bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of inorganic nitrate/nitrite supplementary therapy in heart failure with preserved ejection fraction
Authors: Lv Feng , Zhang Junyi , Tao Yuan 
Published: February 2023

BackgroundApproximately half of patients with heart failure have a preserved ejection fraction (HFpEF). To date, only SGLT-2i, ARNi, and MRAs treatments have been shown to be effective for HFpEF. Exercise intolerance is the primary clinical feature of HFpEF. The aim of this meta-analysis was to explore the effect of inorganic nitrate/nitrite supplementary therapy on the exercise capacity of HFpEF patients.MethodsWe searched PubMed, Embase, Cochrane Library, OVID, and Web of Science for eligible studies for this meta-analysis. The primary outcomes were peak oxygen consumption (peak VO2), exercise time, and respiratory exchange ratio (RER) during exercise. The secondary outcomes were cardiac output, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and systemic vascular resistance during rest and exercise, respectively.ResultsA total of eight randomized-controlled trials were enrolled for this meta-analysis. We found no benefit of inorganic nitrate/nitrite on exercise capacity in patients with HFpEF. Inorganic nitrate/nitrite compared to placebo, did not significantly increased peak VO2 (MD = 0.361, 95% CI = −0.17 to 0.89, p = 0.183), exercise time (MD = 9.74, 95% CI = −46.47 to 65.95, p = 0.734), and respiratory exchange ratio during exercise (MD = −0.003, 95% CI = −0.036 to 0.029, p = 0.834). Among the six diameters reflecting cardiac and artery hemodynamics, inorganic nitrate/nitrite can lower rest SBP, rest/exercise DBP, rest/exercise MAP, and exercise SVR, but has no effect in cardiac output and heart rate for HFpEF patients.ConclusionOur meta-analysis suggested that inorganic nitrate/nitrite supplementary therapy has no benefit in improving the exercise capacity of patients with HFpEF, but can yield a blood pressure lowering effect, especially during exercise.
Novel non-invasive ECG imaging method based on the 12-lead ECG for reconstruction of ventricular activation: A proof-of-concept study
Authors: Fruelund Patricia Zerlang , Van Dam Peter M. , Melgaard Jacob , Sommer Anders , Lundbye-Christensen Søren , Søgaard Peter , Zaremba Tomas , Graff Claus , Riahi Sam 
Published: February 2023

AimCurrent non-invasive electrocardiographic imaging (ECGi) methods are often based on complex body surface potential mapping, limiting the clinical applicability. The aim of this pilot study was to evaluate the ability of a novel non-invasive ECGi method, based on the standard 12-lead ECG, to localize initial site of ventricular activation in right ventricular (RV) paced patients. Validation of the method was performed by comparing the ECGi reconstructed earliest site of activation against the true RV pacing site determined from cardiac computed tomography (CT).MethodsThis was a retrospective study using data from 34 patients, previously implanted with a dual chamber pacemaker due to advanced atrioventricular block. True RV lead position was determined from analysis of a post-implant cardiac CT scan. The ECGi method was based on an inverse-ECG algorithm applying electrophysiological rules. The algorithm integrated information from an RV paced 12-lead ECG together with a CT-derived patient-specific heart-thorax geometric model to reconstruct a 3D electrical ventricular activation map.ResultsThe mean geodesic localization error (LE) between the ECGi reconstructed initial site of activation and the RV lead insertion site determined from CT was 13.9 ± 5.6 mm. The mean RV endocardial surface area was 146.0 ± 30.0 cm2 and the mean circular LE area was 7.0 ± 5.2 cm2 resulting in a relative LE of 5.0 ± 4.0%.ConclusionWe demonstrated a novel non-invasive ECGi method, based on the 12-lead ECG, that accurately localized the RV pacing site in relation to the ventricular anatomy.
One-step versus two-step screening for diagnosis of gestational diabetes mellitus in Iranian population: A randomized community trial
Authors: Ramezani Tehrani Fahimeh , Rahmati Maryam , Farzadfar Farshad , Abedini Mehrandokht , Farahmand Maryam , Hosseinpanah Farhad , Hadaegh Farzad , Torkestani Farahnaz , Valizadeh Majid , Azizi Fereidoun , Behboudi-Gandevani Samira 
Published: February 2023

ObjectivesThere is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women.MethodsWe conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail.ResultsGDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p &lt; 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester.ConclusionWe found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring.Clinical trial registrationhttps://www.irct.ir/trial/518, identifier (IRCT138707081281N1).
Spatial and temporal effects of China’s digital economy on rural revitalization
Authors: Zhou Xiangjun , Du Meng , Dong Hai 
Published: February 2023

The paper constructs an evaluation index system of China’s digital economy and rural revitalization development, including 46 indicators of digital economy and rural revitalization subsystem, and analyzes the impact of China’s digital economy on rural revitalization by combining spatial Markov analysis method and spatial econometric model, and finds that:① The spatial heterogeneity of rural revitalization pattern is obvious, and the difference between north and south is more prominent, and the spatial clustering characteristic of rural revitalization pattern The spatial clustering characteristics are obvious, and the degree of clustering decreases with the increase of the spatial distance threshold. ② Digital economic development can significantly promote the level of rural revitalization in the region, and this finding is found to be robust by introducing the exogenous policy shock test of the Outline of Digital Rural Development Strategy, and digital economic development has a significant spatial siphon effect and can influence the level of rural revitalization in neighboring regions. Considering spatial heterogeneity, the regression results based on the multi-distance economic circle show that the siphoning effect of digital economy on rural revitalization in other regions peaks at 700 km ③Main contribution: It reveals that implementing a differentiated digital economy development strategy and enhancing the radiation of polarized regions are important for reducing regional differences in digital economy and rural revitalization to realize the coordinated development of China’s digital countryside.
Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats
Authors: Zhou Yun , Hong Qingxiao , Xu Wenjin , Chen Weisheng , Xie Xiaohu , Zhuang Dingding , Lai Miaojun , Fu Dan , Xu Zemin , Wang Majie , Zhou Wenhua , Liu Huifen 
Published: February 2023

Transfer RNA-derived small RNAs (tsRNAs) are a novel class of short, non-coding RNAs that are closely associated with the pathogenesis of various diseases. Accumulating evidence has demonstrated their critical functional roles as regulatory factors in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. However, the underlying mechanisms by which tRFs &amp; tiRNAs affect methamphetamine-induced pathophysiological processes are largely unknown. In this study, we used a combination of small RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT‒PCR), bioinformatics, and luciferase reporter assays to screen the expression profiles and identify the functional roles of tRFs and tiRNAs in the nucleus accumbens (NAc) of methamphetamine self-administration rat models. A total of 461 tRFs &amp; tiRNAs were identified in the NAc of rats after 14 days of methamphetamine self-administration training. Of those, 132 tRFs &amp; tiRNAs were significantly differentially expressed: 59 were significantly upregulated, whereas 73 were significantly downregulated in the rats with methamphetamine self-administration. Decreased expression levels of tiRNA-1-34-Lys-CTT-1 and tRF-1-32-Gly-GCC-2-M2, as well as increased expression levels of tRF-1-16-Ala-TGC-4 in the METH group compared with the saline control were validated by using RT‒PCR. Then, bioinformatic analysis was performed to analyse the possible biological functions of tRFs &amp; tiRNAs in methamphetamine-induced pathogenesis. Furthermore, tRF-1-32-Gly-GCC-2-M2 was identified to target BDNF using the luciferase reporter assay. An altered tsRNA expression pattern was proven, and tRF-1-32-Gly-GCC-2-M2 was shown to be involved in methamphetamine-induced pathophysiologic processes by targeting BDNF. The current study provides new insights for future investigations to explore the mechanisms and therapeutic methods for methamphetamine addiction.
Instrumental variable-based high-dimensional mediation analysis with unmeasured confounders for survival data in the observational epigenetic study
Authors: Chen Fangyao , Hu Weiwei , Cai Jiaxin , Chen Shiyu , Si Aima , Zhang Yuxiang , Liu Wei 
Published: February 2023

Background: High dimensional mediation analysis is frequently conducted to explore the role of epigenetic modifiers between exposure and health outcome. However, the issue of high dimensional mediation analysis with unmeasured confounders for survival analysis in observational study has not been well solved.Methods: In this study, we proposed an instrumental variable based approach for high dimensional mediation analysis with unmeasured confounders in survival analysis for epigenetic study. We used the Sobel‘s test, the Joint test, and the Bootstrap method to test the mediation effect. A comprehensive simulation study was conducted to decide the best test strategy. An empirical study based on DNA methylation data of lung cancer patients was conducted to illustrate the performance of the proposed method.Results: Simulation study suggested that the proposed method performed well in the identifying mediating factors. The estimation of the mediation effect by the proposed approach is also reliable with less bias compared with the classical approach. In the empirical study, we identified two DNA methylation signatures including cg21926276 and cg26387355 with a mediation effect of 0.226 (95%CI: 0.108-0.344) and 0.158 (95%CI: 0.065-0.251) between smoking and lung cancer using the proposed approach.Conclusion: The proposed method obtained good performance in simulation and empirical studies, it could be an effective statistical tool for high dimensional mediation analysis.
Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms
Authors: Thompson John S. , Thornton Alice C. , Ainger Timothy , Garvy Beth A. 
Published: February 2023

IntroductionLong COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.MethodsWe report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.ResultsThe patients’ ages ranged from 34 to 79 years—with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.ConclusionLong-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.
Polymorphisms and gene expression of Notch4 in pulmonary tuberculosis
Authors: Fang Weijun , Liu Hua , Qin Lianhua , Wang Jie , Huang Xiaochen , Pan Sha , Zheng Ruijuan 
Published: February 2023

BackgroundTuberculosis (TB) is a serious public health problem to human health, but the pathogenesis of TB remains elusive.MethodsTo identify novel candidate genes associated with TB susceptibility, we performed a population-based case control study to genotype 41SNPs spanning 21 genes in 435 pulmonary TB patients and 375 health donors from China.ResultsWe found Notch4 gene rs206018 and rs422951 polymorphisms were associated with susceptibility to pulmonary tuberculosis. The association was validated in another independent cohort including 790 TB patients and 1,190 healthy controls. Moreover, we identified that the rs206018 C allele was associated with higher level of Notch4 in PBMCs from pulmonary TB patients. Furthermore, Notch4 expression increased in TB patients and higher Notch4 expression correlated with the severer pulmonary TB. Finally, we explored the origin and signaling pathways involved in the regulation of Notch4 expression in response to Mycobacterium tuberculosis (Mtb) infection. We determine that Mtb induced Notch4 and its ligand Jagged1expression in macrophages, and Notch4 through TLR2/P38 signaling pathway and Jagged1 through TLR2/ERK signaling pathway.ConclusionOur work further strengthens that Notch4 underlay an increased risk of TB in humans and is involved in the occurrence and development of TB, which could serve as a novel target for the host-targeted therapy of TB.
GMP development and preclinical validation of CAR-T cells targeting a lytic EBV antigen for therapy of EBV-associated malignancies
Authors: Zhang Xi , Wang Tiaoxia , Zhu Xiaona , Lu Yong , Li Mingpeng , Huang Zhihong , Han Deping , Zhang Longzhen , Wu Yang , Li Liantao , Klawonn Frank , Stripecke Renata 
Published: February 2023

IntroductionEpstein-Barr virus (EBV) is a widely spread pathogen associated with lymphoproliferative diseases, B/ T/ NK cell lymphomas, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). EBV lytic reactivations contribute to the genomic instability, inflammation and tumorigenesis of NPC, promoting cancer progression. Patients with NPC refractory to standard therapies show dismal survival. EBV gp350 is an envelope protein detectable in NPC specimens intracellularly and on the cell membrane of malignant cells, and is a potential viral antigen for T cell-directed immunotherapies. The potency of T cells engineered with a chimeric antigen receptor (CAR) targeting gp350 against EBV+ lymphoproliferative disease was previously shown.MethodsHere, we advanced towards preclinical and non-clinical developments of this virus-specific CAR-T cell immunotherapy against NPC. Different gp350CAR designs were inserted into a lentiviral vector (LV) backbone.ResultsA construct expressing the scFv 7A1-anti−gp350 incorporating the CD8 transmembrane and CD28.CD3ζ signaling domain (ZT002) was selected. High titer ZT002 (~1x108 TU/ml) was manufactured in HEK 293T/17 suspension cells in serum free media as large-scale production under good manufacturing practices (GMP). A LV multiplicity of infection (MOI) of 1 resulted in high frequencies of functional gp350CAR+ T cells (&gt;70%) at a low (&lt;2) vector copy numbers in the genome. ZT002 was therefore used to establish gp350CAR-T batch run production methods. GMP upscaling and validation of T cell transduction and expansion in several runs resulted in average 3x109 gp350CAR-T cells per batch. &gt;80% CD3+ gp350CAR-T cells bound to purified gp350 protein. In vitro cytotoxicity and cytokine secretion assays (IFN-γ and TNF-α) confirmed the specificity of gp350CAR-T cells against gp350+ NPC, GC and lymphoma cell targets. Immunocompromised B-NDG mice (NOD.CB17-PrkdcscidIl2rgtm1/Bcgen) were challenged s.c. with a EBV+ NPC C666.1 cell line expressing gp350 and then treated with escalating doses of gp350CAR-T cells or with non-transduced T cells. gp350CAR-T cells promoted antitumor responses, bio-distributed in several tissues, infiltrated in tumors and rejected gp350+ tumor cells.DiscussionThese results support the use of gp350CAR-T cells generated with ZT002 as an Innovative New Drug to treat patients with solid and liquid EBV-associated malignancies.
Phonaesthetics and personality—Why we do not only prefer Romance languages
Authors: Winkler Anna , Kogan Vita V. , Reiterer Susanne Maria 
Published: February 2023

IntroductionPrevious aesthetic research has set its main focus on visual and auditory, primarily music, stimuli with only a handful of studies exploring the aesthetic potential of linguistic stimuli. In the present study, we investigate for the first time the effects of personality traits on phonaesthetic language ratings.MethodsTwenty-three under-researched, “rarer” (less learned and therefore less known as a foreign language or L2) and minority languages were evaluated by 145 participants in terms of eroticism, beauty, status, and orderliness, subjectively perceived based on language sound.ResultsOverall, Romance languages (Catalan, Portuguese, Romanian) were still among the top six erotic languages of the experiment together with “Romance-sounding,” but less known languages like Breton and Basque. Catalan and Portuguese were also placed among the top six most beautiful languages. The Germanic languages (Swedish, Norwegian, Danish, and Icelandic) were perceived as more prestigious/higher in terms of status, however to some degree conditioned by their recognition/familiarity. Thus, we partly replicated the results of our earlier studies on the Romance language preferences (the so-called Latin Lover effect) and the perceived higher status of the Germanic languages and scrutinized again the effects of familiarity/language recognition, thereby calling into question the above mentioned concepts of the Latin Lover effect and the status of Germanic languages. We also found significant effects of personality traits (neuroticism, extraversion, and conscientiousness) on phonaesthetic ratings. Different personality types appreciated different aspects of languages: e.g., whereas neurotics had strong opinions about languages' eroticism, more conscientious participants gave significantly different ratings for status. Introverts were more generous in their ratings overall in comparison to extroverts. We did not find strong connections between personality types and specific languages or linguistic features (sonority, speech rate). Overall, personality traits were largely overridden by other individual differences: familiarity with languages (socio-cultural construals, the Romanization effect—perceiving a particular language as a Romance language) and participants' native language/L1.DiscussionFor language education in the global context, our results mean that introducing greater linguistic diversity in school and universities might result in greater appreciation and motivation to learn lesser-known and minority languages. Even though we generally prefer Romance languages to listen to and to study, different personality types are attracted to different language families and thus make potentially successful learners of these languages.
Investigation of the running-in process in photoinduced superlubricity
Authors: Han Ke , Ma Pingsu , Ma Liran , Tian Yu , Luo Jianbin 
Published: February 2023

Photoinduced superlubricity on TiO2 surfaces is a newfound phenomenon which draws researchers’ attention. This study provides a new method to achieve superlubricity (COF&lt;0.01) with an external light field. However, photoinduced superlubricity can only be realized under specific conditions. Improper running-in conditions, such as speed, load, and pH value, will lead to superlubricity failure even after ultraviolet illumination on the TiO2 surface. In this paper, different running-in loads, speeds, or pH values were used in the experiment of photoinduced superlubricity, and the worn surfaces after running-in and testing in 70% v/v glycerol aqueous solution were investigated thoroughly. Results reveal that the morphology of worn scars differs under different running-in conditions. While the running-in speeds and loads are too low (&lt;0.03 m/s and &lt;2 N) or too large (&gt;0.1 m/s and &gt;9 N), the photoinduced superlubricity will fail because of wrong lubrication state. When the pH value of running-in solution is less than 4.5, photoinduced superlubricity is easier to achieve. In discuss, mixed lubrication is believed to be the key to success of photoinduced superlubricity, because the elastohydrodynamic effect, doublelayer effect and adsorption of glycerol molecules works at the same time. In addition, due to the formation of the SiO2 layer on the Si3N4 ball and better attraction to lubricant molecules with hydroxyl radicals on the TiO2 surface, running-in in solutions with low pH values contributes to the success of photoinduced superlubricity. In any event, the ultraviolet illumination can reduce the friction coefficient of the TiO2/Si3N4 tribological system and can realize photoinduced superlubricity under appropriate running-in conditions.