bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggression, Aggression-Related Psychopathologies and Their Models
Authors: Haller József
Published: July 2022

Neural mechanisms of aggression and violence are often studied in the laboratory by means of animal models. A multitude of such models were developed over the last decades, which, however, were rarely if ever compared systematically from a psychopathological perspective. By overviewing the main models, I show here that the classical ones exploited the natural tendency of animals to defend their territory, to fight for social rank, to defend themselves from imminent dangers and to defend their pups. All these forms of aggression are functional and adaptive; consequently, not necessarily appropriate for modeling non-natural states, e.g., aggression-related psychopathologies. A number of more psychopathology-oriented models were also developed over the last two decades, which were based on the etiological factors of aggression-related mental disorders. When animals were exposed to such factors, their aggressiveness suffered durable changes, which were deviant in the meaning that they broke the evolutionarily conserved rules that minimize the dangers associated with aggression. Changes in aggression were associated with a series of dysfunctions that affected other domains of functioning, like with aggression-related disorders where aggression is just one of the symptoms. The comparative overview of such models suggests that while the approach still suffers from a series of deficits, they hold the important potential of extending our knowledge on aggression control over the pathological domain of this behavior.
Combination of Ashwagandha Water Extract and Intermittent Fasting as a Therapy to Overcome Cisplatin Resistance in Breast Cancer: An in vitro and in vivo Study
Authors: Jawarneh Sajidah , Talib Wamidh H.
Published: July 2022

Breast cancer is considered a universal public health dilemma in women. Due to the high toxicity and low selectivity of conventional anticancer therapies, there is a growing trend of using plant-derived natural products in cancer prevention and therapy. Ashwagandha (Withania somnifera, WS) has been used in the Mediterranean region and Ayurvedic medicine for millennia as a functional food and a medicinal plant with anticancer activity. Besides, intermittent fasting (IF) has been engaged recently in cancer treatment. Hence, the combination of WS and IF provides possible solutions to treat cancer and reduce chemoresistance when combined with chemotherapy. In this study, WS root (WSR), IF, and cisplatin were tested on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. The phytochemical content of the WSR extract was analyzed using liquid chromatography–mass spectrometry (LC-MS) analysis. Antiproliferative and apoptotic effects were assessed for WSR extract, cisplatin, and their combination in vitro using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) and caspase-3 assays. An in vivo study was used to assess the effect of WSR extract, IF, cisplatin, and their combinations in mice inculcated with EMT6/P and EMT6/CPR cells. The safety profile was also investigated using liver enzymes and creatinine assays. In vitro, WSR extract and cisplatin had a synergistic effect in both cell lines. The same combination induced an apoptotic effect higher than the single treatment in both cell lines. In vivo, several combinations of WSR extract, IF, or cisplatin caused significant tumor size reduction and improved the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. IF-treated groups showed a significant reduction in serum glucose and an elevation in β-hydroxybutyrate (BHB) levels. In the safety profile, WSR extract, IF, and their combinations were safe. Overall, the combination of WSR extract and IF provides a promising solution for breast cancer treatment besides cisplatin by reducing the proliferation of cancer cells through induction of apoptosis. Moreover, they minimize cisplatin toxicity to the liver and kidney.
AMPK-PPARγ-Cidec Axis Drives the Fasting-Induced Lipid Droplet Aggregation in the Liver of Obese Mice
Authors: Li Hongqiang , Sun Jian , Li Bojiang , Jiang Aiwen , Tao Jingli , Ning Caibo , Li Rongyang , Liu Honglin
Published: July 2022

Intermittent fasting is one of the most common clinical treatments for the obesity, a main risk factor of the metabolic syndrome which can lead to a variety of diseases. Fasting-induced fat mobilization alters the metabolic state of lipid in the liver, predisposing to increase the hepatic lipid droplet aggregation and triglyceride levels. However, the underlying mechanisms regarding the lipid droplet aggregation in the liver after fasting remains elusive. Here, we report that a lipid droplet surface binding protein Cidec (cell death inducing DFFA like effector C) is activated by AMPK to regulate the hepatic lipid droplet fusion following fasting in obese mice. Specifically, we found that lipid droplets were significantly aggregated in the liver of high-fat-diet and ob/ob mice after 16 and 24 h of fasting, accompanied by the dramatically up-regulated expression of Cidec. Consistently, overexpression of Cidec in the AML12 cells resulted in the intracellular lipid droplet aggregation. Furthermore, we showed that fasting caused the up-regulated expression of AMPK, which in turn activated the transcription of Cidec through the transcription factor PPARγ. Altogether, our observations reveal that fasting-induced hepatic lipid droplet aggregation is mediated by the AMPK-activated expression of Cidec via PPARγ, extending our understanding about the molecular mechanism of the impact of fasting on the obesity and providing potential targets for the treatment of human obesity.
PDIA2 Bridges Endoplasmic Reticulum Stress and Metabolic Reprogramming During Malignant Transformation of Chronic Colitis
Authors: Tao Jie , Yin Lin , Wu Ao , Zhang Jiaoli , Zhang Jingpu , Shi Huichun , Liu Siyuan , Niu Liangfei , Xu Li , Feng Yanling , Lian Shixian , Li Lei , Zeng Liyan , Meng Xianmin , Zhou Xiaohui , Liu Tiefu , Zhang Lijun
Published: July 2022

Background

Chronic inflammation contributes to approximately 20% of cancers; the underlying mechanisms are still elusive. Here, using an animal model of colitis to colon-cancerous transformation, we demonstrated that endoplasmic reticulum (ER) stress couples with metabolic reprogramming to promote a malignant transformation of chronic inflammation.

Methods

The animal model for chronic colitis to colon-cancerous transformation was established in C57BL/6N mice by azoxymethane (AOM) and dextran sodium sulfate (DSS) treatments. The differential proteins in control and AOM/DSS-treated colon mucosa were determined using proteomic analysis; the kinetics of metabolic modifications were monitored by mitochondrial oxygen flux, extracellular acidification, and targeted metabolomics; the molecule linker between ER stress and metabolic modifications were identified by coimmunoprecipitation, KEGG pathway analysis, and the subcutaneous tumor model using gene-specific knockdown colon cancer cells. Tissue array analysis were used to evaluate the differential protein in cancer and cancer-adjacent tissues.

Results

AOM/DSS treatment induced 38 tumors in 10 mice at the 14th week with the mean tumor size 9.35 ± 3.87 mm2, which was significantly decreased to 5.85 ± 0.95 mm2 by the ER stress inhibitor 4-phenylbutyric acid (4PBA). Seven differential proteins were determined from control (1,067 ± 48) and AOM/DSS-treated mucosa (1,077 ± 59); the level of ER protein PDIA2 (protein disulfide isomerase-associated 2) was increased over 7-fold in response to AOM/DSS treatment. PDIA2 interacted with 420 proteins that were involved in 8 signaling pathways, in particular with 53 proteins in metabolic pathways. PDIA2 translocated from ER to mitochondria and interacted with the components of complexes I and II to inhibit oxophosphorylation but increase glycolysis. Knockdown PDIA2 in colon cancer cells restored the metabolic imbalance and significantly repressed tumor growth in the xenograft animal model. 4PBA therapy inhibited the AOM/DSS-mediated overexpression of PDIA2 and metabolic modifications and suppressed colon cancer growth. In clinic, PDIA2 was overexpressed in colon cancer tissues rather than cancer-adjacent tissues and was related with the late stages and lymph node metastasis of colon cancer.

Conclusions

Persistent ER stress reprograms the metabolism to promote the malignant transformation of chronic colitis; PDIA2 serves as a molecule linker between ER stress and metabolic reprogramming. The inhibition of ER stress restores metabolic homeostasis and attenuates the cancerous transformation of chronic inflammation.
Oncological and Reproductive Outcomes After Fertility-Sparing Surgery for Stage I Mucinous Ovarian Carcinoma
Authors: Lin Wei , Cao Dongyan , Shi Xiaohua , You Yan , Yang Jiaxin , Shen Keng
Published: July 2022

Background

Fertility-sparing surgery (FSS) has been widely used for patients with early-stage mucinous ovarian carcinoma (MOC). However, there is limited evidence regarding the reproductive outcomes as well as the impact of growth pattern on oncological outcomes after FSS. This study aims to evaluate the oncological and reproductive outcomes of patients with stage I primary MOC after FSS.

Methods

This retrospective study enrolled 159 women with histologically confirmed unilateral stage I MOC treated at Peking Union Medical College Hospital between 1997 and 2019. Sixty-seven cases were pathologically reviewed for the growth pattern. Seventy-eight patients had FSS, defined as conservation of the uterus and at least part of one ovary, while 81 underwent radical surgery (RS). Oncofertility outcomes were compared between the groups and clinicopathological factors associated with disease-free survival (DFS) were analyzed by univariate and multivariate analyses. Patients in the FSS group were contacted to collect data on reproductive outcomes.

Results

Eighteen patients developed recurrent disease during a median follow-up of 69 months, including 12 in the FSS and six in the RS group. There was one death each in the FSS and RS groups. There was no significant difference in DFS between the groups. CA125 >35 U/ml, stage IC, and incomplete staging were correlated with worse DFS according to multivariate analysis (P=0.001; 0.020 (stage IC) and 0.004 (incomplete staging) respectively). There was no significant difference in DFS between patients with stage IA and stage IC1 in the FSS group, while DFS was poorer in patients with stage IC2/3 than stage IA (P=0.028). In addition, DFS was significantly poorer in patients who underwent unilateral salpingo-oophorectomy (USO) compared with those receiving USO plus staging surgery (P=0.015). There was a tendency towards poorer DFS in the infiltrative tumors compared with the expansile tumors (P=0.056). Of 23 patients who attempted to conceive, 21 (91.3%) achieved 27 pregnancies, including 26 spontaneous pregnancies and one following assisted reproductive technology. Twenty patients gave birth to 24 healthy babies, including 21 full-term and three premature births. The live-birth rate was 88.9%.

Conclusions

FSS is a suitable option for young women with unilateral stage I expansile MOC, with acceptable oncological outcomes and meaningful pregnancy rates. Re-staging should be proposed in patients who undergo incomplete staging surgery.
Four-Dimensional Image-Guided Adaptive Brachytherapy for Cervical Cancer: A Systematic Review and Meta-Regression Analysis
Authors: Li Fei , Shi Dan , Bu Mingwei , Lu Shuangchen , Zhao Hongfu
Published: July 2022

Purpose

The ICRU/GEC-ESTRO released the ICRU Report No. 89, which introduced the concept of four-dimensional brachytherapy and ushered in a new era of brachytherapy for cervical cancer. The purpose of this study was to evaluate the local control and late toxicity of four-dimensional brachytherapy in cervical cancer through a systematic review and to reveal the dose-response relationship between the volumetric dose paraments and the local control rate via a probit model.

Material and Methods

We identified studies that reported the HR-CTV D90 and local control probabilities by searching the PubMed Database, the Web of Science Core Collection and the Cochrane Library Database through February 1st, 2022. Regression analyses were performed between the HR-CTV D90 and the local control probability using a probit model.

Results

Nineteen studies enrolling 3,616 patients were included. The probit model showed a significant relationship between the HR-CTV D90 value and IR-CTV D90 Vs. the local control probability, P < 0.001 and P = 0.003, respectively. The D90 for HR-CTV and IR-CTV corresponding to a probability of 90% local control was 79.1 GyEQD2,10 (95% CI:69.8 – 83.7 GyEQD2,10) and 66.5 GyEQD2,10 (95% CI: 62.8 - 67.9 GyEQD2,10), respectively. The limits for the prescribed dose of 85 GyEQD2,10 for HR-CTV D90 theoretically warranted a 92.1% (95% CI: 90.2% - 95.3%) local control rate, and 87.2% (95% CI: 82.4% - 91.8%) local control probability was expected for 65 GyEQD2,10 to IR-CTV D90. The probit model showed no significant relationship between the D2cc to organs at risk and the probability of grade 3 and above gastrointestinal or genitourinary toxicity.

Conclusions

Four-dimensional brachytherapy takes into account uncertain factors such as tumour regression, internal organ motion and organ filling, and provides a more accurate and more therapeutic ratio delivery through adaptive delineation and replanning, replacement of the applicator, and the addition of interstitial needles. The dose volume effect relationship of four-dimensional brachytherapy between the HR-CTV D90 and the local control rate provides an objective planning aim dose.
Auto-Segmentation Ultrasound-Based Radiomics Technology to Stratify Patient With Diabetic Kidney Disease: A Multi-Center Retrospective Study
Authors: Chen Jifan , Jin Peile , Song Yue , Feng Liting , Lu Jiayue , Chen Hongjian , Xin Lei , Qiu Fuqiang , Cong Zhang , Shen Jiaxin , Zhao Yanan , Xu Wen , Cai Chenxi , Zhou Yan , Yang Jinfeng , Zhang Chao , Chen Qin , Jing Xiang , Huang Pintong
Published: July 2022

Background

An increasing proportion of patients with diabetic kidney disease (DKD) has been observed among incident hemodialysis patients in large cities, which is consistent with the continuous growth of diabetes in the past 20 years.

Purpose

In this multicenter retrospective study, we developed a deep learning (DL)-based automatic segmentation and radiomics technology to stratify patients with DKD and evaluate the possibility of clinical application across centers.

Materials and Methods

The research participants were enrolled retrospectively and separated into three parts: training, validation, and independent test datasets for further analysis. DeepLabV3+ network, PyRadiomics package, and least absolute shrinkage and selection operator were used for segmentation, extraction of radiomics variables, and regression, respectively.

Results

A total of 499 patients from three centers were enrolled in this study including 246 patients with type II diabetes mellitus (T2DM) and 253 patients with DKD. The mean intersection-over-union (Miou) and mean pixel accuracy (mPA) of automatic segmentation of the data from the three medical centers were 0.812 ± 0.003, 0.781 ± 0.009, 0.805 ± 0.020 and 0.890 ± 0.004, 0.870 ± 0.002, 0.893 ± 0.007, respectively. The variables from the renal parenchyma and sinus provided different information for the diagnosis and follow-up of DKD. The area under the curve (AUC) of the radiomics model for differentiating between DKD and T2DM patients was 0.674 ± 0.074 and for differentiating between the high and low stages of DKD was 0.803 ± 0.037.

Conclusion

In this study, we developed a DL-based automatic segmentation, radiomics technology to stratify patients with DKD. The DL technology was proposed to achieve fast and accurate anatomical-level segmentation in the kidney, and an ultrasound-based radiomics model can achieve high diagnostic performance in the diagnosis and follow-up of patients with DKD.
Progresses in Fluorescence Imaging Guidance for Bone and Soft Tissue Sarcoma Surgery
Authors: Chen Zhenyi , Huang Huayi , He Siyuan , Wang Yi , Cai Lin , Xie Yuanlong
Published: July 2022

R0 surgical resection is the preferred treatment for bone and soft tissue sarcoma. However, there is still a lack of precise technology that can visualize bone and soft tissue sarcoma during surgery to assist the surgeon in judging the tumor surgical boundary. Fluorescence imaging technology has been used in the diagnosis of cancer. It is a simple and essentially safe technique that takes no additional time during the operation. Intraoperative fluorescence imaging has potential application prospects in assisting the surgeons in judging the tumor boundary and improving the accuracy of surgical resection. This review mainly starts with clinical studies, animal experimentation, and newly designed probes of intraoperative fluorescence imaging of bone and soft tissue sarcoma, to appraise the application prospects of fluorescence imaging technology in bone and soft tissue sarcoma.
Comprehensive Analysis of the Brain-Expressed X-Link Protein Family in Glioblastoma Multiforme
Authors: Aisa Adilai , Tan Yinuo , Li Xinyu , Zhang Ding , Shi Yun , Yuan Ying
Published: July 2022

Glioblastoma multiforme (GBM) is the most common, malignant, and deadly primary brain tumor in adults. Brain-expressed X-link (BEX) protein family is involved in tumorigenesis. Here, we have explored the biological function and the prognostic value of the BEX family in GBM. Differentially expressed BEX genes between GBM and normal tissue were screened by using The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses identified the prognosis‐related genes BEX1, BEX2, and BEX4, which were involved in the regulation of immune response. The results of correlation analysis and protein–protein interaction network (PPI network) showed that there was a significant correlation between the BEX family and TCEAL family in GBM. Furthermore, the expression of transcription elongation factor A (SII)-like (TCEAL) family is generally decreased in GBM and related to poor prognosis. With the use of the least absolute shrinkage and selection operator (LASSO) Cox regression, a prognostic model including the BEX family and TCEAL family was built to accurately predict the likelihood of overall survival (OS) in GBM patients. Therefore, we demonstrated that the BEX family and TCEAL family possessed great potential as therapeutic targets and prognostic biomarkers in GBM. Further investigations in large‐scale, multicenter, and prospective clinical cohorts are needed to confirm the prognostic model developed in our study.
A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma
Authors: Pei Dongchen , Xu Chaojie , Wang Dong , Shi Xiaoxue , Zhang Yurui , Liu Yi , Guo Jianhua , Liu Nan , Zhu Haipeng
Published: July 2022

Background

The tumor microenvironment (TME) is a complex and evolving environment, and the tumor immune microenvironment in kidney renal clear cell carcinoma (KIRC) has a strong suppressive profile. This study investigates the potential prognostic role and value of genes of the tumor microenvironment in KIRC.

Methods

The transcriptome sequencing data of 530 cases and 39 cases of KIRC and the corresponding clinical prognosis information were downloaded from TCGA data and GEO data, respectively, and TME-related gene expression profiles were extracted. A prognostic signature was constructed and evaluated using univariate Cox regression analysis and LASSO regression analysis. Gene set enrichment analysis (GSEA) was used to obtain the biological process of gene enrichment in patients with high and low-risk groups.

Results

A prognostic signature consisting of eight TME-related genes (LRFN1, CSF1, UCN, TUBB2B, SERPINF1, ADAM8, ABCB4, CCL22) was constructed. Kaplan-Meier survival analysis yielded significantly lower survival times for patients in the high-risk group than in the low-risk group, and the AUC values for the ROC curves of this prognostic signature were essentially greater than 0.7, and univariate and multifactorial Cox regression analyses indicated that the risk score was independent risk factors for KIRC prognosis. GSEA analysis showed that immune-related biological processes were enriched in the high-risk group and that risk values were strongly associated with multiple immune cell scores and immune checkpoint-related genes (PDCD1, CTLA4).

Conclusions

The prognostic signature can accurately predict the prognosis of KIRC patients, which may provide new ideas for future precision immunotherapy of KIRC.
Epidemiological Evidence for Associations Between Genetic Variants and Osteosarcoma Susceptibility: A Meta-Analysis
Authors: Yuan Dechao , Tian Jie , Fang Xiang , Xiong Yan , Banskota Nishant , Kuang Fuguo , Zhang Wenli , Duan Hong
Published: July 2022

Background

Previous studies have showed that single nucleotide polymorphisms (SNPs) might be implicated in the pathogenesis of osteosarcoma (OS). Numerous studies involving SNPs with OS risk have been reported; these results, however, remain controversial and no comprehensive research synopsis has been performed till now.

Objective

This study seeks to clarify the relationships between SNPs and OS risk using a comprehensive meta-analysis, and assess epidemiological evidence of significant associations.

Methods

The PubMed, Web of Science, and Medline were used to screen for articles that evaluated the association between SNP and OS susceptibility in humans before 24 December 2021. Furthermore, we used Venice Criteria and a false positive report probability (FPRP) test to assess the grades of epidemiological evidence for the statistical relationships.

Results

We extracted useful data based on 43 articles, including 10,255 cases and 13,733 controls. Our results presented that 25 SNPs in 17 genes were significantly associated with OS risk. Finally, we graded strong evidence for 17 SNPs in 14 genes with OS risk (APE1 rs1760944, BCAS1 rs3787547, CTLA4 rs231775, ERCC3 rs4150506, HOTAIR rs7958904, IL6 rs1800795, IL8 rs4073, MTAP rs7023329 and rs7027989, PRKCG rs454006, RECQL5 rs820196, TP53 rs1042522, VEGF rs3025039, rs699947 and rs2010963, VMP1 rs1295925, XRCC3 rs861539), moderate for 14 SNPs in 12 genes and weak for 14 SNPs in 11 genes.

Conclusion

In summary, this study offered a comprehensive meta-analysis between SNPs and OS susceptibility, then evaluated the credibility of statistical relationships, and provided useful information to identify the appropriate candidate SNPs and design future studies to evaluate SNP factors for OS risk.
Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the Evaluation of Patients With Newly Diagnosed Non-Small Cell Lung Cancer
Authors: Wu Junhao , Deng Hao , Zhong Haoshu , Wang Tao , Rao Zijuan , Wang Yingwei , Chen Yue , Zhang Chunyin
Published: July 2022

Purpose

Several studies have demonstrated that 68Ga-FAPI PET/CT shows high intratumoral tracer uptake and low normal tissue uptake, allowing for excellent visualization of cancer. The purpose of this study was to compare the ability of 68Ga-FAPI and 18F-FDG PET/CT for the evaluation of newly diagnosed NSCLC.

Materials and Methods

A prospective analysis of 28 individuals with histopathologically newly confirmed NSCLC that underwent 68Ga-FAPI and 18F-FDG PET/CT was conducted. The performance of two imaging modalities was compared based upon visual assessment, rates of cancer detection, and semi-quantitative parameters (target-to-background ratio [TBR], maximum standard uptake value [SUVmax]) for both primary tumors and metastases.

Results

In total, this study enrolled 28 participants (13 male, 15 female; median age: 60.5 years, range: 34 – 78 years. For primary tumors, 68Ga-FAPI and 18F-FDG PET/CT have similar detection performance (28 vs. 27). However, 68Ga-FAPI PET/CT was found to more effectively evaluate most metastases as compared to 18F-FDG PET/CT. 68Ga-FAPI PET/CT detecting more metastases present within the lymph nodes (53 vs. 49), pleura (8 vs. 7), liver (4 vs. 1), and bone (41 vs. 35). The SUVmax and TBR values for 68Ga-FAPI were substantially superior to those for 18F-FDG in lymph node, pleural, and bone metastases. While the SUVmax for these two imaging approaches was comparable for hepatic metastases, 68Ga-FAPI exhibited a significantly higher TBR in relation to that of 18F-FDG. In addition, 68Ga-FAPI PET/CT demonstrates excellent N (80% [8/10]) and M (92.9% [26/28]) staging accuracy in NSCLC patients.

Conclusions

68Ga-FAPI PET/CT as an examination modality is excellent for evaluation of newly diagnosed NSCLC. 68Ga-FAPI PET/CT improves the detection rates of most metastases and facilitating the superior staging of patients with newly diagnosed NSCLC, relative to that achieved by 18F-FDG PET/CT.
Targeting CD47 as a Novel Immunotherapy for Breast Cancer
Authors: Chen Can , Wang Runlu , Chen Xi , Hou Yulong , Jiang Jingting
Published: July 2022

Nowadays, breast cancer has become the most common cancer worldwide with a high mortality rate. Immune checkpoint blockade holds great promise in tumor‐targeted therapy, and CD47 blockade as one immune therapy is undergoing various preclinical studies and clinical trials to demonstrate its safety and efficacy in breast cancer. In this review, we summarized different therapeutic mechanisms targeting CD47 and its prognostic role and therapeutic value in breast cancer.
Clinical and CT Features of Subsolid Pulmonary Nodules With Interval Growth: A Systematic Review and Meta-Analysis
Authors: Liang Xin , Liu Mengwen , Li Meng , Zhang Li
Published: July 2022

Background

Establishing risk-based follow-up management strategies is crucial to the surveillance of subsolid pulmonary nodules (SSNs). However, the risk factors for SSN growth are not currently clear. This study aimed to perform a systematic review and meta-analysis to identify clinical and CT features correlated with SSN growth.

Methods

Relevant studies were retrieved from Web of Science, PubMed, Cochrane Library, and EMBASE. The correlations of clinical and CT features with SSN growth were pooled using a random-effects model or fixed-effects model depending on heterogeneity, which was examined by the Q test and I2 test. Pooled odds ratio (OR) or pooled standardized mean differences (SMD) based on univariate analyses were calculated to assess the correlation of clinical and CT features with SSN growth. Pooled ORs based on multivariate analyses were calculated to find out independent risk factors to SSN growth. Subgroup meta-analysis was performed based on nodule consistency (pure ground-glass nodule (pGGN) and part-solid nodule (PSN). Publication bias was examined using funnel plots.

Results

Nineteen original studies were included, consisting of 2444 patients and 3012 SSNs. The median/mean follow-up duration of these studies ranged from 24.2 months to 112 months. Significant correlations were observed between SSN growth and eighteen features. Male sex, history of lung cancer, nodule size > 10 mm, nodule consistency, and age > 65 years were identified as independent risk factors for SSN growth based on multivariate analyses results. Eight features, including male sex, smoking history, nodule size > 10 mm, larger nodule size, air bronchogram, higher mean CT attenuation, well-defined border, and lobulated margin were detected to be significantly correlated with pGGNs growth. Smoking history showed no significant correlation with pGGN growth based on the multivariate analysis results.

Conclusions

Eighteen clinical and CT features were identified to be correlated with SSN growth, among which male sex, history of lung cancer, nodule size > 10 mm, nodule consistency and age > 65 years were independent risk factors while history of lung cancer was not correlated with pGGN growth. These factors should be considered when making risk-based follow-up plans for SSN patients.
Telomere Length Regulation
Authors: Lansdorp Peter
Published: July 2022

The number of (TTAGGG)n repeats at the ends of chromosomes is highly variable between individual chromosomes, between different cells and between species. Progressive loss of telomere repeats limits the proliferation of pre-malignant human cells but also contributes to aging by inducing apoptosis and senescence in normal cells. Despite enormous progress in understanding distinct pathways that result in loss and gain of telomeric DNA in different cell types, many questions remain. Further studies are needed to delineate the role of damage to telomeric DNA, replication errors, chromatin structure, liquid-liquid phase transition, telomeric transcripts (TERRA) and secondary DNA structures such as guanine quadruplex structures, R-loops and T-loops in inducing gains and losses of telomere repeats in different cell types. Limitations of current telomere length measurements techniques and differences in telomere biology between species and different cell types complicate generalizations about the role of telomeres in aging and cancer. Here some of the factors regulating the telomere length in embryonic and adult cells in mammals are discussed from a mechanistic and evolutionary perspective.
Feasibility of Same-Day Discharge After Appendectomy in Pediatric Patients: A Systematic Review and Meta-Analysis
Authors: Zheng Yifei , Qi Shiqin
Published: July 2022

Background

To compare the readmission rate, rate of urgent/unplanned visits to emergency, complication rate along with cost of health care among children and adolescents who were discharged the same day following a laparoscopic appendectomy and those who were not discharged on the same day.

Methods

A systematic search was performed in the PubMed, Embase, and Scopus databases. Randomized controlled trials and studies, observational in design, were considered for inclusion. The included studies were conducted in children and adolescents with uncomplicated appendicitis undergoing laparoscopic appendectomy and compared outcomes of interest between patients that were discharged the same day (SDD group) following the operation and patients that were discharged within 2 days post-operatively (non-SSD group). Statistical analysis was performed using STATA software. Effect sizes were reported as pooled odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals.

Results

A total of 13 studies with 32,021 children and adolescents were included. There was no significant difference in the risks of unplanned visit to the emergency department (OR 1.07, 95% CI: 0.78, 1.47), readmission (OR 0.83, 95% CI: 0.66, 1.05), reoperation/re-intervention (OR 1.73, 95% CI: 0.19, 16.2) and complications (OR 0.84, 95% CI: 0.67, 1.06) in both groups of patients. Patients in the SDD group had slightly lower risk of wound infection/complication (OR 0.74, 95% CI: 0.57, 0.96) compared to patients in the non-SDD group. Those with SDD had to incur comparatively lesser hospital expense (in USD) compared to those with no SDD (WMD −2587.4, 95% CI: −4628.3, −546.6).

Conclusion

In children and adolescents with uncomplicated acute appendicitis undergoing laparoscopic appendectomy, same-day discharge is not associated with increased readmission risk, unplanned visits to emergency, and complications. Further, SDD is associated with lower cost of hospital care. Adoption of SDD in this subset of children and adolescents may be encouraged.

Systematic Review Registration

[www.crd.york.ac.uk/prospero], identifier [CRD420 22320539].
AMPK Activation Alleviates Myocardial Ischemia-Reperfusion Injury by Regulating Drp1-Mediated Mitochondrial Dynamics
Authors: Du Jingxia , Li Hongchao , Song Jingjing , Wang Tingting , Dong Yibo , Zhan An , Li Yan , Liang Gaofeng
Published: July 2022

Mitochondrial dysfunction is a salient feature of myocardial ischemia/reperfusion injury (MIRI), while the potential mechanism of mitochondrial dynamics disorder remains unclear. This study sought to explore whether activation of Adenosine monophosphate-activated protein kinase (AMPK) could alleviate MIRI by regulating GTPase dynamin-related protein 1 (Drp1)-mediated mitochondrial dynamics. Isolated mouse hearts in a Langendorff perfusion system were subjected to ischemia/reperfusion (I/R) treatment, and H9C2 cells were subjected to hypoxia /reoxygenation (H/R) treatment in vitro. The results showed that AICAR, the AMPK activator, could significantly improve the function of left ventricular, decrease arrhythmia incidence and myocardial infarction area of isolated hearts. Meanwhile, AICAR increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) content in myocardial homogenate. Mechanistically, AICAR inhibited the phosphorylation of Drp1 at Ser 616 while enhanced phosphorylation of Drp1 at Ser 637. In addition, AICAR reduced the expression of inflammatory cytokines including TNF-ɑ, IL-6, and IL-1β, as well as mitochondrial fission genes Mff and Fis1, while improved the expression of mitochondrial fusion genes Mfn1 and Mfn2. Similar results were also observed in H9C2 cells. AICAR improved mitochondrial membrane potential (MMP), reduced reactive oxygen species (ROS) production, and inhibited mitochondrial damage. To further prove if Drp1 regulated mitochondrial dynamics mediated AMPK protection effect, the mitochondrial fission inhibitor Mdivi-1 was utilized. We found that Mdivi-1 significantly improved MMP, inhibited ROS production, reduced the expression of TNF-a, IL-6, IL-1β, Fis1, and Mff, and improved the expression of Mfn1 and Mfn2. However, the protection effect of Mdivi-1 was not reversed by AMPK inhibitor Compound C. In conclusion, this study confirmed that activation of AMPK exerted the protective effects on MIRI, which were largely dependent on the inhibition of Drp1-mediated mitochondrial fission.
Historical Perspectives, State of Art and Research Trends of SPAD Arrays and Their Applications (Part II: SPAD Arrays)
Authors: Cusini Iris , Berretta Davide , Conca Enrico , Incoronato Alfonso , Madonini Francesca , Maurina Arianna Adelaide , Nonne Chiara , Riccardo Simone , Villa Federica
Published: July 2022

The ability to detect single photons is becoming an enabling key capability in an increasing number of fields. Indeed, its scope is not limited to applications that specifically rely on single photons, such as quantum imaging, but extends to applications where a low signal is overwhelmed by background light, such as laser ranging, or in which faint excitation light is required not to damage the sample or harm the patient. In the last decades, SPADs gained popularity with respect to other single-photon detectors thanks to their small size, possibility to be integrated in complementary metal-oxide semiconductor processes, room temperature operability, low power supply and, above all, the possibility to be fast gated (to time filter the incoming signal) and to precisely timestamp the detected photons. The development of large digital arrays that integrates the detectors and circuits has allowed the implementation of complex functionality on-chip, tailoring the detectors to suit the need of specific applications. This review proposes a complete overview of silicon SPADs characteristics and applications. In the previous Part I, starting with the working principle, simulation models and required frontend, the paper moves to the most common parameters adopted in literature for characterizing SPAD performance and describes single pixels applications and their performance. In this Part II, the focus is posed on the development of SPAD arrays, presenting some of the most notable examples found in literature. The actual exploitation of these designs in real applications (e.g., automotive, bioimaging and radiation detectors) is then discussed.
An Innovative Superconducting Magnetic Trap for Probing β-decay in Plasmas
Authors: Mauro Giorgio Sebastiano , Celona Luigi , Torrisi Giuseppe , Pidatella Angelo , Naselli Eugenia , Russo Filippo , Mazzaglia Maria , Galatà Alessio , Maimone Fabio , Lang Ralf , Tinscher Klaus , Santonocito Domenico , Mascali David
Published: July 2022

The main aim of Plasmas for Astrophysics Nuclear Decays Observation and Radiation for Archaeometry (PANDORA) project is to build a compact and flexible magnetic plasma trap where plasma reaches a densityne∼ 1011–1013 cm−3, and a temperature, in units ofkT,kTe∼ 0.1–30 keV in order to measure, for the first time, nuclearβ-decay rates in stellar-like conditions. One of the most important aspects of an ECR Ion Source (ECRIS) is its magnetic system. In this paper, the numerical design of the PANDORA magnetic system is presented and validated by using the commercial simulators OPERA and CST Studio Suite, showing an excellent agreement between each other in terms of axial and radial field profiles. In conjunction to the magnetic system design, the overall injection system, including the microwave lines for plasma heating and the isotopes injection schemes with a focus on the developments of the oven for solid elements, has been conceived and will be discussed.
Recent Advances in Understanding the Electron Transport Through Metal-Azurin-Metal Junctions
Authors: Romero-Muñiz C. , Vilhena J. G. , Pérez R. , Cuevas J. C. , Zotti L. A.
Published: July 2022

Azurin proteins are the workhorse of protein electronics. This is a branch of biomolecular electronics, a recent research field which investigates electronics based on biomolecules such as proteins, peptides, amino acids, bacterial nanowires or DNA. In general, the possibility of including biosystems in solid-state junctions has opened the way to the development of novel electrical devices, and proteins have attracted enormous attention thanks to their many interesting properties. In the particular case of metal-azurin-metal junctions, experimental measurements have revealed extremely efficient electron transport over large distances, showing conductance values which are higher than certain conjugated molecules of similar lengths. Moreover, the electrical current has often been found to be temperature-independent, which has been used as an evidence of coherent transport or quantum tunneling. Interesting effects have been observed, moreover, upon insertion of single amino-acid mutations. In spite of a huge amount of work, the exact mechanism for the charge flow through these systems is still under debate. In this review, we will revise the recent advances made in the electron-transport measurements of azurin-based junctions as well as the corresponding theoretical modelling. We will discuss the interpretation of the currently-available experimental results as well as the open issues which still remain to be clarified.
Emerging High-Frequency Ultrasound Imaging in Medical Cosmetology
Authors: Tao YaPing , Wei Cong , Su YiMin , Hu Bing , Sun Di
Published: July 2022

Cosmetic skin diseases are a part of many dermatological concerns brought up by patients, which negatively affect mental health and quality of life. Imaging technology has an established role in the diagnosis of cosmetic skin diseases by recognizing information on deep skin lesions. Due to the complex physiological and pathological nature of cosmetic skin diseases, the diagnostic imaging performance varies greatly. Developing noninvasive technology models with wide applicability, particularly high-frequency ultrasound (HFUS), which is able to achieve high-resolution imaging of the skin from the stratum corneum down to the deep fascia, is of great significance to medical cosmetology. To explore the great potential of HFUS in cosmetic skin diseases, a narrative review of literature from PubMed and Web of Science published between 1985 and 2022 was conducted. This narrative review focuses on the progression of HFUS imaging in medical cosmetology, especially on its promising application in the quantitative evaluation and differential diagnosis of cutaneous pathological scar, port wine stain (PWS), acne, skin aging, and other cosmetic applications.
Urinary Tract Infection in Overactive Bladder: An Update on Pathophysiological Mechanisms
Authors: Mansfield Kylie J. , Chen Zhuoran , Moore Kate H. , Grundy Luke
Published: July 2022

Overactive bladder (OAB) is a clinical syndrome defined by urinary urgency, increased daytime urinary frequency and/or nocturia, with or without urinary incontinence, that affects approximately 11% of the western population. OAB is accepted as an idiopathic disorder, and is charactersied clinically in the absence of other organic diseases, including urinary tract infection. Despite this, a growing body of research provides evidence that a significant proportion of OAB patients have active bladder infection. This review discusses the key findings of recent laboratory and clinical studies, providing insight into the relationship between urinary tract infection, bladder inflammation, and the pathophysiology of OAB. We summarise an array of clinical studies that find OAB patients are significantly more likely than control patients to have pathogenic bacteria in their urine and increased bladder inflammation. This review reveals the complex nature of OAB, and highlights key laboratory studies that have begun to unravel how urinary tract infection and bladder inflammation can induce urinary urgency and urinary frequency. The evidence presented in this review supports the concept that urinary tract infection may be an underappreciated contributor to the pathophysiology of some OAB patients.
A Poroelastic Approach for Modelling Myocardial Oedema in Acute Myocarditis
Authors: Lourenço Wesley de Jesus , Reis Ruy Freitas , Ruiz-Baier Ricardo , Rocha Bernardo Martins , dos Santos Rodrigo Weber , Lobosco Marcelo
Published: July 2022

Myocarditis is a general set of mechanisms that manifest themselves into the inflammation of the heart muscle. In 2017, more than 3 million people were affected by this disease worldwide, causing about 47,000 deaths. Many aspects of the origin of this disease are well known, but several important questions regarding the disease remain open. One of them is why some patients develop a significantly localised inflammation while others develop a much more diffuse inflammation, reaching across large portions of the heart. Furthermore, the specific role of the pathogenic agent that causes inflammation as well as the interaction with the immune system in the progression of the disease are still under discussion. Providing answers to these crucial questions can have an important impact on patient treatment. In this scenario, computational methods can aid specialists to understand better the relationships between pathogens and the immune system and elucidate why some patients develop diffuse myocarditis. This paper alters a recently developed model to study the myocardial oedema formation in acute infectious myocarditis. The model describes the finite deformation regime using partial differential equations to represent tissue displacement, fluid pressure, fluid phase, and the concentrations of pathogens and leukocytes. A sensitivity analysis was performed to understand better the influence of the most relevant model parameters on the disease dynamics. The results showed that the poroelastic model could reproduce local and diffuse myocarditis dynamics in simplified and complex geometrical domains.
Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24 h in Preterm Lambs
Authors: Chan Kyra YY , Tran Nhi T. , Papagianis Paris C. , Zahra Valerie A. , Nitsos Ilias , Moxham Alison M. , LaRosa Domenic A. , McDonald Courtney , Miller Suzanne L. , Galinsky Robert , Alahmari Dhafer M. , Stojanovska Vanesa , Polglase Graeme R.
Published: July 2022

Initiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to assess the role of the inflammatory and haemodynamic pathway on ventilation-induced brain injury (VIBI) in the preterm lamb. Fetal lambs (125 ± 1 day gestation) were exteriorised, instrumented and ventilated with a high tidal-volume (VT) injurious strategy for 15 min either with placental circulation intact to induce the inflammatory pathway only (INJINF; n = 7) or umbilical cord occluded to induce both the inflammatory and haemodynamic pathways (INJINF+HAE; n = 7). Sham controls were exteriorised but not ventilated (SHAM; n = 5) while unoperated controls (UNOP; n = 7) did not undergo fetal instrumentation. Fetuses were returned in utero following intervention and the ewe allowed to recover. Arterial blood gases and plasma were sampled periodically. Twenty-four hours following intervention, lambs were delivered and maintained on non-injurious ventilation for ∼40 min then brains were collected post-mortem for immunohistochemistry and RT-qPCR to assess inflammation, vascular pathology and cell death within white matter regions. Compared to INJINF lambs, INJINF+HAE lambs achieved a consistently higher VT during injurious ventilation and carotid blood flow was significantly lower than baseline by the end of ventilation. Throughout the 24 h recovery period, systemic arterial IL-6 levels of INJINF+HAE lambs were significantly higher than SHAM while there was no difference between INJINF and SHAM animals. At 24 h, mRNA expression levels of pro-inflammatory cytokines, tight junction proteins, markers of cell death, and histological injury indices of gliosis, blood vessel protein extravasation, oligodendrocyte injury and cell death were not different between groups. Injurious ventilation, irrespective of strategy, did not increase brain inflammation or injury 24 h later when compared to control animals. However, the haemodynamic pathway did influence carotid blood flow adaptations during injurious ventilation and increased systemic arterial IL-6 that may underlie long-term pathology. Future studies are required to further characterise the pathways and their long-term effects on VIBI.
Red Blood Cell Morphologic Abnormalities in Patients Hospitalized for COVID-19
Authors: Marchi Giacomo , Bozzini Claudia , Bertolone Lorenzo , Dima Francesco , Busti Fabiana , Castagna Annalisa , Stranieri Chiara , Fratta Pasini Anna Maria , Friso Simonetta , Lippi Giuseppe , Girelli Domenico , Vianello Alice
Published: July 2022

Peripheral blood smear is a simple laboratory tool, which remains of invaluable help for diagnosing primary and secondary abnormalities of blood cells despite advances in automated and molecular techniques. Red blood cells (RBCs) abnormalities are known to occur in many viral infections, typically in the form of mild normo-microcytic anemia. While several hematological alterations at automated complete blood count (including neutrophilia, lymphopenia, and increased red cell distribution width—RDW) have been consistently associated with severity of COVID-19, there is scarce information on RBCs morphological abnormalities, mainly as case-reports or small series of patients, which are hardly comparable due to heterogeneity in sampling times and definition of illness severity. We report here a systematic evaluation of RBCs morphology at peripheral blood smear in COVID-19 patients within the first 72 h from hospital admission. One hundred and fifteen patients were included, with detailed collection of other clinical variables and follow-up. A certain degree of abnormalities in RBCs morphology was observed in 75 (65%) patients. Heterogenous alterations were noted, with spiculated cells being the more frequent morphology. The group with >10% RBCs abnormalities had more consistent lymphopenia and thrombocytopenia compared to those without abnormalities or <10% RBCs abnormalities (p < 0.018, and p < 0.021, respectively), thus underpinning a possible association with an overall more sustained immune-inflammatory “stress” hematopoiesis. Follow-up analysis showed a different mortality rate across groups, with the highest rate in those with more frequent RBCs morphological alterations compared to those with <10% or no abnormalities (41.9%, vs. 20.5%, vs. 12.5%, respectively, p = 0.012). Despite the inherent limitations of such simple association, our results point out towards further studies on erythropoiesis alterations in the pathophysiology of COVID-19.