bluuebunny/crossref_metadata_2025_split huggingface dataset:
FAT-GEMs: (field assisted) transparent gaseous-electroluminescence multipliers
Authors: Leardini S. , Saá-Hernández A. , Kuźniak M. , González-Díaz D. , Azevedo C. D. R. , Lucas F. , Amedo P. , Cortez A. F. V. , Fernández-Posada D. , Mehl B. , Nieradka G. , de Oliveira R. , Peskov V. , Sworobowicz T. , Williams S. 
Published: April 2024

The idea of implementing electroluminescence-based amplification through transparent multi-hole structures (FAT-GEMs) has been entertained for some time. Arguably, for such a technology to be attractive it should perform at least at a level comparable to conventional alternatives based on wires or meshes. We present now a detailed calorimetric study carried out for 5.9 keV X-rays in xenon, for pressures ranging from 2 to 10 bar, resorting to different geometries, production and post-processing techniques. At a reference voltage 5 times above the electroluminescence threshold (EEL,th ∼ 0.7 kV/cm/bar), the number of photoelectrons measured for the best structure was found to be just 18% below that obtained for a double-mesh with the same thickness and at the same distance. The energy resolution stayed within 10% (relative) of the double-mesh value. An innovative characteristic of the structure is that vacuum ultraviolet (VUV) transparency of the polymethyl methacrylate (PMMA) substrate was achieved, effectively, through tetraphenylbutadiene (TPB) coating of the electroluminescence channels combined with indium tin oxide (ITO) coating of the electrodes. This resulted in a × 2.25-increased optical yield (compared to the bare structure), that was found to be in good agreement with simulations if assuming a TPB wavelength-shifting-efficiency at the level of WLSE=0.74–1.28, compatible with expected values. This result, combined with the stability demonstrated for the TPB coating under electric field (over 20 h of continuous operation), shows great potential to revolutionize electroluminescence-based instrumentation.
Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites
Authors: de Araujo Fernanda Fortes , Abdeladhim Maha , Teixeira Clarissa , Hummer Kelly , Wilkerson Matthew D. , Ressner Roseanne , Lakhal-Naouar Ines , Ellis Michael W. , Meneses Claudio , Nurmukhambetova Saule , Gomes Regis , Tolbert W. David , Turiansky George W. , Pazgier Marzena , Oliveira Fabiano , Valenzuela Jesus G. , Kamhawi Shaden , Aronson Naomi 
Published: April 2024

IntroductionCutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease.MethodsTo characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining.ResultsA variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens.DiscussionOur results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.
IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition
Authors: Borch Annie , Carri Ibel , Reynisson Birkir , Alvarez Heli M. Garcia , Munk Kamilla K. , Montemurro Alessandro , Kristensen Nikolaj Pagh , Tvingsholm Siri A. , Holm Jeppe Sejerø , Heeke Christina , Moss Keith Henry , Hansen Ulla Kring , Schaap-Johansen Anna-Lisa , Bagger Frederik Otzen , de Lima Vinicius Araujo Barbosa , Rohrberg Kristoffer S. , Funt Samuel A. , Donia Marco , Svane Inge Marie , Lassen Ulrik , Barra Carolina , Nielsen Morten , Hadrup Sine Reker 
Published: April 2024

BackgroundMutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition. MethodTo address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy. ResultsWe evaluated 27 neoepitope characteristics, and created a random forest model, IMPROVE, to predict neoepitope immunogenicity. The presence of hydrophobic and aromatic residues in the peptide binding core were the most important features for predicting neoepitope immunogenicity.ConclusionOverall, IMPROVE was found to significantly advance the identification of neoepitopes compared to other current methods.
Association between dietary flavonoid intake and hypertension among U.S. adults
Authors: Wan Yingying , Ma Dan , Shang Qinghua , Xu Hao 
Published: April 2024

BackgroundHypertension is one of the major risk factors for cardiovascular disease. Dietary flavonoids have been reported to reduce inflammation, protect against oxidative stress, protect the vascular endothelium, and improve vascular health. However, the relationship between dietary flavonoid intake and the prevalence of hypertension remains controversial.MethodsThis study included 8010 adults from the 2007-2010 and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). The relationship between dietary flavonoid intake and the prevalence of hypertension was explored by weighted logistic regression and weighted restricted cubic spline.ResultsWe found an inverse relationship between total anthocyanin intake and the prevalence of hypertension in the fourth quartile compared with the first quartile [0.81(0.66,0.99), p = 0.04]. Moreover, the prevalence of hypertension tended to decrease with increasing total anthocyanin intake in participants over 60 years of age. In addition, we found a U-shaped relationship between the prevalence of hypertension and total flavan-3-ol intake. Total flavan-3-ol intake was inversely associated with hypertension prevalence in the third quartile compared with the first quartile [0.79 (0.63,0.99), p = 0.04]. Moreover, there was a significant negative association between the prevalence of hypertension and total flavan-3-ol intake when total flavan-3-ol intake was below 48.26 mg/day.ConclusionOur study found a negative association between the prevalence of hypertension and moderate total anthocyanins intake and total flavan-3-ols intake. Our study provides evidence from a population-based study for a negative association between dietary flavonoid intake and the prevalence of hypertension.
Causal association between gut microbiota and hyperemesis gravidarum: a two-sample Mendelian randomization study
Authors: Xu Dinglin , Zhang Liang , Zhang Jianwei 
Published: April 2024

BackgroundObservational studies have reported an association between the gut microbiota (GM) and hyperemesis gravidarum (HG). However, the causal relationship is unclear. In this study, Mendelian randomization (MR) was used to infer causal relationships between GM and HG.MethodsInverse-variance weighted MR was performed using summary statistics for genetic variants from genome-wide association studies (GWAS). Sensitivity analyses were performed to validate the MR results and assess the robustness of the causal inference. Reverse MR analysis was performed for bacterial taxa that were causally linked to the HG risk in the forward MR analysis to evaluate reverse causality.ResultsMR analysis revealed that the genera Defluviitaleaceae UCG011, Ruminococcus1, Ruminococcus2, Turicibacter, and unknowngenus and phylum Verrucomicrobiota are positively associated with the risk of HG. Additionally, the genus Coprococcus2 was related to a decreased risk of HG. Sensitivity studies validated the strength and reliability of the link between the composition of the GM and HG. No evidence for reverse causality from HG to identified bacterial taxa was found.ConclusionOur MR analysis provided novel insight into the association between GM and HG. In particular, our results indicated that targeting the GM could serve as an effective therapeutic strategy for HG.
SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment
Authors: Zhang Shuyan , Wu Jiajun , Wang Leilei , Mu Lin , Xu Xiaoyu , Li Jiahui , Tang Guoyi , Chen Guang , Zhang Cheng , Zhang Yinjian , Feng Yibin 
Published: April 2024

Objective:Diabetic retinopathy (DR) is a severe diabetic complication that leads to severe visual impairment or blindness. He-Ying-Qing-Re formula (HF), a traditional Chinese medicinal concoction, has been identified as an efficient therapy for DR with retinal vascular dysfunction for decades and has been experimentally reported to ameliorate retinal conditions in diabetic mice. This study endeavors to explore the therapeutic potential of HF with key ingredients in DR and its underlying novel mechanisms.Methods:Co-expression gene modules and hub genes were calculated by weighted gene co-expression network analysis (WGCNA) based on transcriptome sequencing data from high-glucose-treated adult retinal pigment epithelial cell line-19 (ARPE-19). The chromatographic fingerprint of HF was established by ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-Q-TOF-MS). The molecular affinity of the herbal compound was measured by molecular docking. Reactive oxygen species (ROS) was measured by a DCFDA/H2DCFDA assay. Apoptosis was detected using the TUNEL Assay Kit, while ELISA, Western blot, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used for detecting the cytokine, protein, and mRNA expressions, respectively.Results:Key compounds in HF were identified as luteolin, paeoniflorin, and nobiletin. For WGCNA, ME-salmon (“protein deacetylation”) was negatively correlated with ME-purple (“oxidative impairment”) in high-glucose-treated ARPE-19. Luteolin has a high affinity for SIRT1 and P53, as indicated by molecular docking. Luteolin has a hypoglycemic effect on type I diabetic mice. Moreover, HF and luteolin suppress oxidative stress production (ROS and MDA), inflammatory factor expression (IL-6, TNF-α, IL1-β, and MCP-1), and apoptosis, as shown in the in vivo and in vitro experiments. Concurrently, treatment with HF and luteolin led to an upregulation of SIRT1 and a corresponding downregulation of P53.Conclusion:Using HF and its active compound luteolin as therapeutic agents offers a promising approach to diabetic retinopathy treatment. It primarily suppressed protein acetylation and oxidative stress via the SIRT1/P53 pathway in retinal pigment epithelial cells.
The efficacy and safety of continuous intravenous tirofiban for acute ischemic stroke patients treated by endovascular therapy: a meta-analysis
Authors: Wang Mengmeng , Li Jing , Zhang Lingyu , Li Nana , Li Xuemei , Wang Pengfei 
Published: April 2024

IntroductionTirofiban is a non-peptide selective glycoprotein IIb/IIIa receptor inhibitor with a short half-life. The research assesses the efficacy and safety of continuous intravenous tirofiban in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (ET).MethodsA systematic search of Pubmed, Embase, Web of Science, and Cochrane Library databases is conducted from inception until January 26, 2024. Eligible studies are included based on predefined selection criteria. Efficacy outcomes (favorable functional outcome and excellent functional outcome) and safety outcomes (symptomatic intracranial hemorrhage [sICH], any intracranial hemorrhage [ICH], and 90-day mortality) are calculated using odds ratios (OR) and 95% confidence intervals (CI).ResultsA total of 4,329 patients from 15 studies are included in the analysis. The results indicate a significant trend toward favorable functional outcomes in the tirofiban group (OR, 1.24; 95% CI, 1.09–1.42; p = 0.001). In terms of safety outcomes, tirofiban does not increase the risk of sICH (OR, 0.90; 95% CI, 0.71–1.13; p = 0.35) or any ICH (OR, 0.97; 95% CI, 0.70–1.34; p = 0.85), but it significantly decreases 90–day mortality (OR, 0.75; 95% CI, 0.64–0.88; p = 0.0006). A subgroup analysis suggests that continuous intravenous tirofiban demonstrates better efficacy (OR, 1.24; 95% CI, 1.09–1.42; p = 0.001) for patients with AIS undergoing rescue ET with even better results when used in combination with intra–arterial and intravenous administration (OR, 1.25; 95% CI, 1.07–1.451; p = 0.005).ConclusionContinuous intravenous tirofiban is effective and safe for patients with AIS undergoing rescue ET, particularly when combined with intra-arterial tirofiban.Systematic review registrationPROSPERO, identifier CRD42023385695.
Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage
Authors: Yang Xuan , Wang Kaixin , Shen Ping , Zhou Tong , Xu Yudi , Chen Yufei , Li Yanfei , Yao Yaobing , Gong Zhe , Duan Ranran , Jing Lijun , Jia Yanjie 
Published: April 2024

PurposeSphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH).MethodsData of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis.ResultsPatients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p &lt; 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p &lt; 0.001; 90-day 275.24 vs. 303.25, p &lt; 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p &lt; 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p &lt; 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p &lt; 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p &lt; 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p &lt; 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p &lt; 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020–1.054, p &lt; 0.001) and prognosis (OR = 1.018, 95% CI = 1.006–1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144–0.8759, p &lt; 0.001) for disease severity and 0.7105 (95% CI = 0.6227–0.7983, p &lt; 0.001) for prognosis.ConclusionHigher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.
Stereotactic radiosurgery in the treatment of essential tremor – a systematic review
Authors: Bilski Mateusz , Szklener Katarzyna , Szklener Sebastian , Rudzińska Anna , Kluz Natalia , Klas Jakub , Rodzajewska Anna , Kuryło Weronika , Korga Mateusz , Baranowska Izabela , Mańdziuk Sławomir 
Published: April 2024

IntroductionEssential tremor (ET) is the most common movement disorder in adults, with an estimated incidence of up to 1% of the population and 5% of people older than 65 years of age. ET is manifested primarily by bilateral postural and kinetic tremor of the upper limbs with or without neurological symptoms and cognitive deficits. ET disrupts daily tasks and significantly lowers quality of life. Currently available medications alone are often insufficient to control severe symptoms. Several surgical treatment options are available, including stereotactic radiosurgery (SRS)—a minimally invasive treatment option aimed at relieving and controlling tremors.MethodsWe conducted a systematic review of the scientific literature on the use of SRS in the treatment of ET using PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov registry and adhered to the PRISMA guidelines.ResultsThe results obtained confirm the high efficacy and safety of the SRS procedure in treating drug-resistant intention tremor. The study results present high response rate reaching 80% and achievement of manual task improvement, lessening of the tremor and increase in the quality of life of the majority of the operated patients. The method also stands out for its favorable balance between efficiency and cost.DisscusionStereotactic radiosurgery is a favourable, safe, efficient and cost-effective method in treatment of the essential tremor. Ongoing research is crucial to refine patient selection criteria for this procedure and further improve the effectiveness of the technique.
Respiratory function in adult patients with spinal muscular atrophy treated with nusinersen – a monocenter observational study
Authors: Wurster Claudia Diana , Uzelac Zeljko , Dreyhaupt Jens , Schuster Joachim , Dorst Johannes , Ludolph Albert Christian , Wollinsky Kurt 
Published: April 2024

Background/objectiveInsufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue.MethodsWe examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17–61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models.ResultsBaseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0–44.0), 3 (median 81.0%, IQR 67.0–90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood (p &lt; 0.0001). FVC remained stable during follow-up (mean −0.047, 95% CI −0.115 to 0.020, p = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p &lt; 0.0001) and a decrease in FVC of type 3/4 patients (−0.142, 95% CI −0.239 to −0.044, p = 0.005).ConclusionThe observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.
Optimizing early neurological deterioration prediction in acute ischemic stroke patients following intravenous thrombolysis: a LASSO regression model approach
Authors: Li Ning , Li Ying-Lei , Shao Jia-Min , Wang Chu-Han , Li Si-Bo , Jiang Ye 
Published: April 2024

BackgroundAcute ischemic stroke (AIS) remains a leading cause of disability and mortality globally among adults. Despite Intravenous Thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) emerging as the standard treatment for AIS, approximately 6–40% of patients undergoing IVT experience Early Neurological Deterioration (END), significantly impacting treatment efficacy and patient prognosis.ObjectiveThis study aimed to develop and validate a predictive model for END in AIS patients post rt-PA administration using the Least Absolute Shrinkage and Selection Operator (LASSO) regression approach.MethodsIn this retrospective cohort study, data from 531 AIS patients treated with intravenous alteplase across two hospitals were analyzed. LASSO regression was employed to identify significant predictors of END, leading to the construction of a multivariate predictive model.ResultsSix key predictors significantly associated with END were identified through LASSO regression analysis: previous stroke history, Body Mass Index (BMI), age, Onset to Treatment Time (OTT), lymphocyte count, and glucose levels. A predictive nomogram incorporating these factors was developed, effectively estimating the probability of END post-IVT. The model demonstrated robust predictive performance, with an Area Under the Curve (AUC) of 0.867 in the training set and 0.880 in the validation set.ConclusionThe LASSO regression-based predictive model accurately identifies critical risk factors leading to END in AIS patients following IVT. This model facilitates timely identification of high-risk patients by clinicians, enabling more personalized treatment strategies and optimizing patient management and outcomes.