bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelets regulate ischemia-induced revascularization and angiogenesis by secretion of growth factor–modulating factors
Authors: Nording Henry , Baron Lasse , Sauter Manuela , Lübken Antje , Rawish Elias , Szepanowski Rebecca , von Esebeck Jacob , Sun Ying , Emami Hossein , Meusel Moritz , Saraei Roza , Schanze Nancy , Gorantla Sivahari Prasad , von Bubnoff Nikolas , Geisler Tobias , von Hundelshausen Philipp , Stellos Konstantinos , Marquardt Jens , Sadik Christian D. , Köhl Jörg , Duerschmied Daniel , Kleinschnitz Christoph , Langer Harald F.
Published: May 2023

In ischemic tissue, platelets can modulate angiogenesis. The specific factors influencing this function, however, are poorly understood. Here, we characterized the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) expressed on platelets as a potent regulator of ischemia-driven revascularization. We assessed the relevance of the anaphylatoxin receptor C5aR1 on platelets in patients with coronary artery disease as well as those with peripheral artery disease and used genetic mouse models to characterize its significance for ischemia and growth factor–driven revascularization. The presence of C5aR1-expressing platelets was increased in the hindlimb ischemia model. Ischemia-driven angiogenesis was significantly improved in C5aR1−/− mice but not in C5−/− mice, suggesting a specific role of C5aR1. Experiments using the supernatant of C5a-stimulated platelets suggested a paracrine mechanism of angiogenesis inhibition by platelets by means of antiangiogenic CXC chemokine ligand 4 (CXCL4, PF4). Lineage-specific C5aR1 deletion verified that the secretion of CXCL4 depends on C5aR1 ligation on platelets. Using C5aR1−/−CXCL4−/− mice, we observed no additional effect in the revascularization response, underscoring a strong dependence of CXCL4 secretion on the C5a-C5aR1-axis. We identified a novel mechanism for inhibition of neovascularization via platelet C5aR1, which was mediated by the release of antiangiogenic CXCL4.
Effect of miR-149-5p on intramuscular fat deposition in pigs based on metabolomics and transcriptomics
Authors: Liu Yingke , Wei Yilin , Dou Yaqing , Li Chenlei , Song Chenglei , Zhang Zhe , Qi Kunlong , Li Xinjian , Qiao Ruimin , Wang Kejun , Li Xiuling , Yang Feng , Han Xuelei
Published: May 2023

As one of the important traits in pig production, meat quality has important research significance and value. Intramuscular fat (IMF) content is one of the most important factors affecting pork quality. Many experimental studies have shown that IMF content is closely related to the flavor, tenderness, and juiciness of pork. Therefore, it is of great significance to study the mechanism of porcine IMF deposition. Previous research indicated that miR-149-5p promoted the proliferation of porcine intramuscular (IM) preadipocytes and decreased their ability to differentiate, albeit the exact mechanism of action is unknown. In vitro, foreign pigs showed increased miR-149-5p expression and reduced fat deposition when compared to Queshan Black pigs. This study conducted metabolomics and transcriptomics analyses of porcine IM preadipocytes overexpressing miR-149-5p to verify their effects on lipid formation. According to metabolomics analysis, the overexpression of miR-149-5p has significantly altered the lipid, organic acid, and organic oxygen metabolites of porcine IM preadipocytes. Specially speaking, it has changed 115 metabolites, including 105 up-regulated and 10 down-regulated ones, as well as the composition of lipid, organic acid, and organic oxygen metabolism-related metabolites. RNA-seq analysis showed that overexpression of miR-149-5p significantly altered 857 genes, of which 442 were up-regulated, and 415 were down-regulated, with enrichment to MAPK, IL-17, PI3K-Akt, and ErbB signaling pathways. We found that overexpression of miR-149-5p inhibited adipogenic differentiation by changing cAMP signaling pathway in porcine IM preadipocytes. In addition, the overexpression of miR-149-5p may affect the transport of Cu2+ by targeting ATP7A and inhibiting adipogenic differentiation. These findings elucidate the regulatory function of miR-149-5p in porcine IM preadipocytes, which may be a key target for controlling pork quality.
Metagenome-mining indicates an association between bacteriocin presence and strain diversity in the infant gut
Authors: Ormaasen Ida , Rudi Knut , Diep Dzung B. , Snipen Lars
Published: May 2023

Background

Our knowledge about the ecological role of bacterial antimicrobial peptides (bacteriocins) in the human gut is limited, particularly in relation to their role in the diversification of the gut microbiota during early life. The aim of this paper was therefore to address associations between bacteriocins and bacterial diversity in the human gut microbiota. To investigate this, we did an extensive screening of 2564 healthy human gut metagenomes for the presence of predicted bacteriocin-encoding genes, comparing bacteriocin gene presence to strain diversity and age.

Results

We found that the abundance of bacteriocin genes was significantly higher in infant-like metagenomes (< 2 years) compared to adult-like metagenomes (2–107 years). By comparing infant-like metagenomes with and without a given bacteriocin, we found that bacteriocin presence was associated with increased strain diversities.

Conclusions

Our findings indicate that bacteriocins may play a role in the strain diversification during the infant gut microbiota establishment.
Constructing ferroptosis-related competing endogenous RNA networks and exploring potential biomarkers correlated with immune infiltration cells in asthma using combinative bioinformatics strategy
Authors: Chen Shao-Tian , Yang Nan
Published: May 2023

Background

Asthma is a common chronic respiratory disease worldwide. Recent studies have revealed the critical effects of the ceRNA network and ferroptosis on patients with asthma. Thus, this study aimed to explore the potential ferroptosis-related ceRNA network, investigate the immune cell infiltration level in asthma through integrated analysis of public asthma microarray datasets, and find suitable diagnostic biomarkers for asthma.

Methods

First, three asthma-related datasets which were downloaded from the Gene Expression Omnibus (GEO) database were integrated into one pooled dataset after correcting for batch effects. Next, we screened differentially expressed lncRNAs (DElncRNAs) between patients and healthy subjects, constructed a ceRNA network using the StarBase database and screened ferroptosis–related genes from the predicted target mRNAs for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also performed Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) on the batch effect-corrected mRNA expression profile. Then, Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen potential diagnostic biomarkers, and the diagnostic efficacy was assessed using a receiver operating characteristic (ROC) curve. Finally, we determined the proportion of 22 immune cells in patients with asthma using CIBERSORT and investigated the correlation between key RNAs and immune cells.

Results

We obtained 19 DElncRNAs, of which only LUCAT1 and MIR222HG had corresponding target miRNAs. The differentially expressed ferroptosis-related genes were involved in multiple programmed cell death-related pathways. We also found that the mRNA expression profile was primarily enriched in innate immune system responses. We screened seven candidate diagnostic biomarkers for asthma using LASSO regression (namely, BCL10, CD300E, IER2, MMP13, OAF, TBC1D3, and TMEM151A), among which the area under the curve (AUC) value for CD300E and IER2 were 0.722 and 0.856, respectively. Finally, we revealed the infiltration ratio of different immune cells in asthma and found a correlation between LUCAT1, MIR222HG, CD300E, and IER2 with some immune cells.

Conclusion

This study explored a potential lncRNA-miRNA-mRNA regulatory network and its underlying diagnostic biomarkers (CD300E and IER2) in asthma and identified the immune cells most associated with them, providing possible diagnostic markers and immunotherapeutic targets for asthma.
A preliminary study investigating the neglected domain of mental health in Australian lifesavers and lifeguards
Authors: Fien Samantha , Lawes Jasmin C. , Ledger Jessica , Drummond Murray , Simon Pamela , Joseph Nancy , Daw Shane , Best Talitha , Stanton Robert , de Terte Ian
Published: May 2023

Background

Surf lifesavers and lifeguards have provided essential education, preventative, and rescue services to the Australian community for over 110 years. In this first responder role, surf lifesavers and lifeguards are inadvertently exposed to high risk and trauma related experiences, which may negatively impact mental well-being. To date however, there has been limited research into the mental health of surf lifesavers and lifeguards, and no studies at all on the mental health of adolescent surf lifesavers. The preliminary study aimed to measure the exposure of potentially traumatic events (PTEs), post-traumatic stress symptoms (PTSS), self-efficacy, social support, and attitudes towards mental health problems in Surf Life Saving (SLS) members.

Methods

An anonymous, online survey was developed (adolescent and adult versions) and created to measure the domain of mental health in surf lifesavers and lifeguards. Pearson’s correlations investigated relationships between PTEs, PTSS, self-efficacy, social support, attitudes towards mental health problems, age, years as a SLS member, and years patrolling. Spearman’s Rank was used for violations of normality.

Results

A total of 57 surf lifesavers/lifeguards aged 13–59 years were included in the final analysis. There was a significant positive relationship between exposure to direct trauma and PTSS, which in turn, were associated with greater negative attitudes towards mental health problems towards the mental health of others, and lower levels of self-efficacy. Male and female adults with PTSS reported lower social support, whereas for adolescent males, a positive relationship between direct trauma and PTSS was observed.

Conclusion

This research is the first to explore the mental health of Australian surf lifesavers and lifeguards. The results highlight the potential risks to mental health and well-being associated with this first responder role. More research to protect the vulnerability of this population is warranted.
Integration of human papillomavirus associated anal cancer screening into HIV care and treatment program in Pakistan: perceptions of policymakers, managers, and care providers
Authors: Ejaz Muslima , Ekström Anna Mia , Ali Tazeen Saeed , Salazar Mariano , Ahmed Alyan , Ali Dania , Haroon Ayman , Siddiqi Sameen
Published: May 2023

Background

The incidence of anal cancer, largely associated with anal human papillomavirus (HPV) infection, is increasing among men who have sex with men (MSM), and transgender women living with or without HIV. Screening for anal cancer to detect anal precancerous lesions in high-risk groups is an important opportunity for prevention but still lacking in many low-and-middle-income countries. The aim of this study was to explore the readiness of Pakistan’s healthcare system to integrate anal cancer and HPV screening into a national HIV program, as perceived by policymakers, health managers, and healthcare providers.

Design

This qualitative study using key-informant interviews with participants influence in policy making, implementation and advocacy from public and private sector were conducted between March 2021 to August 2021 in Karachi Pakistan.

Methods

Key informants were purposely selected from different domains of the healthcare system responsible for the target group of interest, MSM and transgender-women in general and people living with HIV in particular. A total of 18 key informants, at different levels of seniority were recruited from governmental and non-governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives. Qualitative content analysis was used to identify the manifest and latent themes, based on socioecological framework.

Results

The results were grouped into five major themes; (1) The policy context and priorities, (2) Health systems factors, (3) Community environment, (4) Healthcare setting & providers and (5) Individual-level obstacles. The policy actors expressed their concerns about their limited voice in country’s health and health related priority setting. Informants reported a lack of political will and suggested that government should bring a change in the paradigm of healthcare service delivery from reactive to proactive approach. Although, participants unanimously favored integration of HPV preventive services into existing HIV program, they also identified several service delivery barriers including trained workforce shortage, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet key-populations needs. Participants also predicted other implementation challenges such as stigma, social victimization, and systemic discrimination against at-risk groups at healthcare facilities.

Conclusion

Although policy makers and health providers in Pakistan saw a clear need to scale-up and integrate anal cancer screening for key populations, the feasibility of this is dependent on political will, financing, anti-stigma and discrimination interventions and health system efficiency.
Predicting self-perceived general health status using machine learning: an external exposome study
Authors: Hoekstra Jurriaan , Lenssen Esther S. , Wong Albert , Loef Bette , Herber Gerrie-Cor M. , Boshuizen Hendriek C. , Strak Maciek , Verschuren W. M. Monique , Janssen Nicole A. H.
Published: May 2023

Background

Self-perceived general health (SPGH) is a general health indicator commonly used in epidemiological research and is associated with a wide range of exposures from different domains. However, most studies on SPGH only investigated a limited set of exposures and did not take the entire external exposome into account. We aimed to develop predictive models for SPGH based on exposome datasets using machine learning techniques and identify the most important predictors of poor SPGH status.

Methods

Random forest (RF) was used on two datasets based on personal characteristics from the 2012 and 2016 editions of the Dutch national health survey, enriched with environmental and neighborhood characteristics. Model performance was determined using the area under the curve (AUC) score. The most important predictors were identified using a variable importance procedure and individual effects of exposures using partial dependence and accumulated local effect plots. The final 2012 dataset contained information on 199,840 individuals and 81 variables, whereas the final 2016 dataset had 244,557 individuals with 91 variables.

Results

Our RF models had overall good predictive performance (2012: AUC = 0.864 (CI: 0.852–0.876); 2016: AUC = 0.890 (CI: 0.883–0.896)) and the most important predictors were “Control of own life”, “Physical activity”, “Loneliness” and “Making ends meet”. Subjects who felt insufficiently in control of their own life, scored high on the De Jong-Gierveld loneliness scale or had difficulty in making ends meet were more likely to have poor SPGH status, whereas increased physical activity per week reduced the probability of poor SPGH. We observed associations between some neighborhood and environmental characteristics, but these variables did not contribute to the overall predictive strength of the models.

Conclusions

This study identified that within an external exposome dataset, the most important predictors for SPGH status are related to mental wellbeing, physical exercise, loneliness, and financial status.
Early disc degeneration in radiotherapy-treated childhood brain tumor survivors
Authors: Grahn Petra , Remes Tiina , Kivisaari Reetta , Suo-Palosaari Maria H. , Arikoski Pekka M. , Koskenkorva Päivi K. T. , Lähteenmäki Päivi M. , Lönnqvist Tuula R. I. , Ojaniemi Marja K. , Sirkiä Kirsti H. , Sutela Anna K. , Toiviainen-Salo Sanna-Maria , Rantala Heikki M. J. , Harila Arja H. , Niinimäki Jaakko , Karppinen Jaro , Ahonen Matti
Published: May 2023

Background

Childhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls.

Methods

In this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5–33.1), 67 survivors (mean age 28.4, range 16.2–43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration.

Results

Childhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05).

Conclusions

Signs of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.
A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells
Authors: Chen Yi-Jou , Chen Michael , Cheng Tian-Lu , Tsai Yi-Shan , Wang Chang-Hung , Chen Che-Yi , Wu Tung-Yun , Tzou Shey-Cherng , Wang Kai-Hung , Cheng Jing-Jy , Kao An-Pei , Lin Shyr-Yi , Chuang Kuo-Hsiang
Published: May 2023

Background

Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity.

Methods

In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs). The anti-CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti-cancer moiety of the BsAb provided these BsAb-armed T cells with the cancer-targeting ability, which transformed the naïve T cells into cancer-specific BsAb-armed T cells.

Results

With this technology, a large amount of cancer-specific BsAb-armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb-armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF-α and IFN-γ) were dramatically released from the BsAb-armed T cells after engaging cancer cells, resulting in a remarkable anti-cancer efficacy. Notably, the BsAb-armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors.

Conclusions

Collectively, the BsAb-armed T cell technology represents a simple, time-saving, and highly safe method to generate highly pure cancer-specific effector T cells, thereby providing an affordable T cell immunotherapy to patients.
Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer
Authors: Chang Wenjing , Zhu Jichao , Yang Dianyu , Shang Anquan , Sun Zujun , Quan Wenqiang , Li Dong
Published: May 2023

Background and aims

This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk.

Materials and methods

There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis.

Results

Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis.

Conclusion

Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk.
Ventilator-associated pneumonia in neurocritically ill patients: insights from the ENIO international prospective observational study
Authors: Battaglini Denise , Parodi Luca , Cinotti Raphael , Asehnoune Karim , Taccone Fabio Silvio , Orengo Giovanni , Zona Gianluigi , Uccelli Antonio , Ferro Giulio , Robba Michela , Pelosi Paolo , Robba Chiara
Published: May 2023

Background

Acute brain injured (ABI) patients are at high risk of developing ventilator-associated pneumonia (VAP). However, incidence, risk factors and effects on outcome of VAP are not completely elucidated in this population. The primary aim of this study was to determine the incidence of VAP in a cohort of ABI patients. The secondary objectives included the identification of risk factors for development of VAP, and the impact of VAP on clinical outcomes. Clinical outcomes were defined as intensive care unit length of stay (ICU-LOS), duration of invasive mechanical ventilation (IMV), and ICU mortality.

Methods

Pre-planned sub-analysis of the Extubation strategies in Neuro-Intensive care unit (ICU) patients and associations with Outcomes (ENIO) international multi-center prospective observational study. Patients with available data on VAP, who received at least 48 h of IMV and ICU-LOS ≥ 72 h were included.

Results

Out of 1512 patients included in the ENIO study, 1285 were eligible for this analysis. The prevalence of VAP was 39.5% (33.7 cases /1000 ventilator-days), with a high heterogeneity across countries and according to the type of brain injury. VAP was significantly more frequent in male patients, in those with smoke habits and when intraparenchymal probe (IP), external ventricular drain (EVD) or hypothermia (p < 0.001) were used. Independent risk factors for VAP occurrence were male gender, the use of IP, hypothermia, and the occurrence of tracheobronchitis during ICU stay. VAP was not an independent risk factor for ICU mortality (Hazard Ratio, HR = 0.71 95%CI 0.43–1.16, p = 0.168), but was independently associated with longer ICU stay (OR = 2.55 95%CI 2.01–3.23, p < 0.001).

Conclusions

VAP is common in ABI patients. Male gender, IP and EVD insertion, tracheobronchitis, and the use of therapeutic hypothermia were significantly associated with VAP occurrence. VAP did not affect mortality but increased ICU-LOS.
Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome
Authors: Edström Dag , Niroomand Anna , Stenlo Martin , Uvebrant Kristina , Bölükbas Deniz A. , Hirdman Gabriel , Broberg Ellen , Lim Hooi Ching , Hyllén Snejana , Lundgren-Åkerlund Evy , Pierre Leif , Olm Franziska , Lindstedt Sandra
Published: May 2023

Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 106 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.
Association between triglyceride-glucose index trajectories and carotid atherosclerosis progression
Authors: Yu Haixu , Tao Liyuan , Li Yan-Guang , Yang Lincheng , Liu Dan , Wang Yang , Hao Xiaoyan , He Honghai , Che Ying , Wang Peng , Zhao Wei , Gao Wei
Published: May 2023

Background

The triglyceride-glucose (TyG) index has been recognized as being an alternative cardiometabolic biomarker for insulin resistance associated with the development and prognosis of cardiovascular disease (CVD). However, the prospective relationship between baseline and long-term trajectories of the TyG index and carotid atherosclerosis (CAS) progression has yet to be investigated.

Methods

This longitudinal prospective cohort study included 10,380 adults with multiple general health checks at Peking University Third Hospital from January 2011 to December 2020. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The latent class trajectory modeling method was used to analyze the TyG index trajectories over the follow-up. Based on univariate and multivariate Cox proportional hazards analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the baseline and trajectory of the TyG index.

Results

During a median follow-up period of 757 days, 1813 participants developed CAS progression. Each 1-standard deviation (SD) increase in the TyG index was associated with a 7% higher risk of CAS progression after adjusting for traditional CVD risk factors (HR = 1.067, 95% CI 1.006–1.132). Similar results were observed when the TyG index was expressed as quartiles. According to different trajectory patterns, participants were categorized into low-stable, moderate-stable, and high-increasing groups. After multivariate adjustment, the moderate-stable group had a 1.139-fold (95% CI 1.021–1.272) risk of CAS progression. The high-increasing trajectory of the TyG index tended to be associated with CAS progression (HR = 1.206, 95% CI 0.961–1.513).

Conclusions

Participants with higher baseline and moderate-stable trajectory of the TyG index were associated with CAS progression. Long-term trajectories of the TyG index can help to identify individuals at a higher risk of CAS progression who deserve specific preventive and therapeutic approaches.
Proof of concept of an accelerometer as a trigger for unilateral diaphragmatic pacing: a porcine model
Authors: Kratz Tobias , Ruff Roman , Koch Timo , Kronberg Anne-Sophie , Breuer Johannes , Asfour Boulos , Herberg Ulrike , Bierbach Benjamin
Published: May 2023

Background

Unilateral diaphragmatic paralysis in patients with univentricular heart is a known complication after pediatric cardiac surgery. Because diaphragmatic excursion has a significant influence on perfusion of the pulmonary arteries and hemodynamics in these patients, unilateral loss of function leads to multiple complications. The current treatment of choice, diaphragmatic plication, does not lead to a full return of function. A unilateral diaphragmatic pacemaker has shown potential as a new treatment option. In this study, we investigated an accelerometer as a trigger for a unilateral diaphragm pacemaker (closed-loop system).

Methods

Seven pigs (mean weight 20.7 ± 2.25 kg) each were implanted with a customized accelerometer on the right diaphragmatic dome. Accelerometer recordings (mV) of the diaphragmatic excursion of the right diaphragm were compared with findings using established methods (fluoroscopy [mm]; ultrasound, M-mode [cm]). For detection of the amplitude of diaphragmatic excursions, the diaphragm was stimulated with increasing amperage by a cuff electrode implanted around the right phrenic nerve.

Results

Results with the different techniques for measuring diaphragmatic excursions showed correlations between accelerometer and fluoroscopy values (correlation coefficient 0.800, P < 0.001), accelerometer and ultrasound values (0.883, P < 0.001), and fluoroscopy and ultrasound values (0.816, P < 0.001).

Conclusion

The accelerometer is a valid method for detecting diaphragmatic excursion and can be used as a trigger for a unilateral diaphragmatic pacemaker.
2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation
Authors: Baďurová Lucia , Polčicová Katarína , Omasta Božena , Ovečková Ingrid , Kocianová Eva , Tomášková Jana
Published: May 2023

Background

Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family.

Methods

The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles.

Results

Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein.

Conclusions

Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses.
Effects of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Wang Xianghong , Wu Niujian , Sun Chuanchuan , Jin Donghua , Lu Hongyun
Published: May 2023

Objective

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors therapies were reported to affect adipose tissue distribution. However, the available evidence about the effect of SGLT-2 inhibitor on adipose tissue is contradictory. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus (T2DM).

Methods

RCTs on SGLT-2 inhibitors on adipose distribution affect in patients with T2DM published in full-text journal databases such as PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched. The fixed or random effect model was used for meta-analysis, the I2 test was used to evaluate the heterogeneity between studies, and the sensitivity analysis and subgroup analysis were used to explore the source of heterogeneity. Funnel chart and Begg’s test were used to estimate publication bias.

Results

Overall, 18 RCTs involving 1063 subjects were evaluated. Compared with placebo or other hypoglycemic drugs, SGLT-2 inhibitors significantly reduced visceral adipose tissue (standard mean deviation [SMD] = − 1.42, 95% confidence interval [CI] [− 2.02, − 0.82], I2 = 94%, p < 0.0001), subcutaneous adipose tissue (SMD = − 1.21, 95% CI [− 1.99, − 0.42], I2 = 93%, p = 0.003), ectopic liver adipose tissue (SMD = − 0.70, 95% CI [− 1.20, − 0.20], I2 = 73%, p = 0.006). In addition, body weight (mean deviation [MD] = − 2.60, 95% CI [− 3.30, − 1.89], I2 = 95%, p < 0.0001), waist circumference (MD = − 3.65, 95% CI [− 4.10, − 3.21], I2 = 0%, p < 0.0001), and body mass index (BMI) (MD = − 0.81, 95% CI [− 0.91, − 0.71], I2 = 23%, p < 0.0001) were significantly decreased. However, epicardial fat tissue showed an insignificant reduction (SMD = 0.03, 95% CI [− 0.52, 0.58], I2 = 69%, p = 0.71). Subgroup analysis revealed that appropriate treatment duration (16 – 40 weeks) or young patients with nonalcoholic fatty liver disease (NAFLD) and obesity were the decisive factors for SGLT-2 inhibitors to effectively reduce visceral and subcutaneous adipose tissues.

Conclusions

Our meta-analysis provides evidence that in patients with T2DM, SGLT-2 inhibitors significantly reduce visceral adipose tissue, subcutaneous adipose tissue, and ectopic liver fat, especially in young T2DM patients with NAFLD and high BMI. Appropriate dosing time (16–40 weeks) may have a more significant and stable beneficial effect on VAT and SAT reduction.
Genome-wide CRISPR/Cas9 library screening identified ATM signaling network genes as critical drivers for resistance to ATR inhibition in soft-tissue sarcomas: synthetic lethality and therapeutic implications
Authors: Spalato-Ceruso M , Laroche-Clary A , Perret R , Valverde Y , Chaire V , Derieppe Marie-Alix , Velasco V , Bourdon A , Italiano A
Published: May 2023

Soft-tissue sarcoma (STS) are a heterogeneous group of rare tumors with different biological behavior that are fatal in more than 40% of cases, due to their metastatic evolution and inadequate treatment options. ATR inhibition already showed an activity, even if modest, in broad pre-clinical models of STS. By using genome-wide CRISPR/Cas9 library screening, we identified ATM signaling network genes as critical drivers for resistance to the specific ATR inhibitor AZD6738. The role of such genes in resistance to AZD6738 was confirmed by using CRISPR/Cas9 knockout models. More strikingly, the ATM inhibitor AZD0156 works synergistically with AZD6738 in vitro and abolishes STS growth in vivo in our models of most frequent histotypes (such as dedifferentiated liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma among others). Moreover, the combination of AZD6738 and AZD0156 induced significantly higher levels of DNA damage than either drug used as single agent alone. In summary, our results demonstrate that targeting ATM is an effective approach to overcome resistance to ATR inhibition in different STS subtypes, including the most frequent histologies.
Single-cell technologies in multiple myeloma: new insights into disease pathogenesis and translational implications
Authors: Chen Mengping , Jiang Jinxing , Hou Jian
Published: May 2023

Multiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of plasma cells. Although therapeutic advances have been made to improve clinical outcomes and to prolong patients’ survival in the past two decades, MM remains largely incurable. Single-cell sequencing (SCS) is a powerful method to dissect the cellular and molecular landscape at single-cell resolution, instead of providing averaged results. The application of single-cell technologies promises to address outstanding questions in myeloma biology and has revolutionized our understanding of the inter- and intra-tumor heterogeneity, tumor microenvironment, and mechanisms of therapeutic resistance in MM. In this review, we summarize the recently developed SCS methodologies and latest MM research progress achieved by single-cell profiling, including information regarding the cancer and immune cell landscapes, tumor heterogeneities, underlying mechanisms and biomarkers associated with therapeutic response and resistance. We also discuss future directions of applying transformative SCS approaches with contribution to clinical translation.
Astrocytic pathology in Alpers’ syndrome
Authors: Smith Laura A , Chen Chun , Lax Nichola Z , Taylor Robert W , Erskine Daniel , McFarland Robert
Published: May 2023

Refractory epilepsy is the main neurological manifestation of Alpers’ syndrome, a severe childhood-onset mitochondrial disease caused by bi-allelic pathogenic variants in the mitochondrial DNA (mtDNA) polymerase gamma gene (POLG). The pathophysiological mechanisms underpinning neuronal hyperexcitabilty leading to seizures in Alpers’ syndrome remain unknown. However, pathological changes to reactive astrocytes are hypothesised to exacerbate neural dysfunction and seizure-associated cortical activity in POLG-related disease. Therefore, we sought to phenotypically characterise astrocytic pathology in Alpers’ syndrome. We performed a detailed quantitative investigation of reactive astrocytes in post-mortem neocortical tissues from thirteen patients with Alpers’ syndrome, eight neurologically normal controls and five sudden unexpected death in epilepsy (SUDEP) patients, to control for generalised epilepsy-associated astrocytic pathology. Immunohistochemistry to identify glial fibrillary acidic protein (GFAP)-reactive astrocytes revealed striking reactive astrogliosis localised to the primary visual cortex of Alpers’ syndrome tissues, characterised by abnormal-appearing hypertrophic astrocytes. Phenotypic characterisation of individual GFAP-reactive astrocytes demonstrated decreased abundance of mitochondrial oxidative phosphorylation (OXPHOS) proteins and altered expression of key astrocytic proteins including Kir4.1 (subunit of the inwardly rectifying K+ ion channel), AQP4 (astrocytic water channel) and glutamine synthetase (enzyme that metabolises glutamate). These phenotypic astrocytic changes were typically different from the pathology observed in SUDEP tissues, suggesting alternative mechanisms of astrocytic dysfunction between these epilepsies. Crucially, our findings provide further evidence of occipital lobe involvement in Alpers’ syndrome and support the involvement of reactive astrocytes in the pathogenesis of POLG-related disease.
Sustainable development goals in nephrology nursing to support social development for Japan’s changing population: recommendations for a new paradigm
Authors: Mimura Nadami , Takuwa Yoshiko , Tamura Yui , Kawamura Harumi , Nishimura Misato , Yamaguchi Noriko
Published: May 2023

Background

In accordance with the United Nations' 2030 Agenda for Sustainable Development and Japan's Diet Members Caucus on Global Health, we prepared a report and recommendations for nephrology nursing care in the context of population aging in Japan. Goals and strategies to support social activities are discussed.

As the population continues to age in Japan, nephrology nursing must evolve to support society amid changes. We should aim for two goals: (1) the construction of a new social system to support people with kidney disease, and (2) the development of clinical nursing by securing nurses who are involved in nephrology nursing.

Conclusions

Creating a new paradigm for nephrology nursing care in communities, creating knowledge, and advancing nursing practices for patients with renal failure care within community settings and at home, developing nurses with high expertise in nephrology nursing practice, and recognizing that nurses involved in the care of renal insufficiency will elevate the value of nephrology nursing. Promoting the role of nurses in the specialty of renal care will, in turn, heighten their ability to continue to provide support to society and contribute to its development.
Economic and environmental analysis of a grid-connected hybrid power system for a University Campus
Authors: Akindeji Kayode Timothy , Ewim Daniel Raphael Ejike
Published: May 2023

Background

The generation of clean and affordable energy by 2030 is a challenging task, necessitating the integration of renewable energy sources to reduce greenhouse gas emissions associated with coal, crude oil, and natural gas. This study examines the optimization and performance analysis of a hybrid microgrid for a university campus as a potential solution to achieve this goal. The primary objective is to decrease the cost of energy and reduce CO2 emissions on the campus using a hybrid approach.

Results

The Howard college campus of the University of KwaZulu Natal (UKZN) was used as a case study, with meteorological data obtained from NASA and real hourly electrical load data for 2019 from the university smart meters. HOMER, an optimization software, was employed to model and simulate the case study. The results demonstrated significant savings of R15.7 million (approximately $ 820 000) in annual utility bills, a 51% reduction in CO2 emissions, a return on investment of 20%, and a payback period of 4 years.

Conclusion

The study's findings suggest that universities can become self-sustaining during load shedding periods, as recently experienced in South Africa. The implementation of a hybrid microgrid system on a university campus offers considerable economic and environmental benefits, providing a potential blueprint for other large institutions seeking to achieve similar sustainability goals.
Robust conductive skin hydrogel e-skin constructed by top–down strategy for motion-monitoring
Authors: Liu Jiachang , Fan Xin , Astruc Didier , Gu Haibin
Published: May 2023

The construction of biomass-based conductive hydrogel e-skins with high mechanical properties is the research hotspot and difficulty in the field of biomass materials. Traditional collagen-based conductive hydrogels, constructed by the typical “bottom–up” strategy, normally have the incompatible problem between high mechanical property and high collagen content, and the extraction of collagen is often necessary. To solve these problems, inspired by the high mechanical properties and high collagen content of animal skins, this work proposed a “top–down” construction strategy, in which the extraction of collagen was unnecessary and the skin collagen skeleton (SCS) with the 3D network structure woven by natural collagen fibers in goatskin was preserved and used as the basic framework of hydrogel. Following a four-step route, namely, pretreatment → soaking in AgNPs (silver nanoparticles) solution → soaking in the mixed solution containing HEA (2-hydroxyethyl methacrylate) and AlCl3 → polymerization, this work successfully achieved the fabrication of a new skin-based conductive hydrogel e-skin with high mechanical properties (tensile strength of 2.97 MPa, toughness of 6.23 MJ·m−3 and breaking elongation of 428%) by using goatskin as raw material. The developed skin hydrogel (called PH@Ag) possessed a unique structure with the collagen fibers encapsulated by PHEA, and exhibited satisfactory adhesion, considerable antibacterial property, cytocompatibility, conductivity (3.06 S·m−1) and sensing sensitivity (the maximum gauge factor of 5.51). The PH@Ag e-skin could serve as strain sensors to accurately monitor and recognize all kinds of human motions such as swallowing, frowning, walking, and so on, and thus is anticipated to have considerable application prospect in many fields including flexible wearable electronic devices, health and motion monitoring.

Graphical abstract
Development and validation of a stability-indicating RP-HPLC method for estimation of Lefamulin in pure and pharmaceutical drug products
Authors: Usman Muhammad , Abbas Tauqeer
Published: May 2023

Background

Commonly occurring serious lung parenchymal infection is community-acquired bacterial pneumonia (CABP). Lefamulin acetate drug products are useful for the treatment of community-acquired bacterial pneumonia (CABP). The main objective of the study was the development and validation of a quick reverse-phase high performance liquid chromatographic analytical testing method for Lefamulin in pure and pharmaceutical dosage forms. The C18 column was the stationary phase for reverse-phase high performance liquid chromatographic separation, and the mobile phase consisted of 0.05 M phosphate buffer with a pH adjustment of 2.5 mixed with an equal volume of acetonitrile. A flow rate of 1.0 mL/min, a column temperature of 30 °C, an injection volume of 10 µL, and a detection wavelength of 210 nm were used as optimum conditions.

Results

The developed method reported that Lefamulin peak’s retention time was 3.1 min, the average theoretical plate count 5000, and the average peak asymmetry 1.12. In both pure and pharmaceutical dosage forms, the method was found to be accurate, precise, specific, linear calibration curve, and robust. Quantitative assay results from laboratory-made formulations showed similarity to existing commercial products of Lefamulin. Lefamulin is stable in acidic and photolytic environmental circumstances, while it degraded in oxidative, basic, and thermal humidity environment, according to the results of stress studies.

Conclusions

The developed analytical method is fast, economic and stability indicating. It is useful for routine pharmaceutical analysis where the Lefamulin is synthesized in pure form, pharmaceutical tablet formulation, and parenteral dosage form, for their quality and safety.