bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity
Authors: Lempesis Ioannis G. , Hoebers Nicole , Essers Yvonne , Jocken Johan W. E. , Dineen Rosemary , Blaak Ellen E. , Manolopoulos Konstantinos N. , Goossens Gijs H. 
Published: June 2023

IntroductionUpper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity.MethodsWe included 23 postmenopausal women with normal weight (n = 13) or obesity (n = 10). In vivo secretion of adipokines from ABD and FEM SAT was measured using the arterio-venous balance technique. Adipokine gene expression and adipocyte morphology were examined in ABD and FEM SAT. Furthermore, adipokine expression and secretion were investigated in vitro using differentiated human primary ABD and FEM subcutaneous adipocytes derived from the study participants.ResultsPlasma leptin and plasminogen activator inhibitor (PAI)-1 concentrations were higher, and ABD and FEM adipocytes were larger in women with obesity than normal weight. No differences in adipocyte size and blood flow were apparent between ABD and FEM SAT. We found significant release of leptin and monocyte chemoattractant protein (MCP)-1 from ABD and FEM SAT, with higher fractional release of MCP-1 from ABD than FEM SAT. Gene expression of leptin, PAI-1, and tumor necrosis factor-α was lower in ABD than FEM SAT and higher in women with obesity than normal weight. In ABD adipocytes, interleukin-6, PAI-1, and leptin gene expression were higher, while adiponectin and dipeptidyl-peptidase-4 gene expression were lower than in FEM adipocytes. Finally, ABD adipocytes secreted less MCP-1 compared to FEM adipocytes.DiscussionThese findings demonstrate that upper and lower body SAT and adipocytes are characterized by distinct inflammatory signatures in postmenopausal women, which seem independent of adipocyte size.
Out to sea: ocean currents and patterns of asymmetric gene flow in an intertidal fish species
Authors: Snead Anthony A. , Tatarenkov Andrey , Avise John C. , Taylor D. Scott , Turner Bruce J. , Marson Kristine , Earley Ryan L. 
Published: June 2023

Passive dispersal via wind or ocean currents can drive asymmetric gene flow, which influences patterns of genetic variation and the capacity of populations to evolve in response to environmental change. The mangrove rivulus fish (Kryptolebias marmoratus), hereafter “rivulus,” is an intertidal fish species restricted to the highly fragmented New World mangrove forests of Central America, the Caribbean, the Bahamas, and Florida. Mangrove patches are biological islands with dramatic differences in both abiotic and biotic conditions compared to adjacent habitat. Over 1,000 individual rivulus across 17 populations throughout its range were genotyped at 32 highly polymorphic microsatellites. Range-wide population genetic structure was evaluated with five complementary approaches that found eight distinct population clusters. However, an analysis of molecular variance indicated significant population genetic structure among regions, populations within regions, sampling locations within populations, and individuals within sampling locations, indicating that rivulus has both broad- and fine-scale genetic differentiation. Integrating range-wide genetic data with biophysical modeling based on 10 years of ocean current data showed that ocean currents and the distance between populations over water drive gene flow patterns on broad scales. Directional migration estimates suggested some significant asymmetries in gene flow that also were mediated by ocean currents and distance. Specifically, populations in the center of the range (Florida Keys) were identified as sinks that received migrants (and alleles) from other populations but failed to export individuals. These populations thus harbor genetic variation, perhaps even from extirpated populations across the range, but ocean currents and complex arrangements of landmasses might prevent the distribution of that genetic variation elsewhere. Hence, the inherent asymmetry of ocean currents shown to impact both genetic differentiation and directional migration rates may be responsible for the complex distribution of genetic variation across the range and observed patterns of metapopulation structure.
Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance
Authors: Rodriguez B. Leticia , Chen Limo , Li Yanli , Miao Shucheng , Peng David H. , Fradette Jared J. , Diao Lixia , Konen Jessica M. , Alvarez Frank R. Rojas , Solis Luisa M. , Yi Xiaohui , Padhye Aparna , Gibson Laura A. , Ochieng Joshua K. , Zhou Xiaofei , Wang Jing , Gibbons Don L. 
Published: June 2023

IntroductionDespite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way to improve response to ICB therapy.ResultsOur results show that combination anti-PD-1/CTLA-4 produces an initial antitumor effect with evidence of an activated immune response. Upon extended treatment with anti-PD-1/CTLA-4 acquired resistance developed with an increase of the immunosuppressive populations, including T-regulatory cells, neutrophils and monocytes. Addition of anti-Ly6C blocking antibody to anti-PD-1/CTLA-4 was capable of completely reversing treatment resistance and restoring CD8 T cell activity in multiple KP lung cancer models and in the autochthonous lung cancer KrasLSL-G12D/p53fl/fl model. We found that there were higher classical Ly6C+ monocytes in anti-PD-1/CTLA-4 combination resistant tumors. B7 blockade illustrated the importance of dendritic cells for treatment efficacy of anti-Ly6C/PD-1/CTLA-4. We further determined that classical Ly6C+ monocytes in anti-PD-1/CTLA-4 resistant tumors are trafficked into the tumor via IFN-γ and the CCL2-CCR2 axis. Mechanistically we found that classical monocytes from ICB resistant tumors were unable to differentiate into antigen presenting cells and instead differentiated into immunosuppressive M2 macrophages or myeloid-derived suppressor cells (MDSC). Classical Ly6C+ monocytes from ICB resistant tumors had a decrease in both Flt3 and PU.1 expression that prevented differentiation into dendritic cells/macrophages.ConclusionsTherapeutically we found that addition of anti-Ly6C to the combination of anti-PD-1/CTLA-4 was capable of complete tumor eradication. Classical Ly6C+ monocytes differentiate into immunosuppressive cells, while blockade of classical monocytes drives dendritic cell differentiation/maturation to reinvigorate the anti-tumor T cell response. These findings support that immunotherapy resistance is associated with infiltrating monocytes and that controlling the differentiation process of monocytes can enhance the therapeutic potential of ICB.
A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing
Authors: Xiang Xiaoqing , Kang Jiawen , Jiang Jingwen , Zhang Yaning , Zhang Yong , Li Lesai , Peng Xiaoning 
Published: June 2023

BackgroundAberrant DNA damage repair (DDR) is one of the hallmarks of tumors, and therapeutic approaches targeting this feature are gaining increasing attention. This study aims to develop a signature of DDR-related genes to evaluate the prognosis of cervical cancer (CC).MethodsDifferentially expressed genes were identified between high and low DDR groups of cells from the single-cell RNA sequencing dataset GSE168652 based on DDR scores. Using the ssGSEA and WGCNA methods, DDR-related differentially expressed genes were identified from different patients within the TCGA-CESC cohort. Using Cox analysis and LASSO regression analysis, a DDR-related gene signature was constructed based on the intersection of two groups of differentially expressed genes and DDR-related genes from WGCNA, and validated in GSE52903. Immune cell infiltration analysis, mutation analysis, survival analysis, drug sensitivity analysis, etc., were performed in different groups which were established based on the DDR gene signature scoring. A key gene affecting prognosis was selected and validated through biological experiments such as wound healing, migration, invasion, and comet assays.ResultsA novel DDR-related signature was constructed and the nomogram results showed this signature performed better in predicting prognosis than other clinical features for CC. The high DDR group exhibited poorer prognosis, weaker immune cell infiltration in the immune microenvironment, lower expression of immune checkpoint-related genes, lower gene mutation frequencies and more sensitivity to drugs such as BI.2536, Bleomycin and etc. ITGB1, ZC3H13, and TOMM20 were expressed at higher levels in CaSki and HeLa cells compared to ECT1 cells. Compared with the native CaSki and HeLa cells, the proliferation, migration, invasion and DDR capabilities of CaSki and HeLa cell lines with ITGB1 suppressed expression were significantly decreased.ConclusionThe 7 DDR-related gene signature was an independent and powerful prognostic biomarker that might effectively evaluate the prognosis of CC and provide supplementary information for a more personalized evaluation and precision therapy. ITGB1 was a potential candidate gene that may affect the DDR capacity of CC cells, and its mechanism of action was worth further in-depth study.
‘Internet+’ comprehensive nursing training course in the post-epidemic era—an exploration of the mixed teaching mode: a randomized trial
Authors: Wang Qing-Ling , Liu Lan-Lan , Liu Cheng-Rui , Zhu Qing-Shuang , Ren Zhi-Ying , Gang Ting-Ting , Zhou Chun-Yan , Li Qiu-Ping , Chen Xi , Han Bin-Ru 
Published: June 2023

ObjectiveTo explore the effect of the application of the ‘Internet+’ nursing teaching mode on the comprehensive teaching ‘Fundamentals of Nursing’.Trial designParallel design and convenient sampling were used to select vocational nursing students from the Nursing College of Capital Medical University.MethodsSelected students were randomly divided into two groups. The control group consisted of 30 students in Grade 2020 higher vocational nursing education (traditional teaching mode). The observation group consisted of 30 students in Grade 2021 higher vocational nursing education (Internet+ mixed teaching mode). Training assessment results, automatic learning ability, professional identity, and satisfaction were compared between the two groups.ResultsCompared with the control group, the students in the observation group scored higher in the following operation practices: venous blood sampling, intradermal injection, cardiopulmonary resuscitation (CPR), sputum aspiration, and putting on and taking off robes (84.01 ± 0.87 vs. 92.14 ± 1.23; 91.41 ± 0.82 vs. 96.86 ± 0.27; 87.56 ± 0.31 vs. 93.91 ± 2.79; 88.11 ± 0.51 vs. 93.75 ± 0.29; and 82.29 ± 0.29 vs. 90.96 ± 0.34, respectively, with p &lt; 0.05 for all scores). The total scores for autonomous learning ability and subjective satisfaction were also higher in the observation group compared with the control group (82.98 ± 4.72 vs. 93.17 ± 5.01 and 96.67% vs. 90.00%, respectively, with p &lt; 0.05 for all scores).ConclusionIn the post-epidemic era, the ‘Internet+ hybrid teaching mode’ was applied to comprehensive nursing teaching. This changed the traditional education mode, which focuses only on professional knowledge. The ‘Internet+’ teaching mode results showed that the professional, ideological, and political courses exhibited the same value guidance, which improved students’ independent learning ability, practical operation ability, professional identity, and satisfaction.
Conjunctival infiltrates and cytokines in an experimental immune-mediated blepharoconjunctivitis rat model
Authors: Hou Aihua , Tin Min Qi , Fenner Beau , Liu Yu-Chi , Tong Louis 
Published: June 2023

PurposeTo characterize the histopathological and immunological findings of a rat model of allergic blepharoconjunctivitis (BC) and demonstrate its potential utility for the assessment of BC therapies.MethodsSprague–Dawley (SD) rats were immunized with ovalbumin (OVA) and topically challenged with OVA (BC group) or PBS (control group), while a corticosteroid group was pre-treated with triamcinolone acetate 24 h before the challenge. Morphological features were evaluated and tissues were harvested for histological, flow cytometry and cytokine analysis.ResultsThe BC group rats developed eyelid excoriations, redness, and conjunctival edema 24 h after the OVA challenge, while corticosteroid pre-treated and PBS-challenged rats were unaffected. The BC features were reduced despite repeated challenges for 5 days. Massive immune cell infiltration was observed in conjunctivae of BC rats, while no significant infiltration was seen in the other groups. Populations of T cells, mono-macrophages, neutrophils, and NK cells made up more than 77% of CD45+7AAD− cells in the conjunctival tissues. T cell proportions were increased at 96 h compared to 24 h post-challenge, while macrophages decreased during the same time period. Eosinophils and intraepithelial neutrophils were detected in the BC rats, but not in the PBS and corticosteroid groups. BC eyes had significantly higher levels of IFN-γ and IL-2, while IL-4 and IL-6 levels were similar to controls.ConclusionA robust BC response was detected in this rat model which was suppressed by corticosteroid pre-treatment. Immune cell composition and cytokine profiles changed over time.
The effects of early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis
Authors: Wang Lijie , Hua Yusi , Wang Luping , Zou Xia , Zhang Yan , Ou Xiaofeng 
Published: June 2023

BackgroundThe effects of early mobilization (EM) on intensive care unit (ICU) patients remain unclear. A meta-analysis of randomized controlled trials was performed to evaluate its effect in mechanically ventilated adult ICU patients.MethodsWe searched randomized controlled trials (RCTs) published in Medline, Embase, and CENTRAL databases (from inception to November 2022). According to the difference in timing and type, the intervention group was defined as a systematic EM group, and comparator groups were divided into the late mobilization group and the standard EM group. The primary outcome was mortality. The secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV), and adverse events. EM had no impact on 180-day mortality and hospital mortality between intervention groups and comparator groups (RR 1.09, 95% CI 0.89–1.33, p = 0.39). Systemic EM reduced the ICU length of stay (LOS) (MD −2.18, 95% CI −4.22–−0.13, p = 0.04) and the duration of MV (MD −2.27, 95% CI −3.99–−0.56, p = 0.009), but it may increase the incidence of adverse events in patients compared with the standard EM group (RR 1.99, 95% CI 1.25–3.16, p = 0.004).ConclusionSystematic EM has no significant effect on short- or long-term mortality in mechanically ventilated adult ICU patients, but systematic EM could reduce the ICU LOS and duration of MV.
Epidemiological characteristics of Vibrio parahaemolyticus outbreaks, Zhejiang, China, 2010–2022
Authors: Chen Lili , Wang Jikai , Chen Jiang , Zhang Ronghua , Zhang Hexiang , Qi Xiaojuan , He Yue 
Published: June 2023

BackgroundVibrio parahaemolyticus is one of the most common foodborne pathogens and poses a significant disease burden. The purpose of the study was to elucidate the epidemiological characteristics of Vibrio parahaemolyticus outbreaks in Zhejiang Province, and provide insights for the targeted prevention and control of foodborne diseases.MethodsDescriptive statistical methods were utilized to analyze the data on Vibrio parahaemolyticus outbreaks reported by all Centers for Disease Control and Prevention (CDCs) through Foodborne Disease Outbreaks Surveillance System (FDOSS) in Zhejiang Province from 2010 to 2022.ResultsFrom 2010 to 2022, a total of 383 outbreaks caused by Vibrio parahaemolyticus were reported by 90 CDCs in 11 prefectures of Zhejiang Province, resulting in 4,382 illnesses, 326 hospitalizations and 1 death. The main symptoms of the outbreak-related cases were diarrhea (95.18%), abdominal pain (89.23%), nausea (55.64%), vomiting (50.57%), fever (24.21%), etc. The outbreaks occurring between July and September accounted for 77.54% of all outbreaks (297 out of 383). Outbreaks associated with restaurants accounted for the majority (57.96%, 222/383) of all outbreaks, followed by those linked to staff canteens (15.40%, 59/383) and rural banquets (11.23%, 43/383). 31.85% of all outbreaks were associated with the consumption of aquatic products, while ready-to-eat foods such as Chinese cold dishes and cooked meat products accounted for 12.53% of all outbreaks. Serotype O3:K6 (81.94%, 118/144) was the predominant serotype responsible for outbreaks from 2010 to 2020, while serotype O10:K4 (57.89%, 33/57) was the predominant serotype from 2021 to 2022.ConclusionIn-depth and comprehensive analysis of long-term surveillance data on Vibrio parahaemolyticus outbreaks is essential to gain insight into the epidemiological characteristics, identify long-term patterns and recent trends, and enable governments to prioritize interventions and develop targeted policies to mitigate such outbreaks.
Collapsin response mediator protein 5-associated optic neuropathy: clinical characteristics, radiologic clues, and outcomes
Authors: Yan Rong , Mao Yu , Zeng Huiyang , Liu Qian , Jiang Hanqiu , Peng Jingting , Yang Qingling , Cui Shilei , Liu Lei , Guo Yanjun , Wang Jiawei 
Published: June 2023

ObjectiveCollapsin response mediator protein 5-associated optic neuropathy (CRMP5-ON) is a rare entity of autoimmune optic neuropathy. This study aimed to review the neuro-ophthalmic findings and outcomes in a series of patients with CRMP5-ON to further characterize its clinical phenotype, radiologic clues, and outcomes.MethodsThis was a retrospective case series and a single-center medical chart review of all patients with CRPM5-seropositive ON at the Department of Neurology, Beijing Tongren Hospital, from December 1, 2020, to March 31, 2023. The main outcome measures were neuro-ophthalmic manifestations, radiologic characteristics, and clinical outcomes of CRMP5-ON; coexisting neural autoantibody, paraneoplastic associations, and the impact of immunosuppressant therapy.ResultsFive patients were identified. Four (80%) were female, and the average age at onset was 59.4 years (range 53–69 years), with an average follow-up of 15.3 months (range 1.4–28.7 months). The average best-corrected visual acuity (BCVA) at nadir was 20/120 (range 20/20 to count fingers). Seven of ten affected eyes (70%) showed diffuse defects of the central field. Painless bilateral involvement and optic disk edema occurred in 100% of patients, combined with vitritis, uveitis, or retinitis in four (80%). Four patients (80%) had MRI abnormalities along the optic nerve (one patient with optic nerve enhancement and three patients had optic nerve sheath enhancement or peribulbar fat enhancement). Three patients (60%) had optic neuropathy with other neurologic symptoms. Four patients (80%) had confirmed cancer (two were small-cell lung carcinoma, one was papillary thyroid carcinoma and another was thymoma and invasive pulmonary adenocarcinoma). All cancers were identified after the presentation of the optic neuropathy. The intervention included IVIG, IVMP, surgery and chemotherapy. The average BCVA at the last follow-up was 20/50 (range 20/20 to count fingers). Three patients had surgery during the initial hospitalization, and were stable during the follow-up. Among two patients who received IVMP, both had improvement after treatment, although one patient had worsening non-ocular neurologic symptoms during the steroid taper.ConclusionCRMP5-ON presented with optic disc edema, often bilateral involved and combined with vitreitis, retinitis, or uveitis. CRMP5-ON can present with MRI optic nerve or perineural optic nerve enhancement, especially in the optic nerve sheath. CRMP5-ON is closely related to paraneoplastic neurologic syndrome. Cancer screening and intervention are crucial to prognosis.
The continuous performance test aids the diagnosis of post-stroke cognitive impairment in patients with right hemisphere damage
Authors: Li XiuLi , Huang FuBiao , Guo TieJun , Feng MengChen , Li Shan 
Published: June 2023

PurposeThe purpose of the study was to investigate the time course difference of relative changes in oxygenated hemoglobin (Oxy-Hb) concentration in the prefrontal cortex (PFC) between controls and patients with post-stroke cognitive impairment (PSCI) who had right hemisphere damage (RHD) using the continuous performance test (CPT) and functional near-infrared spectroscopy (fNIRS) technology. The study aimed to evaluate the feasibility of CPT in the diagnosis and evaluation of PSCI with RHD.MethodsA total of 16 patients with RHD (RHD group) and 32 normal subjects (control group) were recruited. The Montreal Cognitive Assessment Scale was used to assess post-stroke cognitive impairment. The CPT and fNIRS were employed to investigate task-related changes in Oxy-Hb levels.ResultsThe RHD group showed significantly lower accuracy and hit rates than the control group; however, the average reaction time was significantly longer in the former. Although the two groups showed no statistically significant difference in terms of left and right PFC integral values, the mean values were greater in the RHD group. The centroid value of the right PFC was significantly higher in the RHD group than in the control group. The time course of Oxy-Hb concentrations in the PFC differed between the two groups. In the RHD group, neural compensation was observed in both prefrontal lobes; however, the rate of compensation was slower on the affected side.ConclusionThe CPT may be helpful in the clinical diagnosis of PSCI with RHD. It may therefore be used to evaluate the effectiveness of cognitive interventions.