bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial Blood Flow and Flow Reserve in Patients With Acute Myocardial Infarction and Obstructive and Non-Obstructive Coronary Arteries: CZT SPECT Study
Authors: Zavadovsky Konstantin V. , Vorobyeva Darya A. , Mochula Olga V. , Mochula Andrew V. , Maltseva Alina N. , Bayev Andrew E. , Gulya Marina O. , Gimelli Alessia , Ryabov Vyacheslav V.
Published: July 2022

Background

To assess single-photon emission computed tomography cadmium-zinc-telluride (SPECT CZT)-derived myocardial blood flow (MBF) flow reserve (MFR) and flow difference (FD) in patients with acute myocardial infarction (AMI) and to compare this data with serum cardiac troponin and cardiac magnetic resonance (CMR) findings.

Methods

A total of 31 patients with AMI underwent invasive coronary angiography (ICA), serial high-sensitivity serum cardiac troponin I (cTnI) measurement, and CZT SPECT with visual and quantitative (MBF, MFR, and FD) perfusion parameters, and contrast-enhanced CMR. All patients with AMI were divided into two groups: (1) with non-obstructive coronary arteries (MINOCA), n = 10; (2) with obstructive coronary artery disease (MICAD), n = 21.

Results

The values of SSS and SRS were significantly (p < 0.01) higher whereas global stress MBF, MFR significantly lower in patients with MICAD as compared to MINOCA – 5.0 (3.0; 5.0) vs. 9.0 (5.0; 13.0); 2.0 (1.0; 3.0) vs. 6.0 (3.0; 11.0); 2.02 (1.71; 2.37) vs. 0.86 (0.72; 1.02) ml/min/g; and 2.61 (2.23; 3.14) vs. 1.67 (1.1; 1.9), respectively. Stress MBF correlated with cTnI at 24 h and day 4: ρ = −0.39; p = 0.03 and ρ = −0.47; p = 0.007, respectively. FD correlated with cTnI at 24 h and day 4: ρ = −0.39; p = 0.03 and ρ = −0.46; p = 0.009. CMR analysis showed that infarct size, MVO and myocardial edema in patients with MICAD were significantly (< 0.05) higher as compared to MINOCA: 19.4 (10.4; 29.7) vs. 1.8 (0.0; 6.9); 0.1 (0.0; 0.7) vs. 0.0 (0.0; 0.0) and 19.5 (12.0;30.0) vs. 3.0 (0.0; 12.0), respectively. According to vessel-based analysis of CMR data, acute myocardial injury (defined as late gadolinium enhancement and myocardial edema) was observed more frequently in patients with MICAD compared to MINOCA: 34(37%) vs. 5(5%) p = 0.005, respectively. The values of regional stress MBF, MFR and FD were significantly decreased in LV territories characterized by myocardial injury compared to those without: 0.98 (0.73; 1.79) vs. 1.33 (0.94; 2.08) p < 0.01, 1.64 (1.0; 2.36) vs. 2.0 (1.53; 2.89) p < 0.01 and 0.33 (0.05; 0.57) vs. 0.56 (0.36; 1.32) p> 0.01, respectively.

Conclusion

In patients with AMI, SPECT CZT-derived flow measures were associated with the high-sensitivity troponin I as well as the extent of edema, microvascular obstruction, and infarct size detected by CMR. On the regional level, quantitative SPECT CZT measures were significantly lower in vessel territories characterized by myocardial injury.
m6A Regulator-Based Methylation Modification Patterns Characterized by Distinct Tumor Microenvironment Immune Profiles in Rectal Cancer
Authors: Liao Kaili , Hu Jialing , Huang Yu , Yu Siji , Yang Qijun , Sun Fan , Wu Chengfeng , Cheng Yunqi , Zhang Wenyige , Zhang Xue , Li Hongyu , Wang Xiaozhong
Published: July 2022

Background

Previous studies reported the related role of RNA n6-methyladenosine (m6A) modification in tumorigenesis and development. However, it is not clear whether m6A modification also plays a potential role in the immune regulation of rectal cancer (RC) and the formation of tumor microenvironment.

Methods

In this study, we screened 23 m6A regulatory factors from 369 rectal cancer specimens, further determined the modification patterns of m6A in RC, and systematically linked these modification patterns with the characteristics of TME cell infiltration. The principal component analysis (PCA) algorithm was used to evaluate the m6A modification pattern of a single tumor related to immune response.

Results

Three different m6A modification patterns were found in the measurement results, which are related to different clinical results and biological pathways. TME identification results show that the identified m6A pattern is closely related to immune characteristics. According to the m6Ascore extracted from m6A-related signature genes, RC patients were divided into high and low score subgroups combined with tumor mutation burden. Patients with high tumor mutation burden and higher m6Ascore have a significant survival advantage and enhanced immune infiltration. Further analysis showed that patients with higher m6Ascore had higher PD-L1 expression levels and showed better immune response and lasting clinical benefits.

Conclusions

M6A modification plays a crucial role in the formation of TME diversity and complexity. The evaluation of the m6A modification mode will help us to enhance our understanding of the characteristics of TME infiltration and provide new insights for more effective immunotherapy strategies.
The Potential Value of Gastric Histopathology for Predicting Colorectal Adenomatous Polyps Among the Chinese Population: A Retrospective Cross-Sectional Study
Authors: Li Weiwei , Zhang Lin , Jing Yuanming , Yang Yanfei , Wang Yulong
Published: July 2022

Background

It remains unknown whether gastric histopathology is associated with the occurrence of colonic neoplasms. We aimed to clarify the association between gastric histopathology and different types of colorectal polyps (CP) and colorectal cancer (CRC), and whether various gastric histopathologies are risk factors for different types of CP and CRC.

Methods

A retrospective cross-sectional study was conducted on 5,986 patients who underwent gastroscopy and colonoscopy simultaneously at Shaoxing People’s Hospital from August 1, 2019, to May 31, 2020. The Pearson χ2 test was used to analyze the occurrence of various gastric histopathologies in different types of CP and CRC, and logistic regression was used to determine whether various gastric histopathologies were risk factors for different types of CP and CRC.

Results

For the Chinese population, male sex (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.41–1.97, P < 0.001) and old age (OR 1.03, 95% CI 1.02–1.04, P < 0.001) were risk factors for non-adenomatous polyps (NAP), but Helicobacter pylori (H. pylori) and various gastric histopathologies were not significant in the NAP compared with the normal group. Nevertheless, it is noteworthy that, similar to male sex and old age, H. pylori (OR 1.22, 95% CI 1.08–1.38, P = 0.002), low-grade intraepithelial neoplasia (LGIN) (OR 1.79, 95% CI 1.21–2.66, P = 0.004), gastric fundus gland polyps (FGPs) (OR 1.44, 95% CI 1.11–1.87, P = 0.007), hyperplastic/inflammatory gastric polyps (GHP or GIP) (OR 1.50, 95% CI 1.06–2.12, P = 0.022), and atrophy/intestinal metaplasia (AG or IM) (OR 1.27, 95% CI 1.13–1.43, P < 0.001) were all risk factors for colorectal adenomatous polyps (AP). However, the results of CRC showed that old age (OR 1.13, 95% CI 1.10–1.16, P < 0.001) and H. pylori (OR 1.67, 95% CI 0.99–2.75, P < 0.05) were risk factors for CRC (OR 1.67, 95% CI 0.99–2.75, P < 0.05), but not sex and various gastric histopathologies (P > 0.05).

Conclusion

Gastric histopathology, such as AG or IM, LGIN, FGP, and GHP or GIP, were risk factors for AP, but not for NAP and CRC, indicating that gastric histopathology has potential predictive value for AP in the Chinese population.
Increased ASF1B Expression Correlates With Poor Prognosis in Patients With Gliomas
Authors: Zhu Huaxin , Ouyang Hengyang , Pan Xinyi , Zhang Zhixiong , Tan Jiacong , Yu Nianzu , Li Meihua , Zhao Yeyu
Published: July 2022

Background

Several studies have suggested that anti-silencing function 1 B (ASF1B) can serve as a good potential marker for predicting tumor prognosis. But the values of ASF1B in gliomas have not been elucidated and further confirmation is needed.

Methods

Transcriptomic and clinical data were downloaded from The Cancer Genome Atlas database (TCGA), genotypic tissue expression (GTEx), and the Chinese Gliomas Genome Atlas database (CGGA). Univariate and multivariate Cox regression analyses were used to investigate the link between clinical variables and ASF1B. Survival analysis was used to assess the association between ASF1B expression and overall survival (OS). The relationship between ASF1B expression and OS was studied using survival analysis. To investigate the probable function and immunological infiltration, researchers used gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA).

Results

In glioma tissues, ASF1B expression was considerably higher than in normal tissues. The survival analysis found that increased ASF1B expression was linked with a poor prognosis in glioma patients. ASF1B demonstrated a high diagnostic value in glioma patients, according to a Receiver Operating Characteristic (ROC) analysis. ASF1B was found to be an independent predictive factor for OS in a Cox regression study (HR = 1.573, 95% CI: 1.053–2.350, p = 0.027). GO, KEGG, and GSEA functional enrichment analysis revealed that ASF1B was associated with nuclear division, cell cycle, m-phase, and cell cycle checkpoints. Immuno-infiltration analysis revealed that ASF1B was positively related to Th2 cells, macrophages, and aDC and was negatively related to pDC, TFH, and NK CD56 bright cells.

Conclusion

A high level of ASF1B mRNA expression was correlated with a poor prognosis in glioma patients in this study, implying that it could be a reliable prognostic biomarker for glioma patients.
Preoperative Prediction of Lymph Node Metastasis of Pancreatic Ductal Adenocarcinoma Based on a Radiomics Nomogram of Dual-Parametric MRI Imaging
Authors: Shi Lin , Wang Ling , Wu Cuiyun , Wei Yuguo , Zhang Yang , Chen Junfa
Published: July 2022

Purpose

This study aims to uncover and validate an MRI-based radiomics nomogram for detecting lymph node metastasis (LNM) in pancreatic ductal adenocarcinoma (PDAC) patients prior to surgery.

Materials and Methods

We retrospectively collected 141 patients with pathologically confirmed PDAC who underwent preoperative T2-weighted imaging (T2WI) and portal venous phase (PVP) contrast-enhanced T1-weighted imaging (T1WI) scans between January 2017 and December 2021. The patients were randomly divided into training (n = 98) and validation (n = 43) cohorts at a ratio of 7:3. For each sequence, 1037 radiomics features were extracted and analyzed. After applying the gradient-boosting decision tree (GBDT), the key MRI radiomics features were selected. Three radiomics scores (rad-score 1 for PVP, rad-score 2 for T2WI, and rad-score 3 for T2WI combined with PVP) were calculated. Rad-score 3 and clinical independent risk factors were combined to construct a nomogram for the prediction of LNM of PDAC by multivariable logistic regression analysis. The predictive performances of the rad-scores and the nomogram were assessed by the area under the operating characteristic curve (AUC), and the clinical utility of the radiomics nomogram was assessed by decision curve analysis (DCA).

Results

Six radiomics features of T2WI, eight radiomics features of PVP and ten radiomics features of T2WI combined with PVP were found to be associated with LNM. Multivariate logistic regression analysis showed that rad-score 3 and MRI-reported LN status were independent predictors. In the training and validation cohorts, the AUCs of rad-score 1, rad-score 2 and rad-score 3 were 0.769 and 0.751, 0.807 and 0.784, and 0.834 and 0.807, respectively. The predictive value of rad-score 3 was similar to that of rad-score 1 and rad-score 2 in both the training and validation cohorts (P > 0.05). The radiomics nomogram constructed by rad-score 3 and MRI-reported LN status showed encouraging clinical benefit, with an AUC of 0.845 for the training cohort and 0.816 for the validation cohort.

Conclusions

The radiomics nomogram derived from the rad-score based on MRI features and MRI-reported lymph status showed outstanding performance for the preoperative prediction of LNM of PDAC.
Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With BAP1-Frame Shift Mutation: Case Report and Literature Review
Authors: Lian Bi-Jun , Zhang Ke , Fang Xu-Dong , Li Feng , Dai Zhao , Chen Wei-Ying , Qi Xiao-Ping
Published: July 2022

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are VHL, PBRM1, BAP1, and SETD2, respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib–axitinib–everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of BAP1 in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of BAP1 mutations in ccRCC patients was approximately 10%–20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning BAP1 mutation and associated cancers including ccRCC is reviewed.
Survival Outcomes of Patients With Stage IB3 Cervical Cancer Who Undergo Abdominal Radical Hysterectomy Versus Radiochemotherapy
Authors: Li Zhiqiang , Yang Qing , Guo Jianxin , Liang Guoqiang , Duan Hui , Wang Shaoguang , Hao Min , Liang Wentong , Li Donglin , Zhan Xuemei , Xie Qinghuang , Lang Jinghe , Liu Ping , Chen Chunlin
Published: July 2022

Objective

This study aimed to compare the survival outcomes among stage IB3 cervical cancer patients who undergo abdominal radical hysterectomy (ARH)+pelvic lymphadenectomy ± para-aortic lymph node dissection versus radiochemotherapy (R-CT).

Methods

Based on the large number of diagnoses and treatments for cervical cancer in the Chinese database, propensity score matching (PSM) was used to compare the 5-year overall survival (OS) and disease-free survival (DFS) rates of the ARH group and R-CT group.

Results

There were 590 patients with stage IB3 cervical cancer according to the FIGO 2018 staging system, with 470 patients in the ARH group and 120 patients in the R-CT group. The ARH and R-CT groups showed different 5-year OS and DFS rates in the total study population, and the 5-year OS and DFS rates in the R-CT group (n = 120) were lower than those in the ARH group (n = 470) (OS: 78.1% vs. 92.1%, p < 0.001; DFS: 71.6% vs. 90.3%, p < 0.001). R-CT was associated with a worse 5-year OS rate (hazard ratio [HR] = 3.401; 95% confidence interval [CI] = 1.875–6.167; p < 0.001) and DFS rate (HR = 3.440; 95% CI = 2.075–5.703; p < 0.001) by Cox multivariate analysis. After 1:3 PSM, the 5-year OS and DFS rates in the R-CT group (n = 108) were lower than those in the RH group (n = 280) (OS: 76.4% vs. 94.0%, p < 0.001; DFS: 69.3% vs. 92.6%, p < 0.001, respectively). R-CT was associated with a worse 5-year OS rate (HR = 4.071; 95% CI = 2.042–8.117; p < 0.001) and DFS rate (HR = 4.450; 95% CI = 2.441–8.113; p < 0.001) by Cox multivariate analysis.

Conclusion

Our study found that for FIGO 2018 stage IB3 cervical cancer patients, ARH resulted in better OS and DFS than R-CT.
Adapalene and Doxorubicin Synergistically Promote Apoptosis of TNBC Cells by Hyperactivation of the ERK1/2 Pathway Through ROS Induction
Authors: Mehraj Umar , Mir Irfan Ahmad , Hussain Mahboob ul , Alkhanani Mustfa , Wani Nissar Ahmad , Mir Manzoor Ahmad
Published: July 2022

Doxorubicin is a commonly used chemotherapeutic agent to treat several malignancies, including aggressive tumors like triple-negative breast cancer. It has a limited therapeutic index owing to its extreme toxicity and the emergence of drug resistance. As a result, there is a pressing need to find innovative drugs that enhance the effectiveness of doxorubicin while minimizing its toxicity. The rationale of the present study is that combining emerging treatment agents or repurposed pharmaceuticals with doxorubicin might increase susceptibility to therapeutics and the subsequent establishment of improved pharmacological combinations for treating triple-negative breast cancer. Additionally, combined treatment will facilitate dosage reduction, reducing the toxicity associated with doxorubicin. Recently, the third-generation retinoid adapalene was reported as an effective anticancer agent in several malignancies. This study aimed to determine the anticancer activity of adapalene in TNBC cells and its effectiveness in combination with doxorubicin, and the mechanistic pathways in inhibiting tumorigenicity. Adapalene inhibits tumor cell growth and proliferation and acts synergistically with doxorubicin in inhibiting growth, colony formation, and migration of TNBC cells. Also, the combination of adapalene and doxorubicin enhanced the accumulation of reactive oxygen species triggering hyperphosphorylation of Erk1/2 and caspase-dependent apoptosis. Our results demonstrate that adapalene is a promising antitumor agent that may be used as a single agent or combined with present therapeutic regimens for TNBC treatment.
Nomogram Based on CT Radiomics Features Combined With Clinical Factors to Predict Ki-67 Expression in Hepatocellular Carcinoma
Authors: Wu Cuiyun , Chen Junfa , Fan Yuqian , Zhao Ming , He Xiaodong , Wei Yuguo , Ge Weidong , Liu Yang
Published: July 2022

Objectives

The study developed and validated a radiomics nomogram based on a combination of computed tomography (CT) radiomics signature and clinical factors and explored the ability of radiomics for individualized prediction of Ki-67 expression in hepatocellular carcinoma (HCC).

Methods

First-order, second-order, and high-order radiomics features were extracted from preoperative enhanced CT images of 172 HCC patients, and the radiomics features with predictive value for high Ki-67 expression were extracted to construct the radiomic signature prediction model. Based on the training group, the radiomics nomogram was constructed based on a combination of radiomic signature and clinical factors that showed an independent association with Ki-67 expression. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to verify the performance of the nomogram.

Results

Sixteen higher-order radiomic features that were associated with Ki-67 expression were used to construct the radiomics signature (AUC: training group, 0.854; validation group, 0.744). In multivariate logistic regression, alfa-fetoprotein (AFP) and Edmondson grades were identified as independent predictors of Ki-67 expression. Thus, the radiomics signature was combined with AFP and Edmondson grades to construct the radiomics nomogram (AUC: training group, 0.884; validation group, 0.819). The calibration curve and DCA showed good clinical application of the nomogram.

Conclusion

The radiomics nomogram developed in this study based on the high-order features of CT images can accurately predict high Ki-67 expression and provide individualized guidance for the treatment and clinical monitoring of HCC patients.
Proprioceptive Disturbance in Chronic Neck Pain: Discriminate Validity and Reliability of Performance of the Clinical Cervical Movement Sense Test
Authors: Röijezon Ulrik , Jull Gwendolen , Blandford Christian , Daniels Anna , Michaelson Peter , Karvelis Petros , Treleaven Julia
Published: July 2022

Chronic neck pain is associated with sensorimotor dysfunctions, which may develop symptoms, affect daily activities, and prevent recovery. Feasible, reliable, and valid objective methods for the assessment of sensorimotor functions are important to identify movement impairments and guide interventions. The aim of this study was to investigate the discriminative validity of a clinical cervical movement sense test, using a laser pointer and an automatic video-based scoring system. Individuals with chronic neck pain of idiopathic onset (INP), traumatic onset (TNP), and healthy controls (CON) were tested. Associations between movement sense and neck disability were examined and the repeatability of the test was investigated. A total of 106 participants (26 INP, 28 TNP, and 52 CON) were included in a cross-sectional study. Acuity, Speed, Time, and NormAcuity (i.e., normalized acuity by dividing acuity with movement time) were used as outcome measures. ANOVAs were used for group comparisons and Pearson correlations for associations between movement sense variables and neck disability index (NDI). Notably, 60 of the participants (30 CON, 17 INP, and 13 TNP) performed the test on a second occasion to explore test-retest reliability. Results revealed a reduced NormAcuity for both INP and TNP compared with CON (p < 0.05). The neck pain groups had similar Acuity but longer Time compared with CON. Among TNP, there was a fair positive correlation between Acuity and NDI, while there was a negative correlation between Acuity and NDI among INP. Reliability measures showed good to excellent ICC values between tests, but standard error of measurements (SEM) and minimal detectable change (MDC) scores were high. The results showed that NormAcuity is a valuable measure to identify disturbed cervical movement sense among INP and TNP. While Acuity was similar between the groups, different strategies, such as longer Time, to perform the task among neck patient groups were used. Few differences were identified between the neck pain groups, but altered strategies may exist. Reliability was acceptable, and the test is feasible to perform in the clinic. However, the technical complexity of the automated image analysis is a concern. Future developments will provide more feasible solutions.
Co-development and Usability Testing of Research 101: A Patient-Oriented Research Curriculum in Child Health (PORCCH) E-Learning Module for Patients and Families
Authors: Walsh Catharine M. , Jones Nicola L. , McCreath Graham A. , Connan Veronik , Pires Linda , Chen Autumn Q. H. , Karoly Aliza , Macarthur Colin
Published: July 2022

Background

Engaging patients and families as research partners increases the relevance, quality, and impact of child health research. However, those interested in research engagement may feel underequipped to meaningfully partner. We sought to co-develop an online learning (e-learning) module, “Research 101,” to support capacity-development in patient-oriented child health research amongst patients and families.

Methods

Module co-development was co-led by a parent and researcher, with guidance from a diverse, multi-stakeholder steering committee. A mixed-methods usability testing approach, with three iterative cycles of semi-structured interviews, observations, and questionnaires, was used to refine and evaluate the e-learning module. Module feedback was collected during testing and a post-module interview, and with the validated System Usability Scale (SUS), and satisfaction, knowledge, and self-efficacy questionnaires. Transcripts and field notes were analyzed through team discussion and thematic coding to inform module revisions.

Results

Thirty participants fully tested Research 101, and another 15 completed confirmatory usability testing (32 caregivers, 6 patients, and 7 clinician-researchers). Module modifications pertaining to learner-centered design, content, aesthetic design, and learner experience were made in each cycle. SUS scores indicated the overall usability of the final version was “excellent.” Participants' knowledge of patient-oriented research and self-efficacy to engage in research improved significantly after completing Research 101 (p < 0.01).

Conclusions

Co-development and usability testing facilitated the creation of an engaging and effective resource to support the scaling up of patient-oriented child health research capacity. The methods and findings of this study may help guide the integration of co-development and usability testing in creating similar resources.
A Perspective on Pediatric Respiratory Outcomes During California Wildfires Due to Smoke and PM2.5 Exposure
Authors: Naughten Sarah M. , Aguilera Rosana , Gershunov Alexander , Benmarhnia Tarik , Leibel Sydney
Published: July 2022

As wildfires increase in prevalence and intensity across California and globally, it is anticipated that more children will be exposed to wildfire smoke, and thus face associated adverse health outcomes. Here, we provide a concise summary of the respiratory effects of California's wildfires on pediatric healthcare utilization, examine global examples of wildfire smoke exposure within the pediatric population and associated physiological effects, and assess the efficacy of metrics used to measure and communicate air quality during wildfires within the United States and elsewhere.
Effect of Various Preterm Infant Milk Formulas on NEC-Like Gut Injury in Mice
Authors: Rao Karishma , Cuna Alain , Chavez-Bueno Susana , Menden Heather , Yu Wei , Ahmed Ishfaq , Srinivasan Pugazhendhi , Umar Shahid , Sampath Venkatesh
Published: July 2022

Formula feeding is an important risk factor for the development of necrotizing enterocolitis in preterm infants. The potential harmful effects of different preterm formulas on the developing intestinal tract remain incompletely understood. Here we demonstrate that feeding newborn mouse pups with various preterm formulas resulted in differing effects on intestinal inflammation, apoptosis, and activation of the pro-inflammatory transcription factor NFκB. 16S rRNA sequencing revealed that each preterm formula resulted in significant gut microbial alterations that were different from dam-fed controls. Formula feeding with EleCare and Similac Special Care caused greater intestinal injury compared to NeoSure. Pre-treatment with Lactobacillus rhamnosus GG ameliorated severity of intestinal injury from EleCare and Similac Special Care. Our findings indicate that not all preterm formulas are the same, and different formulations can have varying effects on intestinal inflammation, apoptosis, and microbiome composition.
Universal Newborn Screening for Congenital Cytomegalovirus Infection – From Infant to Maternal Infection: A Prospective Multicenter Study
Authors: Chiereghin Angela , Pavia Claudia , Turello Gabriele , Borgatti Eva Caterina , Baiesi Pillastrini Federico , Gabrielli Liliana , Gibertoni Dino , Marsico Concetta , De Paschale Massimo , Manco Maria Teresa , Ruscitto Antonia , Pogliani Laura , Bellini Marta , Porta Alessandro , Parola Luciana , Scarasciulli Maria Luisa , Calvario Agata , Capozza Manuela , Capretti Maria Grazia , Laforgia Nicola , Clerici Pierangelo , Lazzarotto Tiziana
Published: July 2022

Introduction:

Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated.

Methods

To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used.

Results

A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03–7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14–2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother–infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy.

Conclusion

Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease.
Ultrasonographic Evaluation of the Hypospadiac Penis in Children
Authors: Abbas Tariq O.
Published: July 2022

Introduction

Identifying key anatomical features of the hypospadiac penis is crucial to better understanding this pathology and guiding surgical reconstruction plans, thereby achieving superior functional and cosmetic outcomes.

Objective

To Assess the feasibility and precision of penile ultrasonography (PUG) in determining key structural features for hypospadias cases (including distal extent of the spongiosal component of the urethral plate, to elucidate the healing process following tubularised incised-plate urethroplasty).

Patients and Methods

Twenty-five children with hypospadias were assessed using PUG prior to surgical repair and then again under general anesthesia. Preoperative images were acquired using ultrasonography in sagittal and transverse planes, then later compared with anatomical findings obtained during surgical repair of urethral hypoplasia.

Results

Median patient age was 1.2 years (range 0.5–12) and hypospadias types included coronal 17/25 (68%), mid-penile 5/25 (20%), and proximal penile 3/25 (12%). Distinct layers of the corpus spongiosa and mucosal layer, Buck fascia, tunica albuginea, glans, corpora cavernosa, and penile skin were delineated so that their spatial inter-relationship could be assessed. Distal extent of the spongiosal component of the urethral plate was determined by the mid-glans B-B line. The extent of urethral hypoplasia identified by PUG was relatively similar to measurements obtained intraoperatively.

Conclusion

PUG is a feasible and accurate approach to evaluating penile configuration in children with hypospadias. Distal extent of the spongiosal component of the urethral plate was accurately determined, hence PUG could potentially be used to improve surgical planning and appraisal of current repair procedures.
Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity
Authors: Kirsanov Kirill , Fetisov Timur , Antoshina Elena , Trukhanova Lubov , Gor’kova Tatiana , Vlasova Olga , Khitrovo Irina , Lesovaya Ekaterina , Kulbachevskaya Nataliya , Shcherbakova Tatiana , Belitsky Gennady , Yakubovskaya Marianna , Švedas Vytas , Nilov Dmitry
Published: July 2022

7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.
Population Pharmacokinetics and Initial Dosage Optimization of Tacrolimus in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Liu Xiao-Lin , Guan Yan-Ping , Wang Ying , Huang Ke , Jiang Fu-Lin , Wang Jian , Yu Qi-Hong , Qiu Kai-Feng , Huang Min , Wu Jun-Yan , Zhou Dun-Hua , Zhong Guo-Ping , Yu Xiao-Xia
Published: July 2022

Background: There is a substantial lack of tacrolimus pharmacokinetic information in pediatric hematopoietic stem cell transplant (HSCT) patients. This study aimed to develop population pharmacokinetics (PopPK) of tacrolimus in pediatric HSCT patients and to devise model-guided dosage regimens.

Methods: A retrospective analysis was performed on 86 pediatric HSCT patients who received tacrolimus intravenously or orally. A total of 578 tacrolimus trough concentrations (C0) were available for pharmacokinetic analysis using a non-linear mixed-effects modeling method. Demographic and clinical data were included and assessed as covariates via the stepwise method. Bayesian estimators were used to devise pediatric dosage regimens that targeted C0 of 5–15 ng mL−1.

Results: A one-compartment model with first-order absorption adequately described the tacrolimus pharmacokinetics. Clearance (CL), volume of distribution (V), and typical bioavailability (F) in this study were estimated to be 2.42 L h−1 (10.84%), 79.6 L (16.51%), and 19% (13.01%), respectively. Body weight, hematocrit, post-transplantation days, and caspofungin and azoles concomitant therapy were considered significant covariates for tacrolimus CL. Hematocrit had a significant impact on the V of tacrolimus. In the subgroup cohort of children (n = 24) with CYP3A5 genotype, the clearance was 1.38-fold higher in CYP3A5 expressers than in non-expressers. Simulation indicated that the initial dosage optimation of tacrolimus for intravenous and oral administration was recommended as 0.025 and 0.1 mg kg−1 d−1 (q12h), respectively.

Conclusion: A PopPK model for tacrolimus in pediatric HSCT patients was developed, showing good predictive performance. Model-devised dosage regimens with trough tacrolimus concentrations provide a practical strategy for achieving the therapeutic range.
An Integrative Heterogeneous Graph Neural Network–Based Method for Multi-Labeled Drug Repurposing
Authors: Sadeghi Shaghayegh , Lu Jianguo , Ngom Alioune
Published: July 2022

Drug repurposing is the process of discovering new indications (i.e., diseases or conditions) for already approved drugs. Many computational methods have been proposed for predicting new associations between drugs and diseases. In this article, we proposed a new method, called DR-HGNN, an integrative heterogeneous graph neural network-based method for multi-labeled drug repurposing, to discover new indications for existing drugs. For this purpose, we first used the DTINet dataset to construct a heterogeneous drug–protein–disease (DPD) network, which is a graph composed of four types of nodes (drugs, proteins, diseases, and drug side effects) and eight types of edges. Second, we labeled each drug–protein edge, dpi,j = (di, pj), of the DPD network with a set of diseases, {δi,j,1, … , δi,j,k} associated with both di and pj and then devised multi-label ranking approaches which incorporate neural network architecture that operates on the heterogeneous graph-structured data and which leverages both the interaction patterns and the features of drug and protein nodes. We used a derivative of the GraphSAGE algorithm, HinSAGE, on the heterogeneous DPD network to learn low-dimensional vector representation of features of drugs and proteins. Finally, we used the drug–protein network to learn the embeddings of the drug–protein edges and then predict the disease labels that act as bridges between drugs and proteins. The proposed method shows better results than existing methods applied to the DTINet dataset, with an AUC of 0.964.
Potential Anti-Depressive Effects and Mechanisms of Zhi-Zi Hou-Po Decoction Using Behavioral Despair Tests Combined With in Vitro Approaches
Authors: Bai Yongtao , Dai Guoliang , Song Lihua , Gu Xiaolei , Ba Ning , Ju Wenzheng , Zhang Wenzhou
Published: July 2022

Zhi-Zi Hou-Po Decoction (ZHD) has been widely used in the treatment of depression for centuries. This study aimed to investigate the antidepressant effects of the water extract of ZHD (ZHD-WE) and ethanol extract of ZHD (ZHD-EE) using behavioral despair tests in mice, and to further explore the neuroprotective effects in a PC12 cell injury model induced by corticosterone (CORT). Mice were divided into a control group (normal saline), ZHD-WE groups (4, 8, and 16 g kg−1), ZHD-EE groups (4, 8, and 16 g kg−1) and the fluoxetine group (20 mg kg−1). The forced swimming test (FST) and tail suspension test (TST) were used to screen the antidepressant effects of ZHD-WE and ZHD-EE after oral administration for seven consecutive days. The level of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined by ELISA. The MTT, lactate dehydrogenase (LDH) and flow cytometry analysis were performed to elucidate the neuroprotective effect of ZHD-EE on a PC12 cell injury model. Additionally, the mRNA and proteins expression of apoptotic molecules Bax, Bcl-2 and BDNF were detected by RT-PCR and western blot assay. It showed that ZHD-EE at concentrations of 8 and 16 g kg−1 significantly decreased the immobility time in the TST and FST, and increased the BDNF levels in the hippocampus. While ZHD-WE at concentrations of 4, 8, and 16 g kg−1 had no significant effect on the immobility time in the TST, and only the 16 g kg−1 of extract group significantly decreased the immobility time in the FST. In vitro, the obtained results showed that PC12 cells pre-incubated with ZHD-EE at concentrations of 100 and 400 μg ml−1 improved cell viability, decreased LDH release, and reduced apoptosis rate of PC12 cells. Moreover, ZHD-EE significantly increased the mRNA and proteins expression of Bcl-2 and BDNF, while decreased the mRNA and protein expression of Bax. ZHD-EE significantly improved despair-like behavior in mice, and its mechanism may be related to BDNF upregulation in the hippocampus. This study also showed that ZHD-EE had a protective effect on CORT-induced injury in PC12 cells by upregulating the expression of BDNF and restoring Bcl-2/Bax balance.
Helmholtz-Structured Two-Dimensional Super-Diffraction Meta-Lens
Authors: Li He-He , Zheng Bo , Duan Mu-Sen , Han Feng , Hu Yun-Xin , Li Xiao-You , Qian Si-Yu , Chen Xue-Feng , Liu Sheng-Chun
Published: July 2022

Focusing beyond the acoustic diffraction limit has always been expected, especially in acoustic imaging and ultrasonic therapy. Manipulating the acoustic waves beyond the diffraction limit offers an alternative application potential in high-resolution imaging and medical ultrasound diagnosis and treatment. Here, a two-dimensional circular meta-lens is presented, with a sub-wavelength acoustic Helmholtz resonator array to implement the super-diffraction focusing. The proposed acoustic meta-lens consists of 28 units, which possesses the ability to yield designed arbitrary phase shifts and maintain the impedance matching to provide the high sound transmission efficiency. The simulation and experimental results show that the designed acoustic meta-lens can realize subwavelength sound focusing beyond the diffraction limit. The proposed method can greatly promote the application and development of the acoustic superfocusing technology in acoustic imaging, particle manipulation, and other fields.
Post-Activation Performance Enhancement: Save Time With Active Intra-Complex Recovery Intervals
Authors: Trybulski Robert , Makar Piotr , Alexe Dan Iulian , Stanciu Silvius , Piwowar Rafał , Wilk Michal , Krzysztofik Michal
Published: July 2022

This study aimed to determine whether the intra-complex active recovery within the strength-power potentiating complex will impact the upper-body post-activation performance enhancement effect and how the magnitude of this effect will change across the upper-body complex training session. Thirteen resistance-trained males [the age, body mass, height, experience in resistance training, and one-repetition maximum (1RM) in bench press were 27 ± 4 years; 92.3 ± 15.4 kg; 182 ± 6 cm; 6.4 ± 2.4 years, and 118 ± 29 kg, respectively) participated in this study. Each participant completed a baseline bench press throw performance assessment at 30% 1RM. Next, five strength-power potentiating complexes consisting of a bench press at 80% 1RM were tested until the average barbell velocity decreased by 10% as a conditioning activity, and 6 min later, a re-test of bench press throw was carried out. During one experimental session during the rest interval inside the complex, they performed swiss ball leg curls, while between the complexes, a plank exercise (PAP-A) was performed. During the second experimental session, participants performed no exercises within the strength-power potentiating complexes and between them (PAP). Under control conditions, participants ran the same protocol (as the PAP condition) without the conditioning activity (CTRL). Friedman’s test showed significant differences in peak (test = 90.634; p < 0.0001; Kendall’s W = 0.410) and average (test = 74.172; p < 0.0001; Kendall’s W = 0.336) barbell velocities during bench press throw. Pairwise comparisons indicated that the peak and average barbell velocities significantly increased in the fourth set [p = 0.022, effect size (ES) = 0.76 and p = 0.013, ES = 0.69, respectively], and the average barbell velocity was also increased in the second set (p = 0.018, ES = 0.77) in comparison to the baseline value during the PAP-A condition. Moreover, the peak barbell velocity was increased in the second (p = 0.008, ES = 0.72) and third (p = 0.019, ES = 0.76) sets compared to the baseline value during the PAP condition. This study showed that body-weight lower-body exercise as an intra-complex active recovery did not impair the upper-body post-activation performance enhancement effect across the complex training session.
Physiological Responses Manifested by Some Conventional Stress Parameters and Biophoton Emission in Winter Wheat as a Consequence of Cereal Leaf Beetle Infestation
Authors: Lukács Helga , Jócsák Ildikó , Somfalvi-Tóth Katalin , Keszthelyi Sándor
Published: July 2022

Oulema melanopus L. (Coleoptera: Chrysomelidae) is one of the most serious pests of winter wheat that causes peeling of the epidermis and tissue loss. The complex mapping of the physiological responses triggered by O. melanopus as a biotic stressor in winter wheat has not been fully explored with the help of non-invasive imaging and analytical assays, yet. The aim of the present work was to study the effect of O. melanopus on the physiological processes of winter wheat, especially on the extent of lipid peroxidation and antioxidant activity derived from tissue destruction, as well as photosynthetic ability. The results of the measurements enabled the identification of the antioxidant and lipid-oxidation–related physiological reactions, and they were reflected in the dynamics of non-invasive biophoton emissions. Our non-invasive approach pointed out that in the case of O. melanopus infestation the damage is manifested in tissue loss and the systemic signaling of the biotic stress may have reached other plant parts as well, which was confirmed by the results of antioxidant capacity measurements. These results indicate that the plant reacts to the biotic stress at a whole organizational level. We identified that the antioxidant and lipid-oxidation–related physiological reactions were reflected in the dynamics of two aspects of biophoton emission: delayed fluorescence and ultra-weak bioluminescence. Our research further supported that the non-invasive approach to stress assessment may complete and detail the traditional stress indicators.
Delayed Leaf Senescence by Upregulation of Cytokinin Biosynthesis Specifically in Tomato Roots
Authors: Glanz-Idan Noga , Lach Michael , Tarkowski Petr , Vrobel Ondřej , Wolf Shmuel
Published: July 2022

Cytokinins (CKs) regulate numerous plant developmental processes, including photosynthesis and leaf senescence. Isopentenyltransferase (IPT) is a rate-limiting enzyme in the CK-biosynthesis pathway. We overexpressed ipt under tissue-specific promoters to study the long-range effect of CK on the functioning of tomato source leaves. Photosynthetic activity over time provided the measure for leaf aging. Significantly delayed leaf senescence was observed in plants expressing ipt under a root-specific promoter, but not in those expressing the gene under a source leaf-specific promoter. The root-derived influence on leaf aging was further confirmed by grafting experiments. CK concentration in source leaves of both transgenic lines increased significantly, with different proportions of its various derivatives. On the other hand, root CK concentration was only slightly elevated. Nevertheless, the significant change in the proportion of CK derivatives in the root indicated that CK biosynthesis and metabolism were altered. Partial leaf defoliation upregulates photosynthetic rate in the remaining leaf; however, overexpression of ipt in either tissues eliminated this response. Interestingly, stem girdling also eliminated the photosynthetic response. Taken together, our findings suggest that leaf senescence is regulated by a CK-mediated root–shoot communication network. We propose that CK-mediated signal is translocated to the leaf via the xylem where it alters CK biosynthesis, resulting in delayed senescence.
Transfer of Avatar Training Effects to Investigative Field Interviews of Children Conducted by Police Officers
Authors: Kask Kristjan , Pompedda Francesco , Palu Annegrete , Schiff Karolyn , Mägi Mari-Liis , Santtila Pekka
Published: July 2022

Previous research with students and some professional groups (psychologists) has demonstrated that repeated feedback in simulated investigative interviews with computerized child avatars improves the quality of interviews conducted with real children who have witnessed a mock event. However, it is not known whether this type of training would improve the quality of investigative interviews with actual child victims and witnesses of physical and sexual abuse. Twenty-two police investigators participated in the study. Half of them received feedback during four simulated interviews whereas the other half received no feedback during four such interviews followed by another four interviews after which they also received feedback. Transcripts of interviews both before and after the training were coded for interview quality. Receiving feedback after the simulated interviews increased the proportion of recommended questions both within the simulations and, importantly, also during interviewing with actual child victims and witnesses. This study demonstrated for the first time transfer of learning from simulated interviews to actual investigative interviews.