bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cuproptosis-related genes score: A predictor for hepatocellular carcinoma prognosis, immunotherapy efficacy, and metabolic reprogramming
Authors: Nie Guilin , Peng Dingzhong , Wen Ningyuan , Wang Yaoqun , Lu Jiong , Li Bei 
Published: February 2023

BackgroundCuproptosis is a newly identified type of programmed cell death, characterized by aggregation of mitochondrial lipoylated proteins and the destabilization of Fe–S cluster proteins triggered by copper. However, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsWe analyzed the expression and prognostic significance of cuproptosis-related genes using the data obtained from TCGA and ICGC datasets. A cuproptosis-related genes (CRG) score was constructed and validated via least absolute shrinkage and selection operator (LASSO) Cox regression, multivariate Cox regression and nomogram model. The metabolic features, immune profile and therapy guidance of CRG-classified HCC patients were processed via R packages. The role of kidney-type glutaminase (GLS) in cuproptosis and sorafenib treatment has been confirmed via GLS knockdown.ResultsThe CRG score and its nomogram model performed well in predicting prognosis of HCC patients based on the TCGA cohort (training set), ICGC cohort and GEO cohort (validation set). The risk score was proved as an independent predictor for overall survival (OS) of HCC. The area under the curves (AUCs) of the model in the training and validation cohorts were all around 0.83 (TCGA, 1- year), 0.73 (TCGA, 3- year), 0.92 (ICGC, 1- year), 0.75 (ICGC, 3- year), 0.77 (GEO, 1- year), 0.76(GEO, 3- year). Expression levels of metabolic genes and subtypes of immune cells, and sorafenib sensitiveness varied significantly between the high-CRG group and low-CRG group. One of the model-included gene, GLS, might be involved in the process of cuproptosis and sorafenib treatment in HCC cell line.ConclusionThe five cuproptosis-related genes model contributed to prognostic prediction and provided a new sight for cuproptosis-related therapy in HCC.
Different pathological response and histological features following neoadjuvant chemotherapy or chemo-immunotherapy in resected non-small cell lung cancer
Authors: Alì Greta , Poma Anello Marcello , Di Stefano Iosè , Zirafa Carmelina Cristina , Lenzini Alessandra , Martinelli Giulia , Romano Gaetano , Chella Antonio , Baldini Editta , Melfi Franca , Fontanini Gabriella 
Published: February 2023

IntroductionNon-small cell lung cancer (NSCLC) is the leading cause of cancer incidence and mortality worldwide. Neoadjuvant chemo-immunotherapy has led to clinical benefits in resectable NSCLC in comparison to chemo-therapy alone. Major pathological response (MPR) and pathological complete response (pCR) have been used as surrogates of neoadjuvant therapy response and clinical outcomes. However, the factors affecting the pathological response are still controversial. Therefore, in this study we retrospectively examined MPR and pCR in two different cohorts of NSCLC patients, 14 treated by chemotherapy and 12 by chemo-immunotherapy in the neoadjuvant setting.MethodsIn resected tumor specimens, different histological characteristics were evaluated: necrosis, fibrosis, inflammation, presence of organizing pneumonia, granuloma, cholesterol cleft, and reactive epithelial alterations. In addition, we evaluated how MPR impacts on event-free survival (EFS) and overall survival (OS). In a small group of patients treated by chemo-immunotherapy, a gene expression analysis of the Hippo pathway was performed both in preoperative biopsies and matched post-surgical specimens.ResultsWe observed a better pathological response in the chemo-immunotherapy treated cohort: 6/12 patients (50.0%) achieved a MPR ≤10% and 1/12 (8.3%) achieved pCR both on primary tumor and on lymph nodes. On the contrary, no patient treated with chemotherapy alone achieved pCR or MPR ≤10%. A higher amount of stroma in the neoplastic bed was observed in patients treated with immuno-chemotherapy. Moreover, patients achieving better MPR (including pCR) had significantly improved overall survival (OS) and event-free survival (EFS). After neoadjuvant chemo-immunotherapy, residual tumors showed a remarkable upregulation of genes consistent with the activation of YAP/TAZ. Also, alternative checkpoint, such as CTLA-4, were enhanced.DiscussionOur findings showed that neoadjuvant chemo-immunotherapy treatment improves MPR and pCR thus resulting in better EFS and OS. Moreover, a combined treatment could induce different morphological and molecular changes in comparison to chemotherapy alone, thus giving new insights in the assessment of pathological response.
Risk factors for post-transplant relapse and survival in younger adult patients with t(8;21)(q22;q22) acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: A multicenter retrospective study
Authors: Zhou Wei , Chen Guofeng , Gong Dan , Gao Yi , Yu Li 
Published: February 2023

BackgroundOutcomes of patients with t(8;21)(q22;q22) acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain heterogeneous.MethodsTo identify the risk factors for relapse and survival after allo-HSCT in t(8;21) AML patients, we retrospectively evaluated the clinical and prognostic information of 142 patients with t(8;21) AML undergoing allo-HSCT between January 2002 and September 2018 at 15 hematology research centers in China.ResultsTwenty-nine patients (20%) relapsed after undergoing allo-HSCT. A &gt; 1-log reduction in RUNX1/RUNX1T1-based minimal residual disease (MRD) directly before allo-HSCT and a &gt; 3-log reduction within the first 3 months after allo-HSCT were associated with a significantly lower post-transplant 3-year cumulative incidence of relapse (CIR, 9% vs. 62% and 10% vs. 47%,all P &lt; 0.001), whereas transplantation during the second complete remission (CR2, 39% vs. 17% during CR1, P = 0.022), during relapse (62% vs. 17% during CR1, P &lt; 0.001) and KIT D816 mutations at diagnosis (49% vs. 18%, P = 0.039) were related to a significantly higher 3-year CIR. Multivariate analysis demonstrated that a &gt; 1-log reduction in MRD directly before transplantation (CIR: hazard ratio(HR), 0.21 [0.03–0.71], P = 0.029; overall survival (OS): HR = 0.27 [0.08–0.93], P = 0.038) and a &gt; 3-log reduction in post-transplant MRD within the first 3 months (CIR: HR = 0.25 [0.07–0.89], P = 0.019; OS: HR = 0.38 [0.15–0.96], P = 0.040) were independent favorable prognostic factors, and transplantation during relapse (CIR: HR = 5.55 [1.23–11.56], P = 0.041; OS: HR = 4.07 [1.82–20.12], P = 0.045) were independent adverse prognostic factors for post-transplant relapse and survival in patients with t(8;21) AML.ConclusionOur study suggests that for patients with t(8;21) AML undergoing allo-HSCT, it would be better to receive transplantation during CR1 with a MRD directly before transplantation achieving at least 1-log reduction. MRD monitoring in the first 3 months after allo-HSCT might be robust in predicting relapse and adverse survival after allo-HSCT.
Leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation in a pre-clinical model
Authors: Rebouças-Silva Jéssica , Amorim Nathaly Alcazar , Jesus-Santos Flávio Henrique , de Lima Jéssica Aparecida , Lima Jonilson Berlink , Berretta Andresa A. , Borges Valéria M. 
Published: February 2023

Leishmaniasis is a widespread group of neglected vector-borne tropical diseases that possess serious therapeutic limitations. Propolis has been extensively used in traditional medical applications due to its range of biological effects, including activity against infectious agents. Here we evaluated the leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation incorporating EPP-AF®, in both in vitro and in vivo models of Leishmania amazonensis infection. Propolis extract, obtained from a standardized blend following hydroalcoholic extraction, showed the characteristic fingerprint of Brazilian green propolis as confirmed by HPLC/DAD. A carbopol 940 gel formulation was obtained containing propolis glycolic extract at 3.6% w/w. The release profile, assessed using the Franz diffusion cell protocol, demonstrated a gradual and prolonged release of p-coumaric acid and artepillin C from the carbomer gel matrix. Quantification of p-coumaric acid and artepillin C in the gel formulation over time revealed that p-coumaric acid followed the Higuchi model, dependent on the disintegration of the pharmaceutical preparation, while artepillin C followed a zero-order profile with sustained release. In vitro analysis revealed the ability of EPP-AF® to reduce the infection index of infected macrophages (p &lt; 0.05), while also modulating the production of inflammatory biomarkers. Decreases in nitric oxide and prostaglandin E2 levels were observed (p &lt; 0.01), suggesting low iNOS and COX-2 activity. Furthermore, EPP-AF® treatment was found to induce heme oxygenase-1 antioxidant enzyme expression in both uninfected and L. amazonensis-infected cells, as well as inhibit IL-1β production in infected cells (p &lt; 0.01). ERK-1/2 phosphorylation was positively correlated with TNF-α production (p &lt; 0.05), yet no impact on parasite load was detected. In vivo analysis indicated the effectiveness of topical treatment with EPP-AF® gel alone (p &lt; 0.05 and p &lt; 0.01), or in combination with pentavalent antimony (p &lt; 0.05 and p &lt; 0.001), in the reduction of lesion size in the ears of L. amazonensis-infected BALB/c mice after seven or 3 weeks of treatment, respectively. Taken together, the present results reinforce the leishmanicidal and immunomodulatory effects of Brazilian green propolis, and demonstrate promising potential for the EPP-AF® propolis gel formulation as a candidate for adjuvant therapy in the treatment of Cutaneous Leishmaniasis.
Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma
Authors: Meng Shuting , Zhu Tianye , Fan Zhiwei , Cheng Yulan , Dong Yefeng , Wang Fengxu , Wang Xuehai , Dong Deping , Yuan Songtao , Zhao Xinyuan 
Published: February 2023

Background: Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM.Methods: Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms.Results: Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays.Conclusion: The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.
Instigating prevalent abiotic stress resilience in crop by exogenous application of phytohormones and nutrient
Authors: Swain Rinny , Sahoo Smrutishree , Behera Mamata , Rout Gyana Ranjan 
Published: February 2023

In recent times, the demand for food and feed for the ever-increasing population has achieved unparalleled importance, which cannot afford crop yield loss. Now-a-days, the unpleasant situation of abiotic stress triggers crop improvement by affecting the different metabolic pathways of yield and quality advances worldwide. Abiotic stress like drought, salinity, cold, heat, flood, etc. in plants diverts the energy required for growth to prevent the plant from shock and maintain regular homeostasis. Hence, the plant yield is drastically reduced as the energy is utilized for overcoming the stress in plants. The application of phytohormones like the classical auxins, cytokinins, ethylene, and gibberellins, as well as more recent members including brassinosteroids, jasmonic acids, etc., along with both macro and micronutrients, have enhanced significant attention in creating key benefits such as reduction of ionic toxicity, improving oxidative stress, maintaining water-related balance, and gaseous exchange modification during abiotic stress conditions. Majority of phytohormones maintain homeostasis inside the cell by detoxifying the ROS and enhancing the antioxidant enzyme activities which can enhance tolerance in plants. At the molecular level, phytohormones activate stress signaling pathways or genes regulated by abscisic acid (ABA), salicylic acid (SA), Jasmonic acid (JA), and ethylene. The various stresses primarily cause nutrient deficiency and reduce the nutrient uptake of plants. The application of plant nutrients like N, K, Ca, and Mg are also involved in ROS scavenging activities through elevating antioxidants properties and finally decreasing cell membrane leakage and increasing the photosynthetic ability by resynthesizing the chlorophyll pigment. This present review highlighted the alteration of metabolic activities caused by abiotic stress in various crops, the changes of vital functions through the application of exogenous phytohormones and nutrition, as well as their interaction.
Does congruence between a descendant entrepreneur’s personality traits and family business values matter for succession?
Authors: Ahmad Zeshan , Chan Wai Meng , Oon Elaine Yen Nee 
Published: February 2023

PurposeIn this paper, we investigate two research queries pertaining to the success of small family business succession. First, we examine how the Big-5 personality traits of descendant entrepreneurs influence the success of their family business succession. Second, we investigate whether descendant entrepreneurs whose personality traits are congruent with the values of their family business, would lead to the success of their family business succession, through the mediating role of descendant entrepreneur-family business value congruence (DE-FBVC).MethodologyWe rely on the person-organization fit theory for our conceptual framework and we collected primary data from 124 respondents designated as chairman and managing directors in small family businesses.ResultsOur results show that a descendant entrepreneur’s openness, extroversion, conscientiousness, and agreeableness traits are likely to lead to successful family business succession, but a descendant entrepreneur with neuroticism trait is unlikely to do so. In addition, our results reveal that the DE-FBVC mediates the relationship between openness and extroversion traits with succession success positively, but between neuroticism trait and succession success negatively. By contrast, we find that DE-FBVC does not mediate the relationship between conscientiousness and agreeableness traits with succession success.OriginalityThe findings of our study suggest that while four of the Big-5 personality traits matter for the success of small family business succession, specific personality traits of descendant entrepreneurs which are found to be congruent with the values of their family business, will also lead to succession success.
Social identity loss and reverse culture shock: Experiences of international students in China during the COVID-19 pandemic
Authors: Raja Rameez , Ma Jianfu , Zhang Miwei , Li Xi Yuan , Almutairi Nayef Shabbab , Almutairi Aeshah Hamdan 
Published: February 2023

BackgroundInternational students are often exposed to various challenges during life transitions. The ‘mindsponge’ mechanism suggests that individuals absorb and integrate new cultural values that are compatible with their core values while rejecting those of lesser importance. On the basis of this notion, this article explores the experiences of international students in China regarding their unplanned return to their home countries during the COVID-19 pandemic through the lens of the mindsponge mechanism.AimThis article aims to highlight the experiences of international students in China who are going through life transitions due to the global pandemic. The study focuses on the experiences of two groups of international students: (1) Those who remained in China during the pandemic, and (2) those who had left China and were stranded in their home countries due to a ban on international travel amid COVID-19.MethodThis qualitative study comprised of in-depth semi structured in-person and online interviews. Thematic Analysis was used to analyze the data in order to generate study themes.ResultsThe results revealed that students who remained in China experienced challenges which included anxiety, closure of campuses, lockdown, their parents’ concern regarding health issues, and not being able to meet with friends. On the other hand, students who had left China during the pandemic were confined to their home countries. This group of students experienced more severe problems than the students who remained in China. Since the transition to home countries was “unplanned,” they were not ready to readjust to their native culture and were vulnerable to severe reverse culture shock. Upon returning to their home countries, international students faced a number of challenges, including readjustment to their home countries and changes in their lives in host and home countries. In addition, they lost social and academic resources, such as the disruption of study environment, losing important group memberships, financial constraints, visa expiry, graduation delay, and academic suspension.ConclusionThis study concluded that the international students experienced cultural problems after unplanned transition to their home countries during the pandemic. They described effects of reverse culture shock as being more distressing. They perceived dissatisfaction due to loss of previously held social identities and sense of belonging to the traditional society they left behind. There is a need of future studies on the long-term effect of unplanned transition on psychological, social and professional experiences. The process of readjustment has proven to be a challenging endeavor.
Associations between theory of mind and clinical symptoms in recent onset schizophrenia spectrum disorders
Authors: Cayouette Audrey , Thibaudeau Élisabeth , Cellard Caroline , Roy Marc-André , Achim Amélie M. 
Published: February 2023

IntroductionPeople with schizophrenia often present with Theory of mind (ToM) deficits, and the link between these deficits and clinical symptoms remains to be refined, for instance through the use of more recent assessment methods. The objective of this study was to examine the associations between a psychometrically sound ToM task and the clinical symptoms of schizophrenia as measured with the five dimensions of the Positive and Negative Syndrome Scale (PANSS) namely positive, negative, cognitive/disorganization, depression/anxiety and excitability/hostility, while controlling for non-social cognitive abilities.MethodsSeventy participants with recent-onset schizophrenia spectrum disorders (SSD) were assessed for ToM using the Combined stories task (COST) and for clinical symptoms using the PANSS.ResultsThe results revealed significant correlations between ToM and the positive (r= −0.292,p= 0.015) and cognitive/disorganization (r= −0.480,p&lt; 0.001) dimensions when controlling for non-social cognitive abilities. In contrast, the negative symptoms dimension was only significantly correlated with ToM when non-social cognitive abilities were not controlled for (r= −0.278,p= 0.020).DiscussionVery few prior studies used the five-dimensions of the PANSS to examine the link with ToM and this study is the first to rely on the COST, which includes a non-social control condition. This study highlights the importance of taking non-social cognitive abilities into account when considering the relationship between ToM and symptoms.
Examining concurrent validity and item selection of the Session Wants and Needs Outcome Measure (SWAN-OM) in a children and young people web-based therapy service
Authors: De Ossorno Garcia Santiago , Edbrooke-Childs Julian , Salhi Louisa , Ruby Florence J. M. , Sefi Aaron , Jacob Jenna 
Published: February 2023

BackgroundSingle-session mental health interventions are frequently attended by children and young people (CYP) in both web-based and face-to-face therapy settings. The Session “Wants” and “Needs” Outcome Measure (SWAN-OM) is an instrument developed in a web-based therapy service to overcome the challenges of collecting outcomes and experiences of single-session therapies (SSTs). It provides pre-defined goals for the session, selected by the young person prior to the intervention, on which progress toward achievement is scored at the end of the session.ObjectiveThe objective of this study was to evaluate the instrument's psychometric properties, including concurrent validity against three other frequently used outcome and experience measures, at a web-based and text-based mental health service.MethodsThe SWAN-OM was administered for a period of 6 months to 1,401 CYP (aged 10–32 years; 79.3% white; 77.59% female) accessing SST on a web-based service. Item correlations with comparator measures and hierarchical logistic regressions to predict item selection were calculated for concurrent validity and psychometric exploration.ResultsThe most frequently selected items were “Feel better” (N = 431; 11.61%) and “Find ways I can help myself” (N = 411; 11.07%); unpopular items were “Feel safe in my relationships” (N = 53; 1.43%) and “Learn the steps to achieve something I want” (N = 58; 1.56%). The SWAN-OM was significantly correlated with the Experience of Service Questionnaire, particularly the item “Feel better” [rs(109) = 0.48, p &lt; 0.001], the Youth Counseling Impact Scale, particularly the item “Learn the steps to achieve something I want” [rs(22) = 0.76, p &lt; 0.001], and the Positive and Negative Affect Schedule, particularly the items “Learn how to feel better” [rs(22) = 0.72, p &lt; 0.001] and “Explore how I feel” [rs(70) = −0.44, p &lt; 0.001].ConclusionThe SWAN-OM demonstrates good concurrent validity with common measures of outcome and experience. Analysis suggests that lesser-endorsed items may be removed in future iterations of the measure to improve functionality. Future research is required to explore SWAN-OM's potential to measure meaningful change in a range of therapeutic settings.