bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular K+-Responsive Block Copolymer Micelles for Targeted Drug Delivery of Curcumin
Authors: Jiang Mingyue , Chen Le , Chen Bo , Yu Qinghua , Zhang Xianming , Jing Weihong , Ma Limei , Deng Tao , Yang Zhangyou , Yu Chao 
Published: June 2022

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.
The Social and Emotional Well-being of Indigenous Peoples Living With Diabetes: A Systematic Review Protocol
Authors: Speight Jane , Baptista Shaira , Lee Christopher , Sher Louisa , Skinner Timothy C. , Brown Alex 
Published: June 2022

IntroductionGlobally, Indigenous people have a greater incidence and earlier onset of diabetes than the general population and have higher documented rates of emotional distress and mental illness. This systematic review will provide a synthesis and critical appraisal of the evidence focused on the social and emotional well-being of Indigenous peoples living with diabetes, including prevalence, impact, moderators, and the efficacy of interventions.MethodsWe will search MEDLINE Complete, EMBASE, APA PsycINFO, and CINAHL Complete from inception until late April 2021. Search strategies will include keywords related to Indigenous peoples, diabetes, and social and emotional well-being. All abstracts will be rated independently by two researchers against specified inclusion criteria. Eligible studies will report social and emotional well-being data for Indigenous people with diabetes, and/or report on the efficacy of interventions designed to address social and emotional well-being in this population. For each eligible study, quality will be rated using standard checklists to appraise each study’s internal validity, to be determined based on study type. Any discrepancies will be resolved through discussions and consultation with other investigators as needed. We expect to present a narrative synthesis of the evidence.DiscussionThe findings of the systematic review will enable greater understanding of the impact of relationships between diabetes and emotional well-being among Indigenous peoples to inform research, policy and practice. The findings will be accessible to Indigenous people affected by diabetes through a summary published in plain language on our research centre’s website.Systematic Review RegistrationPROSPERO registration number: CRD42021246560.
Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis
Authors: Zheng Yue , Qi Bingcai , Gao Wenqing , Qi Zhenchang , Liu Yanwu , Wang Yuchao , Feng Jianyu , Cheng Xian , Luo Zhiqiang , Li Tong 
Published: June 2022

BackgroundThe macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis.MethodsGSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein–protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model.ResultsA total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) &gt; 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF.ConclusionThe screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.
First-in-Human Implantation of Gutter-Free Design Stent-Graft in in situ Fenestration TEVAR for Aortic Arch Pathology
Authors: Li Xin , Shu Chang , Wang Lunchang , Li Quanming , Fang Kun , Luo Mingyao , Zhang Weichang , Zhou Yang , Zhou Haiyang 
Published: June 2022

PurposeTo report the technology and preliminary result of gutter-free design stent-grafted in in situ fenestration thoracic endovascular aortic repair (TEVAR).DescriptionThe gutter-free stent-graft has a nickel-titanium self-expanding skeleton, double polytetrafluoroethylene coating, and an outer-skirt fabric structure (named C-skirt endograft). The outer skirt fabric prevents endoleak from the gutter around the stent graft fenestration. Further, the skirt structure right under the fenestration in the aortic stent graft can function as a fixation of the side-branch artery endograft. These designs have the following advantages, such as: 1) prevention of endoleak; and 2) fixation tightly between the branch and aorta endograft pieces.EvaluationA patient who was diagnosed with an aortic arch aneurysm, combined with localized dissection, has successfully implanted the aortic stent graft and C-skirt endograft for the left subclavian artery. The 6-month follow-up result of the C-skirt in situ fenestration TEVAR is satisfactory without obvious endoleak.ConclusionsThe new gutter-free C-skirt stent graft is being safely and effectively used for aortic arch TEVAR. Long-term evaluation of safety, effectivity, and durability needs to be proven by future multi-center studies.
A System-Wide Investigation and Stratification of the Hemostatic Proteome in Premature Myocardial Infarction
Authors: Dunster Joanne L. , Wright Joy R. , Samani Nilesh J. , Goodall Alison H. 
Published: June 2022

IntroductionAdvancing understanding of key factors that determine the magnitude of the hemostatic response may facilitate the identification of individuals at risk of generating an occlusive thrombus as a result of an atherothrombotic event such as an acute Myocardial Infarction (MI). While fibrinogen levels are a recognized risk factor for MI, the association of thrombotic risk with other coagulation proteins is inconsistent. This is likely due to the complex balance of pro- and anticoagulant factors in any individual.MethodsWe compared measured levels of pro- and anticoagulant proteins in plasma from 162 patients who suffered an MI at an early age (MI &lt;50 y) and 186 age- and gender-matched healthy controls with no history of CAD. We then used the measurements from these individuals as inputs for an established mathematical model to investigate how small variations in hemostatic factors affect the overall amplitude of the hemostatic response and to identify differential key drivers of the hemostatic response in male and female patients and controls.ResultsPlasma from the MI patients contained significantly higher levels of Tissue Factor (P = 0.007), the components of the tenase (FIX and FVIII; P &lt; 0.0001 for both) and the prothrombinase complexes (FX; P = 0.003), and lower levels of Tissue Factor Pathway Inhibitor (TFPI; P = 0.033) than controls. The mathematical model, which generates time-dependent predictions describing the depletion, activation, and interaction of the main procoagulant factors and inhibitors, identified different patterns of hemostatic response between MI patients and controls, and additionally, between males and females. Whereas, in males, TF, FVIII, FIX, and the inhibitor TFPI contribute to the differences seen between case and controls, and in females, FII, FVIII, and FIX had the greatest influence on the generation of thrombin. We additionally show that further donor stratification may be possible according to the predicted donor response to anticoagulant therapy.ConclusionsWe suggest that modeling could be of value in enhancing our prediction of risk of premature MI, recurrent risk, and therapeutic efficacy.
Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort
Authors: Keestra Sarai M. , Motoc Irina , Ravelli Anita C.J. , Roseboom Tessa J. , Finken Martijn J.J. 
Published: June 2022

BackgroundEarly-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women.MethodsThis study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation.ResultsThere were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p&lt;0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women.ConclusionsThere are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.
A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes
Authors: Kong Wei-ya , Liu Zheng-ai , Zhang Na , Wu Xue , Zhao Xing-bo , Yan Lei 
Published: June 2022

ObjectiveTo investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART).Study DesignThis prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed.Results116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P&gt;0.05).ConclusionRegression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website:Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.
A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma
Authors: Du Kunpeng , Zou Jingwen , Wang Baiyao , Liu Chunshan , Khan Muhammad , Xie Tao , Huang Xiaoting , Shen Piao , Tian Yunhong , Yuan Yawei 
Published: June 2022

BackgroundIn the era of immunotherapy, predictive or prognostic biomarkers for head and neck squamous cell carcinoma (HNSCC) are urgently needed. Metabolic reprogramming in the tumor microenvironment (TME) is a non-negligible reason for the low therapeutic response to immune checkpoint inhibitor (ICI) therapy. We aimed to construct a metabolism-related gene prognostic index (MRGPI) for HNSCC bridging metabolic characteristics and antitumor immune cycling and identified the immunophenotype, genetic alternations, potential targeted inhibitors, and the benefit of immunotherapy in MRGPI-defined subgroups of HNSCC.MethodsBased on The Cancer Genome Atlas (TCGA) HNSCC dataset (n = 502), metabolism-related hub genes were identified by the weighted gene co-expression network analysis (WGCNA). Seven genes were identified to construct the MRGPI by using the Cox regression method and validated with an HNSCC dataset (n = 270) from the Gene Expression Omnibus (GEO) database. Afterward, the prognostic value, metabolic activities, genetic alternations, gene set enrichment analysis (GSEA), immunophenotype, Connectivity map (cMAP), and benefit of immunotherapy in MRGPI-defined subgroups were analyzed.ResultsThe MRGPI was constructed based on HPRT1, AGPAT4, AMY2B, ACADL, CKM, PLA2G2D, and ADA. Patients in the low-MRGPI group had better overall survival than those in the high-MRGPI group, consistent with the results in the GEO cohort (cutoff value = 1.01). Patients with a low MRGPI score display lower metabolic activities and an active antitumor immunity status and more benefit from immunotherapy. In contrast, a higher MRGPI score was correlated with higher metabolic activities, more TP53 mutation rate, lower antitumor immunity ability, an immunosuppressive TME, and less benefit from immunotherapy.ConclusionThe MRGPI is a promising indicator to distinguish the prognosis, the metabolic, molecular, and immune phenotype, and the benefit from immunotherapy in HNSCC.
The Immune Change of the Lung and Bowel in an Ulcerative Colitis Rat Model and the Protective Effect of Sodium Houttuyfonate Combined With Matrine
Authors: Ni Lulu , Jing Shan , Zhu Li , Yang Xue , Wang Xinyue , Tu Su 
Published: June 2022

ObjectiveTo explore the immune change of lung injury of Ulcerative colitis (UC) by observing the changes of inherent immunity and adaptive immunity of the lung and bowel in UC rat models after the treatment of Sodium Houttuyfonate combined with Matrine. MethodUC rat models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 1 week and 5 weeks. 1-week experimental rats were divided into normal group and model group, 5/each group. 5-weeks experimental rats were divided into normal group, model group, Sodium Houttuyfonate (2.9mg/ml) combined with Matrine (1.47mg/ml), and positive control sulfasalazine (10mg/ml), 5/each group. All rats were administered by gavage for 5 weeks. The histopathological and fibrotic changes in the lung and bowel were observed, and the expressions of Tumor Necrosis Factor (TNF)- α, interleukin (IL)-8 in the lung, bowel, and serum were detected by radio-immunity and immunohistochemistry, and the mRNA expressions of Toll-like receptor (TLR)-4, nuclear factor kappa (NF-κB), Macrophage migration inhibitory factor (MIF), Mucosal addressing cell adhesion molecule-1 (MadCAM1) and Pulmonary surfactant protein-A (SP-A) in the lung and bowel were detected by Real time-PCR.ResultCompared with the normal group, the model rats had significant histopathological and fibrotic changes both in the lung and bowel, and all treatment groups were improved. After treatment, TLR4, IL-8, MIF, and TNF-α in the lung decreased (P&lt;0.05); NF-KB, IL-8, and MIF in the bowel increased (P&lt;0.05); MadCAM1 both in lung and bowel decreased (P&lt;0.05); SP-A decreased in bowel and increased in the lung (P&lt;0.05).ConclusionThe cause of lung injury in this model was found to be related to inherent immunity and adaptive immunity, while the cause of bowel injury in this model was found to be mainly related to adaptive immunity. Sodium Houttuyfonate combined with Matrine could improve bowel and lung injury.
Willingness to Be Vaccinated Against COVID-19 Among People With HIV in the United States: Results From a National Survey
Authors: Wickersham Jeffrey A. , Meyer Jaimie P. , Shenoi Sheela , Altice Frederick L. , Barakat Lydia Aoun , Virata Michael , Olivares Miriam , Maviglia Francesca , Khati Antoine , Shrestha Roman 
Published: June 2022

BackgroundApproximately 215 million Americans have been fully vaccinated for COVID-19, representing over 65% of the total population. People with HIV (PWH) may be more susceptible to COVID-19 infection or severe disease, elevating the importance of COVID-19 vaccination uptake in the population. We report results from a national survey of PWH to evaluate the likelihood of receiving a COVID-19 vaccine.MethodsWe conducted an online survey of 1,030 PWH living in the United States between December 6, 2020 and January 8, 2021 to evaluate likelihood of receiving a COVID-19 vaccine.ResultsOverall, participants were highly willing to be vaccinated, with 83.8% stating they “strongly agree” (65.7%) or “somewhat agree” (18.1%). Participants' top vaccine-related concerns were side-effects (39.3%), safety (14.7%), and fair/equitable distribution of the vaccine to affected communities (13.6%). Participants were more willing to be vaccinated if they reported receiving an annual influenza vaccination (p &lt; 0.001), had previously tested positive for (p = 0.043) COVID-19, had been hospitalized for (p = 0.027) COVID-19 infection, or had an undetectable HIV viral load (p = 0.002). Black (p &lt; 0.001), politically conservative (p &lt; 0.001), and participants with an annual income of ≤ $19,999 (p = 0.005) were significantly less willing to be vaccinated for COVID-19.ConclusionsThe vast majority of PWH were willing to be vaccinated, though predominantly those who were already engaged in HIV care or directly affected by COVID-19. Findings from this large survey of PWH suggest intensive outreach efforts are needed to support engagement in vaccination programs, particularly among Black and politically conservative PWH.
Psychobiological Evaluation of Day Clinic Treatment for People Living With Dementia – Feasibility and Pilot Analyses
Authors: Wuttke-Linnemann Alexandra , Palm Svenja , Geschke Katharina , Skoluda Nadine , Bischoff Theresa , Nater Urs M. , Endres Kristina , Fellgiebel Andreas 
Published: June 2022

BackgroundHospitalization is often stressful and burdensome for people living with dementia (PwD) and their informal caregivers (ICs). Day clinic treatment may provide a suitable alternative, but is often precluded by a diagnosis of dementia. Furthermore, it is often caregiver-based ratings that measure treatment success as the validity of self-reports in PwD is critically discussed. We therefore set out to examine the feasibility of psychobiological stress measures in PwD and ICs and to evaluate treatment trajectories considering both the day clinic context and the daily life of the dyads.MethodA total of 40 dyads of PwD (mean age: 78.15 ± 6.80) and their ICs (mean age: 63.85 ± 13.09) completed paper-and-pencil questionnaires (covering stress, depressive symptoms, and caregiver burden among others) in addition to the measurement of hair cortisol concentrations (HCC) at admission, discharge, and follow-up 6 months after day clinic treatment. As part of an ambulatory assessment, for 2 days at the beginning and 2 days at the end of the day clinic treatment, PwD and ICs collected six saliva samples per day for the analysis of salivary cortisol (sCort) and alpha-amylase (sAA).ResultsPaper-and-pencil questionnaires and HCC assessments were more feasible than the ambulatory assessment. We found discrepancies between subjective and physiological markers of stress in PwD. Whereas HCC decreased over time, self-reported stress increased. Child–parent dyads reported decreases in neuropsychiatric symptoms, associated burden, and self-reported stress from admission to follow-up. In daily life, both PwD and ICs showed characteristic diurnal profiles of sAA and sCort, however, we found no differences in summary indicators of salivary stress markers over time.DiscussionThe psychobiological evaluation was feasible and added informative value, underlining the potential of physiological stress markers to complement self-reports on stress in PwD and to objectively evaluate treatment trajectories. In this sample, HCC was more feasible and acceptable as biological marker of stress compared to saliva samples. Concerning treatment trajectories, differential effects on the dyads were found, with child–parent dyads benefiting more from day clinic treatment compared to spousal dyads.