absence of heterogeneity in the effect of instrumental variables, confirmed by leave-one-out analysis, MR_Egger intercept, and MR_PRESSO. The effect was consistent using robust methods. Reverse causality was not detected. The effect was specifically linked to genetic variants near genes involved in trophoblast physiology instead of genes with fetal effect on birth weight or involved in placenta development.ConclusionImpaired trophoblast functioning, probably leading to reduced fetal brain oxygen and nutrient supply, is causally related to broadly defined depression. Considering the therapeutic potential of some agents to treat fetal growth restriction, further research on the effect of trophoblast physiology on mental disorders may have future implications in prevention.
Preventive and therapeutic effect of vitamin D on depression-like behavior in a mouse adolescent depression model and its association with BDNF protein expression
Authors: Yang Xueping , Miao Junxiao , Huang Yinglin , Li Lili , Zhuang Gengsen 
Published: July 2024

IntroductionPrevious studies in different populations have shown that vitamin D supplementation may reduce depression levels. In adolescents, vitamin D deficiency has been identified as a factor contributing to the onset of depression. This study aimed to establish a model of adolescent depression in mice by using the scientific unpredictable chronic mild stress (UCMS) model and to preliminarily evaluate the effect of vitamin D on the occurrence and development of depression and whether it is related to the protein expression of the BDNF pathway.MethodsThe UCMS method was used to establish a model of adolescent depression in 4-week-old C57BL/6 male mice, randomly divided into five groups: Control group, Stress group, Stress+ low-dose group, Stress+ medium-dose group, Stress+ high-dose group. At the same time as chronic stress, the administration groups were given intramuscular injections of different doses of vitamin D. After 8 weeks, behavioral tests, including the forced swimming test (FST) and open field test (OFT), were performed on each group of mice, along with recording of indicators, blood vitamin D level detection, and brain tissue western blot analysis.ResultsThe results showed a significant difference in vitamin D levels among mice in different groups after 8 weeks (P=0.012). The results of behavioral testing showed a significant difference in the static time of forced swimming among the groups (P&lt;0.001). Compared with the UCMS group, the static time of mice with vitamin D injection was significantly reduced (P&lt;0.001). The total number of times mice entered the central area, the total distance of movement, and the time spent in the central area significantly increased after vitamin D injection compared with the UCMS-only group (all P&lt;0.001). There was no significant difference in the expression of BDNF in the brain tissues of experimental mice (P&gt;0.05).DiscussionIn conclusion, in the mouse adolescent depression model, appropriate vitamin D supplementation can reduce the occurrence of stress-induced depression. Furthermore, vitamin D deficiency may also serve as a potential risk factor for depression.