bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-analysis of neoadjuvant immunotherapy for non-metastatic colorectal cancer
Authors: Zhou Long , Yang Xiao-Quan , Zhao Guang-yue , Wang Feng-jian , Liu Xin
Published: January 2023

Background

Immunotherapy has been approved for the treatment of metastatic colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic colorectal cancer remains unclear. We tried to explore clinical effect of neoadjuvant immunotherapy in the treatment of non-metastatic colorectal cancer.

Methods

We searched the databases (PubMed, Wanfang Embase, Cochrane Library and China National Knowledge Infrastructure databases) to obtain suitable articles up to September 2022. The primary outcomes of pathological complete response (pCRs), major pathological response (MPR), objective response rate (ORR), R0-resection and anus preserving rate were collected and evaluated. Secordary outcomes (pCRs and MPR) of subgroup analysis between deficient mismatch repair/microsatellite instability-high group (dMMR/MSI-H) and proficient mismatch repair/microsatellite stable group (pMMR/MSS) and outcomes for rectal cancer were analyzed for the final results.

Results

We included ten articles and 410 cases of non-metastatic colorectal cancer with neoadjuvant immunotherapy. There were 113 (27.5%) cases with the dMMR/MSI-H status and 167 (40.7%) cases with the pMMR/MSS status. pCRs was found in 167/373 (44.6%) patients (ES: 0.49, 95% CI: 0.36 to 0.62, P<0.01, chi2 = 65.3, P<0.01, I2 = 86.2%) and MPR was found in 194/304 (63.8%) patients (ES: 0.66, 95% CI: 0.54 to 0.78, P<0.01, chi2 = 42.55, P<0.01, I2 = 81.2%) with the random-effects model and huge heterogeneity. In the subgroup analysis, pCRs was higher in the dMMR/MSI-H group than the pMMR/MSS group in the fixed-effects model with minimal heterogeneity (OR: 3.55, 95% CI: 1.74 to 7.27, P<0.01, chi2 = 1.86, P=0.6, I2 = 0%). pCRs was found in 58/172 (33.9%) rectal cancer patients (ES: 0.33, 95% CI: 0.26 to 0.40, P<0.01, chi2 = 3.04, P=0.55, I2 = 0%) with the fixed-effects model and little heterogeneity.

Conclusion

Neoadjuvant immunotherapy could increase pCRs and MPR rate for non-metastatic colorectal cancer. Neoadjuvant immunotherapy could achieve better pCRs rate in dMMR/MSI-H group than in the pMMR/MSS group. Neoadjuvant immunotherapy could be another treatment option for non-metastatic colorectal cancer.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42022350523.
A meta-analysis investigating the relationship between inflammation in autoimmune disease, elevated CRP, and the risk of dementia
Authors: Cooper Joseph , Pastorello Ylenia , Slevin Mark
Published: January 2023

Alzheimer’s Disease (AD) represents the most common type of dementia and is becoming a steadily increasing challenge for health systems globally. Inflammation is developing as the main focus of research into Alzheimer’s disease and has been demonstrated to be a major driver of the pathologies associated with AD. This evidence introduces an interesting research question, whether chronic inflammation due to pathologies such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) could lead to a higher risk of developing dementia. In both IBD and RA, increased levels of the inflammatory biomarker C-reactive protein (CRP) can be highlighted, the latter being directly implicated in neuroinflammation and AD. In this meta-analysis both the association between chronic inflammatory diseases and elevated levels of CRP during midlife were investigated to examine if they correlated with an augmented risk of dementia. Moreover, the association between increased CRP and modifications in the permeability of the Blood Brain Barrier (BBB) in the presence of CRP is explored. The results displayed that the odds ratio for IBD and dementia was 1.91 [1.15-3.15], for RA it was 1.90 [1.09-3.32] following sensitivity analysis and for CRP it was 1.62 [1.22-2.15]. These results demonstrate a higher risk of dementia in patients presenting chronic inflammation and that exists an independent association with high CRP in midlife. This paper builds on published research that suggest a critical role for CRP both in stroke and AD and provides an analysis on currently published research on multiple diseases (IBD and RA) in which CRP is raised as well as chronically elevated. CRP and the associated risk of dementia and further research indicated that the monomeric form of CRP can infiltrate the BBB/be released from damaged micro-vessels to access the brain. This meta-analysis provides first-time evidence that chronic elevation of CRP in autoimmune diseases is directly associated with an increased risk of later development of Alzheimer’s disease. Therefore, greater priority should be provided to the effective control of inflammation in patients with chronic inflammatory or autoimmune conditions and further long-term assessment of circulating CRP might inform of an individual’s relative risk of developing dementia.
By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma
Authors: Zhang Pengpeng , Pei Shengbin , Gong Zeitian , Feng Yanlong , Zhang Xiao , Yang Fang , Wang Wei
Published: January 2023

Background

Lung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs.

Methods

The most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells.

Results

A total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate.

Conclusion

The eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD.
Scale dependence of near-inertial wave’s concentration in anticyclones
Authors: Zhang Furu , Xie Jin-Han
Published: January 2023

Near-inertial waves (NIWs), pervasive and dominating the mixing process in the upper ocean, are observed to concentrate in anticyclones. Based on the NIW amplitude equation derived by Young & Ben Jelloul, which captures dispersion and effects of vortical flow’s advection and refraction, this work analytically and numerically studies the influence of scale on the concentration of NIWs. For a sinusoidal background shear flow, the exact solutions expressed as periodic Mathieu functions are approximated by a Gaussian envelope with Hermite polynomial oscillations to determine the distance to the anticyclones. Two dimensionless parameters control NIW’s dynamics: (i) h/Ψ, where h is a constant capturing the strength of wave dispersion and Ψ is the magnitude of the background streamfunction capturing the ratio of dispersion to refraction; (ii) LΨ/LM, the ratio between the spatial scales of background flow and NIWs, where LΨ and LM, respectively, captures the relative strength between advection and refraction. The refraction by the background flow leads to the concentration in the regions with negative vorticity, dispersion controls the variance of the wave packet, and the advection shifts the center of NIWs away from the peak of negative vorticity, which is scale-dependent. When the refraction effect dominates, i. e., small LΨ/LM, NIWs concentrate in anticyclones, and this concentration becomes stronger as h/Ψ decreases; when the advection effect dominates, i.e., large LΨ/LM, the NIW’s concentration is less obvious. Numerical simulations with backgrounds of sinusoidal shear, vortex quadrupoles and random vortices confirm these results. Considering the similarity between the NIW amplitude equation and the Schrödinger equation, we propose a new perspective that the combined effect of uncertainty relation and energy conservation leads to large-scale NIW’s concentration in anticyclones.
The strategies preventing particle transportation into the inlets of nuclear power plants: Mechanisms of physical oceanography
Authors: Li Jintao , Xu Mengdi , Lin Jianwei , Jiang Yuwu
Published: January 2023

The formation of aquatic organism aggregations near the inlets of nuclear power plants (NPPs) has become an important global concern, as the aggregated organisms can block the cooling systems of NPPs, and, therefore, threaten their operational safety. In this study we focus on the trajectory of aquatic organisms, that is., how these organisms can be transported to the inlets of NPPs by physical ocean processes related to currents and waves. The Changjiang NPP, located on the west side of Hainan Island in China, is occasionally subject to serious gulfweed blocking events in spring. To study the physical mechanism, with the use of a three-dimensional numerical current–wave-coupled model, the current and wave conditions near the NPP were simulated. Based on the model, several particle-tracking simulations were run to evaluate the extent of the blocking that occurred in the inlet of the NPP’s cooling system with different forcings introduced. The results showed that the windage effect and the surface Stokes drift induced by waves were the main causes of blocking events in the Changjiang NPP, with the former transporting surface particles from upstream and the latter transporting surrounding particles onshore, into the NPP’s inlet. Further simulations revealed that bending of the inlet and changing the offshore mouth to downstream mouth could limit the blocking greatly, as particles were seldom transported into the mouth by cross-shore transport processes such as the Stokes drift. We suggest that such findings may provide a valuable reference for the development of strategies to prevent aquatic organism aggregation events in other NPPs.
Cranial CT is a mandatory tool to exclude asymptomatic cerebral hemorrhage in elderly patients on anticoagulation
Authors: Schindler Cora R. , Best Alicia , Woschek Mathias , Verboket René D. , Marzi Ingo , Eichler Katrin , Störmann Philipp
Published: January 2023

Background

Traumatic brain injury (TBI) after falls causes death and disability with immense socioeconomic impact through medical and rehabilitation costs in geriatric patients. Diagnosing TBI can be challenging due to the absence of initial clinical symptoms. Misdiagnosis is particularly dangerous in patients on permanent anticoagulation because minimal trauma might result in severe intracranial hemorrhage. The aim of this study is to evaluate the diagnostic necessity of cranial computed tomography (cCT) to rule out intracranial hemorrhage, particularly in the absence of neurologic symptoms in elderly patients on permanent anticoagulation in their premedication.

Patients and methods

Retrospective cohort analysis of elderly trauma patients (≥ 65 years) admitted to the emergency department (ED) of the level-1-trauma center of the University Hospital Frankfurt from 01/2017 to 12/2019. The study included patients who suffered a ground-level fall with suspected TBI and subsequently underwent CT because of preexisting anticoagulation.

Results

A total of 227 patients met the inclusion criteria. In 17 of these patients, cCT showed intracranial hemorrhage, of which 14 were subdural hematomas (SDH). In 8 of the patients with bleeding showed no clinical symptoms, representing 5% (n = 160) of all symptom-free patients. Men and women were equally to suffer a post-traumatic hemorrhage. Patients with intracranial bleeding were hospitalized for 14.5 (±10.4) days. Acetylsalicylic acid (ASA) was the most prescribed anticoagulant in both patient cohorts—with or without intracerebral bleeding (70.6 vs. 77.1%, p = 0.539). Similarly, patients taking new oral anticoagulant (NOAC) (p = 0.748), coumarins, or other platelet inhibitors (p > 0.1) did not show an increased bleeding incidence.

Conclusion

Acetylsalicylic acid and NOAC use are not associated with increased bleeding risk in geriatric trauma patients (≥ 65 years) after fall-related TBI. Even in asymptomatic elderly patients on anticoagulation, intracranial hemorrhage occurs in a relevant proportion after minor trauma to the head. Therefore, cCT is an obligatory tool to rule out cerebral hemorrhage in elderly patients under anticoagulation.
Dynamic changes in fecal microbiota in donkey foals during weaning: From pre-weaning to post-weaning
Authors: Zhang Zhenwei , Huang Bingjian , Gao Xu , Shi Xiaoyuan , Wang Xinrui , Wang Tianqi , Wang Yonghui , Liu Guiqin , Wang Changfa
Published: January 2023

Introduction

A better understanding of the microbiota community in donkey foals during the weaning transition is a prerequisite to optimize gut function and improve feed efficiency. The objective of the present study was to investigate the dynamic changes in fecal microbiota in donkey foals from pre-to post-weaning period.

Methods

A total of 27 fecal samples of donkey foals were collected in the rectum before morning feeding at pre-weaning (30 days of age, PreW group, n = 9), dur-weaning (100 days of age, DurW group, n = 9) and post-weaning (170 days of age, PostW group, n = 9) period. The 16S rRNA amplicon sequencing were employed to indicate the microbial changes during the weaning period.

Results

In the present study, the cessation of breastfeeding gradually and weaning onto plant-based feeds increased the microbial diversity and richness, with a higher Shannon, Ace, Chao and Sobs index in DurW and PostW than in PreW (p < 0.05). The predominant bacterial phyla in donkey foal feces were Firmicutes (>50.5%) and Bacteroidota (>29.5%), and the predominant anaerobic fungi and archaea were Neocallimastigomycota and Euryarchaeota. The cellulolytic related bacteria including phylum Firmicutes, Spirochaetota and Fibrobacterota and genus norank_f_F082, Treponema, NK4A214_group, Lachnospiraceae_AC2044_group and Streptococcus were increased from pre-to post-weaning donkey foals (p < 0.05). Meanwhile, the functions related to the fatty acid biosynthesis, carbohydrate metabolism and amino acid biosynthesis were significantly enriched in the fecal microbiome in the DurW and PostW donkeys. Furthermore, the present study provided the first direct evidence that the initial colonization and establishment of anaerobic fungi and archaea in donkey foals began prior to weaning. The relative abundance of Orpinomyces were the highest in DurW donkey foals among the three groups (p < 0.01). In terms of archaea, the abundance of Methanobrevibacter were higher in PreW than in DurW and PostW (p < 0.01), but the abundance of Methanocorpusculum were significantly increased in DurW and PostW compared to PreW donkey foals (p < 0.01).

Discussion

Altogether, the current study contributes to a comprehensive understanding of the development of the microbiota community in donkey foals from pre-to post-weaning period, which may eventually result in an improvement of the digestion and feed efficiency in donkeys.
Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders
Authors: Nik Akhtar Shayan , Bunner Wyatt P. , Brennan Elizabeth , Lu Qun , Szatmari Erzsebet M.
Published: January 2023

Neurodegeneration is associated with defects in cytoskeletal dynamics and dysfunctions of the vesicular trafficking and sorting systems. In the last few decades, studies have demonstrated that the key regulators of cytoskeletal dynamics are proteins from the Rho family GTPases, meanwhile, the central hub for vesicle sorting and transport between target membranes is the Rab family of GTPases. In this regard, the role of Rho and Rab GTPases in the induction and maintenance of distinct functional and morphological neuronal domains (such as dendrites and axons) has been extensively studied. Several members belonging to these two families of proteins have been associated with many neurodegenerative disorders ranging from dementia to motor neuron degeneration. In this analysis, we attempt to present a brief review of the potential crosstalk between the Rab and Rho family members in neurodegenerative pathologies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease, and amyotrophic lateral sclerosis (ALS).
A mechanical rotation chair provides superior diagnostics of benign paroxysmal positional vertigo
Authors: Bech Mathias Winther , Staffe Alexander Torp , Hougaard Dan Dupont
Published: January 2023

Background

Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disease. Both therapeutic and diagnostic benefits with mechanical rotation chairs (MRCs) for management of BPPV have been reported. No previous studies have compared diagnostics in MRCs to traditional diagnostics on an examination bed.

Objective

To investigate the agreement between BPPV diagnostics performed with an MRC and traditional diagnostics on an examination bed. Secondary objectives were to (1) examine if the two test modalities differ in diagnostic properties when diagnosing largely untreated patients referred from general practitioners (uncomplicated BPPV) compared to patients referred from private ENTs (complicated BPPV) and (2) examine whether impaired participant cooperation during Manual Diagnostics (MDs) alters agreement, sensitivity and specificity.

Method

Prospective randomized clinical trial in which patients with a case history of BPPV were recruited by referrals from general practitioners, otorhinolaryngologists and other hospital departments in the Northern Region of Denmark. Participants underwent diagnostic examinations twice: once by traditional MDs on an examination bed and once with an MRC. Initial examiner and order of test modality were randomized. Examiners were blinded to each other's findings.

Results

When testing the ability to diagnose BPPV, agreement between the two test modalities, was 0.83, Cohen's kappa 0.66. When comparing MD diagnostics to MRC diagnostics (set as gold standard diagnostics following test result interpretation), values for MDs were: sensitivity 71%, specificity 98%, Negative Predictive Value 73%, and Positive Predictive Value 97%. Agreement regarding BPPV subtype classification was found to be 0.71, and Cohen's kappa 0.58. Agreement when isolating the diagnosis to posterior canalolithiasis (p-CAN) was 0.89, Cohen's kappa 0.78.

Conclusion

Diagnostics, aided by an MRC, are more sensitive than traditional manual BPPV diagnostics. The overall agreement level between test modalities was found to be weak to moderate. When isolating diagnostics to p-CAN, the level of agreement increased to “moderate-strong.” Results also showed higher agreement between test modalities and a significantly higher negative predictive value for MDs when examining patients referred directly from General Practitioners following no- or a single treatment attempt. The diagnostic properties of MDs improved in patients with a higher degree of cooperation.
A novel variant of COL6A3 c.6817-2(IVS27)A>G causing Bethlem myopathy: A case report
Authors: Li Maohua , Huang Jiandi , Liu Min , Duan Chunmei , Guo Hong , Chen Xiaoyan , Wang Yue
Published: January 2023

Bethlem myopathy (BM) is a disease that is caused by mutations in the collagen VI genes. It is a mildly progressive disease characterized by proximal muscle weakness and contracture of the fingers, the wrist, the elbow, and the ankle. BM is an autosomal dominant inheritance that is mainly caused by dominant COL6A1, COL6A2, or COL6A3 mutations. However, a few cases of collagen VI mutations with bilateral facial weakness and Beevor's sign have also been reported. This study presents a 50-year-old female patient with symptoms of facial weakness beginning in childhood and with the slow progression of the disease with age. At the age of 30 years, the patient presented with asymmetrical proximal muscle weakness, and the neurological examination revealed bilateral facial weakness and a positive Beevor's sign. Phosphocreatine kinase was slightly elevated with electromyography showing myopathic changes and magnetic resonance imaging (MRI) of the lower limb muscles showing the muscle MRI associated with collagen VI (COL6)-related myopathy (COL6-RM). The whole-genome sequencing technology identified the heterozygous mutation c.6817-2(IVS27)A>G in the COL6A3 gene, which was in itself a novel mutation. The present study reports yet another case of BM, which is caused by the recessive COL6A3 intron variation, widening the clinical spectrum and genetic heterogeneity of BM.
Older adults and healthcare professionals have limited awareness of the link between the Mediterranean diet and the gut microbiome for healthy aging
Authors: O’Mahony Lauren , O’Shea Emma , O’Connor Eibhlís M. , Tierney Audrey , Harkin Mary , Harrington Janas , Kennelly Sharon , Arendt Elke , O’Toole Paul W. , Timmons Suzanne
Published: January 2023

Objectives

Strategies to improve the gut microbiome through consuming an improved diet, including adopting the Mediterranean Diet (MD), may promote healthy aging. We explored older adults’ and healthcare professionals’ (HCPs) perspectives of the MD, gut health, and microbiome for their role in healthy aging.

Design

Phenomenological qualitative.

Setting

Community-dwelling older adults and HCPs in primary and secondary care in Ireland.

Participants

Older adults (aged 55 + years), recruited through social, retirement and disease-support groups. HCPs recruited through researcher networks and professional associations.

Measurements

Semi-structured 1:1 interviews and focus groups (FGs) conducted remotely with older adults and HCPs separately. Interviews/FGs were recorded, transcribed, and coded using inductive thematic analysis.

Results

Forty-seven older adults were recruited (50% male; 49% aged 60–69 years; 28% 70 +), and 26 HCPs including dietitians (n = 8); geriatricians (n = 6); clinical therapists (n = 4); nurses, pharmacists, catering managers, and meal-delivery service coordinators (n = 2 each). Older adults considered the MD “a nice way to enjoy food,” good for cardiovascular health and longevity, but with accessibility and acceptability challenges (increased salads/fish, different food environments, socio-cultural differences). HCPs felt the MD is included in healthy eating advice, but not overtly, mostly through the promotion of mixed-fiber intake. Older adults considered “live” yogurt and probiotics, and to a lesser extent fiber, to maintain a “healthy gut,” suggesting the gut has “something to do with” cognitive and digestive health. Overall, microbiota-health effects were considered “not common knowledge” among most older adults, but becoming more topical among both professionals and the public with advancing scientific communication.

Conclusion

While “gut health” was considered important, specific effects of the MD on gut microbiota, and the significance of this for healthy aging, was under-recognized. Future efforts should explain the importance to older adults of maintaining the gut microbiota through diet, while appreciating perspectives of probiotic products and supplements.
Correlation between the Warburg effect and progression of triple-negative breast cancer
Authors: Liu Shaojun , Li Yuxuan , Yuan Meng , Song Qing , Liu Min
Published: January 2023

Triple-negative breast cancer (TNBC) is ineligible for hormonal therapy and Her-2-targeted therapy due to the negative expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Although targeted therapy and immunotherapy have been shown to attenuate the aggressiveness of TNBC partially, few patients have benefited from them. The conventional treatment for TNBC remains chemotherapy. Chemoresistance, however, impedes therapeutic progress over time, and chemotherapy toxicity increases the burden of cancer on patients. Therefore, introducing more advantageous TNBC treatment options is a necessity. Metabolic reprogramming centered on glucose metabolism is considered a hallmark of tumors. It is described as tumor cells tend to convert glucose to lactate even under normoxic conditions, a phenomenon known as the Warburg effect. Similar to Darwinian evolution, its emergence is attributed to the selective pressures formed by the hypoxic microenvironment of pre-malignant lesions. Of note, the Warburg effect does not disappear with changes in the microenvironment after the formation of malignant tumor phenotypes. Instead, it forms a constitutive expression mediated by mutations or epigenetic modifications, providing a robust selective survival advantage for primary and metastatic lesions. Expanding evidence has demonstrated that the Warburg effect mediates multiple invasive behaviors in TNBC, including proliferation, metastasis, recurrence, immune escape, and multidrug resistance. Moreover, the Warburg effect-targeted therapy has been testified to be feasible in inhibiting TNBC progression. However, not all TNBCs are sensitive to glycolysis inhibitors because TNBC cells flexibly switch their metabolic patterns to cope with different survival pressures, namely metabolic plasticity. Between the Warburg effect-targeted medicines and the actual curative effect, metabolic plasticity creates a divide that must be continuously researched and bridged.
Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis
Authors: Li Jun , Zhang Yu-Rui , Ren Jia-Yu , Li Qiao-Li , Zhu Pei-Shan , Du Ting-Ting , Ge Xiao-Yan , Chen Ming , Cui Xin Wu
Published: January 2023

Purpose

The aim of this study was to investigate the diagnostic efficacy of Acoustic Radiation Force Impulse (ARFI) for benign and malignant thyroid nodules in the presence and absence of non-papillary thyroid cancer (NPTC) and to determine the cut-off values of Shear Wave Velocity (SWV) for the highest diagnostic efficacy of Virtual Touch Quantification (VTQ) and Virtual Touch Tissue Imaging and Quantification (VTIQ).

Methods

The diagnostic accuracy of ARFI for benign and malignant thyroid nodules was assessed by pooling sensitivity, specificity and area under the curve (AUC) in each group in the presence and absence of both non-papillary thyroid glands, using histology and cytology as the gold standard. All included studies were divided into two groups according to VTQ and VTIQ, and each group was ranked according to the magnitude of the SWV cutoff value to determine the SWV cutoff interval with the highest diagnostic efficacy for VTQ and VTIQ.

Results

A total of 57 studies were collected on the evaluation of ARFI for the diagnosis of benign and malignant thyroid nodules. The results showed that the presence of non-papillary thyroid carcinoma led to differences in the specificity of VTIQ for the identification of benign and malignant thyroid nodules, and the differences were statistically significant. In addition, the diagnostic efficacy of VTQ was best when the cutoff value of SWV was in the interval of 2.48-2.55 m/s, and the diagnostic efficacy of VTIQ was best when the cutoff value of SWV was in the interval of 3.01-3.15 m/s.

Conclusion

VTQ and VTIQ have a high diagnostic value for benign and malignant thyroid nodules; however, when the malignant nodules in the study contain non-papillary thyroid carcinoma occupying the thyroid gland, the findings should be viewed in a comprehensive manner.
Poly (lactic-co-glycolic acid)-encapsulated iodine-131 nanoparticles fabricated with rhTSH induce apoptosis and immobilization of thyroid cancer cells
Authors: Fan Yongzeng , Xiong Yalan , Wang Xinhong , Chen Jiahao , Fang Danzhou , Huang Jiahui , Yuan Gengbiao
Published: January 2023

Background

Aggressive thyroid carcinoma (ATC) usually loses radioiodine avidity to iodine-131 (131I) due to the downregulation of sodium/iodide symporter (NIS). The expression of thyroid stimulating hormone receptor (TSHR) is more persistent than NIS and the administration of recombinant human thyroid stimulating hormone (rhTSH) promotes de novo NIS synthesis. Hence, exploring methods integrating 131I with rhTSH might be a feasible therapeutic strategy for selective delivery of 131I into thyroid cancer to fortify the effect of radioiodine ablation.

Methods

The 131I, poly (lactic-co-glycolic acid) (PLGA) and rhTSH were used to synthesize of the 131I-PLGA-rhTSH nanoparticles. The characteristics of the 131I-PLGA-rhTSH nanoparticles was determined using a light microscopy, scanning electron microscopy (SEM), autoradiography and immunofluorescence (IF) staining. The diameter of the 131I-PLGA-rhTSH nanoparticles was measured with a Mastersizer 3000, and the encapsulation efficiency (EF) of 131I in 131I-PLGA-rhTSH nanoparticles and the radioactivity of a single nanoparticle were determined. Then, the mouse tumor xenograft model was established, and the biodistribution and effect of 131I-PLGA-rhTSH nanoparticles on apoptosis of thyroid cance cells were investigated in vivo. Thereafter, the role of 131I-PLGA-rhTSH nanoparticles in cell viability using cell counting kit-8 and lactate dehydrogenase (LDH) release assays. Subsequently, the underlying mechanism of 131I-PLGA-rhTSH nanoparticles in reducing cell viability was assessed using immunostaining, boyden invasion assays and phalloidin staining.

Results

Our results showed that the method of developing nanoparticles-encapsulated 131I using poly (lactic-co-glycolic acid) (PLGA) and modified with rhTSH (131I-PLGA-rhTSH), was a feasible avenue for the integration of 131I and rhTSH. Meanwhile, the encapsulation efficiency (EF) of 131I-PLGA-rhTSH nanoparticles was approximately 60%, and the radioactivity of a single nanoparticle was about 1.1×10-2 Bq. Meanwhile, the 131I-PLGA-rhTSH nanoparticles were selectively delivered into, gradually enriched and slowly downregulated in xenograft tumor after the administration of 131I-PLGA-rhTSH nanoparticles through tail vein in mouse tumor xenograft model. Thereafter, the tumor weight was significantly reduced after the administration of 131I-PLGA-rhTSH nanoparticles. Subsequently, the application of 131I-PLGA-rhTSH nanoparticles facilitated apoptosis and attenuated immobilization via inhibiting F-actin assembling of FTC-133 cells.

Conclusion

The present study develops a suitable approach integrating 131I and rhTSH, and this strategy is a feasible regimen enhancing the effect of radioiodine ablation for the treatment of thyroid cancer.
Identification of thioredoxin-1 as a biomarker of lung cancer and evaluation of its prognostic value based on bioinformatics analysis
Authors: Liu Xiaoting , Dong Xilin , Hu Yaxin , Fang Yanan
Published: January 2023

Background

Thioredoxin-1 (TXN), a redox balance factor, plays an essential role in oxidative stress and has been shown to act as a potential contributor to various cancers. This study evaluated the role of TXN in lung cancer by bioinformatics analyses.

Materials and methods

Genes differentially expressed in lung cancer and oxidative stress related genes were obtained from The Cancer Genome Atlas, Gene Expression Omnibus and GeneCards databases. Following identification of TXN as an optimal differentially expressed gene by bioinformatics, the prognostic value of TXN in lung cancer was evaluated by univariate/multivariate Cox regression and Kaplan–Meier survival analyses, with validation by receiver operation characteristic curve analysis. The association between TXN expression and lung cancer was verified by immunohistochemical analysis of the Human Protein Atlas database, as well as by western blotting and qPCR. Cell proliferation was determined by cell counting kit-8 after changing TXN expression using lentiviral transfection.

Results

Twenty differentially expressed oxidative stress genes were identified. Differential expression analysis identified five genes (CASP3, CAT, TXN, GSR, and HSPA4) and Kaplan–Meier survival analysis identified four genes (IL-6, CYCS, TXN, and BCL2) that differed significantly in lung cancer and normal lung tissue, indicating that TXN was an optimal differentially expressed gene. Multivariate Cox regression analysis showed that T stage (T3/T4), N stage (N2/N3), curative effect (progressive diseases) and high TXN expression were associated with poor survival, although high TXN expression was poorly predictive of overall survival. TXN was highly expressed in lung cancer tissues and cells. Knockdown of TXN suppressed cell proliferation, while overexpression of TXN enhanced cell proliferation.

Conclusion

High expression of TXN plays an important role in lung cancer development and prognosis. Because it is a prospective prognostic factor, targeting TXN may have clinical benefits in the treatment of lung cancer.
Jumonji domain-containing protein RIOX2 is overexpressed and associated with worse survival outcomes in prostate cancers
Authors: He Chenchen , Liu Wang , Sun Jiahao , Zhang Da , Li Benyi
Published: January 2023

Background

Histone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown.

Methods

Transcriptomic profiles of Jumanji domain-containing protein genes were assessed using multiple public expression datasets generated from RNA-seq and cDNA microarray assays. RIOX2 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Gene expression profiles were analyzed using the bioinformatics software R package. Western blot assay examined androgen stimulation on RIOX2 protein expression in LNCaP cells.

Results

Among 35 Jumanji domain-containing protein genes, 12 genes were significantly upregulated in prostate cancers compared to benign compartments. COX regression analysis identified that the ribosomal oxygenase 2 (RIOX2) gene was the only one significantly associated with disease-specific survival outcomes in prostate cancer patients. RIOX2 upregulation was confirmed at the protein levels using immunohistochemical assays on prostate cancer tissue sections. Meanwhile, RIOX2 upregulation was associated with clinicopathological features, including late-stage diseases, adverse Gleason scores, TP53 gene mutation, and disease-free status. In castration-resistant prostate cancers (CRPC), RIOX2 expression was positively correlated with AR signaling index but negatively correlated with the neuroendocrinal progression index. However, androgen treatment had no significant stimulatory effect on RIOX2 expression, indicating a parallel but not a causative effect of androgen signaling on RIOX2 gene expression. Further analysis discovered that RIOX2 expression was tightly correlated with its promoter hypomethylation and MYC gene expression, consistent with the notion that RIOX2 was a c-Myc target gene.

Conclusion

The Jumanji domain-containing protein RIOX2 was significantly overexpressed in prostate cancer, possibly due to c-Myc upregulation. RIOX2 upregulation was identified as an independent prognostic factor for disease-specific survival.
KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma
Authors: He Kang , Li Jingze , Huang Xuemiao , Zhao Weixin , Wang Kai , Wang Taiwei , Chen Junyu , Wang Zeyu , Yi Jiang , Zhao Shuhua , Zhao Lijing
Published: January 2023

Background

The incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC.

Methods

The mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1.

Results

KNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes.

Conclusion

KNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC.
A worldwide bibliometric analysis of malignant peripheral nerve sheath tumors from 2000 to 2022
Authors: Huang Xingfeng , Fu Zexin , Gu Qinhao , Wang Ji , Sun Yi , He Yong , Wu Sufan , Hu Xiaojie , Guo Chengrui
Published: January 2023

Background

Currently, malignant peripheral nerve sheath tumors (MPNST) are the subject of intense research interest. However, bibliometric studies have not been conducted in this field. The purpose of the study was to identify historical trends and presents a bibliometric analysis of the MPNST literature from 2000 to 2022.

Methods

For the bibliometric analysis, publications were retrieved from the Web of Science database based on the following search terms: [TI = (MPNST) OR TI= (malignant peripheral nerve sheath tumors) AND PY = (2000–2022)]. The following information was collected for each document: the publication trends and geographical distribution, important authors and collaboration, keyword distribution and evaluation, most popular journals, and most influential articles.

Results

We included 1400 documents for bibliometric analysis, covering five categories: 824 articles, 17 proceedings papers, 68 letters, 402 meeting abstracts, and 89 reviews. Corrections, editorials, book chapters, data papers, publications with expressed concerns, and retractions were excluded from our research.

Conclusion

Since 2000, the number of publications on MPNST has continuously increased. Among all countries that contributed to the MPNST research, the USA, Japan, and China were the three most productive countries. The journal Modern Pathology has the most publications on MPNST, while those in the Cancer Research journal were the most frequently cited. The University of Texas MD Anderson Cancer Center may be a good partner to collaborate with. Recent research trends in MPNST have focused on tumorigenesis, clinical management, and predictive biomarkers.
MRI-LINAC: A transformative technology in radiation oncology
Authors: Ng John , Gregucci Fabiana , Pennell Ryan T. , Nagar Himanshu , Golden Encouse B. , Knisely Jonathan P. S. , Sanfilippo Nicholas J. , Formenti Silvia C.
Published: January 2023

Advances in radiotherapy technologies have enabled more precise target guidance, improved treatment verification, and greater control and versatility in radiation delivery. Amongst the recent novel technologies, Magnetic Resonance Imaging (MRI) guided radiotherapy (MRgRT) may hold the greatest potential to improve the therapeutic gains of image-guided delivery of radiation dose. The ability of the MRI linear accelerator (LINAC) to image tumors and organs with on-table MRI, to manage organ motion and dose delivery in real-time, and to adapt the radiotherapy plan on the day of treatment while the patient is on the table are major advances relative to current conventional radiation treatments. These advanced techniques demand efficient coordination and communication between members of the treatment team. MRgRT could fundamentally transform the radiotherapy delivery process within radiation oncology centers through the reorganization of the patient and treatment team workflow process. However, the MRgRT technology currently is limited by accessibility due to the cost of capital investment and the time and personnel allocation needed for each fractional treatment and the unclear clinical benefit compared to conventional radiotherapy platforms. As the technology evolves and becomes more widely available, we present the case that MRgRT has the potential to become a widely utilized treatment platform and transform the radiation oncology treatment process just as earlier disruptive radiation therapy technologies have done.
Development of a TGF-β signaling-related genes signature to predict clinical prognosis and immunotherapy responses in clear cell renal cell carcinoma
Authors: Wu Xin , Xie Wenjie , Gong Binbin , Fu Bin , Chen Weimin , Zhou Libo , Luo Lianmin
Published: January 2023

Background

Transforming growth factor (TGF)-β signaling is strongly related to the development and progression of tumor. We aimed to construct a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical prognosis and immunotherapy responses of patients with clear cell renal cell carcinoma (ccRCC).

Methods

The gene expression profiles and corresponding clinical information of ccRCC were collected from the TCGA and the ArrayExpress (E-MTAB-1980) databases. LASSO, univariate and multivariate Cox regression analyses were conducted to construct a prognostic signature in the TCGA cohort. The E-MTAB-1980 cohort were used for validation. Kaplan-Meier (K-M) survival and time-dependent receiver operating characteristic (ROC) were conducted to assess effectiveness and reliability of the signature. The differences in gene enrichments, immune cell infiltration, and expression of immune checkpoints in ccRCC patients showing different risks were investigated.

Results

We constructed a seven gene (PML, CDKN2B, COL1A2, CHRDL1, HPGD, CGN and TGFBR3) signature, which divided the ccRCC patients into high risk group and low risk group. The K-M analysis indicated that patients in the high risk group had a significantly shorter overall survival (OS) time than that in the low risk group in the TCGA (p < 0.001) and E-MTAB-1980 (p = 0.012). The AUC of the signature reached 0.77 at 1 year, 0.7 at 3 years, and 0.71 at 5 years in the TCGA, respectively, and reached 0.69 at 1 year, 0.72 at 3 years, and 0.75 at 5 years in the E-MTAB-1980, respectively. Further analyses confirmed the risk score as an independent prognostic factor for ccRCC (p < 0.001). The results of ssGSEA that immune cell infiltration degree and the scores of immune-related functions were significantly increased in the high risk group. The CIBERSORT analysis indicated that the abundance of immune cell were significantly different between two risk groups. Furthermore, The risk score was positively related to the expression of PD-1, CTLA4 and LAG3.These results indicated that patients in the high risk group benefit more from immunotherapy.

Conclusion

We constructed a novel TGF-β signaling-related genes signature that could serve as an promising independent factor for predicting clinical prognosis and immunotherapy responses in ccRCC patients.
Serology reveals micro-differences in Plasmodium falciparum transmission in the Hohoe municipality of Ghana
Authors: Kyei-Baafour Eric , Kusi Kwadwo A. , Oppong Mavis , Frempong Abena F. , Aculley Belinda , Ofori Ebenezer A. , Theisen Michael , Kweku Margaret , Adu Bright , Hviid Lars , Ofori Michael F.
Published: January 2023

Background

With the decline in malaria transmission due to global efforts, a more sensitive tool is needed to monitor transmission intensity and pattern at the micro-level. Though transmission in a broader area may be similar, factors such as sanitation, practices of open water storage, early morning and evening activities, outdoor sleeping and agricultural practices within communities could cause differences in exposure and thus transmission. This study thus probed malaria transmission at a micro-level using serology in the Hohoe Municipality of Ghana.

Methods

This cross-sectional study involved 327 asymptomatic children aged 1-12 years in both rural (196) and urban (131) communities in the Hohoe municipality. Total IgG responses specific for three P. falciparum antigens (CSP, MSP2-FC27, MSP2-3D7) were determined in plasma eluted from dried blood spots using indirect ELISA.

Results

A higher proportion of individuals in the rural area had parasites by both microscopy and PCR. Total IgG levels and seroprevalence were higher in rural compared to urban communities (p<0.05). In a multiple regression model, adjusting for confounders, levels of PfMSP2-3D7-specific IgG was associated with the higher transmission which occurs in the rural community.

Conclusion

The results suggest that though the district is categorized as having medium malaria transmission, differences within settlements may influence malaria transmission reflecting in antibody levels and prevalence of malaria antigen-specific IgG.