bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of a novel immune-related signature associated with macrophages and CD8 T cell infiltration predicting overall survival for hepatocellular carcinoma
Authors: Huo Junyu , Wu Liqun , Zang Yunjin
Published: September 2021

Background

Although the effects of macrophages and CD8 T cell infiltration on clinical outcome have been widely reported, the association between immunity-associated gene with them for hepatocellular carcinoma (HCC) remains unclear.

Materials and methods

The ssGSEA served for quantifying the macrophages as well as CD8 T cell infiltration in the HCC samples obtained from TCGA database. Kaplan–Meier (KM) survival assay was used to determine the associations between macrophages and CD8 T cell infiltration with OS. LASSO Cox regressive method assisted in developing an immune gene signature as well as building a risk score. The performance was evaluated by the time-dependent ROC together with the KM survival analysis. The ICGC database were adopted for external verification. CIBERSORT was applied to the correlation analysis on the immune-related signature and the immunocyte infiltration. GSEA were employed exploring the underlying molecular mechanisms.

Results

Increased CD8+ T cell infiltration was associated with longer OS, whereas a greater infiltration of macrophages was related to shorter OS. There were 398 differential expression genes (DEGs) between the high- and low infiltration groups with the “edgeR” package. An prognostic signature consisted of 10 immune genes was built in TCGA and examined in ICGC. The uniform cutoff (0.927) was adopted for separating sufferers into the high-risk (HR) and low-risk (LR) groups. The ROC curves revealed that the AUC data for this signature predicting 1, 2, 3, 4 and 5 year were all above 0.7 in both TCGA and ICGC cohort and patients in the HR group exhibited an evidently weaker prognostic results compared with the LR group. The HR group presented evidently greater Tregs and Macrophage M0 relative to the LR group, whereas the LR group saw the enrichment of CD8 T cells.

Conclusion

The immune signature associated with macrophages as well as CD8 T cell infiltration has reliable prognostic and predictive value for HCC patients.
LINC01605, regulated by the EP300-SMYD2 complex, potentiates the binding between METTL3 and SPTBN2 in colorectal cancer
Authors: Yue Meng , Liu Tao , Yan Guoqiang , Luo Xiaofan , Wang Lei
Published: September 2021

Background

Colorectal cancer (CC) is one of the major contributors to tumor-related death worldwide, and its main cause of death is distant metastasis. Dysregulation of long non-coding RNA (lncRNA) LINC01605 has been implicated in CC. However, its role in metastasis of CC remains elusive. The goal of the study is to uncover the biological function and molecular mechanism of LINC01605 in CC.

Methods

The differentially expressed lncRNAs were first screened from GSE97300, GSE84983, GSE110715, GSE70880, and GSE75970 microarrays. The correlation between the expression of LINC01605 and the clinical phenotypes of enrolled CC patients (n = 134) was subsequently analyzed. The upstream and downstream regulatory mechanisms of LINC01605 in CC were identified through bioinformatics and RNA-seq analyses. Finally, the effects of related factors on CC cell growth and metastasis were confirmed through functional validation experiments.

Results

LINC01605, significantly highly expressed in CC, was a prognostic factor for patients with CC. Functional experiments revealed that LINC01605 knockdown inhibited the proliferatory and metastatic potential of CC cells in vitro and in vivo. Moreover, LINC01605 was regulated by SMYD2-EP300-mediated modifications of histone H3K4me3 as well as H3K27ac. LINC01605 was found to bind to METTL3 and promote the m6A modification of SPTBN2 mRNA, thereby facilitating the translation of SPTBN2.

Conclusions

Overexpression of LINC01605, regulated by SMYD2-EP300-mediated H3K27ac and H3K4me3 modifications, bound to METTL3 protein to promote m6A modification of SPTBN2 mRNA, leading to the development of CC.
An insertion variant of MGMT disrupts a STAT1 binding site and confers susceptibility to glioma
Authors: Huang Liming , Xu Wenshen , Yan Danfang , Shi Xi , You Xin , Xu Jiaqi , You Pingping , Ke Yuanyuan , Dai Lian
Published: September 2021

Background

O6-methylguanine-DNA methyltransferase (MGMT) is a pivotal enzyme for repairing DNA alkylation damage. Epigenetic modification of MGMT has been well known as a promising prognostic biomarker for glioma. However, the significance of genetic variations of MGMT in glioma carcinogenesis has not been fully elucidated.

Methods

The associations between expression quantitative trait loci (eQTLs) of MGMT and glioma susceptibility were evaluated in a case–control study of 1056 individuals. The function of susceptibility locus for glioma was explored with a set of biochemical assays, including luciferase reporter gene, EMSA and supershift EMSA, ChIP, and siRNA knockdown.

Results

We found that rs11016798 TT genotype was associated with a significantly decreased risk of glioma (OR = 0.57, 95% CI 0.39–0.85; P = 0.006). Stratification analyses indicated that the association between rs11016798 and glioma was more pronounced in males (OR = 0.62, 95% CI 0.40–0.97; P = 0.035), older subjects (OR = 0.46, 95% CI 0.27–0.80; P = 0.006), WHO grade IV glioma (OR = 0.58, 95% CI 0.35–0.96; P = 0.033), and IDH wildtype glioma (OR = 0.43, 95% CI 0.21–0.88; P = 0.022). We characterized an insertion variant rs10659396 in the upstream of MGMT as a causative variant. The risk allele rs10659396 ins allele was demonstrated to downregulate MGMT expression by disrupting a STAT1 binding site. Knockdown of STAT1 remarkably attenuated MGMT expression. Moreover, the rs10659396 allele-specific positive correlation was observed between the expression of STAT1 and MGMT in population.

Conclusions

The study demonstrates that an insertion variant of MGMT rs10659396 confers susceptibility to glioma by downregulating MGMT expression through disrupting a STAT1 binding site.

Graphic abstract
Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease
Authors: Wang Lixuan , Jia Jianpu , Hong Zhen , Zhang Leguo , Zhang Junling
Published: September 2021

Background

The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD).

Methods

There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD.

Results

No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD.

Conclusions

Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.
Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study
Authors: Luo Fan , Zeng Kang-mei , Cao Jia-xin , Zhou Ting , Lin Su-xia , Ma Wen-juan , Yang Yun-peng , Zhang Zhong-han , Lu Fei-teng , Huang Yan , Zhao Hong-yun , Zhang Li
Published: September 2021

Background

Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown.

Methods

NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed.

Results

Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025).

Conclusions

Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.
The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS)
Authors: Lv Shiqi , Zhang Han , Chen Jing , Shen Ziyan , Zhu Cheng , Gu Yulu , Yu Xixi , Zhang Di , Wang Yulin , Ding Xiaoqiang , Zhang Xiaoyan
Published: September 2021

Background

Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population.

Methods

This longitudinal cohort research examined 7,316 participants (age range: 22–93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline.

Results

The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03–1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21–3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12–3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05–6.38, P = 0.04).

Conclusions

The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.
Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure
Authors: Campagno Keith E. , Lu Wennan , Jassim Assraa Hassan , Albalawi Farraj , Cenaj Aurora , Tso Huen-Yee , Clark Sophia P. , Sripinun Puttipong , Gómez Néstor Más , Mitchell Claire H.
Published: September 2021

Background

The identification of endogenous signals that lead to microglial activation is a key step in understanding neuroinflammatory cascades. As ATP release accompanies mechanical strain to neural tissue, and as the P2X7 receptor for ATP is expressed on microglial cells, we examined the morphological and molecular consequences of P2X7 receptor stimulation in vivo and in vitro and investigated the contribution of the P2X7 receptor in a model of increased intraocular pressure (IOP).

Methods

In vivo experiments involved intravitreal injections and both transient and sustained elevation of IOP. In vitro experiments were performed on isolated mouse retinal and brain microglial cells. Morphological changes were quantified in vivo using Sholl analysis. Expression of mRNA for M1- and M2-like genes was determined with qPCR. The luciferin/luciferase assay quantified retinal ATP release while fura-2 indicated cytoplasmic calcium. Microglial migration was monitored with a Boyden chamber.

Results

Sholl analysis of Iba1-stained cells showed retraction of microglial ramifications 1 day after injection of P2X7 receptor agonist BzATP into mouse retinae. Mean branch length of ramifications also decreased, while cell body size and expression of Nos2, Tnfa, Arg1, and Chil3 mRNA increased. BzATP induced similar morphological changes in ex vivo tissue isolated from Cx3CR1+/GFP mice, suggesting recruitment of external cells was unnecessary. Immunohistochemistry suggested primary microglial cultures expressed the P2X7 receptor, while functional expression was demonstrated with Ca2+ elevation by BzATP and block by specific antagonist A839977. BzATP induced process retraction and cell body enlargement within minutes in isolated microglial cells and increased Nos2 and Arg1. While ATP increased microglial migration, this required the P2Y12 receptor and not P2X7 receptor. Transient elevation of IOP led to microglial process retraction, cell body enlargement, and gene upregulation paralleling changes observed with BzATP injection, in addition to retinal ATP release. Pressure-dependent changes were reduced in P2X7−/− mice. Death of retinal ganglion cells accompanied increased IOP in C57Bl/6J, but not P2X7−/− mice, and neuronal loss showed some association with microglial activation.

Conclusions

P2X7 receptor stimulation induced rapid morphological activation of microglial cells, including process retraction and cell body enlargement, and upregulation of markers linked to both M1- and M2-type activation. Parallel responses accompanied IOP elevation, suggesting ATP release and P2X7 receptor stimulation influence the early microglial response to increased pressure.
Dentition and body condition: tooth wear as a correlate of weight loss in roe deer
Authors: Chirichella Roberta , De Marinis Anna Maria , Pokorny Boštjan , Apollonio Marco
Published: September 2021

Background

In many mammalian species, once the permanent teeth have erupted, the only change to dentition is a gradual loss of tooth surface/height through wear. The crown of the teeth cannot be repaired once worn. When dental crown tissue has been depleted due to wear, the animal is expected to have a suboptimal body condition. We evaluated the role of tooth wear in causing a reduction of physical condition in adult roe deer females (Capreolus capreolus).

Results

The progressive wearing of the lower cheek teeth was assessed in a Northern Apennines (Italy) population with a new scoring scheme based on objectively described tooth characteristics (morphotypes) being either present or absent. Eviscerated body mass and mandible length, which is a good proxy for body size in roe deer, were related to the tooth wear score by the use of linear regressions. The sum of wear scores for molariform teeth correlated most strongly with body condition (i.e., eviscerated body mass/mandible length), showing the importance of the entire chewing surface for acquiring energy by food comminution, chewing, and digestion. In comparison with individuals of comparable size experiencing minor tooth wear, the body mass of those with the most advanced stage of tooth wear was decreased by 33.7%. This method was compared to the height and the hypsodonty index of the first molar, the most commonly used indices of tooth wear. The sum of molariform wear scoring scheme resulted in a more suitable index to describe the variation in body condition of roe deer.

Conclusions

Describing tooth wear patterns in hunted populations and monitoring at which tooth wear level (and therefore dental morphotype) an animal is no longer able to sustain its physical condition (i.e. when it begins to lose body mass) can be a useful tool for improving the management of the most widespread and abundant deer species in Europe. At the same time, such an approach can clarify the role of tooth wear as a proximate cause of senescence in ungulates.
Antibiotic calcium sulfate-loaded hybrid transport versus traditional Ilizarov bone transport in the treatment of large tibial defects after trauma
Authors: Huang Qiang , Ren Cheng , Li Ming , Xu YiBo , Li Zhong , Lin Hua , Zhang Kun , Ma Teng
Published: September 2021

Background

The purpose of this study was to compare the clinical effects of antibiotic calcium sulfate-loaded hybrid transport (ACSLHT) and traditional Ilizarov bone transport (TIBT) in the treatment of large tibial defects after trauma.

Methods

Eighty-five patients with large tibial defects after trauma were selected for retrospective study. The range of tibial defects was 6–22 cm. After thorough debridement and infection controlled, bone transport technique was used to reconstruct tibial defects. Forty-four patients were treated with ACSLHT technique (the ACSLHT group), while the other 41 were treated with TIBT technique (the TIBT group). Time in external fixator was evaluated by EFI score. Enneking score was used to evaluate limb functions. SAS score was used to evaluate postoperative anxiety status. In addition, complication incidence was compared, including axis deviation, docking site nonunion, infection recurrence and so on.

Results

There was no significant difference in preoperative general data between ACSLHT and TIBT group. EFI score in ACSLHT and TIBT group was 0.6 ± 0.1 cm/month and 1.7 ± 0.3 cm/month, respectively (P < 0.05). Enneking score of ACSLHT and TIBT group was 86.5% and 75.1% (P < 0.05). SAS score of ACSLHT group was significantly lower than that of TIBT group (P < 0.05). Complication incidence in ACSLHT group was significantly lower than that in TIBT group (P < 0.05).

Conclusions

Compared with TIBT group, ACSLHT group had shorter time in external fixator, better limb functions, lower postoperative anxiety score and lower complication incidence which is worth of clinical promotion.
Surgical outcomes of one-stage resection for synchronous multiple primary lung adenocarcinomas with no less than three lesions
Authors: Qu Rirong , Tu Dehao , Ping Wei , Cai Yixin , Zhang Ni , Fu Xiangning
Published: September 2021

Background

More and more synchronous multiple primary lung adenocarcinomas (SMPLA) have been diagnosed and surgical treatment has become the mainstay of treatment for them, but there are few reports on the surgical outcome of patients with ≥ 3 lesions who underwent surgical resection. Therefore, we summarized and analyzed the clinical characteristics and surgical outcomes of these patients, hoping to provide some experience in the diagnosis and treatment.

Methods

Clinical characteristics and treatment outcomes of patients with ≥ 3 lesions who have been diagnosed as SMPLA and underwent surgical resection in our hospital from March 2015 to July 2019 were retrospectively reviewed.

Results

Twenty-eight patients, 20 females and 8 males, with a mean age of 57.7 ± 5.69 (45–76) years, were finally included. A total of 95 lesions, 86.4% were ground-glass opacity (GGO) lesions (pure-GGO,45.3%; mixed-GGO,41.1%); 51 lesions had EGFR mutations and the mutation rate of invasive adenocarcinoma was significantly higher than that of other pathological subtypes (P < 0.001); the mutation rate of mGGO was also significantly higher than that of pGGO and solid nodule (SN) (P < 0.05). Four and 24 patients respectively underwent bilateral and unilateral surgical resection. The surgical procedure was mainly sublobar resection, and no severe postoperative complications or deaths occurred. After a median follow-up time of 32.2 months, the rates of overall survival and disease-free survival at 3 years were 94.7% and 88.9%, respectively.

Conclusions

For SMPLA with ≥ 3 lesions, one-stage resection may be safe and feasible, and surgical procedure was mainly sublobar resection as far as possible, which can yield satisfactory prognosis. EGFR mutation testing should be used routinely in the diagnosis and treatment of patients with SMPLA, especially in the presence of mGGO and invasive adenocarcinoma.
Splice-variant specific effects of a CACNA1H mutation associated with writer’s cramp
Authors: Souza Ivana A. , Gandini Maria A. , Zamponi Gerald W.
Published: September 2021

The CACNA1H gene encodes the α1 subunit of the low voltage-activated Cav3.2 T-type calcium channel, an important regulator of neuronal excitability. Alternative mRNA splicing can generate multiple channel variants with distinct biophysical properties and expression patterns. Two major splice variants, containing or lacking exon 26 (± 26) have been found in different human tissues. In this study, we report splice variant specific effects of a Cav3.2 mutation found in patients with autosomal dominant writer’s cramp, a specific type of focal dystonia. We had previously reported that the R481C missense mutation caused a gain of function effect when expressed in Cav3.2 (+ 26) by accelerating its recovery from inactivation. Here, we show that when the mutation is expressed in the short variant of the channel (− 26), we observe a significant increase in current density when compared to wild-type Cav3.2 (− 26) but the effect on the recovery from inactivation is lost. Our data add to growing evidence that the functional expression of calcium channel mutations depends on which splice variant is being examined.
The TEAM instrument for measuring emergency team performance: validation of the Swedish version at two emergency departments
Authors: Karlgren Klas , Dahlström Anders , Birkestam Anderz , Drevstam Norling Annelie , Forss Gustav , Andersson Franko Mikael , Cooper Simon , Leijon Thomas , Paulsson Charlotta
Published: September 2021

Background

The Team Emergency Assessment Measure (TEAM) questionnaire is designed for rating the non-technical performance of emergency medical teams during emergencies, e.g., resuscitation or trauma management. Originally developed in Australia it has today been translated and validated into eleven languages, but a Swedish version is lacking. The aim was therefore to cross-culturally translate and evaluate the reliability and validity of the TEAM questionnaire in a Swedish health care setting.

Methods

The instrument was forward and backward translated and adapted into a Swedish context according to established guidelines for cross-cultural adaptation of survey-based measures. The translated version was tested through 78 pairwise assessments of 39 high-priority codes at the emergency departments of two major hospitals. The raters observed the teams at work in real time and filled in the questionnaires immediately afterwards independently of each other. Psychometric properties of the instrument were evaluated.

Results

The original instrument was translated by pairs of translators independently of each other and reviewed by an expert committee of researchers, nurses and physicians from different specialties, a linguist and one of the original developers of the tool. A few adaptations were needed for the Swedish context. A principal component factor analysis confirmed a single ‘teamwork’ construct in line with the original instrument. The Swedish version showed excellent reliability with a Cronbach’s alpha of 0.955 and a mean inter-item correlation of 0.691. The mean item-scale correlation of 0.82 indicated high internal consistency reliability. Inter-rater reliability was measured by intraclass correlation and was 0.74 for the global score indicating good reliability. Individual items ranged between 0.52 and 0.88. No floor effects but ceiling effects were noted. Finally, teams displaying clear closed-loop communication had higher TEAM scores than teams with less clear communication.

Conclusions

Real time observations of authentic, high priority cases at two emergency departments show that the Swedish version of the TEAM instrument has good psychometric properties for evaluating team performance. The TEAM instrument is thus a welcome tool for assessing non-technical skills of emergency medical teams.
[123I]MIBG is a better early marker of anthracycline cardiotoxicity than [18F]FDG: a preclinical SPECT/CT and simultaneous PET/MR study
Authors: Oudot Alexandra , Courteau Alan , Guillemin Mélanie , Vrigneaud Jean-Marc , Walker Paul Michael , Brunotte François , Cochet Alexandre , Collin Bertrand
Published: September 2021

Background

During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [18F]FDG and [123I]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model.

Methods

Male Wistar Han rats were intravenously administered 3 times at 10 days’ interval with saline or doxorubicin (5 mg/kg). [123I]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [18F]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements.

Results

At week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 ± 6% vs. 70 ± 3%). At weeks 4 and 6, but not at week 2, myocardial [18F]FDG uptake was decreased compared with the control group (respectively, 4.2 ± 0.5%ID/g and 9.2 ± 0.8%ID/g at week 6). Moreover, [18F]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [123I]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6.

Conclusion

This longitudinal study precises that after doxorubicin treatment, cardiac [123I]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [18F]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.
Efficient 3-hydroxypropionic acid production by Acetobacter sp. CIP 58.66 through a feeding strategy based on pH control
Authors: de Fouchécour Florence , Lemarchand Anaïs , Spinnler Henry-Éric , Saulou-Bérion Claire
Published: September 2021

Acetic acid bacteria (AAB) can selectively oxidize diols into their corresponding hydroxyacids. Notably, they can convert 1,3-propanediol (1,3-PDO) into 3-hydroxypropionic acid (3-HP), which is a promising building-block. Until now, 3-HP production with AAB is carried out in batch and using resting cells at high cell densities (up to 10 g L−1 of cell dry weight). This approach is likely limited by detrimental accumulation of the intermediate 3-hydroxypropanal (3-HPA). Herein, we investigate an alternative implementation that allows highly efficient 3-HP production with lower cell densities of growing cells and that prevents 3-HPA accumulation. First, growth and 3-HP production of Acetobacter sp. CIP 58.66 were characterized with 1,3-PDO or glycerol as growth substrate. The strain was then implemented in a bioreactor, during a sequential process where it was first cultivated on glycerol, then the precursor 1,3-PDO was continuously supplied at a varying rate, easily controlled by the pH control. Different pH set points were tested (5.0, 4.5, and 4.0). This approach used the natural resistance of acetic acid bacteria to acidic conditions. Surprisingly, when pH was controlled at 5.0, the performances achieved in terms of titer (69.76 g3-HP L−1), mean productivity (2.80 g3-HP L−1 h−1), and molar yield (1.02 mol3-HP mol−11,3-PDO) were comparable to results obtained with genetically improved strains at neutral pH. The present results were obtained with comparatively lower cell densities (from 0.88 to 2.08 g L−1) than previously reported. This feeding strategy could be well-suited for future scale-up, since lower cell densities imply lower process costs and energy needs.
β-adrenergic receptor inhibition enhances oncolytic herpes virus propagation through STAT3 activation in gastric cancer
Authors: Hu Jiali , Lu Ruitao , Zhang Yu , Li Wei , Hu Qian , Chen Cuiyu , Liu Zhaoqian , Zhang Wei , Chen Ling , Xu Ran , Luo Jia , McLeod Howard L. , He Yijing
Published: September 2021

Background

Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair the viral propagation in tumor cells. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the antitumor efficacy of T1012G virus in gastric cancer models.

Methods

The proliferation of gastric cancer cells treated with monotherapy or combination treatment was detected by CCK8 cell proliferation assay. The effect of propranolol was further evaluated by in vitro viral replication assays. In vivo tumor xenograft experiments were used to observe the effect of combination therapy on gastric cancer growth in mice. The expression levels of viral proteins and interferon responsive genes were detected in the gastric cancer cell lines treated with combined treatment by western blot. The impact of propranolol on IFN-α/β-mediated inhibition of viral propagation and the expression of antiviral gene PKR was detected by viral replication assays and western blot.

Results

Cell viability assay detected a 97.9% decrease of T1012G IC50 in HGC-27 when it was pretreated with propranolol along with a sevenfold increase of virus titers compared with T1012G only group (P < 0.001). Moreover, propranolol pretreatment caused sustained tumor regression (335.3 ± 36.92 mm3 vs. 1118 ± 210.0 mm3, P < 0.01) and enhanced the viral propagation (fourfold increase, P < 0.01) compared with T1012G only group. Propranolol pretreatment significantly enhanced the p-STAT3 (2.9-fold, P < 0.05) and suppressed p-PKR (65.94% ± 10.11%, P < 0.05) compared with T1012G only group. In addition, propranolol could counteract IFN-α/β-mediated inhibition of viral propagation (compared with IFNα: 5.1-fold, P < 0.001; IFNβ: 4.6-fold, P < 0.01) or enhancement of PKR activation (IFNα: 92.57% ± 1.77%, P < 0.001, IFNβ: 99.34% ± 0.13% decrease, P < 0.001).

Conclusions

In summary, β-blocker pretreatment could improve the propagation and therapeutic efficacy of T1012G in human gastric cancer by regulating STAT3-PKR signaling cascade, even in the presence of type I IFNs. These data support new strategies of improving the efficacy of OVs in gastric cancer.
Development and preliminary evaluation of Chinese School-aged Children’s Eating Behavior Scale
Authors: Zhang Hao , Jiang Xun , Zhang Yu-hai , Yuan Jing , Tan Zhi-jun , Xu Tong , Shang Lei
Published: September 2021

Background

The objective of this study was to develop a scale to assess eating behaviors of school-aged children (6–12 years old) in China.

Methods

To develop the scale, a literature review and qualitative interviews were conducted. The draft scale contained 115 items and went through three evaluations among three groups of caregivers (n = 140, 400, 700) selected from suburban and urban kindergartens in Xi’an, Hanzhong, and Yanan, China, from March 2017 to October 2018. The psychometric properties of the scale were assessed using exploratory, confirmatory factor analysis, and variability analysis.

Results

The final scale consisted of 46 items across eight dimensions including food fussiness, satiety responsiveness, food responsiveness, bad eating habits, susceptible diet, restrained eating, enjoyment of food, and junk food addiction. The total cumulative variance contribution rate was 52.16%. The scale and dimensions' Cronbach’s α coefficients, Guttman split-half reliability, and test- retest reliability were all above 0.65. The fitting indices for the confirmatory factor analysis were all close to 1. The scores for education of caregiver, family structure, and the body mass index of children were different among dimensions and groups, thus suggesting good discriminative utility.

Conclusions

All of the results indicated that the scale has good reliability and construct validity for evaluating the eating behaviors of school-aged children in China.
Instructional changes instigated by university faculty during the COVID-19 pandemic: the effect of individual, course and institutional factors
Authors: Lee Jihyun , Jung Insung
Published: September 2021

The purpose of this study was to investigate instructional changes made by faculty for emergency online teaching necessitated by the COVID-19 pandemic, and hence to explore key factors related to those changes from an ecological systems perspective. Data on various individual, course, and institutional factors and instructional change variables were collected from 201 educators at higher education institutions. Results revealed that the level of instructional changes made by faculty was on average between substituting their existing course for an online one with some functional improvement (augmentation-level 3) and critical course redesign (modification-level 4), but that educators did not reach the level of the creation of new tasks which were previously inconceivable (redefinition-level 5). The biggest instructional change was found to be in teaching behaviors, followed by technology use, with only small changes in beliefs about online teaching. Factors that most highly correlated with instructional change were individual educators’ technology acceptance and innovation propensity, media synchronicity of the course, and the fidelity of institutional support. Recommendations are provided to aid strategic coping by universities facing a major crisis, with insights that may ultimately improve the quality of higher education in non-crisis contexts.
Protective effects of Zingiber officinale extract on myocardium and placenta against labetalol-induced histopathological, immune-histochemical, and ultrastructural alterations in pregnant rats
Authors: El-Borm Hend T. , Atallah Marwa N.
Published: September 2021

Background

Labetalol is an antihypertensive drug commonly used in obstetrics for both long-term treatment and the acute management of severe maternal hypertension. However, there have not been published articles about the effects of labetalol on the myocardium and the placenta. This study aimed to estimate the histological, immune-histochemical, and ultrastructural cardio- and placental-toxicity of labetalol administration and the effectiveness of ginger against this toxicity in pregnant rats. Labetalol was daily administrated orally with or without ginger at a dose of 300 mg/kg and 200 mg/kg, respectively, during the gestation days 6 to 20.

Results

In the labetalol-administrated group, the myocardium displayed histological and ultrastructure destructive changes and a significant increase in caspase-3 expression. Labetalol also decreased the placental weight compared with the control group, caused marked degeneration and disorganization of their architecture, and increased caspase-3 expression. Co-administration of ginger after labetalol highly ameliorates the adverse effect of labetalol on both cardiac and placental tissues.

Conclusions

It is concluded that ginger can mitigate cardiac and placental toxicity induced by labetalol administration into pregnant rats.
Bio-efficacy of entomopathogenic nematodes, Steinernema feltiae and Heterorhabditis bacteriophora against the Cabbage butterfly (Pieris brassicae [L.]) under laboratory conditions
Authors: Kasi Indra Kumar , Singh Mohinder , Waiba Kanchhi Maya , Monika S. , Waseem M. A. , Archie D. , Gilhotra Himanshu
Published: September 2021

Background

Entomopathogenic nematodes (EPNs) have the potential to supersede larvicidal activity for the management of various insect pests.

Result

Lab experiments were conducted to test the pathogenicity of 2 EPNs local species; Steinernema feltiae and Heterorhabditis bacteriophora at different (IJs/cm2) concentrations against the cabbage butterfly, Pieris brassicae (L.). The native isolate was obtained from soil samples, collected from Rajgarh, Hamachi Pradesh, India. Petri dish bioassay used the EPNs species (S. feltiae HR1 and H. bacteriophora HR2) at the concentrations (0, 10, 20, 40, 80, 160 IJs/cm2). Based on the pathogenicity of the strains, only 2 isolates effectively showed larvicidal activity. The highest (%) (72.08 and 67.42%), at the 2nd instar larval mortality was recorded in the treatments with H. bacteriophora and S. feltiae at160 IJs/cm2, respectively. At the 4th instar larvae, respective larval mortality (85.38, 69.50%) was recorded in treatment with H. bacteriophora, and S. feltiae, respectively, at160 IJs/cm2. In case of pupae, the mortality rates were (62.12, 58.58%) for H. bacteriophora and S. feltiae, respectively, at 160 IJs/cm2; (74 and 12%) for both the tested EPNs, respectively, at 80 IJs/cm2. Percent of P. brassicae larval mortality treated with the tested EPN isolates was significantly higher than the untreated control. Results revealed that the percent of larval mortality significantly increased with the increase in time periods, being maximum at 72 h. S. feltiae and H. bacteriophora, strains showed potent larvicidal activity at low concentration even at 48 and 72 h of exposure.

Conclusion

This study revealed that the local strains of EPNs (S. feltiae HR1 and H. bacteriophora HR2) were found as a biocontrol agent against P. brassicae.
Frequency and risk factors of carotid artery disease among ischemic stroke patients in the south Egypt: hospital-based study
Authors: Khedr Eman , Tony Abeer A. , Habeel Mohamed , Nasreldein Ahmed
Published: September 2021

Background

Limited data are available on the frequency of carotid artery disease among cerebrovascular ischemic stroke (CVS) patients in south Egypt. The aim of the present study is to determine the prevalence and risk factors of extracranial atherosclerosis among stroke patients using extracranial duplex ultrasound.

Results

142 patients (76.8%) were males and 43 (23.2%) were females. Their mean age was 63.3 ± 9.79 years with no significant difference between the mean age of the male and female groups. NIHSS score ranged from 3 to 25 (mean ± S.D; 11.89 ± 4.91). 66 patients (35.7%) had no atherosclerotic changes, 75 patient (40.5%) had stenosis < 70% and 44 patients (23.8%) had stenosis ≥ 70%. The most prevalent modifiable risk factors for atherosclerosis were hypertension (74.8%), hyperlipidemia (70.6%), smoking (59.7%) and DM (45.4%).

Conclusion

Atherosclerosis among people in the south Egypt is relatively high in comparison to other regions in Egypt and Middle East. This is a call for performing further population-based epidemiological studies, to address the exact magnitude of the problem and invest into prevention.
Invasive mechanical ventilation complications in COVID-19 patients
Authors: Ibrahim Ghada Sobhy , Alkandari Buthaina M. , Shady Islam Ahmed Abo , Gupta Vikash K. , Abdelmohsen Mohsen Ahmed
Published: September 2021

Background

Since late 2019, COVID-19 infection has quickly spread substantially in all countries, forcing the appropriation of noteworthy lockdown and social separating measures. It has been considered as a pandemic by the World Health Organization. Positive pressure ventilation is a non-physiological and invasive intervention that can be lifesaving in COVID-19 patients. Similar to any other interventions, it can cause its own danger and complications as it can prompt ventilator-induced lung injury and barotrauma. The aim of the work was to identify the incidence of invasive mechanical ventilation complication in COVID-19 pneumonias, and to describe patient characteristics and patterns of barotrauma in COVID-19 patients.

Results

This retrospective study included 103 patients with COVID-19 pneumonia, 76 males and 27 females are on invasive mechanical ventilation. Their mean age was 56.6, ranged from 21 to 85 years old. Barotraumas event type in the studied patients, (NB: one or multiple barotrauma events occurring on the same day were considered as single event (95/103 patients-92.23%), while separate multiple events (8/103 patients-7.77%) were recorded when occurring separated by at least 24 h). Single barotrauma events were subdivided into: one event (67/95 patients—70.53%), & multiple events (28/95 patients—29.47%). The mean interval between invasive mechanical ventilation and developing barotraumas was 3–7 days included 41 patients (39.98%). We revealed a strong prevalence of COVID-19 IMV complication with worsening prognosis and subsequent higher death rates in elderly smoker or obese males, as well as those suffering from ARDS. Past medical history (hypertension, DM, chronic renal or cardiac disease) or surgical history of CABG was more liable for these types of complications.

Conclusion

Patients with COVID-19 pneumonia were more liable to the higher incidence of barotraumas with presence of predisposition and high risk factors. In general, an outstanding bad prognostic outcome and a significantly high mortality rate prevailed in COVID-19 patients associated with mechanically ventilated patients.
Management of high inguinal undescended testis: a review of literature
Authors: Shreyas K. , Rathod Kirtikumar J. , Sinha Arvind
Published: September 2021

Background

Undescended testis is one of the most common paediatric surgical diagnoses. A lot of research has been done to date, to standardise the surgical management of intra-abdominal and extra-abdominal undescended testis. High inguinal undescended testis is a unique clinical encounter which demands additional surgical measures over conventional orchidopexy for better surgical results.

Main body of abstract

Open inguinal orchidopexy is a routine and quite straightforward operation for the majority of extra-abdominal undescended testis. However, there are instances in which the testis, even though situated in the inguinal region, poses a challenge for surgeons, to bring it in the scrotum by routine open inguinal orchiopexy. High inguinal testis can be defined as “any intra-canalicular testis present higher up in the inguinal canal and cannot be brought down easily to the scrotum by routine surgery as in standard orchiopexy (open or laparoscopy) and require additional lengthening manoeuvres”. It needs additional surgical lengthening manoeuvres like Prentiss, along with the steps of routine orchiopexy to bring it down in the scrotum. This review article describes the various nomenclatures of undescended testis, appropriate investigations and also various additional surgical measures in the management of difficult high inguinal testis.

Conclusion

High inguinal undescended testis poses a unique technical challenge even to well-experienced surgeons. It is very important that surgeons dealing with this condition are well aware of the anatomy in this region and also various different manoeuvres described to date to bring the testis down in the scrotum.
Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability
Authors: Wang Li , Astone Matteo , Alam Sk. Kayum , Zhu Zhu , Pei Wuhong , Frank David A. , Burgess Shawn M. , Hoeppner Luke H.
Published: September 2021

Vascular permeability triggered by inflammation or ischemia promotes edema, exacerbates disease progression and impairs tissue recovery. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability. VEGF plays an integral role in regulating vascular barrier function physiologically and in pathologies, including cancer, stroke, cardiovascular disease, retinal conditions and COVID-19-associated pulmonary edema, sepsis and acute lung injury. Understanding temporal molecular regulation of VEGF-induced vascular permeability will facilitate developing therapeutics to inhibit vascular permeability, while preserving tissue-restorative angiogenesis. Here, we demonstrate that VEGF signals through signal transducer and activator of transcription 3 (STAT3) to promote vascular permeability. We show that genetic STAT3 ablation reduces vascular permeability in STAT3-deficient endothelium of mice and VEGF-inducible zebrafish crossed with CRISPR/Cas9-generated Stat3 knockout zebrafish. Intercellular adhesion molecule 1 (ICAM-1) expression is transcriptionally regulated by STAT3, and VEGF-dependent STAT3 activation is regulated by JAK2. Pyrimethamine, an FDA-approved antimicrobial agent that inhibits STAT3-dependent transcription, substantially reduces VEGF-induced vascular permeability in zebrafish, mouse and human endothelium. Collectively, our findings suggest that VEGF/VEGFR-2/JAK2/STAT3 signaling regulates vascular barrier integrity, and inhibition of STAT3-dependent activity reduces VEGF-induced vascular permeability.

This article has an associated First Person interview with the first author of the paper.