bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphologic alterations of the fear circuitry: the role of sex hormones and oral contraceptives
Authors: Brouillard Alexandra , Davignon Lisa-Marie , Turcotte Anne-Marie , Marin Marie-France 
Published: November 2023

BackgroundEndogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake.ObjectiveWe investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network.MethodsWe recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users’ salivary ethinyl estradiol (EE) were assessed using liquid chromatography – tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods.ResultsCompared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs.DiscussionOur results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.
The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance
Authors: Mahmoudi-Aznaveh Azam , Tavoosidana Gholamreza , Najmabadi Hossein , Azizi Zahra , Ardestani Amin 
Published: November 2023

IntroductionAn insufficient functional beta cell mass is a core pathological hallmark of type 2 diabetes (T2D). Despite the availability of several effective pharmaceuticals for diabetes management, there is an urgent need for novel medications to protect pancreatic beta cells under diabetic conditions. Integrative organ cross-communication controls the energy balance and glucose homeostasis. The liver and pancreatic islets have dynamic cross-communications where the liver can trigger a compensatory beta cell mass expansion and enhanced hormonal secretion in insulin-resistant conditions. However, the indispensable element(s) that foster beta cell proliferation and insulin secretion have yet to be completely identified. Exosomes are important extracellular vehicles (EVs) released by most cell types that transfer biological signal(s), including metabolic messengers such as miRNA and peptides, between cells and organs.MethodsWe investigated whether beta cells can take up liver-derived exosomes and examined their impact on beta cell functional genes and insulin expression. Exosomes isolated from human liver HepG2 cells were characterized using various methods, including Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), and Western blot analysis of exosomal markers. Exosome labeling and cell uptake were assessed using CM-Dil dye. The effect of liver cell-derived exosomes on Min6 beta cells was determined through gene expression analyses of beta cell markers and insulin using qPCR, as well as Akt signaling using Western blotting.ResultsTreatment of Min6 beta cells with exosomes isolated from human liver HepG2 cells treated with insulin receptor antagonist S961 significantly increased the expression of beta cell markers Pdx1, NeuroD1, and Ins1 compared to the exosomes isolated from untreated cells. In line with this, the activity of AKT kinase, an integral component of the insulin receptor pathway, is elevated in pancreatic beta cells, as represented by an increase in AKT’s downstream substrate, FoxO1 phosphorylation.DiscussionsThis study suggests that liver-derived exosomes may carry a specific molecular cargo that can affect insulin expression in pancreatic beta cells, ultimately affecting glucose homeostasis.
Coordination contracts and numerical analysis of low-carbon competitive supply chains under the influence of low-carbon goodwill
Authors: Xie De-ru , Qin Qin , Xie Jian-min , He Xin-jing , Jiang Mao-ting 
Published: November 2023

Introduction: Under the dual opportunities of low-carbon consumption preference and online consumption platforms, vendors’ low-carbon advertising incursions provide opportunities for decarbonization and market position enhancement, as well as further research on the value of low-carbon advertising. This study aims to explore the contractual choices of green vendors’ online channels participating in low-carbon advertising competition under the low-carbon goodwill effect, and to simulate and evaluate the contractual choices of supply chain members.Methods: Using differential games, through the innovative application of the traditional low-carbon goodwill model and the introduction of the low-carbon advertising competition intensity coefficient, we design one-way and two-way cost-sharing contracts under low-carbon competition, coordinate the vicious competition in the supply chain, and provide contractual choices for supply chain participants.Results and discussion: Under the low-carbon advertising competition decision, the manufacturer has an absolute low-carbon market advantage, but the interests of all supply chain members are weakened, and interestingly, the manufacturer, who dominates the market, is the facilitator of the contractual agreement. Second, well-designed pacts can provide manufacturers and traders with more options for low-carbon strategies. Although both one-way and two-way cost-sharing pacts can generate Pareto gains for the supply chain and its members in advertising competition, two-way cost-sharing pacts are superior to one-way pacts in terms of coordination advantages. In addition, an important finding is that greater profit growth can be achieved through contractual cooperation in low-intensity advertising competition. Thus, moderate competition is desirable, while excessive competition can harm the supply chain system. Manufacturers should actively urge retailers to cooperate in order to optimize profits and establish long-term stable partnerships between upstream and downstream firms in green supply chains.
Combination of verteporfin-photodynamic therapy with 5-aza-2’-deoxycytidine enhances the anti-tumour immune response in triple negative breast cancer
Authors: Banerjee Shramana M. , Acedo Pilar , El Sheikh Soha , Harati Rania , Meecham Amelia , Williams Norman R. , Gerard Gareth , Keshtgar Mohammed R. S. , MacRobert Alexander J. , Hamoudi Rifat 
Published: November 2023

IntroductionTriple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2’-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood.MethodsThe present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients.ResultsFunctional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. DiscussionTo our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.
Social prescribing outcomes: a mapping review of the evidence from 13 countries to identify key common outcomes
Authors: Sonke Jill , Manhas Nico , Belden Cassandra , Morgan-Daniel Jane , Akram Seher , Marjani Stefany , Oduntan Oluwasanmi , Hammond Gabrielle , Martinez Gabriella , Davidson Carroll Gray , Rodriguez Alexandra K. , Burch Shanaé , Colverson Aaron J. , Pesata Virginia , Fancourt Daisy 
Published: November 2023

IntroductionAs a means for supporting a range of health and wellbeing goals, social prescribing programs have been implemented around the world. Reflecting a range of contexts, needs, innovation, and programing, a broad array of outcomes has been studied in relation to these programs. As interest in social prescribing grows, more targeted study of key outcomes and in turn evidence synthesis that can inform evidence-based practice, policy, and investment is needed.Methods and ResultsThis mapping review identified, described, and synthesized the broad array of social prescribing outcomes that have been studied in 13 countries and maps the outcomes that have been most commonly studied. From 87 articles included in this review, a total of 347 unique outcomes were identified, including 278 unique patient outcomes and 69 unique system outcomes. The most commonly studied categories of patient outcomes were found to be mental health, lifestyle and behavior, and patient/service user experience. The most commonly studied system outcomes were healthcare/service utilization and financial/economic outcomes.DiscussionThis review highlights the value of heterogeneity and mixed methods approaches in outcomes studies for capturing nuanced experiences and outcomes in this nascent area of practice, while contributing to the advancement of evidence synthesis for social prescribing globally by quantifying and offering insight into the outcomes that have been studied to date. It also lays a foundation for the development of key common outcomes and a Core Outcomes Set for social prescribing. Additionally, it identified key outcomes that, given their relationship to critical health and social issues, warrant both broader and deeper study.
Treatment of cognitive and mood disorders secondary to traumatic brain injury by the association of bilateral occipital nerve stimulation and a combined protocol of multisite repetitive transcranial magnetic stimulation and cognitive training: A case report
Authors: Caloc'h Tiphanie , Le Saout Estelle , Litaneur Séverine , Suarez Alcira , Durand Sylvain , Lefaucheur Jean-Pascal , Nguyen Jean-Paul 
Published: November 2023

PurposeCognitive impairment secondary to traumatic brain injury (TBI) is difficult to treat and usually results in severe disability.MethodA 48-year-old man presented with chronic refractory headaches and persistent disabling cognitive impairment after TBI. He was first treated with occipital nerve stimulation (ONS) implanted bilaterally to relieve headaches (8 years after the head trauma). Two years later, he was treated with a 6-week protocol combining repetitive transcranial magnetic stimulation (rTMS) delivered to multiple cortical sites (prefrontal cortex, language areas, and areas involved in visuo-spatial functions) and computerized cognitive training (CogT) (targeting memory, language, and visuo-spatial functions) to improve cognitive performance.ResultsExecutive and cognitive functions (attention, ability to perform calculations, and verbal fluency) improved in association with pain relief after ONS (33–42% improvement) and then improved even more after the rTMS-CogT protocol with an additional improvement of 36–40% on apathy, depression, and anxiety, leading to a significant reduction in caregiver burden. The functional improvement persisted and even increased at 6 months after the end of the rTMS-CogT procedure (10 years after the onset of TBI and 2 years after ONS implantation).ConclusionThis is the first observation describing sustained improvement in post-TBI refractory headache, depression, and cognitive impairment by the association of bilaterally implanted ONS and a combined procedure of multisite rTMS and CogT to target various brain functions.
Risk factors for recurrent cerebral amyloid angiopathy-related intracerebral hemorrhage
Authors: Jia Xinglei , Bo Menghan , Zhao Hong , Xu Jia , Pan Luqian , Lu Zhengyu 
Published: November 2023

BackgroundCerebral amyloid angiopathy (CAA) is the most common cause of lobar intracerebral hemorrhage (ICH) in the elderly, and its multifocal and recurrent nature leads to high rates of disability and mortality. Therefore, this study aimed to summarize the evidence regarding the recurrence rate and risk factors for CAA-related ICH (CAA-ICH).MethodsWe performed a systematic literature search of all English studies published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, and CINAHL from inception to June 10, 2023. Studies reporting CAA-ICH recurrence rates and risk factors for CAA-ICH recurrence were included. We calculated pooled odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) using a random/fixed-effects model based on the I2 assessment of heterogeneity between studies. Publication bias was assessed using Egger's test.ResultsThirty studies were included in the final analysis. Meta-analysis showed that the recurrence rate of CAA-ICH was 23% (95% CI: 18–28%, I2 = 96.7%). The risk factors significantly associated with CAA-ICH recurrence were: previous ICH (OR = 2.03; 95% CI: 1.50–2.75; I2 = 36.8%; N = 8), baseline ICH volume (OR = 1.01; 95% CI: 1–1.02; I2 = 0%; N = 4), subarachnoid hemorrhage (cSAH) (OR = 3.05; 95% CI: 1.86–4.99; I2 = 0%; N = 3), the presence of cortical superficial siderosis (cSS) (OR = 2.04; 95% CI: 1.46–2.83; I2 = 0%; N = 5), disseminated cSS (OR = 3.21; 95% CI: 2.25–4.58; I2 = 16.0%; N = 6), and centrum semiovale-perivascular spaces (CSO-PVS) severity (OR = 1.67; 95% CI: 1.14–2.45; I2 = 0%; N = 4).ConclusionCAA-ICH has a high recurrence rate. cSAH, cSS (especially if disseminated), and CSO-PVS were significant markers for recurrent CAA-ICH. The onset of ICH in patients with CAA is usually repeated several times, and recurrence is partly related to the index ICH volume. Identifying clinical and neuroimaging predictors of CAA-ICH recurrence is of great significance for evaluating outcomes and improving the prognosis of patients with CAA-ICH.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400240, identifier [CRD42023400240].
The association between constipation and stroke based on the NHANES and Mendelian randomization study
Authors: Du Wenjuan , Yang Shengkai , Zhou Hai , Wu Yueju , Cai Yong , Meng Hai , Teng Hongwei , He Ai Feng 
Published: November 2023

BackgroundThis study aimed to investigate putative causal effects between constipation and stroke using bidirectional Mendelian randomization (MR) analysis.MethodsBased on the cross-sectional study, logistic regression models were developed to assess the association between constipation and stroke prevalence. Subsequently, genome-wide association studies statistics were employed to perform MR analysis between constipation and stroke, as well as its subtypes. The inverse variance weighting (IVW) method was the primary method, complemented by four additional methods, namely weighted median, weighted mode, simple mode, and MR-Egger regression. Cochran’s Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier, and MR Steiger test were performed to assess heterogeneity and pleiotropy effects.ResultsConstipation was associated with a greater risk of stroke even after adjusting for all covariates in logistic regression [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.01–2.09, p = 0.042]. IVW MR analysis revealed that constipation affected large artery atherosclerosis (LAS; IVW OR = 1.5, 95% CI = 1.07–2.104, p = 0.019). No significant or suggestive association was observed with the risk of stroke or its various subtypes in MR analysis. Meanwhile, reverse MR analysis revealed no significant causal relationship between stroke or other stroke subtypes and constipation. The results of sensitivity analyses revealed no significant horizontal pleiotropy affecting causal estimates.ConclusionWhile cross-sectional studies have established that constipation increases the risk of stroke, this two-sample bidirectional MR analysis revealed a positive correlation between constipation and LAS. However, no such correlation was observed between constipation and stroke, including its various subtypes.
Association between nutritional status, body composition, and fitness level of adolescents in physical education in Casablanca, Morocco
Authors: Oukheda Mourad , Bouaouda Khawla , Mohtadi Karima , Lebrazi Halima , Derouiche Abdelfettah , Kettani Anass , Saile Rachid , Taki Hassan 
Published: November 2023

AimThis study aims to analyze and compare dietary intake, as well as to examine the associations between energy intake in terms of macronutrients, body composition, and physical fitness (PF) specifically cardiorespiratory endurance (CE) among a sample of young adolescents aged 15 to 18 years, who participate in physical education and sports sessions in public schools in Casablanca, Morocco.Materials and methodsA total of 311 participants, including 156 girls and 154 boys, were included in the study. Each participant maintained a food diary for 3 days during the same study week. Additionally, body composition measurements were taken using bioelectrical impedance analysis (BIA). The PF was assessed using the validated mini-Cooper test (6 min).ResultsThe results show that the participants had an average total energy intake of 2386.7 ± 492.7 kcal. A significant difference was observed between boys and girls, with average energy intakes of 2468.8 ± 531.1 kcal and 2304.0 ± 437.0 kcal, respectively. These dietary intakes were significantly lower than their needs and nutritional recommendations. The associations of nutritional status, sex, body mass index (BMI) and physical fitness (PF) were tested and a positive correlation was observed following an adequate intake of carbohydrates (CHO) and proteins on Vo2max, while a negative association was observed with regard to Body fat for both sexes. Boys exhibit significantly better PF than girls (p &lt; 0.01). Obese participants had the lowest PF and an unbalanced nutritional status, the adolescents with a normal weight p &lt; 0.01 displayed a high level of PF compared to individuals in other weight categories.ConclusionThe PF is significantly associated with macronutrient intake status and body composition, especially BMI and BF. The Underweight, overweight, and obese students demonstrated poorer performance in physical fitness indices compared to normal-weight. Adolescents adhering to recommended CHO and protein intake levels tend to exhibit enhanced physical fitness. Implementing strategies to encourage students to maintain a balanced diet and engage in regular physical exercise is essential.
Efficacy and safety of immune checkpoint inhibitors plus recombinant human endostatin therapy as second-line treatment in advanced non-small-cell lung cancer with negative driver gene: a pilot study
Authors: Yang Bo , Li Yuzhi , Deng Jie , Yang Hui , Sun Xiang 
Published: November 2023

BackgroundImmune checkpoint inhibitors (ICIs) have become the standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Recent findings indicating an intertwined regulation of vascular endothelial growth factor (VEGF) signaling and immunosuppression in the tumor microenvironment suggest that the combination of ICIs and angiogenesis inhibitors could have synergistic antitumor activity, along with favorable tolerability. However, ICIs plus anti-angiogenesis therapy has not been widely evaluated. The purpose of this pilot study was to evaluate the efficacy and safety of ICIs plus recombinant human (rh)-endostatin as second-line treatment in advanced NSCLC with negative driver gene.MethodProspectively evaluated the efficacy and safety of ICIs plus rh-endostain as second-line treatment in advanced NSCLC with negative driver gene. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (ORR), and safety.ResultsA total of 34 patients were recruited in this study. 18 patients received ICIs plus anti-angiogenesis therapy (ICIs combination therapy), and 16 patients received ICIs monotherapy. DCR was 88.9% vs 43.8% (P = 0.009). Median PFS (mPFS) was 8.3 months vs. 3.7 months (HR = 0.276, 95% CI 0.125-0.607, P = 0.001). Median OS (mOS) was 18.0 months vs 9.6 months (HR=0.364, 95% CI 0.147-0.902, P=0.009). In multivariate Cox regression analysis, ICI combination therapy prolonged PFS (HR = 0.069, 95% CI 0.019-0.185, P &lt; 0.001) and OS (HR = 0.044, 95% CI 0.011-0.185, P &lt; 0.001). We did not observe a significant difference in the incidence of adverse events (AEs) between the two groups (P &gt; 0.05).ConclusionsCompared with ICIs monotherapy, ICIs combination therapy improves clinical response in patients with advanced NSCLC with negative driver gene, significantly prolongs PFS and OS, and does not significantly difference the incidence of AEs.