bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and functional characteristics of soil microbial communities in response to different ecological risk levels of heavy metals
Authors: Li Dale , Chen Jianwen , Zhang Xiujuan , Shi Wei , Li Junjian
Published: December 2022

Objective

The potential ecological risk index (RI) is the most commonly used method to assess heavy metals (HMs) contamination in soils. However, studies have focused on the response of soil microorganisms to different concentrations, whereas little is known about the responses of the microbial community structures and functions to HMs at different RI levels.

Methods

Here, we conducted soil microcosms with low (L), medium (M) and high (H) RI levels, depending on the Pb and Cd concentrations, were conducted. The original soil was used as the control (CK). High-throughput sequencing, qPCR, and Biolog plate approaches were applied to investigate the microbial community structures, abundance, diversity, metabolic capacity, functional genes, and community assembly processes.

Result

The abundance and alpha diversity indices for the bacteria at different RI levels were significantly lower than those of the CK. Meanwhile, the abundance and ACE index for the fungi increased significantly with RI levels. Acidobacteria, Basidiomycota and Planctomycetes were enriched as the RI level increased. Keystone taxa and co-occurrence pattern analysis showed that rare taxa play a vital role in the stability and function of the microbial community at different RI levels. Network analysis indicates that not only did the complexity and vulnerability of microbial community decrease as risk levels increased, but that the lowest number of keystone taxa was found at the H level. However, the microbial community showed enhanced intraspecific cooperation to adapt to the HMs stress. The Biolog plate data suggested that the average well color development (AWCD) reduced significantly with RI levels in bacteria, whereas the fungal AWCD was dramatically reduced only at the H level. The functional diversity indices and gene abundance for the microorganisms at the H level were significantly lower than those the CK. In addition, microbial community assembly tended to be more stochastic with an increase in RI levels.

Conclusion

Our results provide new insight into the ecological impacts of HMs on the soil microbiome at different risk levels, and will aid in future risk assessments for Pb and Cd contamination.
Analysis on the interactions between the first introns and other introns in mitochondrial ribosomal protein genes
Authors: Li Ruifang , Song Xinwei , Gao Shan , Peng Shiya
Published: December 2022

It is realized that the first intron plays a key role in regulating gene expression, and the interactions between the first introns and other introns must be related to the regulation of gene expression. In this paper, the sequences of mitochondrial ribosomal protein genes were selected as the samples, based on the Smith-Waterman method, the optimal matched segments between the first intron and the reverse complementary sequences of other introns of each gene were obtained, and the characteristics of the optimal matched segments were analyzed. The results showed that the lengths and the ranges of length distributions of the optimal matched segments are increased along with the evolution of eukaryotes. For the distributions of the optimal matched segments with different GC contents, the peak values are decreased along with the evolution of eukaryotes, but the corresponding GC content of the peak values are increased along with the evolution of eukaryotes, it means most introns of higher organisms interact with each other though weak bonds binding. By comparing the lengths and matching rates of optimal matched segments with those of siRNA and miRNA, it is found that some optimal matched segments may be related to non-coding RNA with special biological functions, just like siRNA and miRNA, they may play an important role in the process of gene expression and regulation. For the relative position of the optimal matched segments, the peaks of relative position distributions of optimal matched segments are increased during the evolution of eukaryotes, and the positions of the first two peaks exhibit significant conservatism.
DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians
Authors: Lim Eun-Cheon , Choi Uk-Su , Choi Kyu Yeong , Lee Jang Jae , Sung Yul-Wan , Ogawa Seiji , Kim Byeong Chae , Lee Kun Ho , Gim Jungsoo ,   for The Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer’s and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer’s disease.
Comparison of cytokine/chemokine profiles between dermatomyositis and anti-synthetase syndrome
Authors: Wang Yikang , Zheng Yiming , Zhao Yawen , Liu Yilin , Zhang Wenhao , Yu Meng , Xie Zhiying , Hao Hongjun , Gao Feng , Zhang Wei , Wang Zhaoxia , Yuan Yun
Published: December 2022

Objectives

Dermatomyositis (DM) and anti-synthetase syndrome (ASS) are autoimmune diseases with multisystem involvement. Despite sharing some clinical and myopathological features, these are two diseases with different pathogeneses and prognoses. We aimed to clarify and compare cytokine/chemokine profiles in both disorders, which may help in the differential diagnosis.

Materials and methods

We collected clinical data and serum samples of consecutive patients with DM and ASS. Quantibody® Human Inflammation Array 3 for cytokines/chemokines was performed in the serum of all participants. Receiver operating characteristic analysis with the area under the curve and Youden's index were performed.

Results

Eight newly diagnosed and treatment-naïve patients with DM, nine newly diagnosed and treatment-naïve patients with ASS, and 14 healthy controls were enrolled. Serum C-C motif chemokine ligand (CCL) 2, CCL4, C-X-C motif chemokine ligand (CXCL) 13, and tumor necrosis factor receptor 2 (TNFR2) were increased in patients with both DM and ASS. Serum interleukin (IL)-1 receptor type 1 (IL-1ra), IL-1b, CCL1, CXCL11, and CCL3 were modulated in patients with DM only, and IL-8, CXCL9, and tissue inhibitors of metalloproteinases-1 (TIMP-1) in patients with ASS only. Serum CCL2, CXCL13, and TNFR2 accurately distinguished patients with DM and ASS from healthy controls, as shown by the area under the curve >0.80. Moreover, receiver operating characteristic analysis showed that, as biomarkers for discrimination between DM and ASS, the combination of IL-1ra and TIMP-1, had an area under the curve of 0.944, a sensitivity of 87.5%, and a specificity of 88.9%.

Conclusion

Our study demonstrated that serum levels of cytokines/chemokines showed a different pattern in newly diagnosed patients with DM and ASS, in which serum IL-1ra and TIMP-1 could be used to distinguish between the two diseases.
Integration of structural brain networks is related to openness to experience: A diffusion MRI study with CSD-based tractography
Authors: Talaei Nima , Ghaderi Amirhossein
Published: December 2022

Openness to experience is one of the big five traits of personality which recently has been the subject of several studies in neuroscience due to its importance in understanding various cognitive functions. However, the neural basis of openness to experience is still unclear. Previous studies have found largely heterogeneous results, suggesting that various brain regions may be involved in openness to experience. Here we suggested that performing structural connectome analysis may shed light on the neural underpinnings of openness to experience as it provides a more comprehensive look at the brain regions that are involved in this trait. Hence, we investigated the involvement of brain network structural features in openness to experience which has not yet been explored to date. The magnetic resonance imaging (MRI) data along with the openness to experience trait score from the self-reported NEO Five-Factor Inventory of 100 healthy subjects were evaluated from Human Connectome Project (HCP). CSD-based whole-brain probabilistic tractography was performed using diffusion-weighted images as well as segmented T1-weighted images to create an adjacency matrix for each subject. Using graph theoretical analysis, we computed global efficiency (GE) and clustering coefficient (CC) which are measures of two important aspects of network organization in the brain: functional integration and functional segregation respectively. Results revealed a significant negative correlation between GE and openness to experience which means that the higher capacity of the brain in combining information from different regions may be related to lower openness to experience.
Dairy consumption and risk of esophagus cancer in the prostate, lung, colorectal, and ovarian cohort
Authors: Wang Tingting , Zhu Yi , Zheng Yuanzhu , Cao Yang , Xu Qin , Wang Xiangan , Hu Wenli , Zhang Yun
Published: December 2022

Background

Epidemiological studies provide limited information on the relationship between dairy consumption and the incidence of esophagus cancer (EC). We examined whether eating dairy foods is associated with a lower risk of EC in an American population.

Methods

In our study, we analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, which included 101,723 subjects. Dairy product consumption was assessed using a dietary history questionnaire. We used Cox regression and restricted cubic splines to assess whether dairy consumption is associated with EC incidence.

Results

A total of 154 EC cases were identified after a median follow-up of 12.2 years. After adjusting for confounders, we discovered no statistically significant correlation between total dairy product consumption and EC risk (HR with 95% CI for ≥1.79 servings/day vs. ≤0.6 servings/day: 0.83, 0.50–1.38; p for trend = 0.465). Additionally, no associations were found between EC risk and other dairy foods such as milk, yogurt, and cheese.

Conclusion

We concluded that the findings of the PLCO cohort do not suggest dairy consumption reduces the risk of EC.
Coffee intake may promote sudomotor function activation via the contribution of caffeine
Authors: Kwon Ryeo-Won , Park Jin-Sun , Lee Ha-Gyoung , Park Jong-In , Choo Eon-Ah , Lee Seung-Jea , Lee Jeong-Beom
Published: December 2022

Objectives

To determine whether drinking coffee with caffeine accelerates the sympathetic response to acetylcholine (ACh).

Methods

Tests were performed twice at 1-week intervals following the intake of coffee. Subjects were randomly divided into two groups: Group A was administered 16 fluid oz of water (CON), while Group B was given 16 fluid oz of coffee (Coffee). After 1 week, Group A was administered 16 fluid oz of coffee (Coffee), while Group B was given 16 fluid oz of water (CON). The quantitative sudomotor axon reflex test (QSART) was performed after intake of coffee and water and a 40 min break. QSART with iontophoresis and 10% ACh was performed to determine axon reflex (AXR) mediated with and without iontophoresis [AXR (1) and AXR (2), respectively], and directly activated sweating (DIR).

Results

The sweat onset time of the AXR was shorter in the Coffee compared with the CON (p < 0.05). The sweat rates in AXR (1) AXR (2) and DIR were significantly higher in the Coffee than in the CON (p < 0.05, p < 0.05, p < 0.01, respectively). In addition, the Coffee showed significantly higher density of activated sweat glands and activated sweat gland output than the CON (p < 0.05, p < 0.01, respectively). The overall results of this study showed that coffee intake could stimulate higher activation in both AXR and DIR sweat responses.

Conclusion

Coffee intake can improve sweating sensitivity in both the AXR and DIR by the contribution of caffeine contained in coffee. This suggests that other compounds in coffee may not inhibit the sympathetic response to ACh. Therefore, coffee may be clinically worth considering as a supplement for the activation of the cholinergic and sudomotor function.
Computational screening for new neuroprotective ingredients against Alzheimer's disease from bilberry by cheminformatics approaches
Authors: Xiao Ran , Liang Rui , Cai Yun-hui , Dong Jie , Zhang Lin
Published: December 2022

Bioactive ingredients from natural products have always been an important resource for the discovery of drugs for Alzheimer's disease (AD). Senile plaques, which are formed with amyloid-beta (Aβ) peptides and excess metal ions, are found in AD brains and have been suggested to play an important role in AD pathogenesis. Here, we attempted to design an effective and smart screening method based on cheminformatics approaches to find new ingredients against AD from Vaccinium myrtillus (bilberry) and verified the bioactivity of expected ingredients through experiments. This method integrated advanced artificial intelligence models and target prediction methods to realize the stepwise analysis and filtering of all ingredients. Finally, we obtained the expected new compound malvidin-3-O-galactoside (Ma-3-gal-Cl). The in vitro experiments showed that Ma-3-gal-Cl could reduce the OH· generation and intracellular ROS from the Aβ/Cu2+/AA mixture and maintain the mitochondrial membrane potential of SH-SY5Y cells. Molecular docking and Western blot results indicated that Ma-3-gal-Cl could reduce the amount of activated caspase-3 via binding with unactivated caspase-3 and reduce the expression of phosphorylated p38 via binding with mitogen-activated protein kinase kinases-6 (MKK6). Moreover, Ma-3-gal-Cl could inhibit the Aβ aggregation via binding with Aβ monomer and fibers. Thus, Ma-3-gal-Cl showed significant effects on protecting SH-SY5Y cells from Aβ/Cu2+/AA induced damage via antioxidation effect and inhibition effect to the Aβ aggregation.
The effects of three weight management methods on body composition and serum lipids of overweight and obese people
Authors: Cai Jingjing , Shao Lin , Zhao Shilong , Liu Wen , Liu Peng
Published: December 2022

Introduction

Obesity has become a major health problem worldwide. Diet management is an important means of weight loss. The aim of this study was to explore the improvement effect of a calorie-restricted diet (CRD), 5 + 2 intermittent fasting (5 + 2 IF), and high protein diet (HPD) on weight composition and serum lipid level of overweight and obese people in a short period (3 months).

Methods

Fifty-three participants aged 18–60 years and with body mass index (BMI) ranging from 24 to 35 kg/m2 were screened for inclusion and exclusion criteria and were randomly divided into three groups, i.e., CRD, 5 + 2 IF, and HPD. Basic information, body composition, and venous blood samples were collected at baseline and after 3 months of intervention. Body composition was measured using a body composition analyzer (SK-V9), and serum lipids were assayed using the Roche Cobas e702 automatic biochemistry analysis system. The generalized estimating equation (GEE) was used to analyze and compare the repeated measurements of body composition and levels of serum lipids.

Results

The results showed that total weight, BMI, body fat mass, muscle mass, visceral fat index, and waist and hip circumferences had significantly decreased in all three groups after 3 months of intervention, and the average weight loss was 3.3 ± 1.14, 4.12 ± 0.05, and 2.62 ± 0.13 kg in CRD, 5 + 2 IF, and HPD groups, respectively. The results of the GEE model indicated that compared with the CRD group, the 5 + 2 IF group showed a more significant decrease in weight (β = −0.272, P < 0.001), BMI (β = −0.091, P < 0.001), body fat mass (β = −0.172, P < 0.001), muscle (β = −0.043, P < 0.001), and visceral fat index (β = −0.019, P < 0.001), however, HPD has more advantages in visceral fat index loss (β = −0.011, P < 0.001) and lean body mass preserve (β = 0.229, P < 0.001).

Conclusion

Our findings showed that the 5 + 2 IF may be more effective in reducing total weight and body fat, and HPD may be more helpful in preventing lean body mass loss during a short-term weight loss intervention.
The relationship between nutrition and the immune system
Authors: Munteanu Camelia , Schwartz Betty
Published: December 2022

Nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to immune cells. There are a large number of micronutrients, such as minerals, and vitamins, as well as some macronutrients such as some amino acids, cholesterol and fatty acids demonstrated to exert a very important and specific impact on appropriate immune activity. This review aims to summarize at some extent the large amount of data accrued to date related to the modulation of immune function by certain micro and macronutrients and to emphasize their importance in maintaining human health. Thus, among many, some relevant case in point examples are brought and discussed: (1) The role of vitamin A/all-trans-retinoic-acids (ATRA) in acute promyelocytic leukemia, being this vitamin utilized as a very efficient therapeutic agent via effective modulation of the immune function (2) The involvement of vitamin C in the fight against tumor cells via the increase of the number of active NK cells. (3) The stimulation of apoptosis, the suppression of cancer cell proliferation, and delayed tumor development mediated by calcitriol/vitamin D by means of immunity regulation (4) The use of selenium as a cofactor to reach more effective immune response to COVID vaccination (5). The crucial role of cholesterol to regulate the immune function, which is demonstrated to be very sensitive to the variations of this macronutrient concentration. Other important examples are reviewed as well.
Benign gallbladder disease is a risk factor for colorectal cancer, but cholecystectomy is not: A propensity score matching analysis
Authors: Qin Qiong , Li Wei , Ren Ao , Luo Rong , Luo Shiqiao
Published: December 2022

Background

Previous studies reported controversial results on the relationship between cholecystectomy (CHE) and colorectal cancer (CRC). We hypothesized that gallbladder disease (GBD), instead of cholecystectomy, increased the risk of CRC. We aimed to investigate the incidence of benign gallbladder disease (BGBD) and CHE in CRC patients and local adults undergoing annual health examination by analyzing large data from a tertiary hospital in southwest China.

Methods

A propensity score matching (PSM) analyzed, retrospective study from January 1, 2013, to August 31, 2020, including 7,471 pathologically confirmed CRC patients and 860,160 local annual health examination adults in the First Affiliated Hospital of Chongqing Medical University, was conducted. The prevalence of BGBD and the CHE rate were analyzed before and after a 1:1 PSM.

Results

Of the 7,471 CRC patients, 7,160 were eligible for the case group. In addition, 860,160 local health examination adults were included for comparison. The incidence of BGBD was higher in the CRC patients than in the local adults (19.2% vs. 11.3%, P < 0.001), but no significant difference in CHE rate existed between the case group and the control group (5.0% vs. 4.8%, P = 0.340). In the subgroup analysis, patients with BGBD had a higher risk of colon cancer than rectal cancer (20.4% vs. 18.2%, P = 0.024) and more significantly in the right colon (P = 0.037). A weakly positive correlation between CHE and right colon cancer was observed before PSM but no longer existed after PSM (P = 0.168).

Conclusions

Benign gallbladder disease was positively correlated with colorectal cancer, especially right colon cancer. Cholecystectomy did not increase the risk of colorectal cancer.
Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis
Authors: Palmerini Emanuela , Sanfilippo Roberta , Grignani Giovanni , Buonadonna Angela , Romanini Antonella , Badalamenti Giuseppe , Ferraresi Virginia , Vincenzi Bruno , Comandone Alessandro , Pizzolorusso Antonio , Brunello Antonella , Gelsomino Fabio , De Pas Tommaso , Ibrahim Toni , Gurrieri Lorena , Grosso Federica , Zanelli Francesca , Pantaleo Maria Abbondanza , Milesi Laura , Ciuffreda Libero , Ferrari Vittorio , Marchesi Emanuela , Quattrini Irene , Righi Alberto , Setola Elisabetta , Carretta Elisa , Casali Paolo G. , Picci Piero , Ferrari Stefano
Published: December 2022

Background

Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).

Methods

A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.

Results

Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).

Conclusions

Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.
Prognostic values of ALDOB expression and 18F-FDG PET/CT in hepatocellular carcinoma
Authors: Jia Wenzhi , Wu Qianyun , Yu Xiaofeng , Shen Mengqin , Zhang Ruixue , Li Jiajin , Zhao Li , Huang Gang , Liu Jianjun
Published: December 2022

Purpose

The glycolytic enzyme fructose 1,6-bisphosphate aldolase B (ALDOB) is aberrantly expressed and impacts the prognosis in hepatocellular carcinoma (HCC). Hepatic ALDOB loss leads to paradoxical upregulation of glucose metabolism, favoring hepatocellular carcinogenesis. Nevertheless, the relationship between ALDOB expression and 18F-fluorodeoxyglucose (18F-FDG) uptake, and their effects on HCC prognosis remain unclear. We evaluated whether ALDOB expression is associated with 18F-FDG uptake and their impacts on HCC prognosis prediction.

Methods

Changes in ALDOB expression levels and the prognostic values in HCC were analyzed using data from The Cancer Genome Atlas (TCGA) database. Ultimately, 34 patients with HCC who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) preoperatively were enrolled in this retrospective study. ALDOB expression was determined using immunohistochemistry (IHC) staining, and the maximum standardized uptake value (SUVmax) of HCC was calculated from the 18F-FDG PET/CT scans. The relationship between ALDOB expression and SUVmax was examined, and their impacts on overall survival were evaluated using Cox proportional hazards models and Kaplan–Meier survival analysis. ALDOB overexpression in HUH7 and 7721 cells was used to analyze its role in tumor metabolism.

Results

According to TCGA database, the ALDOB mRNA level was downregulated in HCC compared to normal tissue, and significantly shortened overall survival in HCC patients. ALDOB protein expression was similarly decreased in IHC findings in HCC than that in adjacent normal tissues (P<0.05) and was significantly associated with tumor size (P<0.001), high tumor-node-metastasis stage (P=0.022), and elevated SUVmax (P=0.009). ALDOB expression in HCC was inversely correlated with SUVmax (r=-0.454; P=0.012), and the optimal SUVmax cutoff value for predicting its expression was 4.15. Prognostically, low ALDOB expression or SUVmax ≥3.9 indicated shorter overall survival time in HCC. Moreover, COX regression analysis suggested high SUVmax as an independent prognostic risk factor for HCC (P=0.036). HCC patients with negative ALDOB expression and positive SUVmax (≥3.9) were correlated with worse prognosis. ALDOB overexpression in HCC cells significantly decreases 18F-FDG uptake and lactate production.

Conclusion

SUVmax in HCC patients is inversely correlated with ALDOB expression, and 18F-FDG PET/CT may be useful for ALDOB status prediction. The combined use of ALDOB expression and 18F-FDG PET/CT data can provide additional information on disease prognosis in HCC patients.
Establishment and experimental validation of a novel cuproptosis-related gene signature for prognostic implication in cholangiocarcinoma
Authors: Chen Jialu , Yu Xiaopeng , Tong Huanjun , Tang Chengwei , Tang Zhaohui
Published: December 2022

Background

Cholangiocarcinoma (CCA) is a highly malignant, heterogeneous bile duct malignancy with poor treatment options. A novel type of cell death termed cuproptosis was recently demonstrated to closely correlate with tumor progression. To gain more insight into the role of cuproptosis in CCA, we investigated the prognostic implications of cuproptosis related genes (CRGs) and their relationship to the development of CCA.

Methods

Gene expression data for CCA were obtained from the European Bioinformatics Institute (EMBL-EBI) database. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression was used to construct a prognostic risk model based on CRGs. RNA-seq, qRT−PCR and immunohistochemistry staining were used to verify the expression of CRGs in human CCA tissues or cell lines. Further in vitro experiments were performed to demonstrate the role of cuproptosis in CCA.

Results

We established a 4-gene signature (ATP7A, FDX1, DBT and LIAS) that exhibited good stability and was an independent prognostic factor for CCA. Seventy-five CCA samples were divided into high- and low-risk groups based on the risk score. Enrichment analysis revealed increased extracellular activity in the high-risk group and increased lipid metabolic activity in the low-risk group. Moreover, the 4 signature genes were verified in clinical samples and cell lines by RNA-seq, qRT−PCR and immunohistochemistry. Further experiments confirmed that cuproptosis can significantly inhibit the viability of CCA cells. Knockdown of the key gene LIAS ameliorated the toxicity of cuproptosis to CCA cells.

Conclusion

We established a 4-gene prognostic signature based on cuproptosis and explored the role of cuproptosis in CCA. The results provide an effective indicator for predicting the prognosis of cuproptosis in CCA.
A prognostic model and immune regulation analysis of uterine corpus endometrial carcinoma based on cellular senescence
Authors: Gao Lulu , Wang Xiangdong , Wang Xuehai , Wang Fengxu , Tang Juan , Ji Jinfeng
Published: December 2022

Background

This study aimed to explore the clinical significance of cellular senescence in uterine corpus endometrial carcinoma (UCEC).

Methods

Cluster analysis was performed on GEO data and TCGA data based on cellular senescence related genes, and then performed subtype analysis on differentially expressed genes between subtypes. The prognostic model was constructed using Lasso regression. Survival analysis, microenvironment analysis, immune analysis, mutation analysis, and drug susceptibility analysis were performed to evaluate the practical relevance. Ultimately, a clinical nomogram was constructed and cellular senescence-related genes expression was investigated by qRT-PCR.

Results

We ultimately identified two subtypes. The prognostic model divides patients into high-risk and low-risk groups. There were notable discrepancies in prognosis, tumor microenvironment, immunity, and mutation between the two subtypes and groups. There was a notable connection between drug-sensitive and risk scores. The nomogram has good calibration with AUC values between 0.75-0.8. In addition, cellular senescence-related genes expression was investigated qRT-PCR.

Conclusion

Our model and nomogram may effectively forecast patient prognosis and serve as a reference for patient management.
Canadian perspectives in multiple myeloma on the use of steroids in clinical practice based on patient and healthcare provider interviews
Authors: McKenzie Farah , Gazzé Gabriel , Hewitt Joanne , Kolm Kari , Pollock Debra , Rowland Suzanne , Crosbie Tina
Published: December 2022

Corticosteroid (steroid) medications are associated with challenging adverse effects that can negatively impact patient quality of life. However, owing to a long legacy of effective use in treatment protocols, they remain a cornerstone of multiple myeloma (MM) care. We conducted a roundtable with Canadian healthcare providers (HCPs) with diverse healthcare backgrounds and involvement in MM care as well as with patients with MM. Our goal was to develop clear guidance for steroid management aimed at improving patient quality of life, taking into account patient perspective and experiences with managing the disease. Our recommendations, which are based on the insights acquired from this discussion, can be categorized to the following areas: steroid prescribing, dosing, and modifications; managing adverse effects; and patient-HCP communication. These recommendations can be used by the entire multi-disciplinary hematology team to improve patient quality of life while being treated with steroid medication for multiple myeloma.
Lymph node yield less than 12 is not a poor predictor of survival in locally advanced rectal cancer after laparoscopic TME following neoadjuvant chemoradiotherapy
Authors: Yang Hong , Xing Jiadi , Zhang Chenghai , Yao Zhendan , Wu Xiuxiu , Jiang Beihai , Cui Ming , Su Xiangqian
Published: December 2022

Purpose

Previous studies have confirmed that neoadjuvant chemoradiotherapy (nCRT) may reduce the number of lymph nodes retrieved in rectal cancer. However, it is still controversial whether it is necessary to harvest at least 12 lymph nodes for locally advanced rectal cancer (LARC) patients who underwent nCRT regardless of open or laparoscopic surgery. This study was designed to evaluate the relationship between lymph node yield (LNY) and survival in LARC patients who underwent laparoscopic TME following nCRT.

Methods

Patients with LARC who underwent nCRT followed by laparoscopic TME were retrospectively analyzed. The relationship between LNY and survival of patients was evaluated, and the related factors affecting LNY were explored. To further eliminate the influence of imbalance of clinicopathological features on prognosis between groups, propensity score matching was conducted.

Results

A total of 257 consecutive patients were included in our study. The median number of LNY was 10 (7 to 13) in the total cohort. There were 98 (38.1%) patients with 12 or more lymph nodes harvested (LNY ≥12 group), and 159 (61.9%) patients with fewer than 12 lymph nodes retrieved (LNY <12 group). There was nearly no significant difference between the two groups in clinicopathologic characteristics and surgical outcomes except that the age of LNY <12 group was older (P<0.001), and LNY <12 group tended to have more TRG 0 cases (P<0.060). However, after matching, when 87 pairs of patients obtained, the clinicopathological features were almost balanced between the two groups. After a median follow-up of 65 (54 to 75) months, the 5-year OS was 83.9% for the LNY ≥12 group and 83.6% for the LNY <12 group (P=0.893), the 5-year DFS was 78.8% and 73.4%, respectively (P=0.621). Multivariate analysis showed that only patient age, TRG score and ypN stage were independent factors affecting the number of LNY (all P<0.05). However, no association was found between LNY and laparoscopic surgery-related factors.

Conclusions

For LARC patients who underwent nCRT followed by laparoscopic TME, the number of LNY less than 12 has not been proved to be an adverse predictor for long-term survival. There was no correlation between LNY and laparoscopic surgery-related factors.
Machine-learning based investigation of prognostic indicators for oncological outcome of pancreatic ductal adenocarcinoma
Authors: Chang Jeremy , Liu Yanan , Saey Stephanie A. , Chang Kevin C. , Shrader Hannah R. , Steckly Kelsey L. , Rajput Maheen , Sonka Milan , Chan Carlos H. F.
Published: December 2022

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Surgical resection remains the only potential curative treatment option for early-stage resectable PDAC. Patients with locally advanced or micrometastatic disease should ideally undergo neoadjuvant therapy prior to surgical resection for an optimal treatment outcome. Computerized tomography (CT) scan is the most common imaging modality obtained prior to surgery. However, the ability of CT scans to assess the nodal status and resectability remains suboptimal and depends heavily on physician experience. Improved preoperative radiographic tumor staging with the prediction of postoperative margin and the lymph node status could have important implications in treatment sequencing. This paper proposes a novel machine learning predictive model, utilizing a three-dimensional convoluted neural network (3D-CNN), to reliably predict the presence of lymph node metastasis and the postoperative positive margin status based on preoperative CT scans.

Methods

A total of 881 CT scans were obtained from 110 patients with PDAC. Patients and images were separated into training and validation groups for both lymph node and margin prediction studies. Per-scan analysis and per-patient analysis (utilizing majority voting method) were performed.

Results

For a lymph node prediction 3D-CNN model, accuracy was 90% for per-patient analysis and 75% for per-scan analysis. For a postoperative margin prediction 3D-CNN model, accuracy was 81% for per-patient analysis and 76% for per-scan analysis.

Discussion

This paper provides a proof of concept that utilizing radiomics and the 3D-CNN deep learning framework may be used preoperatively to improve the prediction of positive resection margins as well as the presence of lymph node metastatic disease. Further investigations should be performed with larger cohorts to increase the generalizability of this model; however, there is a great promise in the use of convoluted neural networks to assist clinicians with treatment selection for patients with PDAC.
Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer
Authors: Spira Alexander , Awada Ahmad , Isambert Nicolas , Lorente David , Penel Nicolas , Zhang Yue , Ojalvo Laureen S. , Hicking Christine , Rolfe P. Alexander , Ihling Christian , Dussault Isabelle , Locke George , Borel Christian
Published: December 2022

Background

We report the clinical activity, safety, and identification of a predictive biomarker for bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβRII (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1, in patients with advanced triple-negative breast cancer (TNBC).

Methods

In this expansion cohort of a global phase 1 study, patients with pretreated, advanced TNBC received bintrafusp alfa 1200 mg every 2 weeks intravenously until disease progression, unacceptable toxicity, or withdrawal. The primary objective was confirmed best overall response by RECIST 1.1 assessed per independent review committee (IRC).

Results

As of May 15, 2020, a total of 33 patients had received bintrafusp alfa, for a median of 6.0 (range, 2.0-48.1) weeks. The objective response rate was 9.1% (95% CI, 1.9%-24.3%) by IRC and investigator assessment. The median progression-free survival per IRC was 1.3 (95% CI, 1.2-1.4) months, and median overall survival was 7.7 (95% CI, 2.1-10.9) months. Twenty-five patients (75.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 patients (15.2%); no patients had a grade 4 TRAE. There was 1 treatment-related death (dyspnea, hemolysis, and thrombocytopenia in a patient with extensive disease at trial entry). Responses occurred independently of PD-L1 expression, and tumor RNAseq data identified HMGA2 as a potential biomarker of response.

Conclusions

Bintrafusp alfa showed clinical activity and manageable safety in patients with heavily pretreated advanced TNBC. HMGA2 was identified as a potential predictive biomarker of response.

ClinicalTrials.gov identifier

NCT02517398
Necrotizing pneumonia and purulent meningitis caused by bloodstream infection of CA-MRSA in a child: A rare case report
Authors: Li Peng , Dai Lizhong , Yuan Ke , Song Chunlan , Cheng Yibing , Jing Yu , Chen Na , Cui Junhao , Wang Yangji , Fu Shuqin
Published: December 2022

Case presentation

We report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.

Symptoms and signs

The patient experienced a rapid onset of symptoms with fever, vomiting, and convulsions. Upon physical examination on admission, she presented with the following: temperature 38.6°C; pulse 185 beats/min; respiration 49 beats/min; blood pressure 89/51 mmHg; drowsiness; piebald skin all over her body; rice-grain-sized pustular rashes scattered on the front chest and both lower limbs, protruding from the surface of the skin; bilateral pupils that were equal in size and a circle with a diameter of about 3.0 mm, and slow light reflex; cyanotic lips; shortness of breath; positive for the three-concave sign; a small amount of phlegm that could be heard in both lungs; capillary refill time of 5 s; cold extremities; and a positive Babinski sign.

Diagnostic method

A chest computed tomography scan showed multiple nodular and flake-like high-density shadows of varying sizes in each lobe in bilateral lungs, and a cavity with blurred edges could be seen in some nodules. A cranial magnetic resonance imaging examination demonstrated that the hyperintensity of diffusion-weighted imaging could be observed on the left cerebellar hemisphere and left parietal blade. Blood cultures, sputum, cerebrospinal fluid, and bronchoalveolar lavage fluid (BALF) by fiberoptic bronchoscopy all indicated the growth of methicillin-resistant Staphylococcus aureus (MRSA).

Treatment methods

After admission, the child was given meropenem combined with vancomycin, cefoperazone sulbactam combined with rifamycin, linezolid (oral) for anti-infection successively, and other adjuvant therapies.

Clinical outcomes

The patient recovered clinically and was discharged from our hospital.

Recommended readers

Neurology; Respiratory Medicine; Infectious Diseases Department.
Induction of whole-body gene deletion via R26-regulated tamoxifen-inducible Cre recombinase activity
Authors: Kumar Rahul , Mao Yun , Patial Sonika , Saini Yogesh
Published: December 2022

Germline deletion of certain genes causes embryonic lethality, therefore, understanding the effect of deletion of such genes on mammalian pathophysiology remains challenging. Tamoxifen (TAM)-inducible Cre recombinase is widely used for tissue-specific and temporal induction of gene deletion in mice. However, the tamoxifen treatment regimen for the generation of whole-body deletion of a gene is not yet fully standardized for the majority of organs/tissues. Accordingly, we employed GtROSA26 (R26) promoter-regulated Cre and a reporter gene expression strategy. GtROSA26 (R26) is an ubiquitous promoter and mice carrying the R26Cre−ERT2 transgene express Cre-ERT2 in all the cells. Similarly, mice carrying the R26mTOM-mEGFP transgene express mTOM (membrane-targeted tdTomato), in the absence of Cre or mEGFP (membrane-targeted enhanced green fluorescent protein), in the presence of Cre, in all the cells. The progeny carrying one allele of both transgenes were subjected to different TAM regimens, i.e., IP injections (4 injections; 1.35 mg/injection), diet (400 mg TAM-citrate/kg food), or diet (400 mg TAM-citrate/kg food) combined with either TAM-oral gavage (4 gavages; 1.35 mg/gavage) or TAM IP injections (4 injections; 1.35 mg/injection) for 2-weeks beginning at postnatal day (PND) 21 and the extent of Cre recombination in different tissues was determined at PND35. Tamoxifen administration resulted in a transient loss of body weight in all the treatment regimens with a relatively slower rate of weight gain in the TAM-diet plus TAM-oral gavage group compared to other groups. While the efficiency of Cre recombination, as determined by the expression of mEGFP protein, was variable among tissues, major tissues such as the liver, heart, lungs, spleen, and thymus—showed almost complete recombination. No recombination was evident in any of the tissues examined from the control mice. In general, the efficiency of Cre recombination was better with a combined regimen of TAM-diet with either TAM-injections or TAM-oral gavage compared to TAM-diet alone or TAM-injections alone. Our results demonstrate that a combination of TAM-diet with either TAM-injections or TAM-oral gavage can be employed for the efficient deletion of a gene in the whole body. Our findings will provide technical expertise to the researchers employing TAM-inducible Cre for the deletion of floxed genes in varied tissues.
Essential oils from Dysphania genus: Traditional uses, chemical composition, toxicology, and health benefits
Authors: Dagni Amal , Hegheș Simona Codruta , Suharoschi Ramona , Pop Oana Lelia , Fodor Adriana , Vulturar Romana , Cozma Angela , Aniq filali Oufaa , Vodnar Dan Cristian , Soukri Abdelaziz , El Khalfi Bouchra
Published: December 2022

The genus Dysphania belongs to the Amaranthaceae family and is known for its many health benefits. Therefore, it is commonly available worldwide and includes more than 47 species, five species have been mainly reported, and D. ambrosioides has been one of the most widely used plants for thousands of years as a remedy for a wide range of ailments. In recent investigations, the essential oils of the genus Dysphania have been examined for their antibacterial, antioxidant, and antiviral properties related to specific components such as terpenoid compounds that exhibit pharmacological activity. Moreover, some of Dysphania’s compounds show a toxicological effect. Therefore, the objective of the study was to provide EO chemical composition and pharmacological data of the genus Dysphania.
Gel-forming antagonist provides a lasting effect on CGRP-induced vasodilation
Authors: Chang Chia Lin , Cai Zheqing , Hsu Sheau Yu Teddy
Published: December 2022

Migraine affects ∼15% of the adult population, and the standard treatment includes the use of triptans, ergotamines, and analgesics. Recently, CGRP and its receptor, the CLR/RAMP1 receptor complex, have been targeted for migraine treatment due to their critical roles in mediating migraine headaches. The effort has led to the approval of several anti-CGRP antibodies for chronic migraine treatment. However, many patients still suffer continuous struggles with migraine, perhaps due to the limited ability of anti-CGRP therapeutics to fully reduce CGRP levels or reach target cells. An alternative anti-CGRP strategy may help address the medical need of patients who do not respond to existing therapeutics. By serendipity, we have recently found that several chimeric adrenomedullin/adrenomedullin 2 peptides are potent CLR/RAMP receptor antagonists and self-assemble to form liquid gels. Among these analogs, the ADE651 analog, which potently inhibits CLR/RAMP1 receptor signaling, forms gels at a 6–20% level. Screening of ADE651 variants indicated that residues at the junctional region of this chimeric peptide are important for gaining the gel-forming capability. Gel-formation significantly slowed the passage of ADE651 molecules through Centricon filters. Consistently, subcutaneous injection of ADE651 gel in rats led to the sustained presence of ADE651 in circulation for >1 week. In addition, analysis of vascular blood flow in rat hindlimbs showed ADE651 significantly reduces CGRP-induced vasodilation. Because gel-forming antagonists could have direct and sustained access to target cells, ADE651 and related antagonists for CLR/RAMP receptors may represent promising candidates for targeting CGRP- and/or adrenomedullin-mediated headaches in migraine patients.