bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative use of a self-expanding valve for valve-in-valve transcatheter mitral valve replacement: experience from a four-year single-center study
Authors: Li Yuehuan , Lei Ruobing , Zhou Jiawei , Wu Kaisheng , Shen Jinglun , Zhu Zhihui , Wang Jiangang , Zhang Haibo
Published: June 2023

Background

Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) is a minimally invasive option for patients with bioprosthetic mitral valve failure. Since January 2019, our center has been using a new innovative option, J-Valve, to treat patients with bioprosthetic mitral valve failure who were at high risk for open heart surgery. The aim of this study is to explore the effectiveness and safety of J-Valve and report the results from the four-year follow-up period of the innovative application of the transcatheter valve.

Methods

Patients who underwent the ViV-TMVR procedure between January 2019 and September 2022 in our center were included in the study. J-Valve™ system (JC Medical Inc., Suzhou, China) with three U-shape grippers was used for ViV-TMVR via transapical approach. Data on survival, complications, transthoracic echocardiographic results, New York Heart Association functional class in heart failure, and patient-reported health-related quality of life according to the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were collected during the four-year follow up.

Results

Thirty-three patients (mean age 70.1 ± 1.1 years, 13 men) were included and received ViV-TMVR. The surgery success rate was 97%: only one patient was converted to open-heart surgery due to intraoperative valve embolization to the left ventricle. During the first 30 days all-cause mortality was 0%, risk of stroke 2.5% and risk of mild paravalvular leak 15.2%; mitral valve hemodynamics improved (179.7 ± 8.9 at 30 days vs. 269 ± 49 cm/s at baseline, p < 0.0001). Median time from operation to discharge was six days, and there were no readmissions within 30 days from operation. The median and maximum follow-up durations were 28 and 47 months, respectively; during the entire follow-up, all-cause mortality was 6.1%, and the risk of cerebral infarction 6.1%. Cox regression analysis did not identify any variables significantly associated with survival. The New York Heart Association functional class and the KCCQ-12 score improved significantly compared with their preoperative values.

Conclusion

The use of J-Valve for ViV-TMVR is safe and effective with a high success rate, low mortality and very few associated complications, representing an alternative surgical strategy for the elderly, high-risk patients with bioprosthetic mitral valve failure.
Exploring the prospect of intrinsic wave propagation in evaluating myocardial stiffness among patients with type 2 diabetes
Authors: Cheng Qiao , Huang Xiao , Fan Xinying , Sun Jie , Zhang Jun , Tang Qiaoying , Deng Youbin , Bi Xiaojun
Published: June 2023

Background

Diabetes predisposes affected individuals to impaired myocardial perfusion and ischemia, leading to cardiac dysfunction. Increased myocardial stiffness is an independent and significant risk factor in diastolic dysfunction. This study sought to estimate myocardial stiffness in Type 2 diabetes (T2DM) patients using the intrinsic wave velocity propagation (IVP) along the longitudinal wall motion during late diastole and evaluate the value of IVP in assessing cardiac function and structure.

Methods

87 and 53 participants with and without T2DM (control group) were enrolled. Of the 87 T2DM patients (DM group), 43 were complicated with hypertension (DM + H group), and 44 were not (DM-H group). Ultrasound parameters were measured and analyzed, including color M-mode flow propagation velocity, global longitudinal systolic strain (GLS), and IVP.

Results

IVP was higher in the DM group than in the control group (1.62 ± 0.25 m/s and 1.40 ± 0.19 m/s, P < 0.001). After stratification for hypertension, IVP in both DM + H (1.71 ± 0.25 m/s) and DM-H (1.53 ± 0.20 m/s) groups were found to be significantly higher than that in the control group (1.40 ± 0.19 m/s); also, the difference of IVP between DM + H and DM-H group reached statistical significance. Moreover, IVP was significantly correlated with flow propagation velocity during early diastole (Pve) (r = −0.580, P < 0.001), flow propagation velocity during late diastole (Pva) (r = 0.271, P < 0.001), GLS (r = 0.330, P < 0.001), interventricular septal thickness at end-diastole (IVSd) (r = 0.321, P < 0.001), blood glucose (r = 0.246, P < 0.003), systolic blood pressure (r = 0.370, P < 0.001) and diastolic blood pressure (r = 0.389, P < 0.001).

Conclusions

The results indicated the application potential of IVP in assessing the early detection of cardiac function changes noninvasively and sensitively. The correlation with myocardial stiffness warrants further studies to substantiate its potential clinical utility.
Long-term didactic innovations in higher education teaching caused by the coronavirus pandemic?
Authors: Budke Alexandra , Sanchez-Kirsch Nichol , Quintero-Rivas Erika
Published: June 2023

During the coronavirus pandemic, many universities worldwide were closed and lecturers had to switch from face-to-face teaching to online distance education. Consequently, questions arose which routines in teaching the lecturers were able to use despite this change in teaching environments, and which didactic innovations they implemented in their courses. Lecturers’ evaluation of these innovations and any aspects they intend to continue using after the pandemic and the return to face-to-face teaching were examined. Through a qualitative survey of 24 university lecturers in Germany and Panama, the long-term effects of the pandemic on teaching were investigated. It was found that the creation of new digital media for teaching, the use of new digital tools to ensure interaction and scientific exchange, the finding of new forms of organization, and combinations of synchronous and asynchronous teaching were all considered to be positive didactic innovations that should be maintained after the pandemic.
Recent advances in data-driven prediction for wind power
Authors: Liu Yaxin , Wang Yunjing , Wang Qingtian , Zhang Kegong , Qiang Weiwei , Wen Qiuzi Han
Published: June 2023

Wind power is one of the most representative renewable energy and has attracted wide attention in recent years. With the increasing installed capacity of global wind power, its nature of randomness and uncertainty has posed a serious risk to the safe and stable operation of the power system. Therefore, accurate wind power prediction plays an increasingly important role in controlling the impact of the fluctuations of wind power to in system dispatch planning. Recently, with the rapid accumulation of data resource and the continuous improvement of computing power, data-driven artificial intelligence technology has been popularly applied in many industries. AI-based models in the field of wind power prediction have become a cutting-edge research subject. This paper comprehensively reviews the AI-based models for wind power prediction at various temporal and spatial scales, covering from wind turbine level to regional level. To obtain in-depth insights on performance of various prediction methods, we review and analyze performance evaluation metrics of both deterministic models and probabilistic models for wind power prediction. In addition, challenges arising in data quality control, feature engineering, and model generalization for the data-driven wind power prediction methods are discussed. Future research directions to improving the accuracy of data-driven wind power prediction are also addressed.
CrossDome: an interactive R package to predict cross-reactivity risk using immunopeptidomics databases
Authors: Fonseca Andre F. , Antunes Dinler A.
Published: June 2023

T-cell-based immunotherapies hold tremendous potential in the fight against cancer, thanks to their capacity to specifically targeting diseased cells. Nevertheless, this potential has been tempered with safety concerns regarding the possible recognition of unknown off-targets displayed by healthy cells. In a notorious example, engineered T-cells specific to MAGEA3 (EVDPIGHLY) also recognized a TITIN-derived peptide (ESDPIVAQY) expressed by cardiac cells, inducing lethal damage in melanoma patients. Such off-target toxicity has been related to T-cell cross-reactivity induced by molecular mimicry. In this context, there is growing interest in developing the means to avoid off-target toxicity, and to provide safer immunotherapy products. To this end, we present CrossDome, a multi-omics suite to predict the off-target toxicity risk of T-cell-based immunotherapies. Our suite provides two alternative protocols, i) a peptide-centered prediction, or ii) a TCR-centered prediction. As proof-of-principle, we evaluate our approach using 16 well-known cross-reactivity cases involving cancer-associated antigens. With CrossDome, the TITIN-derived peptide was predicted at the 99+ percentile rank among 36,000 scored candidates (p-value < 0.001). In addition, off-targets for all the 16 known cases were predicted within the top ranges of relatedness score on a Monte Carlo simulation with over 5 million putative peptide pairs, allowing us to determine a cut-off p-value for off-target toxicity risk. We also implemented a penalty system based on TCR hotspots, named contact map (CM). This TCR-centered approach improved upon the peptide-centered prediction on the MAGEA3-TITIN screening (e.g., from 27th to 6th, out of 36,000 ranked peptides). Next, we used an extended dataset of experimentally-determined cross-reactive peptides to evaluate alternative CrossDome protocols. The level of enrichment of validated cases among top 50 best-scored peptides was 63% for the peptide-centered protocol, and up to 82% for the TCR-centered protocol. Finally, we performed functional characterization of top ranking candidates, by integrating expression data, HLA binding, and immunogenicity predictions. CrossDome was designed as an R package for easy integration with antigen discovery pipelines, and an interactive web interface for users without coding experience. CrossDome is under active development, and it is available at https://github.com/AntunesLab/crossdome.
Regulatory effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin on inflammation and immune function in percutaneous nephrolithotomy patients with upper urinary tract calculi complicated with infection
Authors: Zhao Yuan , Zhang Yafei , Liu Jianhe
Published: June 2023

Objective

To study the effect of an injection of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on inflammation and immune function in patients with upper urinary tract calculi complicated by infection who have undergone percutaneous nephrolithotomy.

Methods

We retrospectively recorded the clinical data of patients with upper urinary tract calculi complicated by infection who have undergone Percutaneous nephrolithotomy(PCNL) in the Department of Urology, 2nd Affiliation Hospital of Kunming Medical University, from March to December 2021. Clinical data include general condition, laboratory index, CT, postoperative body temperature, heart rate, respiration, SIRS, sepsis, etc. Patients were divided into treated and control groups according to whether they had received a preoperative PA-MSHA injection. The two groups were compared for indices of inflammation and complications of infection after PCNL. Pre- and post-operative lymphocyte subsets and immunoglobulin changes were compared.

Results

115 patients were included in the study, including 43 in the treatment group and 72 in the control group. After Propensity Score Matching, 90 patients were divided into treatment (n=35) and control (n=55) groups. The postoperative inflammation index was higher in the treatment group than in the control group (P<0.05). The incidence of postoperative SIRS was higher in the treatment group than control (P<0.05). There were no cases of sepsis in either group. The double-positive T cells lymphocyte subsets were higher in the treatment group than in the control group ((P<0.05). Pre- and post-operative changes in immune function: total T lymphocyte count reduced, NK and NKT cell count increased in the control group, double-positive T cell count increased in the treatment group, IgG, IgA, IgM, complement C3 and C4 count reduced in both groups post-operatively.

Conclusion

This study found that patients with upper urinary tract calculi and infection treated with antibiotic-based PA-MSHA before percutaneous nephrolithotomy had an increased inflammatory response after surgery, which may play a role in the prevention and treatment of sepsis. The percentage of double-positive T cells in the peripheral blood was increased after PA-MSHA treatment, which may have an immunomodulatory and protective effect in PCNL patients with stones complicated by infection.
Case Report: Successful liver transplantation after achieving complete clinical remission of advanced HCC with Atezolizumab plus Bevacizumab combination therapy
Authors: Chouik Yasmina , Erard Domitille , Demian Hassan , Schulz Thomas , Mazard Tessa , Hartig-Lavie Kerstin , Antonini Teresa , Mabrut Jean-Yves , Mohkam Kayvan , Rode Agnès , Merle Philippe
Published: June 2023

Background

Atezolizumab plus Bevacizumab combination therapy has recently emerged as the new standard of care for unresectable HCC. Significant tumor burden reduction can be observed under that treatment, raising the question of liver transplantation (LT). The safety of another immune checkpoint inhibitor (ICI), nivolumab, is unclear in the pre-transplant setting.

Method

We report the case of a 57-y old man, with initial unresectable multinodular HCC contraindicated to LT and locoregional therapies, who achieves complete tumor response after Atezolizumab/Bevacizumab, and subsequently underwent LT for liver failure.

Results

Explant analysis revealed complete pathological response with no tumor remnant. The patient suffered from several post-operative complications but no HCC recurrence or biopsy-proven acute rejection occurred 10 months after LT.

Conclusions

Atezolizumab/Bevacizumab therapy may enable complete pathological response of advanced HCC. Safety of prolonged treatment need to be assessed.
Expression of anti-chikungunya single-domain antibodies in transgenic Aedes aegypti reduces vector competence for chikungunya virus and Mayaro virus
Authors: Webb Emily M. , Compton Austin , Rai Pallavi , Chuong Christina , Paulson Sally L. , Tu Zhijian , Weger-Lucarelli James
Published: June 2023

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related alphaviruses that cause acute febrile illness accompanied by an incapacitating polyarthralgia that can persist for years following initial infection. In conjunction with sporadic outbreaks throughout the sub-tropical regions of the Americas, increased global travel to CHIKV- and MAYV-endemic areas has resulted in imported cases of MAYV, as well as imported cases and autochthonous transmission of CHIKV, within the United States and Europe. With increasing prevalence of CHIKV worldwide and MAYV throughout the Americas within the last decade, a heavy focus has been placed on control and prevention programs. To date, the most effective means of controlling the spread of these viruses is through mosquito control programs. However, current programs have limitations in their effectiveness; therefore, novel approaches are necessary to control the spread of these crippling pathogens and lessen their disease burden. We have previously identified and characterized an anti-CHIKV single-domain antibody (sdAb) that potently neutralizes several alphaviruses including Ross River virus and Mayaro virus. Given the close antigenic relationship between MAYV and CHIKV, we formulated a single defense strategy to combat both emerging arboviruses: we generated transgenic Aedes aegypti mosquitoes that express two camelid-derived anti-CHIKV sdAbs. Following an infectious bloodmeal, we observed significant reduction in CHIKV and MAYV replication and transmission potential in sdAb-expressing transgenic compared to wild-type mosquitoes; thus, this strategy provides a novel approach to controlling and preventing outbreaks of these pathogens that reduce quality of life throughout the tropical regions of the world.
Amyloid fibrils degradation: the pathway to recovery or aggravation of the disease?
Authors: Sulatsky Maksim I. , Stepanenko Olga V. , Stepanenko Olesya V. , Mikhailova Ekaterina V. , Kuznetsova Irina M. , Turoverov Konstantin K. , Sulatskaya Anna I.
Published: June 2023

Background: The most obvious manifestation of amyloidoses is the accumulation of amyloid fibrils as plaques in tissues and organs, which always leads to a noticeable deterioration in the patients’ condition and is the main marker of the disease. For this reason, early diagnosis of amyloidosis is difficult, and inhibition of fibrillogenesis, when mature amyloids are already accumulated in large quantities, is ineffective. A new direction for amyloidosis treatment is the development of approaches aimed at the degradation of mature amyloid fibrils. In the present work, we investigated possible consequences of amyloid’s degradation.

Methods: We analyzed the size and morphology of amyloid degradation products by transmission and confocal laser scanning microscopy, their secondary structure and spectral properties of aromatic amino acids, intrinsic chromophore sfGFP, and fibril-bound amyloid-specific probe thioflavin T (ThT) by the absorption, fluorescence and circular dichroism spectroscopy, as well as the cytotoxicity of the formed protein aggregates by MTT-test and their resistance to ionic detergents and boiling by SDS-PAGE.

Results: On the example of sfGFP fibrils (model fibrils, structural rearrangements of which can be detected by a specific change in the spectral properties of their chromophore), and pathological Aβ-peptide (Aβ42) fibrils, leading to neuronal death in Alzheimer’s disease, the possible mechanisms of amyloids degradation after exposure to factors of different nature (proteins with chaperone and protease activity, denaturant, and ultrasound) was demonstrated. Our study shows that, regardless of the method of fibril degradation, the resulting species retain some amyloid’s properties, including cytotoxicity, which may even be higher than that of intact amyloids.

Conclusion: The results of our work indicate that the degradation of amyloid fibrils in vivo should be treated with caution since such an approach can lead not to recovery, but to aggravation of the disease.
Effects of sensory deprivation on glomerular interneurons in the mouse olfactory bulb: differences in mortality and phenotypic adjustment of dopaminergic neurons
Authors: Angelova Alexandra , Tiveron Marie-Catherine , Loizeau Mathieu D. , Cremer Harold , Platel Jean-Claude
Published: June 2023

Neurogenesis persists in the mammalian subventricular zone after birth, producing various populations of olfactory bulb (OB) interneurons, including GABAergic and mixed dopaminergic/GABAergic (DA) neurons for the glomerular layer. While olfactory sensory activity is a major factor controlling the integration of new neurons, its impact on specific subtypes is not well understood. In this study we used genetic labeling of defined neuron subsets, in combination with reversible unilateral sensory deprivation and longitudinal in vivo imaging, to examine the behavior of postnatally born glomerular neurons. We find that a small fraction of GABAergic and of DA neurons die after 4 weeks of sensory deprivation while surviving DA-neurons exhibit a substantial decrease in tyrosine hydroxylase (TH) expression levels. Importantly, after reopening of the naris, cell death is arrested and TH levels go back to normal levels, indicating a specific adaptation to the level of sensory activity. We conclude that sensory deprivation induces adjustments in the population of glomerular neurons, involving both, cell death and adaptation of neurotransmitter use in specific neuron types. Our study highlights the dynamic nature of glomerular neurons in response to sensory deprivation and provide valuable insights into the plasticity and adaptability of the olfactory system.
Delineating effects of angiopoietin-2 inhibition on vascular permeability and inflammation in models of retinal neovascularization and ischemia/reperfusion
Authors: Canonica Jérémie , Foxton Richard , Garrido Marina Garcia , Lin Cheng-Mao , Uhles Sabine , Shanmugam Sumathi , Antonetti David A. , Abcouwer Steven F. , Westenskow Peter D.
Published: June 2023

Introduction

Clinical trials demonstrated that co-targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) with faricimab controls anatomic outcomes and maintains vision improvements, with strong durability, through 2 years in patients with neovascular age-related macular degeneration and diabetic macular edema. The mechanism(s) underlying these findings is incompletely understood and the specific role that Ang-2 inhibition plays requires further investigation.

Methods

We examined the effects of single and dual Ang-2/VEGF-A inhibition in diseased vasculatures of JR5558 mice with spontaneous choroidal neovascularization (CNV) and in mice with retinal ischemia/reperfusion (I/R) injuries.

Results

In JR5558 mice, Ang-2, VEGF-A, and dual Ang-2/VEGF-A inhibition reduced CNV area after 1 week; only dual Ang-2/VEGF-A inhibition decreased neovascular leakage. Only Ang-2 and dual Ang-2/VEGF-A inhibition maintained reductions after 5 weeks. Dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 1 week. Both Ang-2 and dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 5 weeks. In the retinal I/R injury model, dual Ang-2/VEGF-A inhibition was statistically significantly more effective than Ang-2 or VEGF-A inhibition alone in preventing retinal vascular leakage and neurodegeneration.

Discussion

These data highlight the role of Ang-2 in dual Ang-2/VEGF-A inhibition and indicate that dual inhibition has complementary anti-inflammatory and neuroprotective effects, suggesting a mechanism for the durability and efficacy of faricimab in clinical trials.
Nerve trunk healing and neuroma formation after nerve transection injury
Authors: Huang Dong-Xu , Yang Ming-Xi , Jiang Zhen-Min , Chen Miao , Chang Kun , Zhan Yong-Xin , Gong Xu
Published: June 2023

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.
Utility of hybrid PET/MRI in stereoelectroencephalography guided radiofrequency thermocoagulation in MRI negative epilepsy patients
Authors: Li Hongyang , Zhang Miao , Lin Zhengyu , Deng Zhengdao , Cao Chunyan , Zhan Shikun , Liu Wei , Sun Bomin
Published: June 2023

Introduction

Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel advanced non-invasive presurgical examination tool for patients with drug-resistant epilepsy (DRE). This study aims to evaluate the utility of PET/MRI in patients with DRE who undergo stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC).

Methods

This retrospective study included 27 patients with DRE who underwent hybrid PET/MRI and SEEG-guided RFTC. Surgery outcome was assessed using a modified Engel classification, 2 years after RFTC. Potential areas of the seizure onset zone (SOZ) were identified on PET/MRI and confirmed by SEEG.

Results

Fifteen patients (55%) became seizure-free after SEEG-guided RFTC. Engel class II, III, and IV were achieved in six, two, and four patients, respectively at the 2 years follow-up. MRI was negative in 23 patients and structural abnormalities were found in four patients. Hybrid PET/MRI contributed to the identification of new structural or metabolic lesions in 22 patients. Concordant results between PET/MRI and SEEG were found in 19 patients in the identification of SOZ. Among the patients with multifocal onset, seizure-free status was achieved in 50% (6/12).

Conclusion

SEEG-guided RFTC is an effective and safe treatment for drug-resistant epilepsy. Hybrid PET/MRI serves as a useful tool for detecting the potential SOZs in MRI-negative patients and guide the implantation of SEEG electrodes. Patients with multifocal epilepsy may also benefit from this palliative treatment.
Emotional- and cognitive-like responses induced by social defeat stress in male mice are modulated by the BNST, amygdala, and hippocampus
Authors: da Costa Vinícius Fresca , Ramírez Johana Caterin Caipa , Ramírez Stephany Viatela , Avalo-Zuluaga Julian Humberto , Baptista-de-Souza Daniela , Canto-de-Souza Lucas , Planeta Cleopatra S. , Rodríguez Javier Leonardo Rico , Nunes-de-Souza Ricardo Luiz
Published: June 2023

Introduction

Chronic exposure to social defeat stress (SDS) has been used to investigate the neurobiology of depressive- and anxiety-like responses and mnemonic processes. We hypothesized that these affective, emotional, and cognitive consequences induced by SDS are regulated via glutamatergic neurons located in the bed nucleus of the stria terminalis (BNST), amygdaloid complex, and hippocampus in mice.

Methods

Here, we investigated the influence of chronic SDS on (i) the avoidance behavior assessed in the social interaction test, (ii) the anxiety-like behavior (e.g., elevated plus-maze, and open field tests) (iii) depressive-like behaviors (e.g., coat state, sucrose splash, nesting building, and novel object exploration tests), (iv) the short-term memory (object recognition test), (v) ΔFosB, CaMKII as well as ΔFosB + CaMKII labeling in neurons located in the BNST, amygdaloid complex, dorsal (dHPC) and the ventral (vHPC) hippocampus.

Results

The main results showed that the exposure of mice to SDS (a) increased defensive and anxiety-like behaviors and led to memory impairment without eliciting clear depressive-like or anhedonic effects; (b) increased ΔFosB + CaMKII labeling in BNST and amygdala, suggesting that both areas are strongly involved in the modulation of this type of stress; and produced opposite effects on neuronal activation in the vHPC and dHPC, i.e., increasing and decreasing, respectively, ΔFosB labeling. The effects of SDS on the hippocampus suggest that the vHPC is likely related to the increase of defensive- and anxiety-related behaviors, whereas the dHPC seems to modulate the memory impairment.

Discussion

Present findings add to a growing body of evidence indicating the involvement of glutamatergic neurotransmission in the circuits that modulate emotional and cognitive consequences induced by social defeat stress.
Flux estimation analysis systematically characterizes the metabolic shifts of the central metabolism pathway in human cancer
Authors: Yang Grace , Huang Shaoyang , Hu Kevin , Lu Alex , Yang Jonathan , Meroueh Noah , Dang Pengtao , Wang Yijie , Zhu Haiqi , Cao Sha , Zhang Chi
Published: June 2023

Introduction

Glucose and glutamine are major carbon and energy sources that promote the rapid proliferation of cancer cells. Metabolic shifts observed on cell lines or mouse models may not reflect the general metabolic shifts in real human cancer tissue.

Method

In this study, we conducted a computational characterization of the flux distribution and variations of the central energy metabolism and key branches in a pan-cancer analysis, including the glycolytic pathway, production of lactate, tricarboxylic acid (TCA) cycle, nucleic acid synthesis, glutaminolysis, glutamate, glutamine, and glutathione metabolism, and amino acid synthesis, in 11 cancer subtypes and nine matched adjacent normal tissue types using TCGA transcriptomics data.

Result

Our analysis confirms the increased influx in glucose uptake and glycolysis and decreased upper part of the TCA cycle, i.e., the Warburg effect, in almost all the analyzed cancer. However, increased lactate production and the second half of the TCA cycle were only seen in certain cancer types. More interestingly, we failed to detect significantly altered glutaminolysis in cancer tissues compared to their adjacent normal tissues. A systems biology model of metabolic shifts through cancer and tissue types is further developed and analyzed. We observed that (1) normal tissues have distinct metabolic phenotypes; (2) cancer types have drastically different metabolic shifts compared to their adjacent normal controls; and (3) the different shifts in tissue-specific metabolic phenotypes result in a converged metabolic phenotype through cancer types and cancer progression.

Discussion

This study strongly suggests the possibility of having a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors.
Early in vitro evidence indicates that deacetylated sialic acids modulate multi-drug resistance in colon and lung cancers via breast cancer resistance protein
Authors: Tuffour Isaac , Amuzu Setor , Bayoumi Hala , Surtaj Iram , Parrish Colin , Willand-Charnley Rachel
Published: June 2023

Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in multidrug resistant (MDR) pathways, contain Sias in their extracellular domains. The core structure of Sia can contain a variety of functional groups, including O-acetylation on the C6 tail. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer cells to either retain or efflux chemotherapeutics. Via CRISPR-Cas-9 gene editing, acetylation was modulated by the removal of CAS1 Domain-containing protein (CASD1) and Sialate O-Acetyl esterase (SIAE) genes. Using western blot, immunofluorescence, gene expression, and drug sensitivity analysis, we confirmed that deacetylated Sias regulated a MDR pathway in colon and lung cancer in early in vitro models. When deacetylated Sias were expressed on BCRP, colon and lung cancer cells were able to export high levels of BCRP to the cell’s surface, resulting in an increased BCRP efflux activity, reduced sensitivity to the anticancer drug Mitoxantrone, and high proliferation relative to control cells. These observations correlated with increased levels of cell survival proteins, BcL-2 and PARP1. Further studies also implicated the lysosomal pathway for the observed variation in BCRP levels among the cell variants. RNASeq data analysis of clinical samples revealed higher CASD1 expression as a favorable marker of survival in lung adenocarcinoma. Collectively, our findings indicate that deacetylated Sia is utilized by colon and lung cancers to engage in MDR via overexpression and efflux action of BCRP.
Clinical progress of anti-angiogenic targeted therapy and combination therapy for gastric cancer
Authors: Xu Donghan , Luo Yehao , Wang Peng , Li Jiaxin , Ma Linrui , Huang Jie , Zhang Hao , Yang Xiaoman , Li Liqi , Zheng Yuhong , Fang Gang , Yan Peiyu
Published: June 2023

The incidence of gastric cancer is increasing year by year. Most gastric cancers are already in the advanced stage with poor prognosis when diagnosed, which means the current treatment is not satisfactory. Angiogenesis is an important link in the occurrence and development of tumors, and there are multiple anti-angiogenesis targeted therapies. To comprehensively evaluate the efficacy and safety of anti-angiogenic targeted drugs alone and in combination against gastric cancer, we systematically searched and sorted out relevant literature. In this review, we summarized the efficacy and safety of Ramucirumab, Bevacizumab, Apatinib, Fruquintinib, Sorafenib, Sunitinib, Pazopanib on gastric cancer when used alone or in combination based on prospective clinical trials reported in the literature, and sorted response biomarkers. We also summarized the challenges faced by anti-angiogenesis therapy for gastric cancer and available solutions. Finally, the characteristics of the current clinical research are summarized and suggestions and prospects are raised. This review will serve as a good reference for the clinical research of anti-angiogenic targeted drugs in the treatment of gastric cancer.
Risk factors associated with recurrence of Henoch–Schonlein purpura: a retrospective study
Authors: Cao Tongtong , Yang Hui-min , Huang Jing , Hu Yan
Published: June 2023

Background

Recurrence is considered a vital problem for assessing the prognosis of Henoch–Schonlein purpura (HSP). The objective of this study was to evaluate factors affecting the recurrence in children with HSP.

Methods

We retrospectively reviewed records of 368 patients under the age of 16 years diagnosed with HSP from October 2019 to December 2020 in Beijing Children's Hospital. Patients were divided into a non-recurrence group and a recurrence group according to whether there was a recurrence. Incidence of manifestation, possible cause, age, and treatment were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of recurrence in HSP.

Results

Percentages of patients were 65.2% for the non-recurrence group and 34.8% for the recurrence group. The percentage of patients with renal involvement was significantly higher in the recurrence group (40.6%) than in the non-recurrence group (26.3%). Respiratory tract infection was the most frequent trigger: 67.5% in the non-recurrence group and 66.4% in the recurrence group. Recurrence was more likely to occur in patients aged >6 years (53.3% vs. 71.9%). Logistic regression analysis revealed that hematuria plus proteinuria was an independent risk factor for the recurrence of HSP. Conversely, animal protein, exercise restriction, and age ≤6 years were independent favorable factors for the non-recurrence of HSP.

Conclusion

These results suggest that organ involvement, exercise, and diet management during the initial episode of HSP should be strictly monitored for children with HSP. Adequate clinical intervention for these risk factors may limit or prevent HSP recurrence. Moreover, renal involvement is associated with the long-term prognosis of HSP.
Transcriptome analysis reveals that auxin promotes strigolactone-induced adventitious root growth in the hypocotyl of melon seedlings
Authors: Li Jingrui , Fan Mi , Zhang Qinqin , Lü Guiyun , Wu Xiaolei , Gong Binbin , Wang Yubo , Zhang Ying , Gao Hongbo
Published: June 2023

Introduction

Strigolactone (SL) and auxin are two important phytohormones involved in plant root development, but whether they show synergistic or mutual promotion effects during adventitious root (AR) formation has not been adequately explored.

Methods

In this study, we investigated the mechanisms of GR24 (synthetic SL) and indole-3-acetic acid (IAA; a type of auxin) in the formation of ARs using melon as the study material.

Results

Morphological measurements showed that the AR number, length, superficial area, and volume under the GR24 treatment were 1.60–3.27, 1.58–3.99, 2.06–3.42, and 3.00–6.11 times greater than those of the control group, respectively, at 6–10 days; the GR24+IAA treatment further promoted AR formation in melon seedlings, and the AR number, length, superficial area, and volume under the GR24+IAA treatment were 1.44–1.51, 1.28–1.73, 1.19–1.83, and 1.31–1.87 times greater than those obtained with the GR24 treatment, respectively. Transcriptome analysis revealed 2,742, 3,352, and 2,321 differentially expressed genes (DEGs) identified from the GR24 vs. control, GR24+IAA vs. control, and GR24+IAA vs. GR24 comparisons, respectively. The GR24 treatment and GR24+IAA treatment affected auxin and SL synthesis as well as components of the phytohormone signal transduction pathway, such as auxin, brassinosteroid (BR), ethylene (ETH), cytokinin (CK), gibberellin (GA), and abscisic acid (ABA). The concentrations of auxin, GA, zeatin (ZT), and ABA were evaluated using high-performance liquid chromatography (HPLC). From 6 to 10 days, the auxin, GA, and ZT contents in the GR24 treatment group were increased by 11.48%–15.34%, 11.83%–19.50%, and 22.52%–66.17%, respectively, compared to the control group, and these features were increased by 22.00%–31.20%, 21.29%–25.75%, 51.76%–98.96%, respectively, in the GR24+IAA treatment group compared with the control group. Compared to that in the control, the ABA content decreased by 10.30%–11.83% in the GR24 treatment group and decreased by 18.78%-24.00% in the GR24+IAA treatment group at 6–10 days.

Discussion

Our study revealed an interaction between strigolactone and auxin in the induction of AR formation in melon seedlings by affecting the expression of genes related to plant hormone pathways and contents.
Fine mapping of a novel QTL DM9.1 conferring downy mildew resistance in melon
Authors: Zhang Xuejun , Ling Yueming , Yang Wenli , Wei Minghua , Wang Zhenzhu , Li Meihua , Yang Yong , Liu Bin , Yi Hongping , Guo Yang-Dong , Kong Qiusheng
Published: June 2023

Downy mildew (DM) is a major foliar disease globally causing great economic loss in melon production. Utilizing disease-resistant cultivars is the most efficient approach for disease control, while discovery of disease-resistant genes is crucial for the success of DM-resistant breeding. To address this problem, two F2 populations were constructed using the DM-resistant accession PI 442177 in this study, and QTLs conferring DM resistance were mapped using linkage map and QTL-seq analysis, respectively. A high-density genetic map with the length of 1096.7 cM and density of 0.7 cM was generated by using the genotyping-by-sequencing data of a F2 population. A major QTL DM9.1 with the phenotypic variance explained proportion of 24.3-37.7% was consistently detected at the early, middle, and late growth stages using the genetic map. QTL-seq analyses on the two F2 populations also validated the presence of DM9.1. Kompetitive Allele-Specific PCR (KASP) assay was further carried out to fine map DM9.1 into 1.0 Mb interval. A KASP marker co-segregating with DM9.1 was successfully developed. These results not only provided valuable information for DM-resistant gene cloning, but also offered useful markers for melon DM-resistant breeding programs.
The integrative role of parenting styles and parental involvement in young children’s science problem-solving skills
Authors: Lin Xunyi , Yang Weipeng , Xie Wanlin , Li Hui
Published: June 2023

Introduction

How parents encourage and engage young children to learn science and solve scientific problems remains an understudied issue. Parenting styles have been widely studied and found to be associated with children’s various developmental outcomes. However, there is a dearth of research linking parenting styles to early science skills which build from both cognitive and social abilities. This cross-sectional study intended to pilot test a mediation model of parental involvement in the relationship between parenting styles and children’s science problem-solving skills.

Methods

A total of 226 children (M = 62.10 months, SD = 4.14, 108 girls) and their parents was recruited from five kindergartens in Fuzhou in China by adopting stratified random sampling. All parents completed the Demographics Questionnaire, the Parenting Style and Dimension Questionnaire, and the Chinese Early Parental Involvement Scale. Each child was tested with the Picture Problem Solving Task. Pearson’s correlation analysis and intermediary effect analysis were conducted using IBM SPSS 25 in data analysis.

Results and discussion

Parental involvement had a significant mediating effect in the bidirectional associations between parenting styles and children’s science problem-solving skills. The findings suggested that children with higher science problem-solving skills were likely to be raised by parents who were employing a flexible (i.e., authoritative) parenting style and had more involvement in children’s formal and informal learning environments, while children’s higher levels of science problem-solving skills predicted a higher level of parental involvement and a more flexible parenting style.
Practice beats age: co-activation shapes heritage speakers’ lexical access more than age of onset
Authors: Sagarra Nuria , Casillas Joseph V.
Published: June 2023

Probabilistic associations make language processing efficient and are honed through experience. However, it is unclear what language experience factors explain the non-monolingual processing behaviors typical of L2 learners and heritage speakers (HSs). We investigated whether AoO, language proficiency, and language use affect the recognition of Spanish stress-tense suffix associations involving a stressed syllable that cues a present suffix (SALta “s/he jumps”) and an unstressed syllable that cues a past suffix (SALtó “s/he jumped”). Adult Spanish-English HSs, English-Spanish L2 learners, and Spanish monolinguals saw a paroxytone verb (stressed initial syllable) and an oxytone verb (unstressed initial syllable), listened to a sentence containing one of the verbs, and chose the one they heard. Spanish proficiency measured grammatical and lexical knowledge, and Spanish use assessed percentage of current usage. Both bilingual groups were comparable in Spanish proficiency and use. Eye-tracking data showed that all groups fixated on target verbs above chance before hearing the syllable containing the suffix, except the HSs in the oxytones. Monolinguals fixated on targets more and earlier, although at a slower rate, than HSs and L2 learners; in turn, HSs fixated on targets more and earlier than L2 learners, except in oxytones. Higher proficiency increased target fixations in HSs (oxytones) and L2 learners (paroxytones), but greater use only increased target fixations in HSs (oxytones). Taken together, our data show that HSs’ lexical access depends more on number of lexical competitors (co-activation of two L1 lexica) and type (phonotactic) frequency than token (lexical) frequency or AoO. We discuss the contribution of these findings to models in phonology, lexical access, language processing, language prediction, and human cognition.
Academic distress among undergraduate students during COVID-19: the relevance of SES and help-seeking behaviors
Authors: Korn Liat , Zigdon Avi , Davidovitch Nitza
Published: June 2023

Introduction

Academic distress has been frequently reported following the COVID-19 pandemic. This study estimates academic distress among undergraduate students, characterizes its nature in relation to economic, social, and health indicators, and examines the level of request for help following mental distress. Students with higher levels of academic distress were expected to show lower socio-economic status, lower social connections, and lower wellbeing indices.

Methods

A cross-sectional study based on a structured anonymous questionnaire was delivered online to more than 1,400 undergraduate students from one university in Israel (women, 66.7%).

Results

Academic distress was reported by 27.1% of the sample. Students who reported academic distress were more likely to report stress, negative psycho-somatic symptoms, changes in weight since COVID-19, low self-esteem, depressive symptoms, higher COVID-19 concerns, and higher security situation concerns. A hierarchic logistic regression model showed that the probability of reporting academic distress was 2.567 times higher (p < 0.001 95% CI [1.702, 3.871]) for those who reported lower family economic status before COVID-19 and 2.141 times higher (p = 0.004 95% CI [1.284, 3.572]) for those who highly reported depressive symptoms. In contrast, only 15.6% of those who reported academic distress sought help from academic authorities.

Discussion

The significant associations of academic distress with health indices indicate that the self-reported distress was real and highly related to adverse health measures. A comprehensive, collaborative model that integrates psychological, economic, and social aspects of intervention is required in times of crisis within academic institutions.
Estimates of the global, regional, and national burden of atrial fibrillation in older adults from 1990 to 2019: insights from the Global Burden of Disease study 2019
Authors: Jiao Min , Liu Chenglin , Liu Yongwen , Wang Yan , Gao Qianqian , Ma Anning
Published: June 2023

Background

Atrial fibrill ation (AF) is a predominant public health concern in older adults. Therefore, this study aimed to explore the global, regional, and national burden of AF in older adults aged 60–89 between 1990 and 2019.

Methods

The morbidity, mortality, disability-adjusted life years (DALYs), and age-standardized rates of AF were refined from the Global Burden of Diseases study 2019. The epidemiological characteristics were assessed based on numerical values, age-standardized rates per 100,000 person-years, and estimated annual percentage changes (EAPC).

Results

Globally, a total of 33.31 million AF cases, 219.4 thousand deaths, and 65.80 million DALYs were documented in 2019. There were no appreciable changes in EAPC from 1990 to 2019. The disease burden of AF differed significantly across different territories and countries. At the national level, China exhibited the highest number of incident cases [818,493 (562,871–1,128,695)], deaths [39,970 (33,722–46,387)], and DALYs [1,383,674 (1,047,540–1,802,516)]. At the global level, high body mass index (BMI) and high systolic blood pressure (SBP) were two predominant risk factors contributing to the proportion of AF-related deaths.

Conclusion

AF in older adults remains a major public health concern worldwide. The burden of AF varies widely at both national and regional levels. From 1990 to 2019, the cases of incidences, deaths, and DALYs have shown a global increase. The ASIR, ASMR, and ASDR have declined in the high-moderate and high SDI regions; however, the burden of AF increased promptly in the lower SDI regions. Special attention should be paid to the main risk factors for high-risk individuals with AF, which can help control systolic blood pressure and body mass index within normal limits. Over all, it is necessary to illustrate the features of the global AF burden and develop more effective and targeted prevention and treatment strategies.