bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis
Authors: Cao Liangliang , Zhao Yang , Liang Zhuangzhuang , Yang Jian , Wang Jiajia , Tian Shuaiwei , Wang Qinhua , Wang Baocheng , Zhao Heng , Jiang Feng , Ma Jie
Published: September 2022

Minichromosome maintenance proteins are DNA-dependent ATPases that bind to replication origins and allow a single round of DNA replication. One member of this family, MCM3, is reportedly active in most cancers. To systematically elucidate the mechanisms affected by aberrant MCM3 expression and evaluate its clinical significance, we analyzed multi-omics data from the GEO database and validated them in cell lines and tumor samples. First, we showed the upregulation of MCM3 in medulloblastoma (MB) at bulk and single-cell RNA sequence levels and revealed the potential role of MCM3 via DNA replication. Then we found the dysregulation of MCM3 might result from abnormal methylation of MCM3. Moreover, we discovered that MCM3 might affect varied biological processes such as apoptosis, autophagy, and ferroptosis and that MCM3 was correlated with immune components such as fibroblast and neutrophils, which were associated with overall survival in different medulloblastoma subtypes. Furthermore, we found that MCM3 expression was correlated with the IC50 values of cisplatin and etoposide. The nomogram of MCM3-related genes showed the reliable and better prediction of 1- and 5-year survival compared to current histological and molecular classifications. Overall, the results of our study demonstrated that MCM3 might serve as a potential biomarker with clinical significance and better guidance than current histological and molecular classifications for clinical decision-making.
Machine learning based on metabolomics reveals potential targets and biomarkers for primary Sjogren’s syndrome
Authors: Wang Kai , Li Ju , Meng Deqian , Zhang Zhongyuan , Liu Shanshan
Published: September 2022

Background: Using machine learning based on metabolomics, this study aimed to construct an effective primary Sjogren’s syndrome (pSS) diagnostics model and reveal the potential targets and biomarkers of pSS.

Methods: From a total of 39 patients with pSS and 38 healthy controls (HCs), serum specimens were collected. The samples were analyzed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. Three machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (XGBoost), were used to build the pSS diagnosis models. Afterward, four machine learning methods were used to reduce the dimensionality of the metabolomics data. Finally, metabolites with significant differences were screened and pathway analysis was conducted.

Results: The area under the curve (AUC), sensitivity, and specificity of LASSO, RF and XGBoost test set all reached 1.00. Orthogonal partial least squares discriminant analysis was used to classify the metabolomics data. By combining the results of the univariate false discovery rate and the importance of the variable in projection, we identified 21 significantly different metabolites. Using these 21 metabolites for diagnostic modeling, the AUC, sensitivity, and specificity of LASSO, RF, and XGBoost all reached 1.00. Metabolic pathway analysis revealed that these 21 metabolites are highly correlated with amino acid and lipid metabolisms. On the basis of 21 metabolites, we screened the important variables in the models. Further, five common variables were obtained by intersecting the important variables of three models. Based on these five common variables, the AUC, sensitivity, and specificity of LASSO, RF, and XGBoost all reached 1.00.2-Hydroxypalmitic acid, L-carnitine and cyclic AMP were found to be potential targets and specific biomarkers for pSS.

Conclusion: The combination of machine learning and metabolomics can accurately distinguish between patients with pSS and HCs. 2-Hydroxypalmitic acid, L-carnitine and cyclic AMP were potential targets and biomarkers for pSS.
Impact of physiotherapy with telerehabilitation on caregivers of patients with neurological disorders: A systematic review protocol
Authors: Silva Emília Márcia Gomes de Souza e , de Melo Luciana Protásio , de Souza Aline Alves , de Holanda Ledycnarf Januário , Ribeiro Tatiana Souza , Valentim Ricardo Alexsandro de Medeiros , Lindquist Ana Raquel
Published: September 2022

Introduction

Caregivers are essential during and after rehabilitation but exhibit intense physical and mental burdens due to responsibilities, resulting in stress, irritability, depression, anxiety, pain, and financial distress. Telerehabilitation offers several remote health services that improve time, engagement, and physical and mental health care access. Thus, we outlined a systematic review protocol to evaluate the impact of telerehabilitation on the burden, stress, pain, and quality of life of caregivers of patients with neurological disorders.

Methods

Searches will be conducted in Ovid MEDLINE, Pubmed, Scopus, Web of Science, Embase, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, and PsycINFO databases. Clinical trials evaluating the burden, stress, pain, and quality of life of caregivers of patients with neurological disorders using telerehabilitation will be included without publication date or language restriction. Two reviewers will independently select studies from titles, abstracts, and reference lists. The quality of evidence and risk of bias will be assessed according to Cochrane recommendations.

Results

This systematic review to be developed will evaluate the impact of telerehabilitation on the burden, stress, pain, and quality of life of caregivers of patients with neurological disorders.

Discussion

Caregivers, especially of patients with neurological disorders, need more attention since the overload, stress, duties with other personal responsibilities, and low remuneration may impact the quality of life. Therefore, they need intervention, especially physical therapy via telehealth, which values the time of caregivers and may change their perception of health and quality of life.

PROSPERO registration number

CRD42022278523.
Identification of a novel necroptosis-related classifier to predict prognosis and guide immunotherapy in breast invasive carcinoma
Authors: Zhou Qin , Xu Yan , Shen Liang , Yang Xiaochen , Wang Li
Published: September 2022

Background

Necroptosis plays a crucial function in the progression of breast invasive carcinoma (BRCA). It may be triggered in cancer therapy to enhance anti-tumor immunity. However, the functions of necroptosis in tumors and its relationship with the tumor microenvironment (TME) remain largely unclear.

Methods

Necroptosis-related genes (NRGs) were collated from high-quality literature reviews. A robust risk model was constructed to systematically evaluate the clinical value, functional status, effects exerted by the risk model on the TME, and the genomic variations based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) meta-cohorts.

Results

A risk model was constructed which comprised of six NRGs, including TNF receptor-associated factor 5 (TRAF5), Toll-like receptor 3 (TLR3), a riboflavin kinase (RFK), Fas ligand (FASLG), Fas-associated protein with death domain (FADD), and baculoviral IAP repeat-containing 3 (BIRC3). The stability and accuracy of the risk model were demonstrated for both the training and validation cohorts and its utility as an independent prognostic model for BRCA was verified. Patients in the low-risk group exhibited “hot” tumors having active immune and cell killing functions, while those in the high-risk group showed “cold” tumors having active tumor proliferation and immunosuppression. Moreover, patients in the high-risk group had a greater number of CNV events in their genome, while the somatic mutations were fewer. Furthermore, patients in the low-risk group showed high sensitivity toward immunotherapy and chemotherapy.

Conclusion

A reliable risk model based on NRGs to assess patient prognoses and guide clinical decision-making was constructed and validated. Our findings may contribute to the understanding of necroptosis and aid clinical management, along with precision treatment in BRCA.
Transcriptome sequencing of hepatocellular carcinoma uncovers multiple types of dysregulated ncRNAs
Authors: Zhang Li , Wang Chunmei , Lu Xiaojie , Xu Xiao , Shi Tieliu , Chen Jinlian
Published: September 2022

Transcriptome profiling of hepatocellular carcinoma (HCC) by next-generation sequencing (NGS) technology has been broadly performed by previous studies, which facilitate our understanding of the molecular mechanisms of HCC formation, progression, and metastasis. However, few studies jointly analyze multiple types of noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and micro-RNAs (miRNAs), and further uncover their implications in HCC. In this study, we observed that the circRNA cZRANB1 and lncRNA DUXAP10 were not only significantly upregulated in tumor tissues, but also higher expressed in blood exosomes of HCC as compared with healthy donors. From the analysis of subclass-associated dysregulated ncRNAs, we observed that DLX6-AS1, an antisense RNA of DLX6, and the sense gene DLX6 were highly expressed in S1, a subclass with a more invasive/disseminative phenotype. High correlation between DLX6-AS1 and DLX6 suggested that DLX6-AS1 may function via promoting the transcription of DLX6. Integrative analysis uncovers circRNA–miRNA, lncRNA–miRNA, and competing endogenous RNA networks (ceRNAs). Specifically, cZRANB1, LINC00501, CTD-2008L17.2, and SLC7A11-AS1 may function as ceRNAs that regulate mRNAs by competing the shared miRNAs. Further prognostic analysis demonstrated that the dysregulated ncRNAs had the potential to predict HCC patients’ overall survival. In summary, we identified some novel circRNAs and miRNAs, and dysregulated ncRNAs that could participate in HCC tumorigenesis and progression by inducing transcription of their neighboring genes, increasing their derived miRNAs, or acting as miRNA sponges. Moreover, our systematic analysis provides not only rich data resources for related researchers, but also new insights into the molecular basis of how different ncRNAs coordinately or antagonistically participate in the pathogenesis process of diseases.
Proteolytic modulation of tumor microenvironment signals during cancer progression
Authors: Itoh Yoshifumi
Published: September 2022

Under normal conditions, the cellular microenvironment is optimized for the proper functioning of the tissues and organs. Cells recognize and communicate with the surrounding cells and extracellular matrix to maintain homeostasis. When cancer arises, the cellular microenvironment is modified to optimize its malignant growth, evading the host immune system and finding ways to invade and metastasize to other organs. One means is a proteolytic modification of the microenvironment and the signaling molecules. It is now well accepted that cancer progression relies on not only the performance of cancer cells but also the surrounding microenvironment. This mini-review discusses the current understanding of the proteolytic modification of the microenvironment signals during cancer progression.
Immunotherapy in advanced kidney cancer: an alternative meta-analytic method using reconstructed survival data in case of proportional hazard assumption violation
Authors: Nocera Luigi , Fallara Giuseppe , Raggi Daniele , Belladelli Federico , Robesti Daniele , Montorsi Francesco , Karakiewicz Pierre I. , Malavaud Bernard , Ploussard Guillaume , Necchi Andrea , Martini Alberto
Published: September 2022

Background

With the advent of immuno-oncology compounds in randomized trials, we observe more and more survival curves crossing. From a statistical standpoint this corresponds to violation of the proportional hazard assumption. When this occurs, the hazard ratio from the Cox regression is not reliable as an estimate. Herein, we aimed to identify the most appropriate IO-based therapy for metastatic renal cell carcinoma applying an alternative method to overcome the issue of hazard assumption violation for meta-analyses.

Methods

Pubmed, EMBASE, Web of Science and Scopus databases were searched. Only phase III randomized clinical trials on IO-IO (nivo-ipi) or IO-TKI combinations were included. An algorithm to obtain survival data from published Kaplan-Meier curves was used to reconstruct data on overall survival (OS), progression-free survival (PFS) and duration of response (DoR). Differences in restricted mean survival time (RMST) were used for comparisons.

Results

individual survival data from 4,206 patients from five trials were reconciled. Patients who received nivo-ipi or IO-TKI had better OS, PFS and DoR relative to sunitinib (all p<0.001). Patients who received IO-TKI had similar OS and PFS relative to nivo-ipi, with a 36-month ΔRMST of -0.55 (95% CI: -1.71-0.60; p=0.3) and -1.5 (95% CI: -2.9-0.0; p=0.051) months, respectively. Regarding DoR, patients who received nivo-ipi had longer duration of response relative to IO-TKI, with a 24-month ΔRMST of 1.5 (95% CI: 0.2-2.8; p=0.02) months.

Conclusion

Despite overall similar OS and PFS for patients receiving nivo-ipi and IO-TKI combinations, DoR was more favorable in patients who received nivo-ipi compared to IO-TKI. A meta-analysis based on differences in RMST is a useful alternative whenever the proportional hazard assumption is violated.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021241421.
Oncologic outcome of multimodality treatment for sinonasal malignancies: An 18-year experience
Authors: Chen Meng-Yu , Wen Xin , Wei Yi , Chen Lin , Huang Zi-Xuan , Lu Tong , Zheng Nian-Zhen , Li Jian , Wen Wei-Ping , Wen Yi-Hui
Published: September 2022

Purpose

The aim of this study was to retrospectively evaluate the oncologic outcomes of sinonasal malignancies (SNMs) of various histologic subtypes and investigate the impact of multimodality treatment on prognosis of SNM.

Methods

SNM patients treated with curative-intent surgery from 2000 to 2018 were included. The primary outcomes were overall survival (OS). Survival was then assessed through Cox proportional hazards models.

Results

Three hundred and three patients were eligible for the analysis. The 5-year OS and event-free survival (EFS) were 61.0% (95% CI: 55.4%–67.1%) and 46.2% (95% CI: 40.4%–52.7%). The 5-year OS was the worst for malignant melanoma and the best for adenocarcinoma. Patients who received surgery had better OS than those who only received radiotherapy and/or chemotherapy. Endoscopic surgery had better OS than the open approach (p < 0.05). Microscopically margin-negative resection (R0 resection) significantly benefited OS and EFS (p < 0.001). No significant difference in OS was observed between patients who received macroscopic complete resection (R1 resection) followed by adjuvant therapy and patients who received R0 resection. Older age (HR = 1.02, p = 0.02), R1 resection (HR = 1.99, p = 0.02), sinonasal surgical history of more than 3 months before diagnosis (HR = 2.77, p = 0.007), and radiotherapy history (HR = 3, p = 0.006) are risk factors for worse EFS.

Conclusions

Curative-intent surgery is irreplaceable in the treatment of SNM. The endoscopic approach is an effective alternative to the open approach. EFS is worse among patients with older age, R1 resection, sinonasal surgical history of more than 3 months before diagnosis, and radiotherapy history.
Survival after laparoscopy versus laparotomy for apparent early-stage uterine clear cell carcinoma: Results of a large multicenter cohort study
Authors: Shui Chengyu , Ran Lin , Tian Yong , Qin Li , Gu Xin , Xu Hui , Hu Cui , Zhang Lin-Lin , Xu You , Cheng Chen , Huan Wu
Published: September 2022

Objective

To compare the long-term survival between laparoscopic surgery and open surgery in patients with apparent early-stage uterine clear cell carcinoma (UCCC).

Patients and methods

254 patients with apparent early-stage UCCC were reviewed. Comparisons were made between patients who underwent laparoscopic surgery versus those who underwent open surgery. Baseline data, clinicopathological data, and oncological outcomes were analyzed. 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate were estimated and compared using the Kaplan-Meier method and the Log-rank test. The Cox proportional hazard regression model was employed to control the confounding factors.

Results

147 patients underwent laparoscopic surgery, and 107 patients were managed by open surgery. No differences in terms of recurrence rate (laparoscopy versus laparotomy: 10.9% versus 12.9%, P=0.842) and recurrence pattern were observed. For patients who underwent open surgery and patients who underwent laparoscopic surgery, the 5-year DFS rates and 5-year OS rate were 75.8% (95% CI: 65.8%-83.2%) and 69.1% (95% CI: 58.8%-77.4%), 66.0% (95% CI: 57.1%-73.5%) and 60.8% (95% CI: 52.0%-68.5%), respectively. The Cox proportional hazards regression model shown that for apparent early-stage UCCC, the approach of surgical staging was not an independent predictor for survival (laparoscopy versus laparotomy: for DFS, aHR=1.06, 95% CI=0.64-1.75, P=0.826; for OS, aHR=1.10, 95% CI=0.72-1.68, P=0.671).

Conclusion

For apparent early-stage UCCC, in terms of oncological survival, laparoscopic surgery was as safe as open surgery.
Histological features suggestive of survival in patients with renal cell carcinoma and tumor thrombus: A single-center experience
Authors: Wang Tao , Huang Yan , Yang Luojia , Yang Yang , Li Di , Zhang Xiangyi , Ding Xiaohui , Wang Baojun , Ma Xin
Published: September 2022

Purpose

To evaluate the impact of histological subtype on the survival of patients with renal cell carcinoma (RCC) and tumor thrombus (TT).

Patients and methods

We retrospectively analyzed 350 patients with RCC and TT admitted to Chinese People’s Liberation Army General Hospital between January 2006 and June 2021. The patients underwent radical nephrectomy and thrombectomy using robot-assisted laparoscopic, laparoscopic, or open surgery. The clinical and pathological parameters of the patients were taken from their medical records. Survival was calculated with the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of variables on overall survival (OS) and progression-free survival (PFS).

Results

TT levels 0–IV were observed in 132 (37.71%), 43 (12.29%), 134 (38.29%), 20 (5.71) and 21 (6.00%) patients, respectively. Papillary (pRCC), clear cell, and other histological subtypes of RCC were detected in 28 (8.00%), 286 (81.71%), and 36 (10.29%) patients, respectively. Compared to the clear cell cohort, collecting systemic invasion (46.43 vs. 25.17%; p = 0.030) and lymph node metastasis (39.29 vs. 11.54%; p < 0.01) were more common in the pRCC cohort. Kaplan–Meier analyses showed that patients with pRCC and other subtypes had significantly worse OS and PFS compared to patients with the clear cell subtype (p < 0.05). Multivariate analyses revealed that histology was independently associated with reduced OS and PFS, including among patients without lymph node and distant metastasis (N0M0).

Conclusion

Papillary or other subtypes have a considerably shorter OS and PFS compared to clear cell subtype in RCC patients with TT. Strict follow-up and surveillance should be performed for papillary or other subtypes RCC with TT.
Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions
Authors: Takami Hirokazu , Ichimura Koichi
Published: September 2022

CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in KIT and MTOR and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.
Prognostic factors of pediatric pelvic and genitourinary rhabdomyosarcoma: An analysis based on SEER database
Authors: Wu Jiheng , Shou Xinyi , Cai Jiabin , Mao Junqing , Qian Jianqin , Wang Jinhu , Ni Shaoqing
Published: September 2022

Background

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcomas in children. This study aimed to investigate the prognostic factors of pelvic and genitourinary RMS in children and evaluate the survival outcomes of these children treated with or without radiation therapy (RT).

Methods

The Surveillance, Epidemiology, and End Results Program (SEER) database was required for children with pelvic and genitourinary RMS. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses.

Results

For the 262 patients analyzed, the most common biological subtypes were embryonic (n=209, 79.8%) and alveolar (n=29, 11.1%). Patients with alveolar RMS had the worst prognosis (P < 0.05). The testis (n=122, 46.6%) was the most common location, followed by the urinary bladder (n=57, 21.8%) and prostate (n=48, 18.3%). Uterus RMS had the highest survival rate, followed by testis, urinary bladder, and prostate RMS. Favorable prognostic factors were age at diagnosis < 15 years, non-alveolar histological subtype, early tumor stage (localized/regional), specific sites (uterus and testis), and treatment (cancer-directed surgery and chemotherapy) (P < 0.05). Propensity score-matched analyses comparing the cohorts of patients treated with or without RT demonstrated no significant differences in prognostic survival (OS: P=0.872, CSS: P=0.713).

Conclusion

The nomogram constructed based on independent prognostic factors may accurately predict survival rates at 1 and 5 years. Surgery and adjuvant chemotherapy can be effective treatments, but RT fails to guarantee a survival benefit. Therefore, prospective trials evaluating RT for pediatric pelvic and genitourinary RMS are warranted.
Unravelling the Therapeutic Potential of Botanicals Against Chronic Obstructive Pulmonary Disease (COPD): Molecular Insights and Future Perspectives
Authors: Mitra Sicon , Anand Uttpal , Ghorai Mimosa , Vellingiri Balachandar , Jha Niraj Kumar , Behl Tapan , Kumar Manoj , Radha  , Shekhawat Mahipal S. , Proćków Jarosław , Dey Abhijit
Published: September 2022

Background: COPD (chronic obstructive pulmonary disease) is a serious health problem worldwide. Present treatments are insufficient and have severe side effects. There is a critical shortage of possible alternative treatments. Medicinal herbs are the most traditional and widely used therapy for treating a wide range of human illnesses around the world. In several countries, different plants are used to treat COPD.

Purpose: In this review, we have discussed several known cellular and molecular components implicated in COPD and how plant-derived chemicals might modulate them.

Methods: We have discussed how COVID-19 is associated with COPD mortality and severity along with the phytochemical roles of a few plants in the treatment of COPD. In addition, two tables have been included; the first summarizes different plants used for the treatment of COPD, and the second table consists of different kinds of phytochemicals extracted from plants, which are used to inhibit inflammation in the lungs.

Conclusion: Various plants have been found to have medicinal properties against COPD. Many plant extracts and components may be used as novel disease-modifying drugs for lung inflammatory diseases.
Network pharmacology and in vitro experiments-based strategy to investigate the mechanisms of KangXianYiAi formula for hepatitis B virus-related hepatocellular carcinoma
Authors: Cao Xu , Chen Hening , Li Zhiguo , Li Xiaoke , Yang Xianzhao , Jin Qiushuo , Liang Yijun , Zhang Jiaxin , Zhou Meiyue , Zhang Ningyi , Chen Guang , Du Hongbo , Zao Xiaobin , Ye Yong’an
Published: September 2022

The Chinese traditional medicine KangXianYiAi formula (KXYA) is used to treat hepatic disease in the clinic. Here we aim to confirm the therapeutic effects and explore the pharmacological mechanisms of KXYA on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We first collected and analyzed clinical data of 40 chronic hepatitis B (CHB) patients with precancerous liver lesions under KXYA treatment. Then, the cell viability, migration, cell cycle, and apoptosis of HepAD38 cells with KXYA treatment were examined. Next, we performed network pharmacological analysis based on database mining to obtain the key target pathways and genes of KXYA treatment on HBV-related HCC. We finally analyzed the expression of the key genes between normal and HBV-related HCC tissues in databases and measured the mRNA expression of the key genes in HepAD38 cells after KXYA treatment. The KXYA treatment could reduce the liver nodule size of CHB patients, suppress the proliferation and migration capabilities, and promote apoptosis of HepAD38 cells. The key pathways of KXYA on HBV-related HCC were Cancer, Hepatitis B, Viral carcinogenesis, Focal adhesion, and PI3K-Akt signaling, and KXYA treatment could regulate the expression of the key genes including HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1. The KXYA exhibited a curative effect via inhibiting proliferation, migration, and promoting apoptosis of HBV-related HCC and the pharmacological mechanism was related to the regulation of the expression of HNF4A, MAPK8, NR3C1, PTEN, EGFR, and HDAC1.
Effects of hyperventilation length on muscle sympathetic nerve activity in healthy humans simulating periodic breathing
Authors: Spiesshoefer Jens , Giannoni Alberto , Borrelli Chiara , Sciarrone Paolo , Husstedt Imke , Emdin Michele , Passino Claudio , Kahles Florian , Dawood Tye , Regmi Binaya , Naughton Matthew , Dreher Michael , Boentert Matthias , Macefield Vaughan G.
Published: September 2022

Background: Periodic breathing (PB) is a cyclical breathing pattern composed of alternating periods of hyperventilation (hyperpnea, HP) and central apnea (CA). Differences in PB phenotypes mainly reside in HP length. Given that respiration modulates muscle sympathetic nerve activity (MSNA), which decreases during HP and increases during CA, the net effects of PB on MSNA may critically depend on HP length.

Objectives: We hypothesized that PB with shorter periods of HP is associated with increased MSNA and decreased heart rate variability.

Methods: 10 healthy participants underwent microelectrode recordings of MSNA from the common peroneal nerve along with non-invasive recording of HRV, blood pressure and respiration. Following a 10-min period of tidal breathing, participants were asked to simulate PB for 3 min following a computed respiratory waveform that emulated two PB patterns, comprising a constant CA of 20 s duration and HP of two different lengths: short (20 s) vs long (40 s). Results: Compared to (3 min of) normal breathing, simulated PB with short HP resulted in a marked increase in mean and maximum MSNA amplitude (from 3.2 ± 0.8 to 3.4 ± 0.8 µV, p = 0.04; from 3.8 ± 0.9 to 4.3 ± 1.1 µV, p = 0.04, respectively). This was paralleled by an increase in LF/HF ratio of heart rate variability (from 0.9 ± 0.5 to 2.0 ± 1.3; p = 0.04). In contrast, MSNA response to simulated PB with long HP did not change as compared to normal breathing. Single CA events consistently resulted in markedly increased MSNA (all p < 0.01) when compared to the preceding HPs, while periods of HP, regardless of duration, decreased MSNA (p < 0.05) when compared to normal breathing.

Conclusion: Overall, the net effects of PB in healthy subjects over time on MSNA are dependent on the relative duration of HP: increased sympathetic outflow is seen during PB with a short but not with a long period of HP.
Effects of cheerleading practice on advanced glycation end products, areal bone mineral density, and physical fitness in female adolescents
Authors: Wang Lijun , Zhang Hongli , Xu Tuo , Zhang Jing , Liu Yuanyuan , Qu Yue
Published: September 2022

Background: Exercise has been widely reported to promote bone health, but it is unknown whether is associated with a reduction in advanced glycosylation end products (AGEs). This study aimed to investigate the effects of 14 weeks of cheerleading exercise on areal bone mineral density (aBMD) and AGEs.

Methods: In this study, 46 female teenagers (age, 19.52 ± 1.21 years; body mass index, 20.15 ± 2.47 kg/m2) were randomly divided into a cheerleading group (CHE, n = 21) and a control group (CON, n = 25). The CHE group was subjected to cheerleading practice twice a week for 14 weeks; the CON group maintained their daily routine. Dual-energy X-ray absorptiometry was used to measure aBMD, and autofluorescence (AF) values were used to reflect AGEs. Physical fitness testing all-in-one machines are used to test body composition, cardiorespiratory fitness, muscle fitness and flexibility. A mixed ANOVA model was used to examine the effect of the intervention on each outcome. A multiple mediation model with covariates for physical activity and eating behaviors was performed to explore the mediators between cheerleading exercise and aBMD.

Results: After 14 weeks of cheerleading practice, 1) aBMD increased significantly in both groups with significantly higher increases in the CHE group (p < 0.05). 2) AGEs significantly decreased in the CHE group (−2.7%), but not in the CON group (p > 0.05). 3) Vertical jumps and sit-ups significantly increased in the CHE group (p < 0.05), but not in the CON group (p > 0.05). 4) ΔAF values was significantly negatively correlated with Δ aBMD (r = −0.302, p < 0.05). 5) ΔAF values mediated the effect of exercise on the aBMD (indirect effect: 0.0032, 95% CI 0.0002–0.0079).

Conclusion: Cheerleading practice improved aBMD and physical fitness and reduced AGEs accumulation in female adolescents. The effect of exercise on aBMD was partially mediated by AGEs.
Replacing statistical significance and non-significance with better approaches to sampling uncertainty
Authors: Hopkins Will G.
Published: September 2022

A sample provides only an approximate estimate of the magnitude of an effect, owing to sampling uncertainty. The following methods address the issue of sampling uncertainty when researchers make a claim about effect magnitude: informal assessment of the range of magnitudes represented by the confidence interval; testing of hypotheses of substantial (meaningful) and non-substantial magnitudes; assessment of the probabilities of substantial and trivial (inconsequential) magnitudes with Bayesian methods based on non-informative or informative priors; and testing of the nil or zero hypothesis. Assessment of the confidence interval, testing of substantial and non-substantial hypotheses, and assessment of Bayesian probabilities with a non-informative prior are subject to differing interpretations but are all effectively equivalent and can reasonably define and provide necessary and sufficient evidence for substantial and trivial effects. Informative priors in Bayesian assessments are problematic, because they are hard to quantify and can bias the outcome. Rejection of the nil hypothesis (presented as statistical significance), and failure to reject the nil hypothesis (presented as statistical non-significance), provide neither necessary nor sufficient evidence for substantial and trivial effects. To properly account for sampling uncertainty in effect magnitudes, researchers should therefore replace rather than supplement the nil-hypothesis test with one or more of the other three equivalent methods. Surprisal values, second-generation p values, and the hypothesis comparisons of evidential statistics are three other recent approaches to sampling uncertainty that are not recommended. Important issues beyond sampling uncertainty include representativeness of sampling, accuracy of the statistical model, individual differences, individual responses, and rewards of benefit and costs of harm of clinically or practically important interventions and side effects.
The Construction of Psychological Intervention Mechanism of Deep Learning in the Prevention of Legal Anomie
Authors: Zou Caixia
Published: September 2022

The convenience of big data processing technology has played a great advantage in many scenarios, and its deep learning can effectively mine different types of data in data sets. Applying this method to mining psychological prediction data set of legal anomie behavior can effectively prevent the occurrence of illegal behavior. The effective analysis of its psychological characteristics and the changes of psychological emotions will have hidden dangers, so it is necessary to extract this kind of data in such cases. Therefore, the forest algorithm under deep learning uses weight factors, simple sampling, and other ideas to build the intervention mechanism, which will improve psychological quality to prevent anomie. The experimental results of this paper are as follows: (1) In the case of testing psychological fluctuation by three algorithms, the forest algorithm calculates the psychological change area steadily, with the increase of the number of samples. (2) In the data sample extraction of different dimensions, the test value increases with the increase of dimensions, and it is stable at 12 dimensions. (3) Preventive intervention is extremely important to construct the mechanism before the anomie behavior occurs, and the longest running time of the roll neural network is as much as 950 s. (4) The data mining technology for constructing the intervention mechanism accounts for 15.4% of counseling, which also shows that the auxiliary measures for preventing behavior are particularly important.
Survival model database of human digestive system cells exposed to electroporation pulses: An in vitro and in silico study
Authors: Han Xuan , Zhang Nana , Zhang Yuchi , Li Zhuoqun , Wang Yingxue , Mao Lujing , He Tianshuai , Li Qingshan , Zhao Jiawen , Chen Xue , Li Yixuan , Qin Zitong , Lv Yi , Ren Fenggang
Published: September 2022

Background and objectives

This study aimed to establish a mathematical survival model database containing cell-specific coefficients from human digestive system cells exposed to electroporation pulses (EPs).

Materials and methods

A total of 20 types of human digestive system cell lines were selected to investigate the effect of EPs on cell viability. Cell viability was measured after exposure to various pulse settings, and a cell survival model was established using the Peleg–Fermi model. Next, the cell-specific coefficients of each cell line were determined.

Results

Cell viability tended to decrease when exposed to stronger electric field strength (EFS), longer pulse duration, and more pulse number, but the decreasing tendency varied among different cell lines. When exposed to a lower EFS (<1,000 V/cm), only a slight decrease in cell viability occurred. All cell lines showed a similar tendency: the extent of electrical injury (EI) increased with the increase in pulse number and duration. However, there existed differences in heat sensitivity among organs.

Conclusions

This database can be used for the application of electroporation-based treatment (EBT) in the digestive system to predict cell survival and tissue injury distribution during the treatment.
Effects of immersion and navigation agency in virtual environments on emotions and behavioral intentions
Authors: Weller René , Cepok Joscha , Arzaroli Roman , Marnholz Kevin , Große Cornelia S. , Reuter Hauke , Zachmann Gabriel
Published: September 2022

We present a study investigating the question whether and how people’s intention to change their environmental behavior depends on the degrees of immersion and freedom of navigation when they experience a deteriorating virtual coral reef. We built the virtual reef on top of a biologically sound model of the ecology of coral reefs, which allowed us to simulate the realistic decay of reefs under adverse environmental factors. During their experience, participants witnessed those changes while they also explored the virtual environment. In a two-factorial experiment (N = 224), we investigated the effects of different degrees of immersion and different levels of navigation freedom on emotions, the feeling of presence, and participants’ intention to change their environmental behavior. The results of our analyses show that immersion and navigation have a significant effect on the participants’ emotions of sadness and the feeling of helplessness. In addition, we found a significant effect, mediated by the participants’ emotions, on the intention to change their behavior. The most striking result is, perhaps, that the highest level of immersion combined with the highest level of navigation did not lead to the highest intentions to change behavior. Overall, our results show that it is possible to raise awareness of environmental threats using virtual reality; it also seems possible to change people’s behavior regarding these threats. However, it seems that the VR experience must be carefully designed to achieve these effects: a simple combination of all affordances offered by VR technology might potentially decrease the desired effects.
Therapy of chronic extensor mechanism deficiency after total knee arthroplasty using a monofilament polypropylene mesh
Authors: Fuchs M , Gwinner C , Meißner N , Pfitzner T , Perka C. , von Roth P.
Published: September 2022

Introduction

Lesions of the quadriceps or patellar tendon after total knee arthroplasty (TKA) are a rare but serious complication which, if left untreated, can lead to loss of function of the knee joint. While acute and subacute extensor mechanism disruptions may have several causes, chronic deficiencies are often related to multiple prior revision surgeries for joint infection or aseptic TKA failure. Up to date, biological allograft reconstruction showed unsatisfying results. The use of a monofilament polypropylene mesh is a promising approach for this pathological condition. The aim of the present study was to evaluate clinical, functional and patient reported outcomes of this procedure in patients with chronic extensor mechanism deficiency.

Materials and Methods

Twenty-eight patients with chronic extensor mechanism deficiency (quadriceps tendon rupture n = 9, patellar tendon rupture n = 19) after TKA were included in this retrospective study. None of the patients were lost to follow-up. Surgical reconstruction was performed at one institution between 2014 and 2020 with a monofilament polypropylene mesh (Marlex Mesh, Bard, Murray Hill, USA). The mean age at the time of surgery was 69 years. Patients presented with a mean BMI of 33 kg/m2. The mean follow-up period was 23 months.

Results

The 2-year survivorship free of mesh revision was 89% [95% confidence interval (CI): 75% to 100%]. Three patients (11%) had to undergo revision because of mechanical mesh failure and received another polypropylene mesh. No further revisions were performed thereafter. Flexion was 87° (range, 30–120°) on average. The majority of patients (75%, 21/28) had a full active extension. The mean active extension lag after surgery was 4 degrees (range, 0–30°).

Discussion

We observed a substantial improvement of extensor mechanism function. The majority of patients had full extension and showed good clinical results. A failure rate of over 50% has been published for alternative procedures. Thus, the use of the described augmentation technique represents a reasonable treatment option for chronic extensor mechanism disruptions of the patellar tendon as well as the quadriceps tendon after total knee arthroplasty. However, there might be a potentially higher risk for infection persistence in periprosthetic joint infection cases due to the presence of a foreign material.
The feasibility and safety of adopting the left lumbar vein to localize the renal artery location during left transperitoneal laparoscopic partial nephrectomy
Authors: Yao Zhongshun , Zhao Jiming , Zheng Bin , Cong Zixiang , Zhang Yiming , Lv Jiaju , Niu Zhihong , Cheng Fajuan , He Wei
Published: September 2022

Background

Laparoscopic partial nephrectomy (LPN) is the standard of care for localized small renal cancer. The most critical step in this form of surgery is to localize the renal artery. In the present study, we describe a novel technique that uses the left lumbar vein (LV) to access the left renal artery during LPN.

Materials and methods

This was a retrospective review of 130 cases of transperitoneal laparoscopic partial nephrectomies (TLPNs) performed on patients with renal cancer in our center between January 2018 and December 2021. Either the LV or non-lumbar vein (N-LV) technique was used to locate and manage the left renal artery. We recorded relevant clinical data from all patients, including patient characteristics, tumor data, and perioperative outcomes (artery mobilization time, operative time, estimated blood loss, and complications). Comparative analysis was then carried out between the cases using LV or N-LV vein techniques.

Results

All TLPNs were successfully accomplished without conversion to open approaches. There were no complications involving the renal vessels during the entire study. The LV technique resulted in a significantly shorter time to mobilize the renal and significantly less estimated blood loss (p < 0.05). There was no significant difference between the two techniques with regard to perioperative complications.

Conclusion

The left LV represents an anatomical landmark for locating the left renal artery in TLPN. This approach has numerous advantages over the transperitoneal approach including facilitating access to the left renal artery and reducing the duration of surgery.
Removal of large fibrotic bladder blood clots using prostatic tissue morcellator under real-time ultrasound guidance
Authors: Wu Ronghua , Shang Yonggang , Liu Xing , Chen Wei , Yi Shanhong
Published: September 2022

Objective

Large fibrotic bladder blood clots are difficult to treat via conventional methods. Hence, we investigated the safety and reliability of real-time ultrasound guidance combined with prostate tissue morcellator in the removal of large fibrotic bladder blood clots in this study.

Methods

We chose 9 patients with large fibrotic bladder blood clots who were treated in our department from January 2019 to December 2020. Under the condition that conventional methods were ineffective in removing the bladder blood clot, real-time ultrasound guidance combined with a prostatic tissue morcellator was used to remove the large fibrotic bladder blood clot through the steps of positioning, breaking, adjusting repositioning and recrushing. After removal, the bipolar electrocautery was replaced to stop bleeding of the bladder mucosa.

Results

All patients successfully underwent the operation. After the blood clot was removed, the bladder mucosa was examined. There was no damage to the bladder mucosa or muscle layer. The urine was clear at the end of the procedure with slow irrigation, and no bleeding was found again.

Conclusion

Real-time ultrasound guidance combined with a prostate tissue morcellator was a safe, effective and quick method for the removal of large fibrotic bladder blood clots.
Autologous vs. implant-based breast reconstruction after skin- and nipple-sparing mastectomy—A deeper insight considering surgical and patient-reported outcomes
Authors: von Glinski Maxi , Holler Nikla , Kümmel Sherko , Reinisch Mattea , Wallner Christoph , Wagner Johannes Maximilian , Dadras Mehran , Sogorski Alexander , Lehnhardt Marcus , Behr Björn
Published: September 2022

Introduction

Autologous (ABR) and implant-based breast reconstruction (IBR) represent the most common procedures after skin- and nipple-sparing mastectomy. This cross-sectional study is a comprehensive analysis of ABR and IBR considering surgical and patient-reported outcomes.

Patients and methods

Eligible patients underwent breast reconstruction (ABR and IBR) after skin- and nipple-sparing mastectomy between January 2014 and December 2020. Outcome parameters included quality of life (European Organisation for Research and Treatment of Cancer - EORTC - QLQ30, BR23, Breast-Q, CES-D), complication rates, aesthetic result, and breast sensitivity.

Results

108 patients participated in the study (IBR: n = 72, age 48.9 ± 9.9 years; ABR: n = 36, age: 46.6 ± 7.3 years). Mean follow-up was 27.1 ± 9.3 (IBR) and 34.9 ± 20.5 (ABR), respectively. IBR patients suffered significantly more often from major complications (30.6% vs. 8.3%; p = 0.01), while ABR patients underwent secondary procedures significantly more often to improve the aesthetic result (55.6% vs. 29.2%, p = 0.004). Unilateral reconstructions revealed superior aesthetic results in ABR (n.s.), while in bilateral reconstruction IBR tended to score higher (n.s.). Scar evaluation resulted in a better result of IBR in both categories (p < 0.01). Breast sensitivity was severely impaired in both groups. The Breast-Q revealed a significantly higher “patient satisfaction with breast” after ABR (p = 0.033), while the other QoL-tests and subscales showed no significant differences between the two procedures.

Conclusion

ABR is associated with a higher patient satisfaction despite the high probability of secondary procedures to improve the aesthetic outcome, whereas IBR-patients suffer more often from major complications. Furthermore, the laterality of reconstruction should be included in the individual decision-making process.