bluuebunny/crossref_metadata_2025 huggingface dataset:
A new neurosurgical adjustable pressure suction apparatus with a mechanically controlled air inlet: the study of precise regulation and atraumatic suction
Authors: Nie Pan , Chen Mengxi , Zhang Jibo , Pan Meicheng , Gu Xiqian , Xu Chengshi , Li Zhengwei , Zhang Jianjian , Zhao Wenyuan , Li Xiang , Zhang Jie , Chen Jincao
Published: September 2022

Background

An essential surgical tool in neurosurgery is the suction tube. The skillful and accurate use of a suction tube facilitates the neurosurgical operation.

Objective

This study is to verify the practicality of an adjustable pressure suction tube (APS tube) and to explore the ideal APS tube diameter and tip negative pressure for different intracranial structures.

Methods

APS tubes were used to aspirate brain tissues and carotid arteries of rats. Laser speckle contrast imaging (LSCI) was used to record the blood flow velocity (BFV). We measured APS tube diameter, air inlet size, tip negative pressure and central negative pressure and calculated the correlation between them. In our department, intraoperative real-time parameters including APS tube diameter, length, air inlet size, and central negative pressure were recorded, and the tube tip negative pressure suitable for different intracranial structures and parts was calculated.

Results

All experiments were carried out using APS tubes. Experiments on rats objectively reflected a severe structural damage to the brain and blood vessels by the suction tube, which might even result in an irreversible reduction in blood flow., Rat carotid arteries and brain tissue suffered severe damage when the tip negative pressure exceeded 33.4 ± 1.8 and 29.2 ± 2.0 kPa, respectively. BFV failed to return to the preoperative level 3 min after the operation (p < 0.05), and this decrease was more pronounced when the suction tube diameter was large (p < 0.05). The tip negative pressure was positively and negatively correlated with central negative pressure and the air inlet size, and was independent of APS tube diameter. A total of 50 operations including 39 tumor resection operations and 11 moyamoya disease bypass operations were recorded. Large-diameter APS tubes (3.5 mm) with an closed air inlet were frequently used to maintain a greater tip negative pressure before the incision of dura mater. When important structures such as motor cortex and brainstem were involved, 1.5- or 2.0-mm-diameter APS tubes were mostly used, and an air inlet was opened up to 0.7–2.1 mm to maintain a safe tip negative pressure (7.4–27.9 kPa).

Conclusion

APS tubes with a mechanical knob provide stable and precise adjustment of the tip negative pressure, avoiding excessive negative pressure that causes serious damage to the intracranial structure. And, this allows the surgeon to hold the suction tube more freely and operate at any angle with an appropriate fulcrum near the incision to achieve efficient atraumatic suction and enhance surgical safety.
Metagenomics next-generation sequencing for the diagnosis of central nervous system infection: A systematic review and meta-analysis
Authors: Qu Chunrun , Chen Yu , Ouyang Yuzhen , Huang Weicheng , Liu Fangkun , Yan Luzhe , Lu Ruoyu , Zeng Yu , Liu Zhixiong
Published: September 2022

Objective

It is widely acknowledged that central nervous system (CNS) infection is a serious infectious disease accompanied by various complications. However, the accuracy of current detection methods is limited, leading to delayed diagnosis and treatment. In recent years, metagenomic next-generation sequencing (mNGS) has been increasingly adopted to improve the diagnostic yield. The present study sought to evaluate the value of mNGS in CNS infection diagnosis.

Methods

Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2022 guidelines, we searched relevant articles published in seven databases, including PubMed, Web of Science, and Cochrane Library, published from January 2014 to January 2022. High-quality articles related to mNGS applications in the CNS infection diagnosis were included. The comparison between mNGS and the gold standard of CNS infection, such as culture, PCR or serology, and microscopy, was conducted to obtain true positive (TP), true negative (TN), false positive (FP), and false negative (FN) values, which were extracted for sensitivity and specificity calculation.

Results

A total of 272 related studies were retrieved and strictly selected according to the inclusion and exclusion criteria. Finally, 12 studies were included for meta-analysis and the pooled sensitivity was 77% (95% CI: 70–82%, I2 = 39.69%) and specificity was 96% (95% CI: 93–98%, I2 = 72.07%). Although no significant heterogeneity in sensitivity was observed, a sub-group analysis was conducted based on the pathogen, region, age, and sample pretreatment method to ascertain potential confounders. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for CNS infection was 0.91 (95% CI: 0.88–0.93). Besides, Deek's Funnel Plot Asymmetry Test indicated no publication bias in the included studies (Figure 3, p > 0.05).

Conclusion

Overall, mNGS exhibits good sensitivity and specificity for diagnosing CNS infection and diagnostic performance during clinical application by assisting in identifying the pathogen. However, the efficacy remains inconsistent, warranting subsequent studies for further performance improvement during its clinical application.

Study registration number

INPLASY202120002
Immune response treated with bone marrow mesenchymal stromal cells after stroke
Authors: Wang Zili , Wang Xudong , Liao Yidong , Chen Guangtang , Xu Kaya
Published: September 2022

Stroke is a leading cause of death and long-term disability worldwide. Tissue plasminogen activator (tPA) is an effective treatment for ischemic stroke. However, only a small part of patients could benefit from it. Therefore, finding a new treatment is necessary. Bone marrow mesenchymal stromal cells (BMSCs) provide a novel strategy for stroke patients. Now, many patients take stem cells to treat stroke. However, the researches of the precise inflammatory mechanism of cell replacement treatment are still rare. In this review, we summarize the immune response of BMSCs treated to stroke and may provide a new perspective for stem cell therapy.
Key biomarkers and latent pathways of dysferlinopathy: Bioinformatics analysis and in vivo validation
Authors: Xie Yan , Li Ying-hui , Chen Kai , Zhu Chun-yan , Bai Jia-ying , Xiao Feng , Tan Song , Zeng Li
Published: September 2022

Background

Dysferlinopathy refers to a group of muscle diseases with progressive muscle weakness and atrophy caused by pathogenic mutations of the DYSF gene. The pathogenesis remains unknown, and currently no specific treatment is available to alter the disease progression. This research aims to investigate important biomarkers and their latent biological pathways participating in dysferlinopathy and reveal the association with immune cell infiltration.

Methods

GSE3307 and GSE109178 were obtained from the Gene Expression Omnibus (GEO) database. Based on weighted gene co-expression network analysis (WGCNA) and differential expression analysis, coupled with least absolute shrinkage and selection operator (LASSO), the key genes for dysferlinopathy were identified. Functional enrichment analysis Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to disclose the hidden biological pathways. Following that, the key genes were approved for diagnostic accuracy of dysferlinopathy based on another dataset GSE109178, and quantitative real-time polymerase chain reaction (qRT-PCR) were executed to confirm their expression. Furthermore, the 28 immune cell abundance patterns in dysferlinopathy were determined with single-sample GSEA (ssGSEA).

Results

1,579 differentially expressed genes (DEGs) were screened out. Based on WGCNA, three co-expression modules were obtained, with the MEskyblue module most strongly correlated with dysferlinopathy. 44 intersecting genes were recognized from the DEGs and the MEskyblue module. The six key genes MVP, GRN, ERP29, RNF128, NFYB and KPNA3 were discovered through LASSO analysis and experimentally verified later. In a receiver operating characteristic analysis (ROC) curve, the six hub genes were shown to be highly valuable for diagnostic purposes. Furthermore, functional enrichment analysis highlighted that these genes were enriched mainly along the ubiquitin-proteasome pathway (UPP). Ultimately, ssGSEA showed a significant immune-cell infiltrative microenvironment in dysferlinopathy patients, especially T cell, macrophage, and activated dendritic cell (DC).

Conclusion

Six key genes are identified in dysferlinopathy with a bioinformatic approach used for the first time. The key genes are believed to be involved in protein degradation pathways and the activation of muscular inflammation. And several immune cells, such as T cell, macrophage and DC, are considered to be implicated in the progression of dysferlinopathy.
White matter tract changes in pediatric posterior fossa brain tumor survivors after surgery and chemotherapy
Authors: Tanedo Jeffrey , Gajawelli Niharika , Guo Sharon , Baron Nelson Mary , Lepore Natasha
Published: September 2022

Background

Survivors of pediatric posterior fossa brain tumors are susceptible to the adverse effects of treatment as they grow into adulthood. While the exact neurobiological mechanisms of these outcomes are not yet understood, the effects of treatment on white matter (WM) tracts in the brain can be visualized using diffusion tensor (DT) imaging. We investigated these WM microstructural differences using the statistical method tract-specific analysis (TSA). We applied TSA to the DT images of 25 children with a history of posterior fossa tumor (15 treated with surgery, 10 treated with surgery and chemotherapy) along with 21 healthy controls. Between these 3 groups, we examined differences in the most used DTI metric, fractional anisotropy (FA), in 11 major brain WM tracts.

Results

Lower FA was found in the splenium of the corpus callosum (CC), the bilateral corticospinal tract (CST), the right inferior frontal occipital fasciculus (IFOF) and the left uncinate fasciculus (UF) in children with brain tumors as compared to healthy controls. Lower FA, an indicator of microstructural damage to WM, was observed in 4 of the 11 WM tracts examined in both groups of children with a history of posterior fossa tumor, with an additional tract unique to children who received surgery and chemotherapy (left UF).

Conclusions

Our findings indicate that a history of tumor in the posterior fossa and surgical resection may have effects on the WM in other parts of the brain.
Safety and audiological outcome in a case series of tertiary therapy of sudden hearing loss with a biodegradable drug delivery implant for controlled release of dexamethasone to the inner ear
Authors: Plontke Stefan K. , Liebau Arne , Lehner Eric , Bethmann Daniel , Mäder Karsten , Rahne Torsten
Published: September 2022

Background

Intratympanic injections of glucocorticoids have become increasingly common in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL). However, due to their fast elimination, sustained applications have been suggested for local drug delivery to the inner ear.

Materials and methods

The study is based on a retrospective chart review of patients treated for ISSHL at a single tertiary (university) referral center. We included patients who were treated with a solid, biodegradable, poly(D,L-lactic-co-glycolic acid) (PLGA)-based drug delivery system providing sustained delivery of dexamethasone extracochlear into the round window niche (n = 15) or intracochlear into scala tympani (n = 2) for tertiary therapy of ISSHL in patients without serviceable hearing after primary systemic and secondary intratympanic glucocorticoid therapy. We evaluated the feasibility and safety through clinical evaluation, histological examination, and functional tests [pure-tone threshold (PTA), word recognition scores (WRS)].

Results

With adequate surgical preparation of the round window niche, implantation was feasible in all patients. Histologic examination of the material in the round window niche showed signs of resorption without relevant inflammation or foreign body reaction to the implant. In patients where the basal part of scala tympani was assessable during later cochlear implantation, no pathological findings were found. In the patients with extracochlear application, average preoperative PTA was 84.7 dB HL (SD: 20.0) and 76.7 dB HL (SD: 16.7) at follow-up (p = 0.08). The preoperative average maximum WRS was 14.6% (SD: 17.9) and 39.3% (SD: 30.7) at follow-up (p = 0.11). Six patients (40%), however, reached serviceable hearing. The two patients with intracochlear application did not improve.

Conclusion

The extracochlear application of the controlled release system in the round window niche and – based on limited observations - intracochlear implantation into scala tympani appears feasible and safe. Due to the uncontrolled study design, conclusions about the efficacy of the treatment are limited. These observations, however, may encourage the initiation of prospective controlled studies using biodegradable controlled release implants as drug delivery systems for the treatment of inner ear diseases.
Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity
Authors: Olivares-Barraza Rossy , Marcos José Luis , Martínez-Pinto Jonathan , Fuenzalida Marco , Bravo Javier A. , Gysling Katia , Sotomayor-Zárate Ramón
Published: September 2022

Obesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.
A multifaceted evaluation of microgliosis and differential cellular dysregulation of mammalian target of rapamycin signaling in neuronopathic Gaucher disease
Authors: Zhang Zhenting , Wang Xiaohong , Lin Yi , Pan Dao
Published: September 2022

Neuronopathic Gaucher disease (nGD) is an inherited neurodegenerative disease caused by mutations in GBA1 gene and is associated with premature death. Neuroinflammation plays a critical role in disease pathogenesis which is characterized by microgliosis, reactive astrocytosis, and neuron loss, although molecular mechanisms leading to neuroinflammation are not well-understood. In this report, we developed a convenient tool to quantify microglia proliferation and activation independently and uncovered abnormal proliferation of microglia (∼2-fold) in an adult genetic nGD model. The nGD-associated pattern of inflammatory mediators pertinent to microglia phenotypes was determined, showing a unique signature favoring pro-inflammatory chemokines and cytokines. Moreover, highly polarized (up or down) dysregulations of mTORC1 signaling with varying lysosome dysfunctions (numbers and volume) were observed among three major cell types of nGD brain. Specifically, hyperactive mTORC1 signaling was detected in all disease-associated microglia (Iba1high) with concurrent increase in lysosome function. Conversely, the reduction of neurons presenting high mTORC1 activity was implicated (including Purkinje-like cells) which was accompanied by inconsistent changes of lysosome function in nGD mice. Undetectable levels of mTORC1 activity and low Lamp1 puncta were noticed in astrocytes of both diseased and normal mice, suggesting a minor involvement of mTORC1 pathway and lysosome function in disease-associated astrocytes. These findings highlight the differences and complexity of molecular mechanisms that are involved within various cell types of the brain. The quantifiable parameters established and nGD-associated pattern of neuroinflammatory mediators identified would facilitate the efficacy evaluation on microgliosis and further discovery of novel therapeutic target(s) in treating neuronopathic Gaucher disease.
Gut microbiota–mitochondrial inter-talk in non-alcoholic fatty liver disease
Authors: Zhang Qi , Xing Wenmin , Wang Qiao , Tang Zhan , Wang Yazhen , Gao Wenyan
Published: September 2022

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD), which is a progressive disease, has exerted huge a healthcare burden worldwide. New investigations have suggested that the gut microbiota closely participates in the progression of NAFLD through the gut–liver axis or gut–brain–liver axis. The composition of the microbiota can be altered by multiple factors, primarily dietary style, nutritional supplements, or exercise. Recent evidence has revealed that gut microbiota is involved in mitochondrial biogenesis and energy metabolism in the liver by regulating crucial transcription factors, enzymes, or genes. Moreover, microbiota metabolites can also affect mitochondrial oxidative stress function and swallow formation, subsequently controlling the inflammatory response and regulating the levels of inflammatory cytokines, which are the predominant regulators of NAFLD. This review focuses on the changes in the composition of the gut microbiota and metabolites as well as the cross-talk between gut microbiota and mitochondrial function. We thus aim to comprehensively explore the potential mechanisms of gut microbiota in NAFLD and potential therapeutic strategies targeting NAFLD management.
Probiotics, a promising therapy to reduce the recurrence of bacterial vaginosis in women? a systematic review and meta-analysis of randomized controlled trials
Authors: Chieng Wei Keong , Abdul Jalal Muhammad Irfan , Bedi Jashveerdeep Singh , Zainuddin Ani Amelia , Mokhtar Mohd Helmy , Abu Muhammad Azrai , Chew Kah Teik , Nur Azurah Abdul Ghani
Published: September 2022

Introduction

The evidence for probiotic efficacy in preventing bacterial vaginosis (BV) recurrences among women aged 18 years and above is sparse. We aimed to ascertain the efficacy of probiotics in preventing BV recurrences after at least one menstrual cycle in this population.

Methods

We conducted a systematic literature search using PubMed, MEDLINE (Ovid interface), Web of Science (WoS), Scopus, Embase, ProQuest Dissertations and Theses Global, Cochrane Library databases and registries comprised of Open Science Framework (OSF) preprints registry, the ClinicalTrials.gov (USA), WHO International Clinical Trials Registry Platform (WHO-ICTRP), International Standard RCT Number (ISRCTN) registry, limited to randomized clinical trials (RCTs) in English published between January 2000 and December 2021. The inclusion criteria were trials that administered probiotics to BV-positive women in an experimental arm of at least 20 samples. The usage of probiotics should be preceded with standard antibiotic regimen and followed by a reassessment of BV status after at least a single menstrual cycle. Risk of bias assessment was completed using revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The PROSPERO registration number of the review is CRD42022302044.

Results

From 8,162 identified records, we included 10 studies (n = 1,234 participants) for final analysis; 7 trials compared probiotics vs. placebo, whereas 3 trials compared probiotics vs. metronidazole alone. Using random-effects meta-analysis, probiotics were shown to reduce the risk of BV recurrences by 45% compared to either placebo or metronidazole [14.8 vs. 25.5%, RR: 0.55 (95%CI: 0.33, 0.91), p = 0.03, I2 = 45.4% (95%CI: 0, 73.7%)]. Sensitivity analysis revealed the robustness of results upon removal of studies with high risk of bias [RR: 0.54 (95%CI: 0.38, 0.77), p = 0.006] and reporting bias (RR: 0.53, 95%CI: 0.39, 0.74, p = 0.002). Meta-regression demonstrated that the route of administration (pvaginal = 0.67; poral = 0.44), the total dosage of probiotics (p = 0.17), cumulative days of probiotic administration (p = 0.76), and the number of species in probiotic preparation (p = 0.40) were not linked to BV recurrences.

Interpretation

Probiotics were associated with more than twofold reduction in BV recurrences when BV status was assessed after at least 1-month postintervention. Further high-quality and methodologically standardized RCTs should evaluate probiotic efficacy for BV prevention in a diverse community setting.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290613], identifier [CRD42021290613].
The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study
Authors: Wu Kaiwen , Liu Lei , Shu Tao , Li Aoshuang , Xia Demeng , Sun Xiaobin
Published: September 2022

Background

Observational studies have suggested processed and red meat may increase the risk of cancer. However, the causal effects and direction between them were still unclear. We conducted two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of processed meat and red meat on the risk of nine common types of cancer, namely, lung, ovarian, endometrial, breast, kidney, gastric, prostate, skin, and oropharyngeal cancer.

Methods

Genome-wide association studies (GWAS) for processed meat and red meat (pork, beef, and mutton) were obtained from the UK Biobank. GWAS of types of cancer in this study were extracted from the genetic consortia and the FinnGen consortium. The inverse variance weighted (IVW) was carried out as the main method for two-sample MR analysis. Sensitivity analyses were used to assess the robustness of the results.

Results

Genetically predicted processed meat intake was causally associated with increased risk of lung cancer (OR [odds ratio] = 1.923, 95% CI = 1.084–3.409, P = 0.025). There is no convincing evidence for the associations between genetically determined processed meat, red meat, and the risk of other cancers we studied.

Conclusion

Our results suggested that intake of processed meat may increase the risk of lung cancer. These findings provided no evidence to support that consumption of processed and red meat has a large effect on the risk of other cancers we studied. Further research is needed to clarify the results.
Association between tea consumption and frailty among Chinese older adults: A cross-sectional study
Authors: Li Shaojie , Cui Guanghui , Yin Yongtian , Lv Faqin , Yao Yao
Published: September 2022

Background

Chronic inflammation is considered one of the main mechanisms leading to frailty. It has been demonstrated that tea consumption reduces chronic inflammation. Few epidemiological studies have investigated the association between tea consumption and frailty.

Objective

This study aimed to analyze the association between tea consumption and frailty in Chinese older adults.

Methods

Between March and May 2021, we enrolled 2,144 older adults aged ≥60 years in Jinan City, Shandong Province, China, using multi-stage stratified cluster sampling. We assessed tea consumption and frailty in older adults using the Tilburg Frailty Indicator (TFI) and the frequency of tea consumption, respectively. We applied multiple logistic regression analysis to examine the association between tea consumption and frailty, controlling for a set of potential covariates.

Results

The prevalence of frailty among older Chinese adults was 38.3% (821/2,144). Tea consumption was categorized as daily (30.4%), occasionally (20.9%), and rarely or never (48.7%). As indicated by the fully adjusted model, daily tea consumption was associated with a lower prevalence of frailty (OR = 0.73, 95%CI = 0.57–0.94). However, this association only applied to men, younger older adults aged 60–79 years, rural residents, and regular participants in community activities. In addition, we observed a linear relationship between tea consumption and the prevalence of frailty (P for trend = 0.017).

Conclusions

Higher tea consumption was associated with a lower prevalence of frailty in older adults, especially those men, older adults aged 60–79, rural residents, and individuals who regularly participated in community activities. Further longitudinal and experimental studies are needed to determine the causation between tea consumption and frailty.
LGBTQI cancer patients’ quality of life and distress: A comparison by gender, sexuality, age, cancer type and geographical remoteness
Authors: Ussher Jane M. , Allison Kimberley , Perz Janette , Power Rosalie ,   The Out with Cancer Study Team
Published: September 2022

Background

There is growing acknowledgement of the psycho-social vulnerability of lesbian, gay, bisexual, transgender, queer and/or intersex (LGBTQI) people with cancer. The majority of research to date has focused on cisgender adults with breast or prostate cancer.

Study Aim

This study examined psycho-social factors associated with distress and quality of life for LGBTQI cancer patients and survivors, across a range of sexualities and gender identities, intersex status, tumor types, ages and urban/rural/remote location using an intersectional theoretical framework.

Method

430 LGBTQI people with cancer completed an online survey, measuring distress, quality of life (QOL), and a range of psycho-social variables. Participants included 216 (50.2%) cisgender women, 145 (33.7%) cisgender men, and 63 (14.7%) transgender and gender diverse (TGD) people. Thirty-one (7.2%) participants reported intersex variation and 90 (20%) were adolescents or young adults (AYA), aged 15-39. The majority lived in urban areas (54.4%) and identified as lesbian, gay or bisexual (73.7%), with 10.9% identifying as bisexual, and 10.5% as queer, including reproductive (32.4%) and non-reproductive (67.6%) cancers.

Results

Forty-one percent of participants reported high or very high distress levels, 3-6 times higher than previous non-LGBTQI cancer studies. Higher rates of distress and lower QOL were identified in TGD compared to cisgender people, AYAs compared to older people, those who identify as bisexual or queer, compared to those who identify as lesbian, gay or homosexual, and those who live in rural or regional areas, compared to urban areas. Elevated distress and lower QOL was associated with greater minority stress (discrimination in life and in cancer care, discomfort being LGBTQI, lower outness) and lower social support, in these subgroups. There were no differences between reproductive and non-reproductive cancers. For the whole sample, distress and poor QOL were associated with physical and sexual concerns, the impact of cancer on gender and LGBTQI identities, minority stress, and lack of social support.

Conclusion

LGBTQI people with cancer are at high risk of distress and impaired QOL. Research and oncology healthcare practice needs to recognize the diversity of LGBTQI communities, and the ways in which minority stress and lack of social support may affect wellbeing.
Radiomics-based nomogram as predictive model for prognosis of hepatocellular carcinoma with portal vein tumor thrombosis receiving radiotherapy
Authors: Huang Yu-Ming , Wang Tsang-En , Chen Ming-Jen , Lin Ching-Chung , Chang Ching-Wei , Tai Hung-Chi , Hsu Shih-Ming , Chen Yu-Jen
Published: September 2022

Background

This study aims to establish and validate a predictive model based on radiomics features, clinical features, and radiation therapy (RT) dosimetric parameters for overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with RT for portal vein tumor thrombosis (PVTT).

Methods

We retrospectively reviewed 131 patients. Patients were randomly divided into the training (n = 105) and validation (n = 26) cohorts. The clinical target volume was contoured on pre-RT computed tomography images and 48 textural features were extracted. The least absolute shrinkage and selection operator regression was used to determine the radiomics score (rad-score). A nomogram based on rad-score, clinical features, and dosimetric parameters was developed using the results of multivariate regression analysis. The predictive nomogram was evaluated using Harrell’s concordance index (C-index), area under the curve (AUC), and calibration curve.

Results

Two radiomics features were extracted to calculate the rad-score for the prediction of OS. The radiomics-based nomogram had better performance than the clinical nomogram for the prediction of OS, with a C-index of 0.73 (95% CI, 0.67–0.79) and an AUC of 0.71 (95% CI, 0.62–0.79). The predictive accuracy was assessed by a calibration curve.

Conclusion

The radiomics-based predictive model significantly improved OS prediction in HCC patients treated with RT for PVTT.
Detection of thyroglobulin in fine-needle aspiration for diagnosis of metastatic lateral cervical lymph nodes in papillary thyroid carcinoma: A retrospective study
Authors: Wang Yuxuan , Duan Yuansheng , Li Hong , Yue Kai , Liu Jin , Lai Qingchuan , Zhou Mengqian , Ye Beibei , Wu Yue , Zhu Jiajia , Chen Peng , Jing Chao , Wu Yansheng , Wang Xudong
Published: September 2022

Objective

We analysed the diagnostic performance of thyroglobulin in fine-needle aspiration (FNA-Tg) in the suspicious lateral cervical lymph nodes (CLNs) in patients with papillary thyroid cancer (PTC), proposed the best cutoff value and discussed the factors that may affect the diagnostic value of FNA-Tg.

Methods

In the present study, a retrospective analysis of 403 patients with PTC with 448 suspected lateral CLNs metastasis from October 2019 to May 2021 was performed. The cutoff value according to the receiver operating characteristic (ROC) curve was determined, and the Wilcoxon rank-sum test was used to evaluate the correlation between FNA-Tg and factors.

Results

According to the ROC curve, the cutoff value of FNA-Tg was 3.69 ng/ml (sensitivity, 92.48%; specificity, 75.00%). Patients who underwent total thyroidectomy were excluded. Compared with US and FNAC, the diagnostic performance of FNA-Tg was the greatest, especially for small CLNs (diameter ≤ 1 cm), cystic CLNs, and patients with Hashimoto’s thyroiditis (HT). Moreover, FNA-Tg levels were correlated with the presence of HT (p = 0.003), the anti-thyroglobulin antibody (Tg-Ab) (p < 0.001), the ratio of metastatic lateral CLNs (p = 0.004) and Tg assay kits (p < 0.001).

Conclusions

FNA-Tg measurement is sensitive enough for diagnosing lateral CLN metastases from PTC, but its diagnostic value is compromised by a number of factors.
Nomogram for the prediction of triple-negative breast cancer histological heterogeneity based on multiparameter MRI features: A preliminary study including metaplastic carcinoma and non- metaplastic carcinoma
Authors: Kong Qing-cong , Tang Wen-jie , Chen Si-yi , Hu Wen-ke , Hu Yue , Liang Yun-shi , Zhang Qiong-qiong , Cheng Zi-xuan , Huang Di , Yang Jing , Guo Yuan
Published: September 2022

Objectives

Triple-negative breast cancer (TNBC) is a heterogeneous disease, and different histological subtypes of TNBC have different clinicopathological features and prognoses. Therefore, this study aimed to establish a nomogram model to predict the histological heterogeneity of TNBC: including Metaplastic Carcinoma (MC) and Non-Metaplastic Carcinoma (NMC).

Methods

We evaluated 117 patients who had pathologically confirmed TNBC between November 2016 and December 2020 and collected preoperative multiparameter MRI and clinicopathological data. The patients were randomly assigned to a training set and a validation set at a ratio of 3:1. Based on logistic regression analysis, we established a nomogram model to predict the histopathological subtype of TNBC. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. According to the follow-up information, disease-free survival (DFS) survival curve was estimated using the Kaplan-Meier product-limit method.

Results

Of the 117 TNBC patients, 29 patients had TNBC-MC (age range, 29–65 years; median age, 48.0 years), and 88 had TNBC-NMC (age range, 28–88 years; median age, 44.5 years). Multivariate logistic regression analysis demonstrated that lesion type (p = 0.001) and internal enhancement pattern (p = 0.001) were significantly predictive of TNBC subtypes in the training set. The nomogram incorporating these variables showed excellent discrimination power with an AUC of 0.849 (95% CI: 0.750−0.949) in the training set and 0.819 (95% CI: 0.693−0.946) in the validation set. Up to the cutoff date for this analysis, a total of 66 patients were enrolled in the prognostic analysis. Six of 14 TNBC-MC patients experienced recurrence, while 7 of 52 TNBC-NMC patients experienced recurrence. The DFS of the two subtypes was significantly different (p=0.035).

Conclusions

In conclusion, we developed a nomogram consisting of lesion type and internal enhancement pattern, which showed good discrimination ability in predicting TNBC-MC and TNBC-NMC.
mRNA-miRNA networks identify metabolic pathways associated to the anti-tumorigenic effect of thyroid hormone on preneoplastic nodules and hepatocellular carcinoma
Authors: Serra Marina , Pal Rajesh , Puliga Elisabetta , Sulas Pia , Cabras Lavinia , Cusano Roberto , Giordano Silvia , Perra Andrea , Columbano Amedeo , Kowalik Marta Anna
Published: September 2022

Background

Thyroid hormones (THs) inhibit hepatocellular carcinoma (HCC) through different mechanisms. However, whether microRNAs play a role in the antitumorigenic effect of THs remains unknown.

Methods

By next generation sequencing (NGS) we performed a comprehensive comparative miRNomic and transcriptomic analysis of rat hepatic preneoplastic lesions exposed or not to a short-term treatment with triiodothyronine (T3). The expression of the most deregulated miRs was also investigated in rat HCCs, and in human hepatoma cell lines, treated or not with T3.

Results

Among miRs down-regulated in preneoplastic nodules following T3, co-expression networks revealed those targeting thyroid hormone receptor-β (Thrβ) and deiodinase1, and Oxidative Phosphorylation. On the other hand, miRs targeting members of the Nrf2 Oxidative Pathway, Glycolysis, Pentose Phosphate Pathway and Proline biosynthesis – all involved in the metabolic reprogramming displayed by preneoplastic lesions– were up-regulated. Notably, while the expression of most miRs deregulated in preneoplastic lesions was not altered in HCC or in hepatoma cells, miR-182, a miR known to target Dio1 and mitochondrial complexes, was down-deregulated by T3 treatment at all stages of hepatocarcinogenesis and in hepatocarcinoma cell lines. In support to the possible critical role of miR-182 in hepatocarcinogenesis, exogenous expression of this miR significantly impaired the inhibitory effect of T3 on the clonogenic growth capacity of human HCC cells.

Conclusions

This work identified several miRNAs, so far never associated to T3. In addition, the precise definition of the miRNA-mRNA networks elicited by T3 treatment gained in this study may provide a better understanding of the key regulatory events underlying the inhibitory effect of T3 on HCC development. In this context, T3-induced down-regulation of miR-182 appears as a promising tool.
Glycosyltransferase-related long non-coding RNA signature predicts the prognosis of colon adenocarcinoma
Authors: Zhang Jiawei , Wu Yinan , Mu Jiayi , Xin Dijia , Wang Luyao , Fan Yili , Zhang Suzhan , Xu Yang
Published: September 2022

Purpose

Colon adenocarcinoma (COAD) is the most common type of colorectal cancer (CRC) and is associated with poor prognosis. Emerging evidence has demonstrated that glycosylation by long noncoding RNAs (lncRNAs) was associated with COAD progression. To date, however, the prognostic values of glycosyltransferase (GT)-related lncRNAs in COAD are still largely unknown.

Methods

We obtained the expression matrix of mRNAs and lncRNAs in COAD from The Cancer Genome Atlas (TCGA) database. Then, the univariate Cox regression analysis was conducted to identify 33 prognostic GT-related lncRNAs. Subsequently, LASSO and multivariate Cox regression analysis were performed, and 7 of 33 GT-related lncRNAs were selected to conduct a risk model. Gene set enrichment analysis (GSEA) was used to analyze gene signaling pathway enrichment of the risk model. ImmuCellAI, an online tool for estimating the abundance of immune cells, and correlation analysis were used to explore the tumor-infiltrating immune cells in COAD. Finally, the expression levels of seven lncRNAs were detected in colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results

A total of 1,140 GT-related lncRNAs were identified, and 7 COAD-specific GT-related lncRNAs (LINC02381, MIR210HG, AC009237.14, AC105219.1, ZEB1-AS1, AC002310.1, and AC020558.2) were selected to conduct a risk model. Patients were divided into high- and low-risk groups based on the median of risk score. The prognosis of the high-risk group was worse than that of the low-risk group, indicating the good reliability and specificity of our risk model. Additionally, a nomogram based on the risk score and clinical traits was built to help clinical decisions. GSEA showed that the risk model was significantly enriched in metabolism-related pathways. Immune infiltration analysis revealed that five types of immune cells were significantly different between groups, and two types of immune cells were negatively correlated with the risk score. Besides, we found that the expression levels of these seven lncRNAs in tumor cells were significantly higher than those in normal cells, which verified the feasibility of the risk model.

Conclusion

The efficient risk model based on seven GT-related lncRNAs has prognostic potential for COAD, which may be novel biomarkers and therapeutic targets for COAD patients.
Clinical analysis of deceased donor liver transplantation in the treatment of hepatocellular carcinoma with segmental portal vein tumor thrombus: A long-term real-world study
Authors: Sha Meng , Chen Chen , Shen Chuan , Jeong Seogsong , Sun Han-yong , Xu Ning , Hang Hua-lian , Cao Jie , Tong Ying
Published: September 2022

Background

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) have conventionally been regarded as a contraindication for liver transplantation (LT). However, the outcomes of deceased donor liver transplantation (DDLT) in patients with segmental PVTT remain unknown. The aim of this study is to evaluate the feasibility and effectiveness of DDLT in the treatment of HCC with segmental PVTT.

Methods

We retrospectively analyzed 254 patients who underwent DDLT for HCC in our institution from January 2015 to November 2019. To assess the risks of PVTT, various clinicopathological variables were evaluated. Overall (OS) and recurrence-free survival (RFS) analyses based on different PVTT types were performed in HCC patients.

Results

Of the 254 patients, a total of 46 patients had PVTT, of whom 35 had lobar PVTT and 11 had segmental PVTT in second-order branches or below. Alpha-fetoprotein (AFP) level, tumor maximal diameter, histological grade, micro-vascular invasion (MVI), RFS, and OS were significantly different between the control and PVTT groups. Lobar PVTT was associated with unfavorable 5-year RFS and OS compared with MVI group (28.6% and 17.1%, respectively). Instead, no significant difference was observed between the segmental PVTT and MVI group in terms of 5-year RFS and OS (RFS: 36.4% vs. 40.4%, p=0.667; OS: 54.5% vs. 45.1%, p=0.395). Further subgroup analysis showed segmental PVTT with AFP levels ≤100 ng/ml presented significantly favorable RFS and OS rates than those with AFP level >100 ng/ml (p=0.050 and 0.035, respectively).

Conclusions

In summary, lobar PVTT remains a contraindication to DDLT. HCC patients with segmental PVTT and AFP level ≤100 ng/ml may be acceptable candidates for DDLT.
GLUD1 suppresses renal tumorigenesis and development via inhibiting PI3K/Akt/mTOR pathway
Authors: Wang Lei , Fang Zhiyu , Gao Peixiang , Zheng Junfang
Published: September 2022

Growing cancer cells are addicted to glutamine. Glutamate dehydrogenase 1 (GLUD1) is one of key enzymes in glutamine metabolism and plays a critical role in the malignancy of diverse tumors. However, its role and molecular mechanism in clear cell renal cell carcinoma (ccRCC) development and progression remain unknown. In this study, analysis results of the GEO/TCGA/UALCAN database showed that GLUD1 level was downregulated in ccRCC tissues. Immunohistochemistry and western blotting results further validated the downregulation of GLUD1 level in ccRCC tissues. GLUD1 level was gradually decreased as ccRCC stage and grade progressed. Low GLUD1 level was associated with a shorter survival and higher IC50 value for tyrosine kinase inhibitors (TKIs) in ccRCC, reminding that GLUD1 level could predict the prognosis and TKIs sensitivity of ccRCC patients. High level of methylation in GLUD1 promoter was positively correlated with the downregulation of GLUD1 level and was negatively correlated with survival of ccRCC patients. GLUD1 overexpression suppressed RCC cell proliferation, colony formation and migration by inhibiting PI3K/Akt/mTOR pathway activation. Low GLUD1 level correlated with suppressive immune microenvironment (TIME) in ccRCC. Together, we found a novel tumor-suppressing role of GLUD1 in ccRCC which was different from that in other tumors and a new mechanism for inhibiting PI3K/Akt/mTOR activation and TIME in ccRCC. These results provide a theoretical basis for GLUD1 as a therapeutic target and prognostic marker in ccRCC.
Validation of deep learning-based fully automated coronary artery calcium scoring using non-ECG-gated chest CT in patients with cancer
Authors: Choi Joo Hyeok , Cha Min Jae , Cho Iksung , Kim William D. , Ha Yera , Choi Hyewon , Lee Sun Hwa , You Seng Chan , Chang Jee Suk
Published: September 2022

This study aimed to demonstrate clinical feasibility of deep learning (DL)-based fully automated coronary artery calcium (CAC) scoring software using non-electrocardiogram (ECG)-gated chest computed tomography (CT) from patients with cancer. Overall, 913 patients with colorectal or gastric cancer who underwent non-contrast-enhanced chest CT between 2013 and 2015 were included. Agatston scores obtained by manual segmentation of CAC on chest CT were used as reference. Reliability of automated CAC score acquisition was evaluated using intraclass correlation coefficients (ICCs). The agreement for cardiovascular disease (CVD) risk stratification was assessed with linearly weighted k statistics. ICCs between the manual and automated CAC scores were 0.992 (95% CI, 0.991 and 0.993, p<0.001) for total Agatston scores, 0.863 (95% CI, 0.844 and 0.880, p<0.001) for the left main, 0.964 (95% CI, 0.959 and 0.968, p<0.001) for the left anterior descending, 0.962 (95% CI, 0.956 and 0.966, p<0.001) for the left circumflex, and 0.980 (95% CI, 0.978 and 0.983, p<0.001) for the right coronary arteries. The agreement for cardiovascular risk was excellent (k=0.946, p<0.001). Current DL-based automated CAC software showed excellent reliability for Agatston score and CVD risk stratification using non-ECG gated CT scans and might allow the identification of high-risk cancer patients for CVD.
Circulating maternal chimeric cells have an impact on the outcome of biliary atresia
Authors: Masuya Ryuta , Muraji Toshihiro , Kanaan Sami B. , Harumatsu Toshio , Muto Mitsuru , Toma Miki , Yanai Toshihiro , Stevens Anne M. , Nelson J. Lee , Nakame Kazuhiko , Nanashima Atsushi , Ieiri Satoshi
Published: September 2022

Introduction

We aimed to quantify the DNA of maternal chimeric (MC) cells in the peripheral blood of the BA patients and investigated the impact on the outcome.

Methods

Patients with progressive jaundice because of no bile flow, which necessitated liver transplantation, or who showed inadequate bile flow with or without episodes of cholangitis and progressive hepatic fibrosis and portal hypertension were classified into the poor group. Those with adequate bile flow with completely normal liver function tests beyond 2 years were classified into the good group. The qPCR were separately carried out in buffy coat samples and plasma samples, targeting the non-inherited maternal HLA alleles in the DNA samples.

Results

MC-DNA was present in the buffy coat (10–328 gEq per 106 host cells) in seven patients. There was no MC-DNA in the remaining five patients. MC-DNA (214–15,331 gEq per 106 host cells) was observed in the plasma of five patients. The quantity of MC-DNA in the buffy coat showed a significant difference between the two prognostic groups (p = 0.018), whereas there was no significant difference in the quantity of MC-DNA in plasma (p = 0.205). MC-DNA in the buffy coat was significantly associated with the outcome (p = 0.028), whereas MC-DNA in the plasma did not influence the outcome (p = 0.56).

Conclusions

Poor outcomes in BA were correlated with circulating maternal chimeric lymphocytes.
Case report: Corticosteroids as an adjunct treatment for the management of liver abscess in Papillon–Lefèvre syndrome: A report on two cases
Authors: Basu Suprit , Tyagi Reva , Jindal Ankur Kumar , Medha Apurva , Banday Aaqib Zaffar , Babbar Alisha , Sharma Apoorva , Mahajan Rahul , Vignesh Pandiarajan , Rawat Amit
Published: September 2022

Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized clinically by palmoplantar keratoderma, periodontitis, and recurrent pyogenic infections. Liver abscess is rarely reported in patients. The use of corticosteroids for the treatment of liver abscess akin to chronic granulomatous disease (CGD) has not been reported previously. Here, we report 2 cases of liver abscess in PLS that responded to corticosteroids.
Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy
Authors: Dubchak Eden , Obasanmi Gideon , Zeglinski Matthew R. , Granville David J. , Yeung Sonia N. , Matsubara Joanne A.
Published: September 2022

Age-related ocular diseases are the leading cause of blindness in developed countries and constitute a sizable socioeconomic burden worldwide. Age-related macular degeneration (AMD) and Fuchs endothelial corneal dystrophy (FECD) are some of the most common age-related diseases of the retina and cornea, respectively. AMD is characterized by a breakdown of the retinal pigment epithelial monolayer, which maintains retinal homeostasis, leading to retinal degeneration, while FECD is characterized by degeneration of the corneal endothelial monolayer, which maintains corneal hydration status, leading to corneal edema. Both AMD and FECD pathogenesis are characterized by disorganized local extracellular matrix (ECM) and toxic protein deposits, with both processes linked to aberrant protease activity. Granzyme B (GrB) is a serine protease traditionally known for immune-mediated initiation of apoptosis; however, it is now recognized that GrB is expressed by a variety of immune and non-immune cells and aberrant extracellular localization of GrB substantially contributes to various age-related pathologies through dysregulated cleavage of ECM, tight junction, and adherens junction proteins. Despite growing recognition of GrB involvement in multiple age-related pathologies, its role in AMD and FECD remains poorly understood. This review summarizes the pathophysiology of, and similarities between AMD and FECD, outlines the current knowledge of the role of GrB in AMD and FECD, as well as hypothesizes putative contributions of GrB to AMD and FECD pathogenesis and highlights the therapeutic potential of pharmacologically inhibiting GrB as an adjunctive treatment for AMD and FECD.