bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Mouse and Human Tissue-Resident γδ T Cells
Authors: Qu Guanyu , Wang Shengli , Zhou Zhenlong , Jiang Dawei , Liao Aihua , Luo Jing
Published: June 2022

Circulating immune cell compartments have been extensively studied for decades, but limited access to peripheral tissue and cell yield have hampered our understanding of tissue-based immunity, especially in γδ T cells. γδ T cells are a unique subset of T cells that are rare in secondary lymphoid organs, but enriched in many peripheral tissues including the skin, uterus, and other epithelial tissues. In addition to immune surveillance activities, recent reports have revealed exciting new roles for γδ T cells in homeostatic tissue physiology in mice and humans. It is therefore important to investigate to what extent the developmental rules described using mouse models transfer to human γδ T cells. Besides, it will be necessary to understand the differences in the development and biogenesis of human and mouse γδ T cells; to understand how γδ T cells are maintained in physiological and pathological circumstances within different tissues, as well as characterize the progenitors of different tissue-resident γδ T cells. Here, we summarize current knowledge of the γδ T phenotype in various tissues in mice and humans, describing the similarities and differences of tissue-resident γδ T cells in mice and humans.
Mechanical Performance and Failure Mode Research on the Braced Frame Joint of Tower Cranes in High-Rise Building Construction
Authors: Yang Yang , Zhang Zhen , Xu Liangjin , Yao Gang
Published: June 2022

The collapsing number of tower cranes has increased with the development of the building industry. The safety of tower cranes has the potential to improve practices of building and outcomes in construction. The mechanical performance and failure mode of braced frame joints are analyzed in this research. Firstly, a mechanical model of a braced frame joint (BFJ) is established, and the experiment is designed. The destruction process and failure mode are researched by experiment. Then finite element model is established by ABAQUS. Moreover, working conditions with different concrete strength grades (CSG) and tension direction are researched. The results prove that braced frame joint cracks seriously with ultimate bearing capacity, simultaneously, the pre-embedded steel component (PESC) is pulled out. The failure mode is tensile and bending failure of BFJ in the test. The ultimate bearing capacity of failure is controlled by concrete strength grades. The tensile strength increases with the CSG, and the ultimate capacity of BFJ improves equally. The brittle fracture characteristic is more obvious in the ultimate state. The failure mode changes from crushing failure to tensile and bending failure with increasing tension angle. The research results could provide a better understanding of the working mechanism and performance evaluation of the BFJ of the tower crane.
Implementation of a Finite Element Deformation Model Within an Elasto-Hydrodynamic Lubrication Numerical Solver for a Ball in Socket Tribopair
Authors: Ruggiero Alessandro , Sicilia Alessandro
Published: June 2022

In the framework of the elasto-hydrodynamic lubrication simulation algorithms of lubricated tribopairs, a key role is played by the chosen deformation model, since it affects the surfaces’ separation, which guarantees the existence of a thin lubricant film thickness, even when the tribo-system is subjected to high loads. The aim of this article is to merge a finite element deformation model based on linear tetrahedra, previously developed by the same authors, within the Reynolds equation solver in the elasto-hydrodynamic mode, with reference to a generic ball in socket lubricated tribo-system. The main novelty of this research is the implementation of the finite element deformation model, allowing the authors to relate the deformation vector to the pressure one through an influence matrix which takes into account the spherical motion of the ball with respect to the socket. The computer code for the problem–solution was developed in a MATLAB environment and simulated a planar motion condition in terms of eccentricity and angular velocity vectors, in order to calculate the meatus fluid pressure field, surfaces’ separation, shear stress, deformation, and wear depth. The integration over time of the output fields led to the time evolution of the load vector, friction torque vector, and wear volume. Moreover, the lubrication algorithm takes into account the fluid non-Newtonian behavior and the surfaces’ progressive geometrical modification over time due to cumulated wear. The obtained results reproduced the classical elasto-hydrodynamic shapes of the involved quantities, following the meatus minimum thickness predicted by the Hamrock–Dowson model; furthermore, it provided information about the mechanical behavior of the whole bodies belonging to the spherical joint thanks to the finite element deformation model.
Multi-Target Antibacterial Mechanism of Moringin From Moringa oleifera Seeds Against Listeria monocytogenes
Authors: Wen Yanlong , Li Wenyun , Su Rongzhen , Yang Min , Zhang Nan , Li Ximing , Li Lingfei , Sheng Jun , Tian Yang
Published: June 2022

Moringin [4-(α-L-rhamnosyloxy) benzyl isothiocyanate] is an isothiocyanate from Moringa oleifera seeds. It is the bioactivated form of the glucosinolate precursor glucomoringin with various health benefits. However, few studies have examined the antibacterial activity of moringin. This study aimed to investigate the antimicrobial activity and mechanism of moringin against Listeria monocytogenes. The minimum inhibitory concentration (MIC), and growth curves were used to evaluate the bacteriostatic effect of moringin against L. monocytogenes. Transcriptome analysis by RNA sequencing was performed to elucidate the underlying mechanism of moringin against L. monocytogenes. The transcriptome results were validated. The results showed that moringin inhibited the growth of L. monocytogenes with a MIC of 400 μM. RNA sequencing results showed that the differences in the expression of genes related to the cell wall and membrane biosynthesis, phosphotransferase system (PTS), oxidative stress, energy metabolism, and DNA binding were significantly affected. As with the transcriptome results, the results of the mechanism verification found that moringin damaged the integrity of the cell wall and cell membrane, stimulated oxidative stress, interfered with energy metabolism and DNA replication, and finally led to the death of L. monocytogenes. The present study provides evidence that moringin exhibits strong antimicrobial activity against L. monocytogenes and insight into its potential mechanism.
Single Cell Meta-Analysis of Endothelial to Mesenchymal Transition (EndMT) in Glucose Metabolism of the Digestive Diseases
Authors: Zhou Qiao , Zhang Xin , Tong Xia , Tang Chuang , Chen Xin , Peng Ling , Xia Xiangen , Zhang Lanlan
Published: June 2022

Background: Endothelial-to-mesenchymal transition (EndMT) is poorly understood in digestive diseases, and the function of metabolism in EndMT is uncertain.

Objective: The goal of this study is to elucidate the role of EndMT in digestive diseases and to describe its metabolic state.

Method: The GEO database was used to extract single-cell data in order to discover EndMT subpopulations in digestive organs such as premalignant lesions and cancer of the stomach, intestine, and pancreas.

Results: By single-cell RNA sequencing in digestive diseases, we generated a single-cell atlas from tissues of patients spanning a cascade of premalignant lesions and cancer. We next established a single-cell network elucidating the cellular and molecular characteristics of endothelial cells (ECs) across many lesions and identified key genes linked with EndMT in premalignant lesions and cancer lesions. The EndMT activation of a wide variety of metabolic signaling pathways was discovered in ECs, and further study of premalignant lesions and cancer tissue indicated that glucose metabolism increased in premalignant lesions and reached a maximum in cancer tissue. Finally, it was shown that INSR and LDHA might be used as prognostic markers for developing premalignant lesions to cancer involving glucose metabolism in digestive diseases.

Conclusion: For the first time, we discovered EndMT’s role in digestive diseases and described its metabolism, underscoring its crucial role in glucose metabolism in the disease. We found several targets via gene screening that are beneficial for predicting premalignant lesions that progress to cancer.
PINK1/Parkin Pathway Activation for Mitochondrial Quality Control – Which Is the Best Molecular Target for Therapy?
Authors: Silvian Laura F.
Published: June 2022

There has been long-term interest in drugging the PINK1-Parkin pathway with therapeutics as a treatment for Parkinson’s disease (PD). Despite significant structural data on Parkin as well as the PINK1 kinase and the multiple conformational changes it undergoes, activation of these targets is non-trivial. This review highlights small molecule screening results that suggests that activation of Parkin biochemically does not necessarily translate to activation of Parkin within cells. There are also issues with activation of PINK1 with kinetin analogs, which do not appear to rescue rodent models of PD. The counter-measure of activating the mitophagy pathway with deubiquitinase (DUB) inhibitors such as USP30 inhibitors is progressing in the clinic for kidney disease and the proof of biology for this target will be tested in these trials. An alternative mechanism of activating Parkin in response to oxidative stress via Parkin phosphorylation by the AMPK-ULK1 pathway may be a simpler way to lower the energy barrier Parkin activation.
High Fall Risk Associated With Memory Deficit and Brain Lobes Atrophy Among Elderly With Amnestic Mild Cognitive Impairment and Mild Alzheimer’s Disease
Authors: Huang Shuyun , Zhou Xinhan , Liu Yajing , Luo Jiali , Lv Zeping , Shang Pan , Zhang Weiping , Lin Biqing , Huang Qiulan , Feng YanYun , Wang Wei , Tao Shuai , Wang Yukai , Zhang Chengguo , Chen Lushi , Shi Lin , Luo Yishan , Mok Vincent C. T. , Pan Suyue , Xie Haiqun
Published: June 2022

Objectives

This study aimed to primarily examine the association between memory deficit and increased fall risk, second, explore the underlying neuroanatomical linkage of this association in the elderly with aMCI and mild AD.

Methods

In this cross-sectional study, a total of 103 older adults were included (55 cognitively normal, CN; 48 cognitive impairment, CI, elderly with aMCI, and mild AD). Memory was assessed by the Auditory Verbal Learning Test (AVLT). Fall risk was evaluated by the Timed Up and Go (TUG) Test, heel strike angles, and stride speed, which were collected by an inertial-sensor-based wearable instrument (the JiBuEn™ gait analysis system). Brain volumes were full-automatic segmented and quantified using AccuBrain® v1.2 from three-dimensional T1-weighted (3D T1W) MR images. Multivariable regression analysis was used to examine the extent of the association between memory deficit and fall risk, the association of brain volumes with memory, and fall risk. Age, sex, education, BMI, and HAMD scores were adjusted. Sensitivity analysis was conducted.

Results

Compared to CN, participants with aMCI and mild AD had poorer cognitive performance (p < 0.001), longer TUG time (p = 0.018), and smaller hippocampus and medial temporal volumes (p = 0.037 and 0.029). In the CI group, compared to good short delayed memory (SDM) performance (AVLT > 5), the elderly with bad SDM performance (AVLT ≤ 3) had longer TUG time, smaller heel strike angles, and slower stride speed. Multivariable regression analysis showed that elderly with poor memory had higher fall risk than relative good memory performance among cognitive impairment elderly. The TUG time increased by 2.1 s, 95% CI, 0.54∼3.67; left heel strike angle reduced by 3.22°, 95% CI, −6.05 to −0.39; and stride speed reduced by 0.09 m/s, 95% CI, −0.19 to −0.00 for the poor memory elderly among the CI group, but not found the association in CN group. In addition, serious medial temporal atrophy (MTA), small volumes of the frontal lobe and occipital lobe were associated with long TUG time and small heel strike angles; small volumes of the temporal lobe, frontal lobe, and parietal lobe were associated with slow stride speed.

Conclusion

Our findings suggested that memory deficit was associated with increased fall risk in the elderly with aMCI and mild AD. The association might be mediated by the atrophy of medial temporal, frontal, and parietal lobes. Additionally, increased fall risk, tested by TUG time, heel stride angles, and stride speed, might be objective and convenient kinematics markers for dynamic monitoring of both memory function and fall risk.
Comparative Efficacy and Safety of Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Ovarian Cancer: A Systematic Review and Network Meta-Analysis
Authors: Luo Jing , Ou Shunlong , Wei Hua , Qin Xiaoli , Jiang Qian
Published: June 2022

Objective

This study aims to compare the efficacy and safety of different poly (ADP-ribose) polymerase (PARP) inhibitors in patients with ovarian cancer through a network meta-analysis to support clinical treatment choices.

Methods

The Cochrane Library, PubMed, Embase, Science Citation Index, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP (CQVIP), and Chinese BioMedical Literature Database (CBM) were searched with a cutoff date of 14 January 2021. ClinicalTrials.gov was also checked for supplementary data. Phase II or III randomized controlled trials that compared a PARP inhibitor with a placebo in patients with relapsed or newly diagnosed advanced ovarian cancer were included. The hazard ratios (HRs) for progression-free survival and overall survival and odds ratios (ORs) for grade 3 or higher adverse events were analyzed. The network meta-analysis was conducted in a Bayesian framework based on the Markov Chain Monte Carlo model in the R gemtc package (version 4.0.3).

Results

Eight eligible articles reporting six trials with a total of 2,801 patients were incorporated in this network meta-analysis. Three trials compared olaparib with placebo. Two trials compared niraparib with placebo. One trial compared rucaparib with placebo. The network meta-analysis failed to show significant differences in progression-free survival among the three PARP inhibitors: HR of 0.64, 95% confidence interval of 0.3 to 1.42 for olaparib versus niraparib, and olaparib versus rucaparib (0.86; 0.33 to 2.33). The comparison between niraparib and rucaparib also did not express a statistical difference (1.34; 0.47 to 3.72). Subgroup analysis bybreast cancer susceptibility gene (BRCA) status showed no obvious difference in progression-free survival among the three PARP inhibitors regardless of BRCA mutation status. Olaparib had fewer grade 3 or higher adverse events than niraparib (OR, 0.27; 95% confidence interval, 0.13 to 0.55) and rucaparib (0.34; 0.14 to 0.86). However, the analysis failed to show a significant difference between niraparib and rucaparib (1.27; 0.49 to 3.27).

Conclusion

Current evidence indicates that there is no significant difference observed in efficacy among olaparib, niraparib, and rucaparib. However, olaparib might have fewer grade 3 or higher adverse events.
Common Multiple Primary Cancers Associated With Breast and Gynecologic Cancers and Their Risk Factors, Pathogenesis, Treatment and Prognosis: A Review
Authors: Ge Shuwen , Wang Bo , Wang Zihao , He Junjian , Ma Xiaoxin
Published: June 2022

The mammary gland is closely related to the female reproductive system in many aspects, affecting the whole gynecological system. Breast cancer (BC) is the most common malignancy in women and associated with considerable negative effects. Due to various factors including co-pathogenic genetic mutations, environment factors, lifestyle, behavioral factors, treatment regimens and in-creased survival of patients with BC, there is an increased probability of developing additional primary gynecologic cancers such as ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC). More and more studies have been conducted in recent years. Multiple primary cancers (MPCs), also known as multiple primary malignancies, refers to two or more different primary cancers in the same patient occurring in the same or different organs or tissues. The pathogenesis of multiple primary cancers is complex and has a negative effect on the prognosis and survival of patients. This review discusses the common types of BC-associated MPCs, namely, BC associated with OC, BC associated with EC and BC associated with CC, as well as risk factors, pathogenesis, treatment, and prognosis of MPCs associated with breast and gynecologic cancers. It provides new intervention and treatment ideas for patients with BC-associated MPCs to improve quality of life and prognosis.
Cross-Sectional and Longitudinal Associations Between the Serum G\lobulin Level, and Renal Impairment and All-Cause Deaths in Chinese Patients With Newly Diagnosed Multiple Myeloma
Authors: Cheng Jun , Sun Jia , Zhao Yi , Li Xiayu , Jiang Yan , Lv Rong , Li Heng , Chen Jianghua
Published: June 2022

Background

A large number of studies have shown that serum globulin plays an important role in a variety of cancers; However, few studies have identified the association between serum globulin levels and end-stage renal disease (ESRD) and all-cause death in Chinese patients with multiple myeloma (MM).

Methods

A generalized additive model and smooth curve fitting were fitted to assess the cross-sectional relationship between the serum globulin levels and renal impairment (RI) at baseline. Multivariate-adjusted Cox regression models were performed to determine the associations between the baseline serum globulin levels and the onset of all-cause death and ESRD in patients with MM.

Results

288 participants who were followed for > 3 months were eligible for the retrospective study. The median serum globulin level was 5.1 ± 2.6 mg/dL. The average follow-up time was 23.3 months. Thirty-two patients (11.5%) had ESRD and 24 patients (8.33%) died after diagnosis. In patients with a serum globulin level < 6.1 mg/dL, the serum globulin level had an independent, negative correlation with the occurrence of MM-related RI. Patients were divided into three groups on the basis of serum globulin tertiles: low (L group), 3.3 mg/dL; middle (M group), 3.3–6.0 mg/dL; and high (H group), 6.0 mg/dL. Cox regression analysis showed that low serum globulin levels may be independent risk factors for all-cause death and the occurrence of ESRD in patients with MM; however, an elevated baseline serum globulin can predict all-cause deaths in patients with MM, but cannot predict the onset of ESRD.

Conclusions

This observational study suggested that there was a non-linear relationship between the serum globulin level and the occurrence of RI in patients with MM. This finding showed that the serum globulin level had a U-shaped association with all-cause death and an L-shaped association with ESRD in patients with MM.
PD-L2 Serves as a Potential Prognostic Biomarker That Correlates With Immune Infiltration and May Predict Therapeutic Sensitivity in Lower-Grade Gliomas
Authors: Xie Qijun , Huang Xianlong , Huang Wu , Liu Fang
Published: June 2022

Although patients with lower-grade gliomas (LGGs; grades II and III) have a relatively favorable prognosis, patients frequently relapse and tend to progress to higher-grade gliomas, leading to treatment resistance, poor survival, and ultimately treatment failure. However, until now, thorough research has not yet been reported on the relationship between PD-L2 and immune infiltration and therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy of LGGs. In this study, we found that the expression of PD-L2 is upregulated in glioma, with high PD-L2 expression predicting a worse prognosis. Univariate and multivariate Cox regression analysis both indicated that PD-L2 represented an independent prognostic factor with high accuracy in survival prediction for LGGs. A nomogram comprising of age, grade, IDH mutation, and PD-L2 was established for predicting OS. Additionally, PD-L2 was found to be remarkably correlated with immune infiltration and some anti-tumor immune functions. The degree of PD-L2 expression was also found to be strongly related to the prediction of therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy. Furthermore, immunohistochemistry demonstrated that PD-L2 and the macrophage biomarker CD68 were both increased in glioma, with PD-L2 expression having a strong positive connection with CD68 expression. Taken together, PD-L2 is a prognostic biomarker for LGGs patients that may provide novel insights into glioma individualized therapeutic strategies and guide effective immunotherapy and chemotherapy.
Trends in Women’s Leadership of Oncology Clinical Trials
Authors: Waldhorn Ithai , Dekel Ayelet , Morozov Anna , Alon Elisa Sardas , Stave Danielle , Tsrooya Noam Ben , Schlosser Shir , Markel Gal , Bomze David , Meirson Tomer
Published: June 2022

It has been widely reported that women are underrepresented in leadership positions within academic medicine. This study aimed to assess trends in women representation as principal investigators (PIs) in oncology clinical trials and to characterize trends in women’s leadership in such trials conducted between 1999 and 2019. The gender of 39,240 PIs leading clinical trials was determined using the gender prediction software Genderize.io. In total, 11,516 (27.7%) women served as PIs. Over the past 20 years, an annual increase of 0.65% in women PIs was observed. Analysis by geographic distribution revealed higher women representation among PIs in North America and Europe compared to Asia. Industry-funded trials were associated with lower women PI representation than academic-funded trials (31.4% vs. 18.8%, p<0.001). Also, women PIs were found to be underrepresented in late-phase as compared to early-phase studies (27.9%, 25.7%, 21.6%, and 22.4% in phase I, II, III, and IV, respectively; Cochran-Armitage test for trend, p<0.001). Furthermore, an association was found between the PI’s gender and enrolment of female subjects (50% vs. 43% female participants led by women vs men PIs, respectively, p<0.001). Taken together, while the gender gap in women’s leadership in oncology trials has been steadily closing, prominent inequalities remain in non-Western countries, advanced study phases, industry-funded trials and appear to be linked to a gender gap in patient accrual. These observations can serve for the development of strategies to increase women’s representation and to monitor progress toward gender equality in PIs of cancer clinical trials.
Distinguishable Prognostic Signatures and Tumor Immunogenicity Between Pancreatic Head Cancer and Pancreatic Body/Tail Cancer
Authors: Ge Weiyu , Ma Jingyu , Mao Tiebo , Xu Haiyan , Zhang Xiaofei , Li Shumin , Wang Yongchao , Yao Jiayu , Yue Ming , Jiao Feng , Wang Yu , Zhuo Meng , Han Ting , Hu Jiong , Zhang Xiao , Cui Jiujie , Wang Liwei
Published: June 2022

Background

Pancreatic head cancer and pancreatic body/tail cancer are considered to have different clinical presentations and to have altered outcomes.

Methods

Ninety cases of pancreatic adenocarcinoma (PDAC) from our institution were used as a discovery set and 166 cases of PDAC from the TCGA cohort were used as a validation set. According to the anatomical location, the cases of PDAC were divided into the pancreatic head cancer group and the pancreatic body/tail cancer group. Firstly, the different biological functions of the two groups were assessed by ssGSEA. Meanwhile, ESTIMATE and CIBERSORT were conducted to estimate immune infiltration. Then, a novel anatomical site-related risk score (SRS) model was constructed by LASSO and Cox regression. Survival and time-dependent ROC analysis was used to prove the predictive ability of our model in two cohorts. Subsequently, an integrated survival decision tree and a scoring nomogram were constructed to improve prognostic stratification and predictive accuracy for individual patients. In addition, gseaGO and gseaKEGG pathway analyses were performed on genes in the key module by the R package.

Results

Overall survival and the objective response rate (ORR) of patients with pancreatic body/tail cancer were markedly superior to those with pancreatic head cancer. In addition, distinct immune characteristics and gene patterns were observed between the two groups. Then, we screened 5 biomarkers related to the prognosis of pancreatic cancer and constructed a more powerful novel SRS model to predict prognosis.

Conclusions

Our research shed some light on the revelation of gene patterns, immune and mutational landscape characterizations, and their relationships in different PDAC locations.
Real World Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Only Available Sunitinib and Pazopanib in First-Line Setting
Authors: Nikic Predrag , Babovic Nada , Dzamic Zoran , Salma Svetlana , Stojanovic Vesna , Matkovic Suzana , Pejcic Zoran , Juskic Kristina , Soldatovic Ivan
Published: June 2022

Background

The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available.

Methods

This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date.

Results

The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4).

Conclusions

With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC.
Multi-Sequence MR-Based Radiomics Signature for Predicting Early Recurrence in Solitary Hepatocellular Carcinoma ≤5 cm
Authors: Wang Leyao , Ma Xiaohong , Feng Bing , Wang Shuang , Liang Meng , Li Dengfeng , Wang Sicong , Zhao Xinming
Published: June 2022

Purpose

To investigate the value of radiomics features derived from preoperative multi-sequence MR images for predicting early recurrence (ER) in patients with solitary hepatocellular carcinoma (HCC) ≤5 cm.

Methods

One hundred and ninety HCC patients were enrolled and allocated to training and validation sets (n = 133:57). The clinical–radiological model was established by significant clinical risk characteristics and qualitative imaging features. The radiomics model was constructed using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm in the training set. The combined model was formed by integrating the clinical–radiological risk factors and selected radiomics features. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC).

Results

Arterial peritumoral hyperenhancement, non-smooth tumor margin, satellite nodules, cirrhosis, serosal invasion, and albumin showed a significant correlation with ER. The AUC of the clinical–radiological model was 0.77 (95% CI: 0.69–0.85) and 0.76 (95% CI: 0.64–0.88) in the training and validation sets, respectively. The radiomics model constructed using 12 radiomics features selected by LASSO regression had an AUC of 0.85 (95% CI: 0.79–0.91) and 0.84 (95% CI: 0.73–0.95) in the training and validation sets, respectively. The combined model further improved the prediction performance compared with the clinical–radiological model, increasing AUC to 0.90 (95% CI: 0.85–0.95) in the training set and 0.88 (95% CI: 0.80–0.97) in the validation set (p < 0.001 and p = 0.012, respectively). The calibration curve fits well with the standard curve.

Conclusions

The predictive model incorporated the clinical–radiological risk factors and radiomics features that could adequately predict the individualized ER risk in patients with solitary HCC ≤5 cm.
Cucurbitacin B, Purified and Characterized From the Rhizome of Corallocarpus epigaeus Exhibits Anti-Melanoma Potential
Authors: Aiswarya Sreekumar Usha Devi , Vikas Gowda , Haritha Nair Hariprasad , Liju Vijayasteltar Belsamma , Shabna Anwar , Swetha Mundanattu , Rayginia Tennyson Prakash , Keerthana Chenicheri Kizhakkeveettil , Nath Lekshmi Raghu , Reshma Mullan Vellandy , Sundaram Sankar , Anto Nikhil Ponnoor , Lankalapalli Ravi Shankar , Anto Ruby John , Bava Smitha Vadakkeveettil
Published: June 2022

The ethnomedicinal plant from the Cucurbitaceae family, Corallocarpus epigaeus, or its bioactive derivatives have been widely utilized in traditional medicine owing to their distinct applications against various human ailments and have lured the interest of ethnobotanists and biochemists. Here, we report for the first time, the anti-cancer potential of a bio-active fraction isolated from the dried rhizome of C. epigaeus, and the bioactive principle identified as cucurbitacin B (Cu-B). The purification processes involving the utilization of multiple organic extracts of C. epigaeus rhizome powder, yielded Cu-B from the Ethyl acetate Cytotoxic Fraction (ECF), obtained by the chromatographic separation of the ethyl acetate extract. Amongst the various cancer lines tested, melanoma cells exhibit maximal sensitivity towards the Cu-B-containing ECF fraction. Cu-B induces an apoptotic mode of cell death initiated intrinsically as well as extrinsically in A375 melanoma cells whilst remaining comparatively less toxic to normal skin fibroblasts. In vivo studies involving a NOD-SCID murine model of human melanoma demonstrate the ability of Cu-B to attenuate tumor growth, while being pharmacologically safe in vivo, as assessed in Swiss albino mice. Furthermore, Cu-B inhibits MEK 1/2 as well as the constitutive and EGF-induced ERK 1/2 activation, indicating a definitive involvement of MAPK signal transducers in regulating Cu-B-mediated anti-melanoma activity. Together, our study demonstrates the anti-melanoma potential of C. epigaeus-derived Cu-B, which indicates the Cucurbitaceae succulent as a prospective source for deriving potent and pharmacologically safe anti-cancer compounds.
Impact of Using Unedited CT-Based DIR-Propagated Autocontours on Online ART for Pancreatic SBRT
Authors: Magallon-Baro Alba , Milder Maaike T. W. , Granton Patrick V. , Toom Wilhelm den , Nuyttens Joost J. , Hoogeman Mischa S.
Published: June 2022

Purpose

To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking.

Materials and Methods

The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints.

Results

Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans.

Conclusion

For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC.
Effectiveness and Safety of Ayurvedic Medicines in Type 2 Diabetes Mellitus Management: A Systematic Review and Meta-Analysis
Authors: Chattopadhyay Kaushik , Wang Haiquan , Kaur Jaspreet , Nalbant Gamze , Almaqhawi Abdullah , Kundakci Burak , Panniyammakal Jeemon , Heinrich Michael , Lewis Sarah Anne , Greenfield Sheila Margaret , Tandon Nikhil , Biswas Tuhin Kanti , Kinra Sanjay , Leonardi-Bee Jo
Published: June 2022

Introduction:Many Ayurvedic medicines have the potential for managing type 2 diabetes mellitus (T2DM), with previous systematic reviews demonstrating effectiveness and safety for specific Ayurvedic medicines. However, many of the reviews need updating and none provide a comprehensive summary of all the Ayurvedic medicines evaluated for managing T2DM.

Objective:The objective of this systematic review was to evaluate and synthesize evidence on the effectiveness and safety of Ayurvedic medicines for managing T2DM.

Inclusion criteria:Published and unpublished RCTs assessing the effectiveness and safety of Ayurvedic medicines for managing T2DM in adults.

Methods:The JBI systematic review methodology was followed. A comprehensive search of sources (including 18 electronic databases) from inception to 16 January 2021 was made. No language restrictions were applied. Data synthesis was conducted using narrative synthesis and random effects meta-analyses, where appropriate. Pooled results are reported as mean differences (MD) with 95% confidence intervals (CI).

Results:Out of 32,519 records identified from the searches, 219 articles were included in the systematic review representing 199 RCTs (21,191 participants) of 98 Ayurvedic medicines. Overall, in the studies reviewed the methodology was not adequately reported, resulting in poorer methodological quality scoring. Glycated hemoglobin (HbA1c) was reduced usingAegle marmelos(L.) Corrêa (MD -1.6%; 95% CI −3 to −0.3),Boswellia serrataRoxb. (−0.5; −0.7 to −0.4),Gynostemma pentaphyllum(Thunb.) Makino (−1; −1.5 to −0.6),Momordica charantiaL. (−0.3; −0.4 to −0.1),Nigella sativaL. (−0.4; −0.6 to −0.1),Plantago ovataForssk. (−0.9; −1.4 to −0.3),Tinospora cordifolia(Willd.) Hook.f. and Thomson (−0.5; −0.6 to −0.5),Trigonella foenum-graecumL. (−0.6; −0.9 to −0.4), andUrtica dioicaL. (−1.3; −2.4 to −0.2) compared to control. Similarly, fasting blood glucose (FBG) was reduced by 4–56 mg/dl for a range of Ayurvedic medicines. Very few studies assessed health-related quality of life (HRQoL). Adverse events were not reported in many studies, and if reported, these were mostly none to mild and predominately related to the gastrointestinal tract.

Conclusion:The current evidence suggests the benefit of a range of Ayurvedic medicines in improving glycemic control in T2DM patients. Given the limitations of the available evidence and to strengthen the evidence base, high-quality RCTs should be conducted and reported.
Current Insights Into the Maintenance of Structure and Function of Intervertebral Disc: A Review of the Regulatory Role of Growth and Differentiation Factor-5
Authors: Lv Bin , Gan Weikang , Cheng Zhangrong , Wu Juntao , Chen Yuhang , Zhao Kangchen , Zhang Yukun
Published: June 2022

Intervertebral disc degeneration (IDD), characterized by conversion of genotypic and phenotypic, is a major etiology of low back pain and disability. In general, this process starts with alteration of metabolic homeostasis leading to ongoing inflammatory process, extracellular matrix degradation and fibrosis, diminished tissue hydration, and impaired structural and mechanical functionality. During the past decades, extensive studies have focused on elucidating the molecular mechanisms of degeneration and shed light on the protective roles of various factors that may have the ability to halt and even reverse the IDD. Mutations of GDF-5 are associated with several human and animal diseases that are characterized by skeletal deformity such as short digits and short limbs. Growth and differentiation factor-5 (GDF-5) has been shown to be a promise biological therapy for IDD. Substantial literature has revealed that GDF-5 can decelerate the progression of IDD on the molecular, cellular, and organ level by altering prolonged imbalance between anabolism and catabolism. GDF family members are the central signaling moleculars in homeostasis of IVD and upregulation of their gene promotes the expression of healthy nucleus pulposus (NP) cell marker genes. In addition, GDF signaling is able to induce mesenchymal stem cells (MSCs) to differentiate into NPCs and mobilize resident cell populations as chemotactic signals. This review will discuss the promising critical role of GDF-5 in maintenance of structure and function of IVDs, and its therapeutic role in IDD endogenous repair.
Post-Marketing Safety Concerns With Secukinumab: A Disproportionality Analysis of the FDA Adverse Event Reporting System
Authors: Shu Yamin , Ding Yufeng , Liu Yanxin , Wu Pan , He Xucheng , Zhang Qilin
Published: June 2022

Purpose: Secukinumab was approved for the treatment of psoriasis, psoriatic arthritis, and ankylosing spondylitis. However, the long-term safety of secukinumab in large sample population was unknown. The current study was to evaluate the secukinumab-assocaited adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Reports in the FAERS from the first quarter of 2015 (FDA approval of secukinumab) to the third quarter of 2021 were collected and analyzed. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of secukinumab-related AEs.

Results: A total of 89,228 reports of secukinumab as the “primary suspected (PS)” and 254,886 AEs induced by secukinumab were identified. Secukinumab-induced AE occurrence targeted 27 system organ classes (SOCs). A total of 257 signals of secukinumab-induced AEs in 19 SOCs were detected after conforming to the four algorithms simultaneously. Common significant signals of infections, respiratory disorders, skin and subcutaneous tissue disorders, immune system disorders, and ear and labyrinth disorders have emerged. Unexpected significant AEs such as injection site pain, vessel puncture site haemorrhage, arthralgia, hypokinesia, Bell’s palsy, parotid gland enlargement, and stress might also occur. The median onset time of secukinumab-associated AEs was 56 days (interquartile range [IQR] 5–214 days), and most of the onsets occurred within the first 1, 2, 3, and 4 months after initiation of secukinumab.

Conclusion: Our study found potential new AE signals and provided a broader understanding of secukinumab’s safety profiles, supporting its rational use in chronic systemic inflammatory diseases.
The Effects of Vagus Nerve Stimulation on Ventricular Electrophysiology and Nitric Oxide Release in the Rabbit Heart
Authors: Allen Emily , Pongpaopattanakul Pott , Chauhan Reshma A. , Brack Kieran E. , Ng G. André
Published: June 2022

Background: Abnormal autonomic activity including impaired parasympathetic control is a known hallmark of heart failure (HF). Vagus nerve stimulation (VNS) has been shown to reduce the susceptibility of the heart to ventricular fibrillation, however the precise underlying mechanisms are not well understood and the detailed stimulation parameters needed to improve patient outcomes clinically are currently inconclusive.

Objective: To investigate NO release and cardiac electrophysiological effects of electrical stimulation of the vagus nerve at varying parameters using the isolated innervated rabbit heart preparation.

Methods: The right cervical vagus nerve was electrically stimulated in the innervated isolated rabbit heart preparation (n = 30). Heart rate (HR), effective refractory period (ERP), ventricular fibrillation threshold (VFT) and electrical restitution were measured as well as NO release from the left ventricle.

Results: High voltage with low frequency VNS resulted in the most significant reduction in HR (by −20.6 ± 3.3%, −25.7 ± 3.0% and −30.5 ± 3.0% at 0.1, 1 and 2 ms pulse widths, with minimal increase in NO release. Low voltage and high frequency VNS significantly altered NO release in the left ventricle, whilst significantly flattening the slope of restitution and significantly increasing VFT. HR changes however using low voltage, high frequency VNS were minimal at 20Hz (to 138.5 ± 7.7 bpm (−7.3 ± 2.0%) at 1 ms pulse width and 141.1 ± 6.6 bpm (−4.4 ± 1.1%) at 2 ms pulse width).

Conclusion: The protective effects of the VNS are independent of HR reductions demonstrating the likelihood of such effects being as a result of the modulation of more than one molecular pathway. Altering the parameters of VNS impacts neural fibre recruitment in the ventricle; influencing changes in ventricular electrophysiology, the protective effect of VNS against VF and the release of NO from the left ventricle.
Functional Role of Suprahyoid Muscles in Bolus Formation During Mastication
Authors: Sasa Anna , Kulvanich Sirima , Hao Naohito , Ita Reiko , Watanabe Masahiro , Suzuki Taku , Magara Jin , Tsujimura Takanori , Inoue Makoto
Published: June 2022

It still remains unclear how the suprahyoid muscles function in bolus formation during mastication. This study aimed to investigate the contributory role of the suprahyoid muscles during mastication. A total of 20 healthy young volunteers were asked to perform tongue pressure generation tasks and unilateral mastication tasks using peanuts and two different types of rice crackers. Surface electromyographic (EMG) activity of the masseter and suprahyoid muscles and mandibular kinematics were recorded. Suprahyoid activity increased with increasing tongue pressure. Masticatory duration until the first deglutition differed significantly among the different foods; the harder the food, the longer the duration. This was also the case in masseter activity per masticatory cycle. Masticatory rate and suprahyoid activity per masticatory cycle were significantly higher during soft rice cracker mastication. Masseter activity was higher on the masticatory side than on the non-masticatory side, however, there was no difference in suprahyoid activity between the sides. Suprahyoid activity and jaw gape showed significant positive correlation in the early stage on both the masticatory and non-masticatory sides. The suprahyoid muscles functioned dominantly for jaw-opening during peanut mastication, and for bolus formation, especially in the late stage during soft rice cracker mastication. Bolus formation was performed dominantly on the masticatory side during rice cracker mastication. These findings clearly demonstrate a functional role of the suprahyoid muscles during mastication of solid foods from assessments using both EMG activity and mandibular kinematic recordings.
Combined Effects of Block-Based Programming and Physical Computing on Primary Students' Computational Thinking Skills
Authors: Kastner-Hauler Oliver , Tengler Karin , Sabitzer Barbara , Lavicza Zsolt
Published: June 2022

Basic Digital Education (BDE) is already planned to be integrated with the forthcoming curriculum for Austrian primary schools (6–10 years) as it was already implemented for lower secondary schools (10–14 years) in 2018. BDE includes the most essential and novel developments of Computational Thinking (CT), which are fundamentally responsible for nurturing students' problem-solving skills. Thus, evaluating teaching materials, scaffolding guidelines, and assessments is becoming increasingly important for the successful implementation of CT in Austrian classrooms. This study is a part of a longitudinal multi-cycle educational design research project aiming to explore how to foster CT and to raise the awareness, importance, and confidence of teachers and students in applying CT for everyday uses. Our paper focuses on a sub-study in which teaching units for grade 3 and 4 students (8–10 years) were designed by combining an Open Educational Resource (OER) textbook and Physical Computing with the micro:bit device. The designed learning environment consists of three units and was implemented in two classes over 3 weeks. The two classes were further split into two groups each, to ensure better support during implementation. The class teachers received upfront teacher training and conducted pre- and post-test assessments with the students. The resulting data was then analyzed to gain insights into the effects on CT skills of the young learners. Results showed that combining block-based programming and physical computing devices could become a promising approach to promote computational thinking skills in lower school grades. Furthermore, the observed direction of the designed units supports low-barrier access to increase the desired uses of CT in classrooms.
Five Dimensional Bianchi Type-I Anisotropic Cloud String Cosmological Model With Electromagnetic Field in Saez-Ballester Theory
Authors: Daimary Jagat , Roy Baruah Rajshekhar
Published: June 2022

Within the context of Saez-Ballester theory, we explored the interaction of a five-dimensional Bianchi type-I anisotropic cloud string cosmological model Universe with an electromagnetic field. With an electromagnetic field, the energy momentum tensor is assumed to be the sum of the rest energy density and string tension density in this paper. We use the average scale factor as an integrating function of time to get exact answers to Saez-Ballester equations. The dynamics and importance of the model’s many physical parameters are also examined.