bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between craving to drugs, emotional manipulation and interoceptive awareness for social acceptance: the addictive perspective
Authors: Khedr Mahmoud Abdelwahab , El-Ashry Ayman Mohamed , Ali Eman Abdeen , Eweida Rasha Salah 
Published: October 2023

Abstract
Background
Drug addiction (DA) is a global psychiatric worldwide problem. Patients with substance use disorder are more likely to use the numerous defenses at their disposal to control their surroundings emotionally. This could virtually cause a tidal wave of social rejection of them in the community. The study aims to investigate drug craving, emotional manipulation, and interoceptive awareness for social acceptance among patients with substance use disorder.

Methods
This study followed a descriptive correlational design on a sample of 110 patients with substance use disorder who were recruited to complete the Penn Alcohol Craving Scale, the Emotion Manipulation Questionnaire, and the Perceived Acceptance Scale.

Results
Most respondents recorded high levels of PACS and emotional manipulation ability. A highly positive and significant correlation was found between scores on emotional manipulation ability and PACS.

Conclusion
Craving for drugs was a significant predictor of emotional manipulation ability. Incorporation of effective nursing interventions to enable patients with substance use disorder to engage in self-reflection related to how their cravings for drugs may lead them to prioritize their needs over others.
Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics
Authors: Tabnak Peyman , Hasanzade Bashkandi Aysa , Ebrahimnezhad Mohammad , Soleimani Mahdieh 
Published: October 2023

AbstractGlioma is the most aggressive and malignant type of primary brain tumor, comprises the majority of central nervous system deaths, and is categorized into different subgroups according to its histological characteristics, including astrocytomas, oligodendrogliomas, glioblastoma multiforme (GBM), and mixed tumors. The forkhead box (FOX) transcription factors comprise a collection of proteins that play various roles in numerous complex molecular cascades and have been discovered to be differentially expressed in distinct glioma subtypes. FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma. Although recent studies considered FOXO subgroups as tumor suppressors, there are pieces of evidence that they may have an oncogenic role. This review will discuss the subtle functions of FOXOs and FOXM1 in gliomas, dissecting their regulatory network with other proteins, microRNAs and their role in glioma progression, including stem cell differentiation and therapy resistance/sensitivity, alongside highlighting recent pharmacological progress for modulating their expression.
Elderly patients with stage II gastric cancer do not benefit from adjuvant chemotherapy
Authors: Guo Jianping , Xiong Zhizhong , Yin Shi , Wen Yue’e , Jin Longyang , Wang Caiqin , Chen Huaxian , Luo Dandong , Deng Zijian , Huang Dayin , Li Xianzhe , Yi Biying , Mao Chaobin , Lian Lei 
Published: October 2023

Abstract
Background
With the aging of the population, the burden of elderly gastric cancer (EGC) increases worldwide. However, there is no consensus on the definition of EGC and the efficacy of adjuvant chemotherapy in patients with stage II EGC. Here, we investigated the effectiveness of adjuvant chemotherapy in defined EGC patients.

Methods
We enrolled 5762 gastric cancer patients of three independent cohorts from the Sixth Affiliated Hospital of Sun Yat-sen University (local), the Surveillance, Epidemiology, and End Results (SEER), and the Asian Cancer Research Group (ACRG). The optimal age cutoff for EGC was determined using the K-adaptive partitioning algorithm. The defined EGC group and the efficacy of adjuvant chemotherapy for them were confirmed by Cox regression and Kaplan–Meier survival analyses. Furthermore, gene set variation analyses (GSVA) were performed to reveal pathway enrichment between groups.

Results
The optimal age partition value for EGC patients was 75. In the local, SEER, and ACRG cohorts, the EGC group exhibited significantly worse overall survival and cancer-specific survival than the non-EGC group (P < 0.05) and was an independent risk factor. Stratified analyses based on chemotherapy showed that EGC patients derived little benefit from adjuvant chemotherapy. Furthermore, GSVA analysis revealed the activation of DNA repair-related pathways and downregulation of the p53 pathway, which may partially contribute to the observed findings.

Conclusion
In this retrospective, international multi-center study, 75 years old was identified as the optimal age cutoff for EGC definition, and adjuvant chemotherapy proved to be unbeneficial for stage II EGC patients.
The effect of an app-based dietary intervention on diet-related greenhouse gas emissions – results from a randomized controlled trial
Authors: Pitt Stephanie , Sjöblom Linnea , Bälter Katarina , Trolle Lagerros Ylva , Bonn Stephanie E 
Published: October 2023

Abstract
Background
Dietary change towards a diet low in greenhouse gas emissions (GHGEs) can reduce climate impact and improve individual-level health. However, there is a lack of understanding if diet interventions can achieve low-GHGE diets.

Methods
A randomized controlled trial was conducted to assess the effects of an app-based intervention. The intervention was designed to improve dietary intake of people with Type 2 diabetes, and was delivered via an app over 12 weeks, with each week covering one diet-related topic. Dietary intake was assessed at baseline and 3-month follow up by a 95-item food frequency questionnaire and linked to GHGE values. A total of n = 93 participants (n = 46 and n = 47 for the intervention and control group, respectively) were included in the analysis. Changes to GHGEs within and between the groups were analysed with inferential statistics.

Results
The majority (60%) of participants were male, with a mean age of 63.2 years and body mass index of 30 kg/m2. At baseline, diet-related GHGEs were 4.8 and 4.9 kg CO2-eq/day in the intervention and control group, respectively. At 3-month follow up the corresponding GHGEs were 4.7 and 4.9 kg CO2-eq/day. We found no statistically significant changes to diet-related GHGEs within or between groups, or within food categories, from baseline to 3-month follow up.

Conclusion
No evidence was found for the effectiveness of the app-based intervention to generate changes to diet-related GHGEs in a population of people with Type 2 diabetes. However, future interventions that target reducing meat consumption specifically may have the potential to result in a reduction of individual-level diet-related GHGEs.

Trial registration
ClinicalTrials.gov, NCT03784612. Registered 24 December 2018. www.clinicaltrials.gov/ct2/show/NCT03784612.
Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study
Authors: Huang Hsiang-Po , Chen Chung-Hsin , Chang Kai-Hsiung , Lee Ming-Shyue , Lee Cheng-Fan , Chao Yen-Hsiang , Lu Shih-Yu , Wu Tzu-Fan , Liang Sung-Tzu , Lin Chih-Yu , Lin Yuan Chi , Liu Shih-Ping , Lu Yu-Chuan , Shun Chia-Tung , Huang William J. , Lin Tzu-Ping , Ku Ming-Hsuan , Chung Hsiao-Jen , Chang Yen-Hwa , Liao Chun-Hou , Yu Chih-Chin , Chung Shiu-Dong , Tsai Yao-Chou , Wu Chia-Chang , Chen Kuan-Chou , Ho Chen-Hsun , Hsiao Pei-Wen , Pu Yeong-Shiau 
Published: October 2023

Abstract
Purpose
Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.

Methods
Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).

Results
In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.

Conclusion
This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.
Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer’s disease and brain aging
Authors: Corraliza-Gomez Miriam , Bermejo Teresa , Lilue Jingtao , Rodriguez-Iglesias Noelia , Valero Jorge , Cozar-Castellano Irene , Arranz Eduardo , Sanchez Diego , Ganfornina Maria Dolores 
Published: October 2023

AbstractThe insulin-degrading enzyme (IDE) is an evolutionarily conserved zinc-dependent metallopeptidase highly expressed in the brain, where its specific functions remain poorly understood. Besides insulin, IDE is able to cleave many substrates in vitro, including amyloid beta peptides, making this enzyme a candidate pathophysiological link between Alzheimer's disease (AD) and type 2 diabetes (T2D). These antecedents led us to address the impact of IDE absence in hippocampus and olfactory bulb. A specific induction of microgliosis was found in the hippocampus of IDE knockout (IDE-KO) mice, without any effects in neither hippocampal volume nor astrogliosis. Performance on hippocampal-dependent memory tests is influenced by IDE gene dose in 12-month-old mice. Furthermore, a comprehensive characterization of the impact of IDE haploinsufficiency and total deletion in metabolic, behavioral, and molecular parameters in the olfactory bulb, a site of high insulin receptor levels, reveals an unambiguous barcode for IDE-KO mice at that age. Using wildtype and IDE-KO primary microglial cultures, we performed a functional analysis at the cellular level. IDE absence alters microglial responses to environmental signals, resulting in impaired modulation of phenotypic states, with only transitory effects on amyloid-β management. Collectively, our results reveal previously unknown physiological functions for IDE in microglia that, due to cell-compartment topological reasons, cannot be explained by its enzymatic activity, but instead modulate their multidimensional response to various damaging conditions relevant to aging and AD conditions.
Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis
Authors: Grun L K , Maurmann R M , Scholl J N , Fogaça M E , Schmitz C R R , Dias C K , Gasparotto J , Padoin A V , Mottin C C , Klamt F , Figueiró F , Jones M H , Filippi-Chiela E C , Guma F C R , Barbé-Tuana F M 
Published: October 2023

Abstract
Background
Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control.

Results
Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated β-galactosidase (SA-β-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli.

Conclusions
Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.
DENV-2 NS1 promotes AMPK-LKB1 interaction to activate AMPK/ERK/mTOR signaling pathway to induce autophagy
Authors: Wu Ning , Ji Jinzhong , Gou Xiaoqin , Hu Pan , Cheng Yao , Liu Yuhang , Wang Yuanying , Zhang Qilong , Zuo Li 
Published: October 2023

AbstractThe global incidence of dengue fever has gradually increased in recent years, posing a serious threat to human health. In the absence of specific anti-dengue drugs, understanding the interaction of Dengue virus (DENV) with the host is essential for the development of effective therapeutic measures. Autophagy is often activated during DENV infection to promote viral replication, but the mechanism of how DENV's own proteins induce autophagy has not been clarified. In this study, we first preliminarily identified DENV-2 NS1 as the most likely viral protein for DENV-2-induced autophagy with the help of molecular docking techniques. Further experimental results confirmed that DENV-2 NS1 regulates DENV-2 infection of HUVEC-induced autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, DENV-2 NS1 mainly interacted with AMPK by means of its Wing structural domain, and NS1 bound to all three structural domains on the AMPKα subunit. Finally, the experimental results showed that DENV-2 NS1 promoted the interaction between LKB1 and AMPKα1 and thus activated AMPK by both increasing the expression of LKB1 and binding LKB1. In conclusion, the results of this study revealed that DENV-2 NS1 protein served as a platform for the interaction between AMPK and LKB1 after DENV-2 infection with HUVEC, and pulled AMPK and LKB1 together to form a complex. LKB1 to form a complex, promoting LKB1 action on the kinase structural domain of AMPKα1, which in turn promotes phosphorylation of the Thr172 site on the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy. The present discovery improves our understanding of DENV-2-induced host autophagy and contributes to the development of anti-dengue drugs.
Tumor removal limits prostate cancer cell dissemination in bone and osteoblasts induce cancer cell dormancy through focal adhesion kinase
Authors: Liu Ruihua , Su Shang , Xing Jing , Liu Ke , Zhao Yawei , Stangis Mary , Jacho Diego P. , Yildirim-Ayan Eda D. , Gatto-Weis Cara M. , Chen Bin , Li Xiaohong 
Published: October 2023

Abstract
Background
Disseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause metastases progression and lethal relapses. In prostate cancer (PCa), relapse can happen after curative treatments such as primary tumor removal. The impact of surgical removal on PCa dissemination and dormancy remains elusive. Furthermore, as dormant DTCs are asymptomatic, dormancy-induction can be an operational cure for preventing metastases and relapse of PCa patients.

Methods
We used a PCa subcutaneous xenograft model and species-specific PCR to survey the DTCs in various organs at different time points of tumor growth and in response to tumor removal. We developed in vitro 2D and 3D co-culture models to recapitulate the dormant DTCs in the bone microenvironment. Proliferation assays, fluorescent cell cycle reporter, qRT-PCR, and Western Blot were used to characterize the dormancy phenotype. We performed RNA sequencing to determine the dormancy signature of PCa. A drug repurposing algorithm was applied to predict dormancy-inducing drugs and a top candidate was validated for the efficacy and the mechanism of dormancy induction.

Results
We found DTCs in almost all mouse organs examined, including bones, at week 2 post-tumor cell injections. Surgical removal of the primary tumor reduced the overall DTC abundance, but the DTCs were enriched only in the bones. We found that osteoblasts, but not other cells of the bones, induced PCa cell dormancy. RNA-Seq revealed the suppression of mitochondrial-related biological processes in osteoblast-induced dormant PCa cells. Importantly, the mitochondrial-related biological processes were found up-regulated in both circulating tumor cells and bone metastases from PCa patients’ data. We predicted and validated the dormancy-mimicking effect of PF-562,271 (PF-271), an inhibitor of focal adhesion kinase (FAK) in vitro. Decreased FAK phosphorylation and increased nuclear translocation were found in both co-cultured and PF-271-treated C4-2B cells, suggesting that FAK plays a key role in osteoblast-induced PCa dormancy.

Conclusions
Our study provides the first insights into how primary tumor removal enriches PCa cell dissemination in the bones, defines a unique osteoblast-induced PCa dormancy signature, and identifies FAK as a PCa cell dormancy gatekeeper.
Risk prediction for liver injury in Epstein-Barr virus infection in pediatric respiratory tract infections
Authors: Mao Song , Wu Liangxia , Shi Wenjing 
Published: October 2023

Abstract
Background
Epstein-Barr virus (EBV) infection is likely to co-occur in pediatric respiratory tract infections (RTIs). Liver injury is the common complication of EBV infection. The detailed risk factors for liver injury in EBV infection remain elusive. We aimed to investigate the incidence, characteristics and potential risk factors for liver injury in EBV infection for early risk prediction.

Methods
We retrospectively recruited the pediatric RTIs cases with EBV infection according to a predefined criteria from our hospital between January 2015 and December 2017. We extracted the clinical and laboratory data from the electronical medical records. The impact of age, gender, and various parameters on the liver injury risk was investigated. Univariate logistic regression analysis was performed to analyse the association between clinical/laboratory parameters and liver injury. The related indexes were enrolled in the multivariate logistic regression analysis. Decision curve analysis was used to yield the value of related parameters in predicting liver injury. Receiver operating curve (ROC) analysis was applied to produce the C-index of white blood cell (WBC) count for liver injury. We also tested the non-linear association between WBC count and alanine aminotransferase (ALT).

Results
A total of 216 pediatric RTIs with EBV infection were enrolled. EBV infection is more likely to occur during the winter season. Cytomegalovirus infection was independently associated with liver injury in EBV infection (OR = 6.972, 95% CI = 1.648–29.490, p = 0.008). WBC count was independently associated with liver injury in EBV infection (OR = 1.169, 95% CI = 1.051–1.301, p = 0.004). The P interaction value between WBC count and cytomegalovirus was 0.149. The decision curve analysis showed that WBC count had larger area under curve compared with platelet (PLT) and birthweight (BW). ROC analysis yielded the c-index of WBC count: 0.75 and cut-point of 8.3. The turning point of WBC count in its association with ALT was 16.8. The p value before and after the turning point was < 0.001 and 0.123, respectively.

Conclusions
Cytomegalovirus co-infection demonstrated 5.972 more times of liver injury risk in EBV infection. WBC count was an independent biomarker for liver injury before the turning point of 16.8 in EBV infection. More attention should be paid to the risk of EBV infection in the winter. Cytomegalovirus infection and WBC count merit attention in the monitoring of possible liver injury in EBV infection among pediatric RTIs.
System inflammation response index: a novel inflammatory indicator to predict all-cause and cardiovascular disease mortality in the obese population
Authors: Kong Fanliang , Huang Junhao , Xu Chunhua , Huang Tingyuan , Wen Grace , Cheng Wenke 
Published: October 2023

Abstract
Aim
This study aims to investigate the relationship between two novel inflammatory markers, namely, the Systemic Inflammatory Response Index (SIRI) and the Systemic Immune Inflammatory Index (SII), as well as the all-cause and cardiovascular disease (CVD) mortality in the obese population.

Materials and methods
We conducted a prospective cohort study based on the data of 13,026 obese adults (age ≥ 18 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed until December 2019. SIRI was calculated by the formula: (neutrophil count × monocyte count) / lymphocyte count, while that of SII was: (platelet count × neutrophil count)/lymphocyte count. The association of SIRI and SII with all-cause and CVD mortality was evaluated using Cox regression. In addition, the nomogram was performed to predict 10-year survival probability.

Results
During a median follow-up of 137 months, 1959 and 553 all-cause and CVD deaths were recorded, respectively. Spearman correlation analysis indicated that SIRI and SII were unrelated to almost all baseline characteristics (r < 0.15). Multivariate Cox regression models displayed that each standard deviation (SD) increase in SIRI was associated with a 16% (HR 1.16; 95% CI 1.09–1.24) and 22% (HR 1.22; 95% CI 1.10–1.36) increase in the risk of all-cause and CVD mortality, respectively. Likewise, every SD increase in SII was correlated with a 9% (HR 1.09; 95% CI 1.02–1.16) and 14% (HR 1.14; 95% CI 1.04–1.26) increase in the risk of all-cause and CVD mortality, respectively. The predictive value of SIRI for all-cause and CVD mortality (AUC = 0.601 and 0.624) exceeded that of SII (AUC = 0.528 and 0.539). Moreover, the nomogram displayed a substantial predictive value for 10-year survival (AUC = 0.847) with sensitivity and specificity exceeding 75%.

Conclusions
In the obese population, SIRI and SII are independent risk factors for all-cause and CVD mortality. Notably, the predictive ability of SIRI for both all-cause and CVD mortality significantly outperforms that of SII, suggesting that SIRI is a more valuable marker of inflammation.