bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance
Authors: Krieg Laura , Didt Konrad , Karkossa Isabel , Bernhart Stephan H , Kehr Stephanie , Subramanian Narmadha , Lindhorst Andreas , Schaudinn Alexander , Tabei Shirin , Keller Maria , Stumvoll Michael , Dietrich Arne , von Bergen Martin , Stadler Peter F , Laurencikiene Jurga , Krüger Martin , Blüher Matthias , Gericke Martin , Schubert Kristin , Kovacs Peter , Chakaroun Rima , Massier Lucas 
Published: October 2021

ObjectiveHuman white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism.DesignMesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR.ResultsWhile mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels.ConclusionMulti-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.
Activation of GM-CSF and TLR2 signaling synergistically enhances antigen-specific antitumor immunity and modulates the tumor microenvironment
Authors: Yan Wan-Lun , Wu Chiao-Chieh , Shen Kuan-Yin , Liu Shih-Jen 
Published: October 2021

BackgroundThe major challenge of antitumor immunotherapy is dealing with the immunosuppressive tumor microenvironment, which involves immature myeloid cell accumulation that results in T cell dysfunction. Myeloid cell activation is induced by Toll-like receptor agonists. Additionally, granulocyte/macrophage colony stimulating factor (GM-CSF) promotes myelopoiesis and recruits myeloid cells. Here, we combined the Toll-like receptor 2 (TLR2) agonist lipoprotein and GM-CSF to assess whether this bifunctional immunotherapy has synergistic effects on myeloid cells and could be further developed as a therapeutic intervention that enhances the antitumor response.MethodsWe investigated the synergistic effects of biadjuvanted tumor antigen on antigen-presenting cell (APC) activation in bone marrow-derived dendritic cells. Furthermore, therapeutic efficacy was monitored in different tumor models treated via intratumoral or subcutaneous administration routes. The immune effects of the bifunctional fusion protein on myeloid cells in the tumor mass and draining lymph nodes were analyzed by flow cytometry. The induction of cytotoxic T lymphocytes was evaluated via intracellular cytokine levels, perforin/granzyme B staining and an in vivo killing assay.ResultsThe TLR2 agonist lipoprotein combined with GM-CSF synergistically induced DC maturation, which subsequently enhanced antitumor immunity. In addition, rlipoE7m-MoGM modulated tumor-infiltrating myeloid cell populations. Vaccination with rlipoE7m-MoGM therapy increased the number of CCR7+CD103+ cDC1s, whereas the number of suppressive tumor-associated macrophages was reduced in the tumor lesions. Consistent with this observation, proliferating antigen-specific CD8+ T cells are highly infiltrated within the tumor, and the expression of IFN-r and perforin was most pronounced within antigen-specific CD8+ T cells in mice administered rlipoE7m-MoGM therapy. This finding corresponded with observation that the combination of a TLR2 agonist and GM-CSF provides increased antitumor activity by inhibiting established tumor outgrowth and protecting against metastatic cancer compared with a TLR2 agonist alone. Importantly, tumor growth inhibition was not due to the direct effects of the TLR2 agonist or GM-CSF but was instead due to the induction of antigen-specific immunity.ConclusionsThe combination of a TLR2 agonist and GM-CSF has synergistic effects that inhibit tumor growth and modulate tumor-infiltrating APCs. This therapeutic approach could be applied to other tumor antigens to treat different cancers.
Eliciting an immune-mediated antitumor response through oncolytic herpes simplex virus-based shared antigen expression in tumors resistant to viroimmunotherapy
Authors: Ghonime Mohammed G , Saini Uksha , Kelly Michael C , Roth Justin C , Wang Pin-Yi , Chen Chun-Yu , Miller Katherine , Hernandez-Aguirre Ilse , Kim Yeaseul , Mo Xiaokui , Stanek Joseph R , Cripe Tim , Mardis Elaine , Cassady Kevin A 
Published: October 2021

BackgroundOncolytic virotherapy (OV) is an immunotherapy that incorporates viral cancer cell lysis with engagement of the recruited immune response against cancer cells. Pediatric solid tumors are challenging targets because they contain both an inert immune environment and a quiet antigenic landscape, making them more resistant to conventional OV approaches. Further complicating this, herpes simplex virus suppresses host gene expression during virotherapy infection.MethodsWe therefore developed a multimodal oncolytic herpes simplex virus (oHSV) that expresses ephrin A2 (EphA2), a shared tumor-associated antigen (TAA) expressed by many tumors to improve immune-mediated antitumor activity. We verified the virus genotypically and phenotypically and then tested it in an oHSV-resistant orthotopic model (including immunophenotypic analysis), in flank and in T cell-deficient mouse models. We then assessed the antigen-expressing virus in an unrelated peripheral tumor model that also expresses the shared tumor antigen and evaluated functional T-cell response from the treated mice.ResultsVirus-based EphA2 expression induces a robust acquired antitumor immune responses in both an oHSV-resistant murine brain and peripheral tumor model. Our new multimodal oncolytic virus (1) improves survival in viroimmunotherapy resistant tumors, (2) alters both the infiltrating and peripheral T-cell populations capable of suppressing tumor growth on rechallenge, and (3) produces EphA2-specific CD8 effector-like populations.ConclusionsOur results suggest that this flexible viral-based platform enables immune recognition of the shared TAA and improves the immune-therapeutic response, thus making it well suited for low-mutational load tumors.
Indication-specific tumor evolution and its impact on neoantigen targeting and biomarkers for individualized cancer immunotherapies
Authors: Lo Amy A , Wallace Andrew , Oreper Daniel , Lounsbury Nicolas , Havnar Charles , Pechuan-Jorge Ximo , Wu Thomas D , Bourgon Richard , Jones Ryan , Krogh Katrina , Yang Guang-Yu , Zill Oliver A 
Published: October 2021

BackgroundIndividualized neoantigen-specific immunotherapy (iNeST) requires robustly expressed clonal neoantigens for efficacy, but tumor mutational heterogeneity, loss of neoantigen expression, and variable tissue sampling present challenges. It is assumed that clonal neoantigens are preferred targets for immunotherapy, but the distributions of clonal neoantigens are not well characterized across cancer types.MethodsWe combined multiregion sequencing (MR-seq) analysis of five untreated, synchronously sampled metastatic solid tumors with re-analysis of published MR-seq data from 103 patients in order to characterize their globally clonal neoantigen content and factors that would impact neoantigen targeting.ResultsBranching evolution in colorectal cancer and renal cell carcinoma led to fewer clonal neoantigens and to clade-specific neoantigens (those shared across a subset of tumor regions but not fully clonal), with the latter not being readily distinguishable in single tumor samples. In colorectal, renal, and bladder cancer, most tumors had few globally clonal neoantigens. Prioritizing mutations with higher purity-adjusted and ploidy-adjusted variant allele frequency enriched for globally clonal neoantigens (those found in all tumor regions), whereas estimated cancer cell fraction derived from clustering-based tools, surprisingly, did not. Neoantigen quality was associated with loss of neoantigen expression in the bladder cancer case, and HLA-allele loss was observed in the renal and non-small cell lung cancer cases.ConclusionsWe show that tumor type, multilesion sampling, neoantigen expression, and HLA allele retention are important factors for iNeST targeting and patient selection, and may also be important factors to consider in the development of biomarker strategies.
Improving the Selection of Candidates for Royal Marine Recruit Training by the use of a Combination of Performance Tests
Authors: Allsopp A. J. , Shariff A. 
Published: October 2021

AbstractCandidates who wish to undertake Royal Marine recruit training, a physically strenuous course which now extends 32 weeks, must first of all successfully complete a Personal Qualities Assessment (PQA) and four psychomotor tests (Naval Recruiting Tests or RTs) before attending a three-day selection course at the Commando Training Centre, Lympstone, where their Physical capabilities are tested to the full. The effectiveness of theses procedures was untested until the Institute of Naval Medicine conducted a retrospective study during 1999-2000 from which the present study is taken.Data from 1232 recruits were examined to explore the relationship between the outcome of Commando training (pass or fail) with these various selection measures. Estimated aerobic power, time to complete the assault course and age were associated with outcome, as were PQA, RTs 1, 3, 4 and total RT score. A regression equation comprising aerobic fitness, assault course time, RT4 and age gave the best overall prediction of outcome (64%). It is suggested that this mathematical approach provides a scientifically valid and objective assessment tool for future selection strategies.
The Pathophysiology of Exertional Heatstroke
Authors: Smith J. E. 
Published: October 2021

AbstractExertional heat illness remains a major cause of morbidity and occasional mortality within the Armed Forces. This review explores the normal responses to heat, known causes of exertional heatstroke, and suggests possible answers to the question of why one member of a military unit collapses with heat stroke, while matched controls at his side remain unaffected.
An Observational Study on Diagnoses of 3,233 Gulf Veterans (Op Granby 1990-91) who attended the Ministry of Defence’s Medical Assessment Programme 1993-2004
Authors: Bale A. J. , Lee H. A. 
Published: October 2021

SummaryBackgroundThis is the result of an observational study on 3,233 Gulf veterans who have attended our medical assessment programme. We wanted to determine as a result of in-depth interviews, full medical examination and appropriate investigations, whether there was any unique Gulf war related medical condition.MethodsOver a period of 10 years, 3,233 veterans have been assessed. All diagnoses have been made according to ICD-10 classifications. All psychiatric diagnoses have been confirmed by consultant psychiatrists.Findings75% of veterans were well. Of the 25% unwell, 83% of ill health was accounted for by a psychiatric disorder. 3% of veterans had organic conditions which could be linked to Gulf deployment. The most common of these were respiratory disorders, followed by digestive disorders, injuries and skin disorders. Only 11 of these cases could be linked to the use of medical countermeasures. A further, 51 cases (41 respiratory disorders, 6 infections, 2 skin disorders and 2 eye conditions) could be linked to environmental conditions.InterpretationAll veterans seen with health problems could be identified as per ICD-10 classification of disease. We did not find any medically unexplained conditions. We found no evidence of a unique ‘Gulf War Syndrome’.
Postoperative Vigilance in Patients with Total Intravenous Anaesthesia with Ketamine/Propofol
Authors: Felfernig Michael , Andel Dorothea , Weintraud Marion , Connor Daniel , Andel Harald , Blaicher Alex M. 
Published: October 2021

AbstractKetamine is a strong acting analgesic drug, used mainly in trauma and emergency medicine settings, as well as for minor procedures. Its pharmacological properties make it a useful drug for military anaesthesia. Ketamine acts by blocking activation of the spinal and supraspinal NMDA-type glutamate and opioid receptors. It produces dissociative anaesthesia, which means that patients might remain conscious, though insensitive to pain and amnesic (anterograde), Dysphoria and hallucinations are the main side effects in the early recovery period. We studied the incidence of post operative nausea and vomiting, vigilance disturbances and haemodynamic instability during combined ketamine and propofol anaesthesia.No patient suffered from postoperative nausea and vomiting. No haemodynamic instabilily could be observed in any of the patients. Tie interesting point is that though there were no unpleasant emergence phenomenons, no patient reached the preoperative state of vigilance within two hours after extubation.These results indicate that for plastic/dermatological surgical procedures, patients undergoing ketamine/propofol anaesthesia do not require excessive haemodynamic monitoring, but do need prolonged personal observation in the spostoperative period.
Unexplained early neurological deterioration after endovascular treatment for acute large vessel occlusion: incidence, predictors, and clinical impact: Data from ANGEL-ACT registry
Authors: Sun Dapeng , Tong Xu , Huo Xiaochuan , Jia Baixue , Raynald  , Wang Anxin , Ma Gaoting , Ma Ning , Gao Feng , Mo Dapeng , Song Ligang , Sun Xuan , Liu Lian , Deng Yiming , Li Xiaoqing , Wang Bo , Luo Gang , Wang Yongjun , Miao Zhongrong 
Published: September 2021

BackgroundEarly neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplainedafter EVT in patients with acute LVO.MethodsSubjects were selected from the ANGEL-ACT registry. ENDunexplainedwas defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplainedand 90-day outcomes assessed by modified Rankin Scale (mRS) score.ResultsAmong the 1557 enrolled patients, the incidence of ENDunexplainedwas 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p<0.001), general anesthesia (OR=3.15, 95% CI 1.81 to 5.48, p<0.001), admission neutrophil to lymphocyte ratio >5 (OR=2.82, 95% CI 1.61 to 4.94, p<0.001), and number of EVT attempts >3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplainedwere associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, p<0.001).ConclusionsENDunexplainedassociated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplainedwere identified in this study, which should be considered in daily practice to improve acute LVO management.Clinical trial Registrationhttp://wwwclinicaltrialsgovNCT03370939.
A quantum strategy to compute the jet quenching parameter $$\hat{q}$$
Authors: Barata João , Salgado Carlos A. 
Published: October 2021

AbstractJet quenching, the modification of the properties of a QCD jet when the parton cascade takes place inside a medium, is an intrinsically quantum process, where color coherence effects play an essential role. Despite a very significant progress in the last years, the simulation of a full quantum medium induced cascade remains inaccessible to classical Monte Carlo parton showers. In this situation, alternative formulations are worth being tried and the fast developments in quantum computing provide a very promising direction. The goal of this paper is to introduce a strategy to quantum simulate single particle momentum broadening, the simplest building block of jet quenching. Momentum broadening is the modification of the quark or gluon transverse momentum due interactions with the underlying medium, modeled as a QCD background field. At the lowest order in $$\alpha _s$$

α
s

that we consider here, momentum broadening does not involve parton splittings and particle number is conserved, greatly simplifying the quantum algorithmic implementation. This quantity is, however, very relevant for the phenomenology of RHIC, LHC or the future EIC.
Structural and geochemical ore-forming processes in deformed gold deposits: towards a multiscale and multimethod approach
Authors: Perret Julien , André-Mayer Anne-Sylvie , Eglinger Aurélien , Feneyrol Julien , Voinot Alexandre , Morlot Christophe , Barou Fabrice , Teitler Yoram , Seira Diego , Bosc Rémi 
Published: October 2021

Abstract
Integrating structural control on mineralization and geochemical ore-forming processes is crucial when studying deformed ore deposits. Yet structural and geochemical data are rarely acquired at the same scale: structural control on mineralization is typically investigated from the district to the deposit and macroscopic scales whereas geochemical ore processes are described at the microscopic scale. The deciphering of a deformation–mineralization history valid at every scale thus remains challenging. This study proposes a multiscale approach that enables the reconciliation of structural and geochemical information collected at every scale, applied to the example of the Galat Sufar South gold deposit, Nubian shield, NE Sudan. It gathers field and laboratory information by coupling a classical petrological–structural study with high-resolution X-ray computed tomography, electron back-scattered diffraction and laser ablation inductively coupled plasma mass spectrometry on mineralized sulfide mineral assemblages. This approach demonstrates that there is a linear control on mineralization expressed from the district to microscopic scales at the Galat Sufar South gold deposit. We highlight the relationships between Atmur–Delgo suturing tectonics, microdeformation of sulfide minerals, syn-pyrite recrystallization metal remobilization, gold liberation and ore upgrading. Our contribution therefore represents another step forward in a holistic field-to-laboratory approach for the study of any other sulfide-bearing, structurally controlled ore deposit type.
Magnetic Resonance Imaging Features under Deep Learning Algorithms in Evaluated Cerebral Protection of Craniotomy Evacuation of Hematoma under Propofol Anesthesia
Authors: Xin Deqian , An Zhongzhe , Ding Juan , Li Zhi , Qiao Leyan 
Published: October 2021

This study aimed to explore the value of magnetic resonance imaging (MRI) features based on deep learning super-resolution algorithms in evaluating the value of propofol anesthesia for brain protection of patients undergoing craniotomy evacuation of the hematoma. An optimized super-resolution algorithm was obtained through the multiscale network reconstruction model based on the traditional algorithm. A total of 100 patients undergoing craniotomy evacuation of hematoma were recruited and rolled into sevoflurane control group and propofol experimental group. Both were evaluated using diffusion tensor imaging (DTI) images based on deep learning super-resolution algorithms. The results showed that the fractional anisotropic image (FA) value of the hind limb corticospinal tract of the affected side of the internal capsule of the experimental group after the operation was 0.67 ± 0.28. The National Institute of Health Stroke Scale (NIHSS) score was 6.14 ± 3.29. The oxygen saturation in jugular venous (SjvO2) at T4 and T5 was 61.93 ± 6.58% and 59.38 ± 6.2%, respectively, and cerebral oxygen uptake rate (CO2ER) was 31.12 ± 6.07% and 35.83 ± 7.91%, respectively. The difference in jugular venous oxygen (Da-jvO2) at T3, T4, and T5 was 63.28 ± 10.15 mL/dL, 64.89 ± 13.11 mL/dL, and 66.03 ± 11.78 mL/dL, respectively. The neuron-specific enolase (NSE) and central-nerve-specific protein (S100β) levels at T5 were 53.85 ± 12.31 ng/mL and 7.49 ± 3.16 ng/mL, respectively. In terms of the number of postoperative complications, the patients in the experimental group were better than the control group under sevoflurane anesthesia, and the differences were substantial (

P

< 0.05). In conclusion, MRI images based on deep learning super-resolution algorithm have great clinical value in evaluating the degree of brain injury in patients anesthetized with propofol and the protective effect of propofol on brain nerves.