bluuebunny/crossref_metadata_2025_split huggingface dataset:
100 k.y. pacing of the East Asian summer monsoon over the past five glacial cycles inferred from land snails
Authors: Bao Rui , Sheng Xuefen , Meng Xianqiang , Li Tao , Li Chenglong , Shen Hua , Da Jiawei , Ji Junfeng , Chen Jun 
Published: December 2022

Abstract
The effects of orbital forcing on the East Asian summer monsoon (EASM) after the mid-Pleistocene transition are controversial. Chinese cave δ18O records only show low-latitude ∼20 k.y. cycles, while pedogenic proxy records from Chinese loess are dominated by highlatitude 100 k.y. cycles. This discrepancy may result from the multicomponent origin of proxies, particularly for pedogenic signals in loess deposits, where the primary climatic signals are modified by pedogenic smoothing, leaching, and changes in sedimentation rate, and the latter are also being forced by 100 k.y. cycles. We present an EASM record spanning the past 470 k.y. from the central Chinese Loess Plateau based on the δ13C values of land snail shells (δ13Cshell), which eliminates the influence of the above processes and exclusively records the local past EASM precipitation. The δ13Cshell record is dominated by the 100 k.y. cycle, with more depleted values during interglacials compared to glacials. At the end of marine isotope stage (MIS) 11, δ13Cshell-based precipitation remained at an interglacial level following the MIS 11 super-interglacial climate in the Northern Hemisphere, although a glacial period had commenced on a global basis. Overall, our δ13Cshell record is highly coupled with high-northern-latitude ice-volume variations, possibly supporting the high-latitude forcing of the EASM.
Subsurface heat and salts cause exceptionally limited methane hydrate stability in the Mediterranean Basin
Authors: Camerlenghi A. , Corradin C. , Tinivella U. , Giustiniani M. , Bertoni C. 
Published: December 2022

Abstract
Knowledge of the global reservoir of submarine gas hydrates is of great relevance for understanding global climate dynamics, submarine geohazards, and unconventional hydrocarbon energy resources. Despite the expected presence of gas hydrates from modeling studies, the land-locked Mediterranean Basin displays a lack of evidence of extensive gas hydrate presence from samples and seismic data. We modeled the theoretical Mediterranean distribution of methane hydrate below the seafloor and in the water column using available geological information provided by 44 Deep Sea Drilling Project (DSDP) and Ocean Drilling Program (ODP) boreholes, measured geothermal gradients, and thermohaline characteristics of the water masses. We find that the pervasive presence of high-salinity waters in sediments, coupled with the unique warm and salty water column, limit the thickness of the theoretical methane hydrate stability zone in the subsurface and deepen its top surface to 1163–1391 m water depth. The theoretical distribution of methane hydrates coincides well with the distribution of shallow, low-permeability Messinian salt deposits, further limiting the formation of pervasive gas hydrate fronts and controlling their or distribution due to the prevention of upward hydrocarbon gas migration. We conclude that the Mediterranean Basin, hosting the youngest salt giant on Earth, is not prone to the widespread formation and preservation of gas hydrates in the subsurface and that the gas hydrate potential of salt-bearing rifted continental margins may be considerably decreased by the presence of subsurface brines.
Higher fasting glucose, triglycerides, resting pulse rate and high-sensitivity C reactive protein in adipose insulin-resistant but normal weight young Japanese women
Authors: Minato-Inokawa Satomi , Honda Mari , Tsuboi-Kaji Ayaka , Takeuchi Mika , Kitaoka Kaori , Takenouchi Akiko , Kurata Miki , Wu Bin , Kazumi Tsutomu , Fukuo Keisuke 
Published: December 2022

IntroductionAdipose insulin-resistant but normal weight phenotype has not been reported and hence was characterized in young Japanese women.Research design and methodsBody composition, a broad range of cardiometabolic health and dietary intake were cross-sectionally measured in 166 normal weight young Japanese women. They were grouped into tertile of adipose tissue-insulin resistance (AT-IR) index (fasting insulin×free fatty acids) and analyzed by analysis of variance and then Bonferroni’s multiple comparison procedure.ResultsBody mass index averaged <21 kg/m2and waist <72 cm, and did not differ among three groups of women. Fasting glucose and triglycerides and homeostasis model assessment-insulin resistance were higher in the highest compared with the median and lowest AT-IR tertile. However, there was no difference in fat mass and distribution, high-density lipoprotein cholesterol and blood pressure. In addition, high-sensitivity C reactive protein (hsCRP) and resting pulse rate were higher as well. In multivariate logistic regression analyses, fasting glucose (OR: 1.10, 95% CI: 1.02 to 1.18, p=0.012), fasting triglycerides (OR: 1.04, 95% CI: 1.02 to 1.06, p<0.001), resting pulse rate (OR: 1.07, 95% CI: 1.03 to 1.11, p<0.001) and hsCRP (OR: 2.30, 95% CI: 1.01 to 5.2, p=0.04) were associated with the high AT-IR tertile.ConclusionsAdipose insulin-resistant but normal weight phenotype may be associated with increased sympathetic nervous system and low-grade systemic inflammation in addition to glucose and lipid dysmetabolism through mechanisms unrelated to adiposity in young Japanese women.
Effects of metabolic traits, lifestyle factors, and pharmacological interventions on liver fat: mendelian randomisation study
Authors: Yuan Shuai , Chen Jie , Vujkovic Marijana , Chang Kyong-Mi , Li Xue , Larsson Susanna C , Gill Dipender 
Published: December 2022

ObjectiveTo investigate the effects of metabolic traits, lifestyle factors, and drug interventions on liver fat using the mendelian randomisation paradigm.DesignMendelian randomisation study.SettingPublicly available summary level data from genome-wide association studies.ParticipantsGenome-wide association studies of 32 974 to 1 407 282 individuals who were predominantly of European descent.ExposuresGenetic variants predicting nine metabolic traits, six lifestyle factors, four lipid lowering drug targets, three antihypertensive drug targets, and genetic association estimates formagnetic resonance imaging measured liver fat.Main outcome measuresMendelian randomisation analysis was used to investigate the effects of these exposures on liver fat, incorporating sensitivity analyses that relaxed the requisite modelling assumptions.ResultsGenetically predicted liability to obesity, type 2 diabetes, elevated blood pressure, elevated triglyceride levels, cigarette smoking, and sedentary time watching television were associated with higher levels of liver fat. Genetically predicted lipid lowering drug effects were not associated with liver fat; however, β blocker and calcium channel blocker antihypertensive drug effects were associated with lower levels of liver fat.ConclusionThese analyses provide evidence of a causal effect of various metabolic traits, lifestyle factors, and drug targets on liver fat. The findings complement existing epidemiological associations, further provide mechanistic insight, and potentially supports a role for drug interventions in reducing the burden of hepatic steatosis and related disease. Further clinical study is now warranted to investigate the relevance of these genetic analyses for patient care.
Macrophage GSK3β-deficiency inhibits the progression of hepatocellular carcinoma and enhances the sensitivity of anti-PD1 immunotherapy
Authors: Sun Guangshun , Liu Hanyuan , Zhao Jie , Zhang Jinyu , Huang Tian , Sun Guoqiang , Zhao Siqi , Zhang Zihao , Cao Hengsong , Rong Dawei , Kong Xiangyi , Ji Qinghua , Liu Li , Wang Xuehao , Tang Weiwei , Xia Yongxiang 
Published: December 2022

BackgroundGlycogen synthase kinase 3β (GSK3β) was originally discovered to regulate glycogen synthesis and show a relationship to tumors. However, the biological functions of GSK3β in tumor-associated macrophages (TAMs) in cancers including hepatocellular carcinoma (HCC) remain unclear.MethodsThe enrichment of GSK3β in tumor tissues was assessed by Gene Expression Omnibus (GEO) database. The in vitro and in vivo assays assisted in evaluating how GSK3β in TAMs affected HCC in terms of proliferation, invasion and migration. Immunofluorescence was used to assess GSK3β expression in TAMs in the anti-PD1 therapy non-responsive HCC group and the responsive group. Western blot and coimmunoprecipitation were performed to demonstrate the interaction between GSK3β and PD-L1. We carried out in vivo experiments in a C57BL/6 mouse model of HCC established through subcutaneous injection.ResultsGEO single-cell RNA sequencing data suggested that GSK3β was highly enriched in TAMs of HCC. According to in vitro and in vivo experiments, reducing GSK3β in TAMs inhibits the cancer cell proliferation, invasion, and migration. The immunofluorescence and immunohistochemistry results confirmed that the GSK3β is significantly upregulated in TAMs of the anti-PD1 therapy non-responsive group in comparison with the responsive group. In vitro and in vivo experiments confirmed that reduced GSK3β in TAMs are capable of enhancing the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. Mass spectrometry results suggested that high expression of CD14+GSK3β+in the peripheral blood mononuclear cell (PBMC) can predict non-responsive to anti-PD1 treatment. Moreover, escitalopram is confirmed to act as GSK3β inhibitor that can increase the sensitivity of anti-PD1 immunotherapy for HCC.ConclusionsThis study revealed that macrophage GSK3β deficiency can inhibit the development of HCC by inhibiting the M2 phenotype and enhance the sensitivity of anti-PD1 immunotherapy for HCC by decreasing PD-L1 ubiquitination. The expression of CD14+GSK3β+in PBMC can noninvasively predict anti-PD1 sensitivity in HCC patients, which provides novel strategies to predict anti-PD1 sensitivity, increase anti-PD1 therapeutic effect, and bring new hope for HCC patients.
Systemic cellular viroimmunotherapy for canine high-grade gliomas
Authors: Cloquell Ana , Mateo Isidro , Gambera Stefano , Pumarola Martí , Alemany Ramon , García-Castro Javier , Perisé-Barrios Ana Judith 
Published: December 2022

BackgroundOncolytic viruses constitute a growing field of interest, both in human and veterinary oncology, given that they are particularly helpful for treating non-surgical tumors and disseminated cancer, such as high-grade gliomas. Companion dogs present malignant gliomas with biological, genetic, phenotypic, immunological, and clinical similarities to human gliomas. These features favor comparative approaches, leading to the treatment of canine oncological patients to achieve translational applications to the human clinic. The systemic administration of oncolytic viruses presents a challenge due to their limitations in effectively targeting tumors and metastases. Therefore, the aim of this study is to evaluate the safety and antitumor activity of a virotherapy used in spontaneous canine tumors.MethodsTen dogs with high-grade rostrotentorial gliomas underwent weekly systemic endovenous cellular virotherapy with dCelyvir (canine mesenchymal stem cells infected with the canine oncolytic adenovirus ICOCAV17) for 8 weeks. Efficacy was determined in seven dogs according to the Response Assessment in Veterinary Neuro-Oncology criteria considering clinical status and MRI measurements. Medical history, physical and neurological examinations, and vaccination status were evaluated prior to and during follow-up. Safety was evaluated by physical examinations and hematological and biochemical changes in peripheral blood. Immune populations were analyzed by flow cytometry in peripheral blood and by gene expression and immunohistochemistry in the tumor microenvironment.ResultsThe treatment was well tolerated and major adverse effects were not observed. Two dogs had partial responses (76% and 86% reduction in tumor size), and 3/7 showed stable disease. ICOCAV17 was detected in peripheral blood in nine dogs, and a correlation between the ICOCAV17 particles and anti-canine adenovirus (CAV) antibodies was observed. ICOCAV17 was detected in 3/9 tumor tissues after necropsies. Regarding tumor-infiltrating lymphocytes, the dogs with disease stabilization and partial response tended to have reduced memory B-cell infiltration and increased monocyte/macrophage lineage cells.ConclusionsThese findings indicate that dCelyvir is safe and presents efficacy in canine rostrotentorial high-grade gliomas. These data are relevant to the ongoing phase Ib regulated human clinical trial that is administering this virotherapy to children, adolescents, and young adults with diffuse pontine glioma. Celyvir should be further explored as a treatment in veterinary and human neuro-oncology.
Shortcuts to Edge-of-Chaos Domains of Memristive Circuits and Historic Measurement of Contiguous Triple-Branch V – I Curve of Chua Corsage Memristor
Authors: Jin Peipei , Liang Yan , Wang Guangyi , Chen Long , Iu Herbert Ho-Ching , Chua Leon O. 
Published: December 2022

Locally-active memristors blessed with an edge-of-chaos domain, which can be destabilized for generating action potentials, are natural candidates for emulating biological neurons. Pinpointing the edge-of-chaos domain, where neuromorphic behaviors may occur, is important for studying neuromorphic dynamics of memristors. This paper proposes a short-cut method for locating the edge-of-chaos domains in two kinds of generic memristors, and in several typical memristive 1-port circuits using only the Jacobian matrix in terms of their equations. Taking the Chua Corsage Memristor (CCM) and several CCM-based memristive 1-port circuits as examples, we verify the proposed new methods, and calculates their edge-of-chaos domains. Also, we carry out a complete classification of all the parameter regions of the CCM and several CCM-based memristive 1-port circuits, namely the locally-passive, locally-active but unstable, and edge-of-chaos domains, under both voltage and frequency control. Near the calculated edge-of-chaos domain, we uncover some new neuromorphic behaviors. To confirm the physical interpretations and predictions of the edge-of-chaos theorem, this paper presents an inexpensive electronic circuit realization of the complete set of equations defining the CCM using only off-the-shelf circuit components. When this poor-man’s memristor is connected to various linear passive R, L, C circuits, and a battery, the resulting circuit can be tuned to generate action potentials, and a garden variety of neuromorphic phenomena, including chaos. But the highlight of this paper is reserved for the CCM itself where the world’s first oscilloscope picture of a contiguous self-intersecting triple-branch DC V–I curve of the CCM is displayed in real time.
Hespanha e uma crítica do liberalismo português
Authors: Wehling Arno 
Published: December 2022

A proposta deste estudo, que se constitui antes de mais numa homenagem ao grande historiador que foi António Manuel Hespanha, é a de situar algumas de suas contribuições para o conhecimento do liberalismo em Portugal. A análise dessas contribuições permite não apenas levantar questões nessa temática, como estendê-las à problemática geral do liberalismo e a aspectos do próprio conhecimento histórico.
Early Outcomes of Heart Transplantation Using Donation After Circulatory Death Donors in the United States
Authors: Kwon Jennie H. , Ghannam Alexander D. , Shorbaji Khaled , Welch Brett , Hashmi Z.A. , Tedford Ryan J. , Kilic Arman 
Published: December 2022

Background:
Limited donor availability and evolution in procurement techniques have renewed interest in heart transplantation (HT) with donation after circulatory death (DCD). The aim of this study is to evaluate outcomes of HT using DCD in the United States.

Methods:
The United Network for Organ Sharing registry was used to identify adult HT recipients from 2019 to 2021. Recipients were stratified between DCD and donation after brain death. Propensity-score matching was performed. Cox proportional hazards was used to identify independent predictors of 1-year mortality. Kaplan-Meier analysis was used to estimate 1-year survival.

Results:

Of 7496 HTs, 229 DCD and 7267 donation after brain death recipients were analyzed. The frequency of DCD HT increased from 0.2% of all HT in 2019 to 6.4% in 2021 (
P
<0.001), and the number of centers performing DCD HT increased from 3 of 120 centers to 20 of 121 centers (
P
<0.001). DCD donors were more likely to be younger, male, and White. After propensity matching, 1-year survival was 92.5% for DCD versus 90.3% for donation after brain death (hazard ratio, 0.80 [95% CI, 0.44–1.43];
P
=0.44). Among DCD HTs, increasing recipient age and waitlist time predicted 1-year mortality on univariable analysis.

Conclusions:
Rates of DCD HT in the United States are increasing. This practice appears safe and feasible as mortality outcomes are comparable to donation after brain death. Although this study represents early adopting centers, outcomes of the experience for DCD HT in the United States is consistent with existing international data and encourages broader utilization of this practice.
Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis
Authors: Sarangi Surjyapratap , Nahak Suraj K , Padhi Sunali , Pradhan Bidyutprabha , Nayak Nisha , Pati Abhijit , Panda Aditya K 
Published: December 2022

Background The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. Materials and methods Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. Results Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). Conclusions IFN-γ +874 T>A variant is associated with predisposition to SLE development.
The need of rebubbling in case of small graft detachments after Descemet Membrane Endothelial Keratoplasty (DMEK)
Authors: Kramer Nane , Unterlauft Jan Darius , Girbardt Christian 
Published: December 2022

Purpose To investigate the need of rebubbling for small graft detachments after Descemet Membrane Endothelial Keratoplasty (DMEK). Methods In this retrospective study we evaluated 111 eyes from 111 patients that showed graft detachment after DMEK surgery and have achieved graft adherence by injection of air or 20% sulfur hexafluoride (SF6) to the anterior chamber (rebubbling group; n = 57) or by spontaneous adherence without intervention (control group; n = 54) at final examination. Subgroups in terms of the maximum height and in terms of the detachment area in relation to graft area were formed. Outcome measures were the increase in best-corrected visual acuity (BCVA) and the decrease in central corneal thickness (CCT) from the measurement before DMEK to six months after surgery and postoperative endothelial cell density. Results BCVA increased in the rebubbling group and the control group, the difference being 0.22 logMAR, p = 0.048. For eyes with a maximum height less than 500  µm, the increase of BCVA was 0.39 ± 0,36 logMAR in the control group and 0.62 ± 0,53 logMAR in the rebubbling group, p = 0.045. There was no difference of statistical significance of BCVA between both groups regarding the detachment area of less than 20% in relation to graft area. The mean decrease in CCT and postoperative endothelial cell density showed no significant difference between the rebubbling group and the control group. Conclusion Compared to spontaneous graft adherence, a rebubbling shows no beneficial effect on the clinical outcome for small detached DMEK grafts. Rebubbling does not decrease postoperative endothelial cell density.
Analgesic effect of epidural anesthesia via the intervertebral foramen approach in percutaneous transforaminal endoscopic discectomy: a retrospective study
Authors: Zhang Jingyue , Wang Xueyao , Cai Zhenhua , Kang Jiyu , Liu Yongliang , Nie Chunyan , Zhou Huacheng 
Published: December 2022

AbstractBackgroundSatisfactory intraoperative analgesia is critical for percutaneous transforaminal endoscopic discectomy (PTED). Local anesthesia (LA) and epidural anesthesia (EA) are recommended for PTED. LA alone does not achieve satisfactory pain management during PTED and other analgesics or sedatives are usually needed. Traditional EA, which involves implanting an epidural catheter through the midline or paramedian, has disadvantages such as difficulty in catheterization and increased preoperative preparation time. Rather than performing conventional EA, we injected local anesthetics through the intervertebral foramen during the puncture process, which we termed lumbar transforaminal EA (LTEA), and observed its feasibility and safety. This study aimed to conduct a comprehensive comparison of differences in analgesia between LA and LTEA in patients with PTED.MethodsWe performed a retrospective analysis of patients who underwent PTED between January 2018 and January 2021. Patients were divided into LA and LTEA groups. Data obtained from the electronic medical records included primary outcomes (visual analog scale [VAS] scores and anesthesia satisfaction rate) and secondary outcomes, including vital signs such as heart rate (HR), mean arterial pressure (MAP), total dosage of fentanyl, operation time, X-ray exposure time, Oswestry Disability Index (ODI) scores, and complications.ResultsIn total, 160 patients (80 in each group) were analyzed in this study. The VAS scores for lumbar and leg pain were significantly lower in the LTEA group than in the LA group (P < 0.0001). The anesthesia satisfaction rate was 90.0% in the LTEA group and 72.5% in the LA group (P < 0.005). MAP and HR values in the LTEA group were significantly lower than those in the LA group (P < 0.05). The total dose of fentanyl in the LTEA group was significantly lower than that in the LA group (P < 0.05). As for ODI values, the average operation time, X-ray exposure time, and incidence of complications were not significantly different between the two groups (P > 0.05).ConclusionsLTEA simplifies the process of EA and can achieve a good analgesic effect intraoperatively without increasing the preoperative preparation time; thus, it may be adopted as an alternative mode of anesthesia during PTED surgery.