bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycolicibacterium lacusdiani sp. nov., an Attached Bacterium of Microcystis aeruginosa
Authors: Xiao Yao , Chen Jian , Chen Min , Deng Shao-Ji , Xiong Zhi-Qian , Tian Bao-Yu , Zhang Bing-Huo
Published: May 2022

In eutrophic water, attached bacteria of Microcystis play an important role in the formation, development, and degradation of Microcystis blooms. A novel actinobacterium, designated as JXJ CY 35T, was isolated from the culture mass of Microcystis aeruginosa FACHB-905 (Maf) collected from Lake Dianchi, Yunnan Province, China. Strain JXJ CY 35T was gram-positive, acid-fast staining, aerobic, with short rod-shaped cells, positive for catalase, and negative for oxidase. The isolate was able to grow at 10.0–36.0°C, pH 4.0–10.0, and tolerate up to 5.0% (w/v) NaCl, with optimal growth at 28°C, pH 7.0–8.0, and 0% (w/v) NaCl. Cell-wall peptidoglycan contains aspartic acid, glutamic acid, glycine, and alanine, with mannose, ribose, galactose, and arabinose as whole-cell sugars. Polar lipids consist of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), glycolipid (GL1-3), phosphoglycolipid (PGL), phosphatidylinositol (PI), and unidentified lipid (L1). The predominant menaquinone was MK-9. Major fatty acids (>10%) were C17:1ω7c (37.0%) and C18:1ω9c (18.9%). The complete genome sequence of strain JXJ CY 35T was 6,138,096 bp in size with a DNA G + C content of 68.3%. Based on 16S rRNA gene sequences, it has 98.2% similarity to Mycolicibacterium arabiense JCM 18538T. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain JXJ CY 35T and the closest five type strains M. arabiense JCM 18538T, M. goodii ATCC 700504T, M. mageritense DSM 44476T, M. austroafricanum DSM 44191T, and Mycobacterium neglectum CECT 8778T were 52.1, 20.3, 20.3, 20.6, and 19.8%, and 92.7, 75.5, 75.6, 76.0, and 75.2%, respectively. On the basis of the above taxonomic data and differences in physiological characteristics from the closely related type strain, strain JXJ CY 35T was determined to represent a novel species of genus Mycolicibacterium, for which the name Mycolicibacterium lacusdiani sp. nov., is proposed. The type strain is JXJ CY 35T (=KCTC 49379T = CGMCC 1.17501T). Different inoculation dosages of the type strain JXJ CY 35T could exhibit different effects on the growth of Maf and its toxin synthesis and release. Strain JXJ CY 35T could promote the growth of Maf by providing it with available phosphorus, nitrogen, probably vitamins, and plant growth hormones.
Effect of Environmental pH on Mineralization of Anaerobic Iron-Oxidizing Bacteria
Authors: Jiang Na , Feng Yiqing , Huang Qiang , Liu Xiaoling , Guo Yuan , Yang Zhen , Peng Chao , Li Shun , Hao Likai
Published: May 2022

Freshwater lakes are often polluted with various heavy metals in the Anthropocene. The iron-oxidizing microorganisms and their mineralized products can coprecipitate with many heavy metals, including Al, Zn, Cu, Cd, and Cr. As such, microbial iron oxidation can exert a profound impact on environmental remediation. The environmental pH is a key determinant regulating microbial growth and mineralization and then influences the structure of the final mineralized products of anaerobic iron-oxidizing bacteria. Freshwater lakes, in general, are neutral-pH environments. Understanding the effects of varying pH on the mineralization of iron-oxidizing bacteria under neutrophilic conditions could aid in finding out the optimal pH values that promote the coprecipitation of heavy metals. Here, two typical neutrophilic Fe(II)-oxidizing bacteria, the nitrate-reducing Acidovorax sp. strain BoFeN1 and the anoxygenic phototrophic Rhodobacter ferrooxidans strain SW2, were selected for studying how their growth and mineralization response to slight changes in circumneutral pH. By employing focused ion beam/scanning electron microscopy (FIB–SEM) and transmission electron microscopy (TEM), we examined the interplay between pH changes and anaerobic iron-oxidizing bacteria and observed that pH can significantly impact the microbial mineralization process and vice versa. Further, pH-dependent changes in the structure of mineralized products of bacterial iron oxidation were observed. Our study could provide mechanical insights into how to manipulate microbial iron oxidation for facilitating remediation of heavy metals in the environment.
Reversible Hydrogenase Activity Confers Flexibility to Balance Intracellular Redox in Moorella thermoacetica
Authors: Kobayashi Shunsuke , Kato Junya , Wada Keisuke , Takemura Kaisei , Kato Setsu , Fujii Tatsuya , Iwasaki Yuki , Aoi Yoshiteru , Morita Tomotake , Matsushika Akinori , Murakami Katsuji , Nakashimada Yutaka
Published: May 2022

Hydrogen (H2) converted to reducing equivalents is used by acetogens to fix and metabolize carbon dioxide (CO2) to acetate. The utilization of H2enables not only autotrophic growth, but also mixotrophic metabolism in acetogens, enhancing carbon utilization. This feature seems useful, especially when the carbon utilization efficiency of organic carbon sources is lowered by metabolic engineering to produce reduced chemicals, such as ethanol. The potential advantage was tested using engineered strains ofMoorella thermoaceticathat produce ethanol. By adding H2to the fructose-supplied culture, the engineered strains produced increased levels of acetate, and a slight increase in ethanol was observed. The utilization of a knockout strain of the major acetate production pathway, aimed at increasing the carbon flux to ethanol, was unexpectedly hindered by H2-mediated growth inhibition in a dose-dependent manner. Metabolomic analysis showed a significant increase in intracellular NADH levels due to H2in the ethanol-producing strain. Higher NADH level was shown to be the cause of growth inhibition because the decrease in NADH level by dimethyl sulfoxide (DMSO) reduction recovered the growth. When H2was not supplemented, the intracellular NADH level was balanced by the reversible electron transfer from NADH oxidation to H2production in the ethanol-producing strain. Therefore, reversible hydrogenase activity confers the ability and flexibility to balance the intracellular redox state ofM. thermoacetica. Tuning of the redox balance is required in order to benefit from H2-supplemented mixotrophy, which was confirmed by engineering to produce acetone.
Molecular Detection of Parvovirus in Captive Siberian Tigers and Lions in Northeastern China From 2019 to 2021
Authors: Huang Shuping , Li Xiang , Xie Wei , Guo Lijun , You Dan , Xu Haitao , Liu Dan , Wang Yulong , Hou Zhijun , Zeng Xiangwei , Yang Siyuan , Chai Hongliang , Wang Yajun
Published: May 2022

The fact that wild felines are carriers of pernicious infectious viruses should be a major concern due to the potential cross-species transmission between the felines and human or domestic animals. However, studies on the virus in the captive wild felines, especially in tigers, are thin on the ground. In this study, we screened four infectious viruses, namely, feline parvovirus (FPV), feline coronavirus (FCoV), canine distemper virus (CDV), and influenza A virus (IAV), in the blood samples of 285 captive Siberian tigers (Panthera tigris altaica) and in the spleen samples of two deceased lions (Panthera leo), which were collected from 2019 to 2021 in three Siberian Tiger Parks from the northeast of China. Nucleic acids isolated from the blood samples collected from tigers and the spleen samples collected from two deceased lions were positive for FPV by PCR, and the positive rate was 4.6% (13/285) in tigers. Furthermore, the VP2 gene of FPV was amplified by nested PCR, and the sequences of the VP2 gene from these six FPV positive strains shared 98.3–99.9% homology with the reference. The key amino acid sites of VP2 protein were consistent with that of FPV reference strains. Phylogenetic analysis based on the VP2 gene showed that in this study, FPV-positive strains were grouped within the FPV clade and closely related to the Asian strains clade. The results of this study showed that FPV circulated in the captive Siberian tigers and lions in northeastern China and provided valuable information for the study of FPV epidemiology in wild felines. Therefore, we suggest that regular antibody monitoring and booster immunization for tigers should be performed.
Risk Factors of Severe Clostridioides difficile Infection; Sequential Organ Failure Assessment Score, Antibiotics, and Ribotypes
Authors: Choi Min Hyuk , Kim Dokyun , Jeong Seok Hoon , Lee Hyuk Min , Kim Heejung
Published: May 2022

We aimed to determine whether the Sequential Organ Failure Assessment (SOFA) score predicts the prognosis of patients with Clostridioides difficile infection (CDI). In addition, the association between the type of antibiotic used and PCR ribotypes was analyzed. We conducted a propensity score (PS)-matched study and machine learning analysis using clinical data from all adult patients with confirmed CDI in three South Korean hospitals. A total of 5,337 adult patients with CDI were included in this study, and 828 (15.5%) were classified as having severe CDI. The top variables selected by the machine learning models were maximum body temperature, platelet count, eosinophil count, oxygen saturation, Glasgow Coma Scale, serum albumin, and respiratory rate. After propensity score-matching, the SOFA score, white blood cell (WBC) count, serum albumin level, and ventilator use were significantly associated with severe CDI (P < 0.001 for all). The log-rank test of SOFA score ≥ 4 significantly differentiated severe CDI patients from the non-severe group. The use of fluoroquinolone was more related to CDI patients with ribotype 018 strains than to ribotype 014/020 (P < 0.001). Even after controlling for other variables using propensity score matching analysis, we found that the SOFA score was a clinical predictor of severe CDI. We also demonstrated that the use of fluoroquinolones in hospital settings could be associated with the PCR ribotype in patients with CDI.
Molecular Typing and Rapid Identification of Human Adenoviruses Associated With Respiratory Diseases Using Universal PCR and Sequencing Primers for the Three Major Capsid Genes: Penton Base, Hexon, and Fiber
Authors: Wu Xiaowei , Zhang Jing , Lan Wendong , Quan Lulu , Ou Junxian , Zhao Wei , Wu Jianguo , Woo Patrick C. Y. , Seto Donald , Zhang Qiwei
Published: May 2022

Human adenoviruses (HAdVs) within species B, C, and E are responsible for highly contagious and potentially severe respiratory disease infections. The traditional method to type these pathogens was based on virus neutralization and hemagglutination assays, which are both time-consuming and difficult, particularly due to the nonavailability of reagents. Subsequent molecular typing based on the partial characterization of the hexon gene and/or the restriction enzyme analysis (REA) of the genomes is inadequate, particularly in identifying recombinants. Here, a rapid, simple, and cost-effective method for molecular typing HAdV respiratory pathogens is presented. This incorporates three pairs of universal PCR primers that target the variable regions of the three major capsid genes, i.e., hexon, penton base, and fiber genes, that span the genome. The protocol enables typing and characterization of genotypes within species B, C, and E, as well as of some genotypes within species D and F. To validate this method, we surveyed 100 children with HAdV-associated acute respiratory infections identified by direct immunofluorescence (Hong Kong; July through October, 2014). Throat swab specimens were collected and analyzed by PCR amplification and sequencing; these sequences were characterized by BLAST. HAdVs were detected in 98 out of 100 (98%) samples, distributing as follows: 74 HAdV-B3 (74%); 10 HAdV-E4 (10%); 7 HAdV-C2 (7%); 2 HAdV-C6 (2%); 1 HAdV-B7 (1%); 1 HAdV-C1 (1%); 2 co-infection (2%); and 1 novel recombinant (1%). This study is the first detailed molecular epidemiological survey of HAdVs in Hong Kong. The developed method allows for the rapid identification of HAdV respiratory pathogens, including recombinants, and bypasses the need for whole genome sequencing for real-time surveillance of circulating adenovirus strains in outbreaks and populations by clinical virologists, public health officials, and epidemiologists.
Dynamic Responses of Ammonia-Oxidizing Archaea and Bacteria Populations to Organic Material Amendments Affect Soil Nitrification and Nitrogen Use Efficiency
Authors: Zheng Jie , Tao Liang , Dini-Andreote Francisco , Luan Lu , Kong Peijun , Xue Jingrong , Zhu Guofan , Xu Qinsong , Jiang Yuji
Published: May 2022

Organic material amendments have been proposed as an effective strategy to promote soil health by enhancing soil fertility and promoting nitrogen (N) cycling and N use efficiency (NUE). Thus, it is important to investigate the extent to which the structure and function of ammonia-oxidizing archaea (AOA) and bacteria (AOB) differentially respond to the organic material amendments in field settings. Here, we conducted a 9-year field experiment to track the responses of AOA and AOB populations to the organic material amendments and measured the potential nitrification activity (PNA), plant productivity, and NUE in the plant rhizosphere interface. Our results revealed that the organic material amendments significantly enhanced the abundance and diversity of AOA and AOB populations. Further, significant differences were observed in the composition and co-occurrence network of AOA and AOB. A higher occurrence of potential competitive interactions between taxa and enumerated potential keystone taxa was observed in the AOA-AOB network. Moreover, we found that AOA was more important than AOB for PNA under the organic material amendments. Structural equation modeling suggested that the diversity of AOA and AOB populations induced by the potential competitive interactions with keystone taxa dynamically accelerated the rate of PNA, and positively affected plant productivity and NUE under the organic material amendments. Collectively, our study offers new insights into the ecology and functioning of ammonia oxidizers and highlights the positive effects of organic material amendments on nitrogen cycling dynamics.
Estrogen, Cognitive Performance, and Functional Imaging Studies: What Are We Missing About Neuroprotection?
Authors: Marchant Ivanny Carolina , Chabert Stéren , Martínez-Pinto Jonathan , Sotomayor-Zárate Ramón , Ramírez-Barrantes Ricardo , Acevedo Lilian , Córdova Claudio , Olivero Pablo
Published: May 2022

Menopause transition can be interpreted as a vulnerable state characterized by estrogen deficiency with detrimental systemic effects as the low-grade chronic inflammation that appears with aging and partly explains age-related disorders as cancer, diabetes mellitus and increased risk of cognitive impairment. Over the course of a lifetime, estrogen produces several beneficial effects in healthy neurological tissues as well as cardioprotective effects, and anti-inflammatory effects. However, clinical evidence on the efficacy of hormone treatment in menopausal women has failed to confirm the benefit reported in observational studies. Unambiguously, enhanced verbal memory is the most robust finding from longitudinal and cross-sectional studies, what merits consideration for future studies aiming to determine estrogen neuroprotective efficacy. Estrogen related brain activity and functional connectivity remain, however, unexplored. In this context, the resting state paradigm may provide valuable information about reproductive aging and hormonal treatment effects, and their relationship with brain imaging of functional connectivity may be key to understand and anticipate estrogen cognitive protective effects. To go in-depth into the molecular and cellular mechanisms underlying rapid-to-long lasting protective effects of estrogen, we will provide a comprehensive review of cognitive tasks used in animal studies to evaluate the effect of hormone treatment on cognitive performance and discuss about the tasks best suited to the demonstration of clinically significant differences in cognitive performance to be applied in human studies. Eventually, we will focus on studies evaluating the DMN activity and responsiveness to pharmacological stimulation in humans.
Supratotal Resection of Gliomas With Awake Brain Mapping: Maximal Tumor Resection Preserving Motor, Language, and Neurocognitive Functions
Authors: Motomura Kazuya , Ohka Fumiharu , Aoki Kosuke , Saito Ryuta
Published: May 2022

Gliomas are a category of infiltrating glial neoplasms that are often located within or near the eloquent areas involved in motor, language, and neurocognitive functions. Surgical resection being the first-line treatment for gliomas, plays a crucial role in patient outcome. The role of the extent of resection (EOR) was evaluated, and we reported significant correlations between a higher EOR and better clinical prognosis of gliomas. However, recurrence is inevitable, even after aggressive tumor removal. Thus, efforts have been made to achieve extended tumor resection beyond contrast-enhanced mass lesions in magnetic resonance imaging (MRI)-defined areas, a process known as supratotal resection. Since it has been reported that tumor cells invade beyond regions visible as abnormal areas on MRI, imaging underestimates the true spatial extent of tumors. Furthermore, tumor cells have the potential to spread 10–20 mm away from the MRI-verified tumor boundary. The primary goal of supratotal resection is to maximize EOR and prolong the progression-free and overall survival of patients with gliomas. The available data, as well as our own work, clearly show that supratotal resection of gliomas is a feasible technique that has improved with the aid of awake functional mapping using intraoperative direct electrical stimulation. Awake brain mapping has enabled neurosurgeons achieve supratotal resection with favorable motor, language, and neurocognitive outcomes, ensuring a better quality of life in patients with gliomas.
Newly Diagnosed Hepatic Encephalopathy Presenting as Non-convulsive Status Epilepticus: A Case Report and Literature Review
Authors: Olivero Marco , Gagliardi Delia , Costamagna Gianluca , Velardo Daniele , Magri Francesca , Triulzi Fabio , Conte Giorgio , Comi Giacomo P. , Corti Stefania , Meneri Megi
Published: May 2022

Background

Hepatic encephalopathy is characterized by psychiatric and neurological abnormalities, including epileptic seizure and non-convulsive and convulsive status epilepticus. Conventional brain magnetic resonance imaging is useful in supporting diagnosis since it can reveal specific radiological findings. In the literature, there is no description of hepatic encephalopathy onset as non-convulsive status epilepticus; we provide the first report.

Case Summary

We report a case of a 67-year-old woman, without history of cirrhosis, presenting altered mental state, normal brain computed tomography imaging, and electroencephalography suggestive of epileptic activity. We suspected non-convulsive status epilepticus, and we administered diazepam and levetiracetam with clinical improvement. Thus, we made a diagnosis of non-convulsive status epilepticus. A radiological study with brain magnetic resonance imaging showed bilateral hyperintensity on T1-weighted sequences of globus pallidus and hyperintensity of both corticospinal tracts on T2-weighted fluid-attenuated inversion recovery sequences. Blood tests revealed hyperammonemia, mild abnormality of liver function indices, and chronic Hepatitis B and D virus coinfection. Hepatic elastosonography suggested liver cirrhosis. The patient started antiviral therapy with entecavir and prevention of hepatic encephalopathy with rifaximin and lactulose; she was discharged with a normal mental state.

Conclusions

Hepatic encephalopathy can present as an initial manifestation with non-convulsive status epilepticus. Electroencephalography is useful for differentiating non-convulsive status epilepticus from an episode of hepatic encephalopathy, and neuroimaging aids the diagnostic process.
Joint Association of Low Vitamin K1 and D Status With First Stroke in General Hypertensive Adults: Results From the China Stroke Primary Prevention Trial (CSPPT)
Authors: Wei Yaping , Ma Hai , Xu Benjamin , Wang Zhuo , He Qiangqiang , Liu Lishun , Zhou Ziyi , Song Yun , Chen Ping , Li Jianping , Zhang Yan , Mao Guangyun , Wang Binyan , Tang Genfu , Qin Xianhui , Zhang Hao , Xu Xiping , Huo Yong , Guo Huiyuan
Published: May 2022

Background

Vitamin K plays a role in preventing vascular calcification and may have a synergetic influence with vitamin D on cardiovascular health. However, whether this relationship applies to stroke, especially in a high-risk population of hypertensive individuals, remains unclear. The present study aims to study the joint association of low vitamin K1 and D status with first stroke in general hypertensive adults.

Methods

This study used a nested, case–control design with data from the China Stroke Primary Prevention Trial. The analysis included 604 first total stroke patients and 604 matched controls from a Chinese population with hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.

Results

There was a non-linear negative association between plasma vitamin K1 and the risk of first total stroke or ischemic stroke in the enalapril-only group. Compared to participants in vitamin K1 quartile 1, a significantly lower risk of total stroke (OR = 0.58, 95% CI: 0.36, 0.91, P = 0.020) or ischemic stroke (OR = 0.34, 95% CI: 0.17, 0.63, P < 0.001) was found in participants in vitamin K1 quartile 2-4 in the enalapril-only group. When further divided into four subgroups by 25(OH)D and vitamin K1, a significantly higher risk of total stroke or ischemic stroke was observed in participants with both low vitamin K1 and 25(OH)D compared to those with both high vitamin K1 and 25(OH)D in the enalapril-only group. No increased risk was observed in the groups low in one vitamin only.

Conclusion

Low concentrations of both vitamin K1 and 25(OH)D were associated with increased risk of stroke.
Acidic Activated Charcoal Prevents Obesity and Insulin Resistance in High-Fat Diet-Fed Mice
Authors: Zhang Xuguang , Diao Pan , Yokoyama Hiroaki , Inoue Yoshiki , Tanabe Kazuhiro , Wang Xiaojing , Hayashi Chihiro , Yokoyama Tomoki , Zhang Zhe , Hu Xiao , Nakajima Takero , Kimura Takefumi , Nakayama Jun , Nakamuta Makoto , Tanaka Naoki
Published: May 2022

Obesity is becoming a major public health problem worldwide. Making charcoal from wood (“Sumi-yaki”) has been a traditional activity in the southern part of Nagano Prefecture for centuries, with activated charcoal having reported detoxifying effects. However, it is unclear whether activated charcoal also possesses anti-obesity properties. Additionally, since activated charcoal is usually alkaline and might be affected by gastric juice, we evaluated the effect of acidic activated charcoal on high-fat diet (HFD)-induced obesity. This study demonstrated that co-treatment of acidic activated charcoal with a HFD significantly improved obesity and insulin resistance in mice in a dose-dependent manner. Metabolomic analysis of cecal contents revealed that neutral lipids, cholesterol, and bile acids were excreted at markedly higher levels in feces with charcoal treatment. Moreover, the hepatic expressions of genes encoding cholesterol 7 alpha-hydroxylase and hydroxymethylglutaryl-CoA reductase/synthase 1 were up-regulated by activated charcoal, likely reflecting the enhanced excretions from the intestine and the enterohepatic circulation of cholesterol and bile acids. No damage or abnormalities were detected in the gastrointestinal tract, liver, pancreas, and lung. In conclusion, acidic activated charcoal may be able to attenuate HFD-induced weight gain and insulin resistance without serious adverse effects. These findings indicate a novel function of charcoal to prevent obesity, metabolic syndrome, and related diseases.
Limonin Isolated From Pomelo Seed Antagonizes Aβ25-35-Mediated Neuron Injury via PI3K/AKT Signaling Pathway by Regulating Cell Apoptosis
Authors: Qiu Yuanxin , Yang Jingxian , Ma Lukai , Song Mingyue , Liu Guo
Published: May 2022

Pomelo seed as a by-product from pomelo consumption is rich in bioactive compounds, however, a huge volume of pomelo seed was disposed as wastes, the comprehensive utilization of pomelo seed could not only generate valued-added products/ingredients, but also decrease the environmental pollution. In this study, the main active substance limonin in pomelo seed was considered as a high-value bioactive compound. The purification of limonin from pomelo seed was investigated, and the neuroprotective and mechanism were characterized. The UPLC-MS/MS results indicated that 29 compounds in pomelo seed were identified, including 14 flavonoids, 3 limonids, 9 phenols and 3 coumarins. Moreover, high purity of limonin was obtained by crystallization and preparative-HPLC. Furthermore, limonin pretreatment can antagonize the cell damage mediated by Aβ25−35 in a concentration-dependent relationship. The regulation of Bax/Bcl-2, expression of caspase-3 protein and the activation of PI3K/Akt signaling pathway were observed in the cells pretreated with limonin. Treatment of PC12 cells with PI3K inhibitor LY294002 weakened the protective effect of limonin. These results indicated that limonin prevented Aβ25−35-induced neurotoxicity by activating PI3K/Akt, and further inhibiting caspase-3 and up-regulating Bcl-2. This study enables comprehensive utilization of pomelo seed as by-product and offers a theoretical principle for a waste-to-wealth solution, such as potential health benefits of food ingredient and drug.
The Long Non-Coding RNA FAM222A-AS1 Negatively Modulates MiR-Let-7f to Promote Colorectal Cancer Progression
Authors: Song Mengmeng , Li Ye , Chen Zhewen , Zhang Jie , Yang Liuqing , Zhang Fan , Song Chunhua , Miao Mingyong , Chang Wenjun , Shi Hanping
Published: May 2022

Accumulating evidence indicates that lncRNAs are potential biomarkers and key regulators of tumor development and progression. The present study aimed to screen abnormal expression lncRNAs and investigate the mechanisms underlying the function in the progression of colorectal cancer (CRC). Potential CRC prognosis-associated dysregulated lncRNAs were screened and identified using bioinformatics analysis. Loss/gain-of-function experiments were performed to detect the biological roles of FAM222A-AS1 in CRC cell phenotypes in vitro and in vivo. The potential microRNAs that interact with FAM222A-AS1 were identified using online tools and were verified using qRT-PCR and luciferase reporter assay. The expression of FAM222A-AS1 is significantly upregulated in CRC tumor samples and cell lines. CRC patients with elevated FAM222A-AS1 expression in the tumor samples had unfavorable overall survival and disease-free survival. Silencing FAM222A-AS1 expression significantly inhibited CRC cell proliferation, migration, and invasion both in vitro and in vivo. Furthermore, FAM222A-AS1 was mainly distributed in the cytoplasm. It may directly bound to miR-let-7f and inhibit its expression and upregulate MYH9. In summary, FAM222A-AS1, as a novel oncogene in CRC, may promote the CRC progression by inhibiting miR-let-7f/MYH9 axis. The FAM222A-AS1/miR-let-7f/MYH9 signaling pathway may be a novel valuable target for inhibiting CRC.
MRI-Based Radiomics Features to Predict Treatment Response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer: A Single Center, Prospective Study
Authors: Chen Bi-Yun , Xie Hui , Li Yuan , Jiang Xin-Hua , Xiong Lang , Tang Xiao-Feng , Lin Xiao-Feng , Li Li , Cai Pei-Qiang
Published: May 2022

This is a prospective, single center study aimed to evaluate the predictive power of peritumor and intratumor radiomics features assessed using T2 weight image (T2WI) of baseline magnetic resonance imaging (MRI) in evaluating pathological good response to NAC in patients with LARC (including Tany N+ or T3/4a Nany but not T4b). In total, 137 patients with LARC received NAC between April 2014 and August 2020. All patients were undergoing contrast-enhanced MRI and 129 patients contained small field of view (sFOV) sequence which were performed prior to treatment. The tumor regression grade standard was based on pathological response. The training and validation sets (n=91 vs. n=46) were established by random allocation of the patients. Receiver operating characteristic curve (ROC) analysis was applied to estimate the performance of different models based on clinical characteristics and radiomics features obtained from MRI, including peritumor and intratumor features, in predicting treatment response; these effects were calculated using the area under the curve (AUC). The performance and agreement of the nomogram were estimated using calibration plots. In total, 24 patients (17.52%) achieved a complete or near-complete response. For the individual radiomics model in the validation set, the performance of peritumor radiomics model in predicting treatment response yield an AUC of 0.838, while that of intratumor radiomics model is 0.805, which show no statically significant difference between then(P>0.05). The traditional and selective clinical features model shows a poor predictive ability in treatment response (AUC=0.596 and 0.521) in validation set. The AUC of combined radiomics model was improved compared to that of the individual radiomics models in the validation sets (AUC=0.844). The combined clinic-radiomics model yield the highest AUC (0.871) in the validation set, although it did not improve the performance of the radiomics model for predicting treatment response statically (P>0.05). Good agreement and discrimination were observed in the nomogram predictions. Both peritumor and intratumor radiomics features performed similarly in predicting a good response to NAC in patients with LARC. The clinic-radiomics model showed the best performance in predicting treatment response.
Seven DNA Methylation Biomarker Prediction Models for Monitoring the Malignant Progression From Advanced Adenoma to Colorectal Cancer
Authors: Wang Wei , Zhang Xuecong , Zhu Xiaohui , Cui Wenzhi , Ye Danli , Tong Guihui , Huang Dingpeng , Zhou Juan , Lai Xuwen , Yan Guangning , Li Xia , Fan Jianbing , Zhu Hongwu , Lei Chengyong
Published: May 2022

Advanced adenoma (AA) holds a significantly increased risk for progression to colorectal cancer (CRC), and we developed a noninvasive DNA methylation prediction model to monitor the risk of AA progression to CRC. We analyzed the differential methylation markers between 53 normal mucosa and 138 CRC tissues, as well as those in cfDNA (cell-free DNA) between 59 AA and 68 early-stage CRC patients. We screened the overlapping markers between tissue DNA and cfDNA for model variables and optimized the selected variables. Then, we established a cfDNA methylation prediction model (SDMBP model) containing seven methylation markers that can effectively discriminate early-stage CRC and AA in the training and validation cohorts, and the AUC (area under the curve) reached 0.979 and 0.918, respectively. Our model also reached high precision (AUC=0.938) in detecting advanced CRC (stage III/IV) and presented better performance than serum CEA and CA199 in screening CRC. The cd-score of the SDMBP model could also robustly predict the TNM stage of CRC. Overall, our SDMBP model can monitor the malignant progression from AA to CRC, and may provide a noninvasive monitoring method for high-risk populations with AA.
Predictive Efficacy of a Radiomics Random Forest Model for Identifying Pathological Subtypes of Lung Adenocarcinoma Presenting as Ground-Glass Nodules
Authors: Zhao Fen-hua , Fan Hong-jie , Shan Kang-fei , Zhou Long , Pang Zhen-zhu , Fu Chun-long , Yang Ze-bin , Wu Mei-kang , Sun Ji-hong , Yang Xiao-ming , Huang Zhao-hui
Published: May 2022

Purpose

To establish and verify the ability of a radiomics prediction model to distinguish invasive adenocarcinoma (IAC) and minimal invasive adenocarcinoma (MIA) presenting as ground-glass nodules (GGNs).

Methods

We retrospectively analyzed 118 lung GGN images and clinical data from 106 patients in our hospital from March 2016 to April 2019. All pathological classifications of lung GGN were confirmed as IAC or MIA by two pathologists. R language software (version 3.5.1) was used for the statistical analysis of the general clinical data. ITK-SNAP (version 3.6) and A.K. software (Analysis Kit, American GE Company) were used to manually outline the regions of interest of lung GGNs and collect three-dimensional radiomics features. Patients were randomly divided into training and verification groups (ratio, 7:3). Random forest combined with hyperparameter tuning was used for feature selection and prediction modeling. The receiver operating characteristic curve and the area under the curve (AUC) were used to evaluate model prediction efficacy. The calibration curve was used to evaluate the calibration effect.

Results

There was no significant difference between IAC and MIA in terms of age, gender, smoking history, tumor history, and lung GGN location in both the training and verification groups (P>0.05). For each lung GGN, the collected data included 396 three-dimensional radiomics features in six categories. Based on the training cohort, nine optimal radiomics features in three categories were finally screened out, and a prediction model was established. We found that the training group had a high diagnostic efficacy [accuracy, sensitivity, specificity, and AUC of the training group were 0.89 (95%CI, 0.73 - 0.99), 0.98 (95%CI, 0.78 - 1.00), 0.81 (95%CI, 0.59 - 1.00), and 0.97 (95%CI, 0.92-1.00), respectively; those of the validation group were 0.80 (95%CI, 0.58 - 0.93), 0.82 (95%CI, 0.55 - 1.00), 0.78 (95%CI, 0.57 - 1.00), and 0.92 (95%CI, 0.83 - 1.00), respectively]. The model calibration curve showed good consistency between the predicted and actual probabilities.

Conclusions

The radiomics prediction model established by combining random forest with hyperparameter tuning effectively distinguished IAC from MIA presenting as GGNs and represents a noninvasive, low-cost, rapid, and reproducible preoperative prediction method for clinical application.
Peripheral T-Cell Lymphomas Involving the Central Nervous System: A Report From the Czech Lymphoma Study Group Registry
Authors: Mocikova Heidi , Pytlík Robert , Benesova Katerina , Janikova Andrea , Duras Juraj , Sykorova Alice , Steinerova Katerina , Prochazka Vit , Campr Vit , Belada David , Trneny Marek
Published: May 2022

Introduction

We analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066).

Materials and Methods

Out of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse.

Results

Patients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1).

Conclusions

The incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.
Case Report: Radiotherapy Plus Immunotherapy and Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma With a Right Atrium and Inferior Vena Cava Tumor Thrombus
Authors: Qian Yuting , Gong Long , Li Su , Mao Kun , Li Xianming , Liao Guixiang
Published: May 2022

Background

The treatment of hepatocellular carcinoma (HCC) with right atrium (RA) and inferior vena cava (IVC) tumor thrombi is challenging, with the standard treatment being not well established. Immunotherapy plus antiangiogenic therapy is a potentially effective treatment for patients with advanced HCC. Here, we described the case of a patient with HCC with RA and IVC tumor thrombi who achieved a successful response from radiotherapy and targeted therapy plus immunotherapy.

Case Summary

A 62-year-old women presented with severe bilateral lower extremity edema identified as recurrent HCC with RA and IVC tumor thrombi based on past medical history and computed tomography. The patient received palliative radiotherapy plus pembrolizumab and lenvatinib treatment and was relieved of disease symptoms of bilateral lower extremity edema. The HCC with RA and IVC tumor thrombi shrunk, and the progression-free survival of this patient was > seven months.

Conclusion

Tumor thrombus-directed radiotherapy plus concurrent immunotherapy and targeted therapy might be a feasible and safe approach for patients with HCC with RA and IVC tumor thrombi.
Measurement of Sarcopenia in Head and Neck Cancer Patients and Its Association With Frailty
Authors: de Bree Remco , Meerkerk Christiaan D. A. , Halmos Gyorgy B. , Mäkitie Antti A. , Homma Akihiro , Rodrigo Juan P. , López Fernando , Takes Robert P. , Vermorken Jan B. , Ferlito Alfio
Published: May 2022

In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients.
Association Between Benign Ovarian Tumors and Ovarian Cancer Risk: A Meta-Analysis of Ten Epidemiological Studies
Authors: Guo Jiao , Feng Haoshen , Gu Xi
Published: May 2022

Background

Epidemiological evidence on the relationship between benign ovarian tumors and ovarian cancer risk has been controversial; therefore, this systematic review and meta-analysis evaluated this association.

Methods

The PubMed and Web of Knowledge databases were searched for eligible studies published up to April 30, 2020. The study-specific risk estimates were pooled using a random-effects model.

Results

Ten articles (two cohorts, seven case-control studies, and one pooled analysis of eight case-control studies) with 10331 ovarian cancer patients were included. Benign ovarian tumors were associated with an increased risk of ovarian cancer (pooled relative risk [RR]=1.39, 95% confidence interval [CI]: 1.01–1.90), with high heterogeneity among studies. The pooled RR was 2.02 (95%CI: 1.32–3.11) for two cohort studies, which was higher than the pooled result of eight case-control studies (pooled RR: 1.15; 95%CI: 0.92–1.44). When stratifying by histological type, the pooled RRs were 1.53 (95% CI: 0.37–6.29) and 3.62 (95%CI: 0.81–16.20) for serous and mucinous tumors, respectively. The pooled RRs were 1.61 (95%CI: 0.65–3.95) and 1.54 (95%CI: 1.29–1.84) for the associations of ovarian cyst with invasive and borderline cancers, respectively.

Conclusions

Benign ovarian tumors were associated with an increased risk of ovarian cancer. Due to the high heterogeneity among the studies and the risks of bias, more studies are warranted to confirm these findings.
XGBG: A Novel Method for Identifying Ovarian Carcinoma Susceptible Genes Based on Deep Learning
Authors: Sun Ke Feng , Sun Li Min , Zhou Dong , Chen Ying Ying , Hao Xi Wen , Liu Hong Ruo , Liu Xin , Chen Jing Jing
Published: May 2022

Ovarian carcinomas (OCs) represent a heterogeneous group of neoplasms consisting of several entities with pathogenesis, molecular profiles, multiple risk factors, and outcomes. OC has been regarded as the most lethal cancer among women all around the world. There are at least five main types of OCs classified by the fifth edition of the World Health Organization of tumors: high-/low-grade serous carcinoma, mucinous carcinoma, clear cell carcinoma, and endometrioid carcinoma. With the improved knowledge of genome-wide association study (GWAS) and expression quantitative trait locus (eQTL) analyses, the knowledge of genomic landscape of complex diseases has been uncovered in large measure. Moreover, pathway analyses also play an important role in exploring the underlying mechanism of complex diseases by providing curated pathway models and information about molecular dynamics and cellular processes. To investigate OCs deeper, we introduced a novel disease susceptible gene prediction method, XGBG, which could be used in identifying OC-related genes based on different omics data and deep learning methods. We first employed the graph convolutional network (GCN) to reconstruct the gene features based on both gene feature and network topological structure. Then, a boosting method is utilized to predict OC susceptible genes. As a result, our model achieved a high AUC of 0.7541 and an AUPR of 0.8051, which indicates the effectiveness of the XGPG. Based on the newly predicted OC susceptible genes, we gathered and researched related literatures to provide strong support to the results, which may help in understanding the pathogenesis and mechanisms of the disease.
Saliva Cortisol in Girls With Functional Abdominal Pain Disorders: A Randomized Controlled Dance and Yoga Intervention
Authors: Areskoug Sandberg Elin , Duberg Anna , Lorenzon Fagerberg Ulrika , Mörelius Evalotte , Särnblad Stefan
Published: May 2022

Introduction

Functional abdominal pain disorders (FAPDs) are common among girls and has been associated with stress. Cortisol is one of the major stress hormones. Dance and yoga have been shown to reduce abdominal pain among girls with FAPDs.

Aim

To investigate the effect of an 8-month intervention with dance and yoga on cortisol levels in saliva among girls with FAPDs.

Methods

A total of 121 girls aged 9–13 years with irritable bowel syndrome (IBS) or functional abdominal pain were included in the study. Participants were randomized into an intervention group and a control group. The intervention group attended a combined dance and yoga session twice a week for 8 months. Saliva samples were collected during 1 day, in the morning and evening, at baseline, and at 4 and 8 months. Subjective pain and stress were assessed as well.

Results

No significant effects on saliva cortisol levels between groups were observed after completion of the intervention at 8 months. However, evening cortisol and evening/morning quotient were significantly reduced at 4 months in the intervention group compared to the control group (p = 0.01, p = 0.004). There was no association between cortisol quota and pain or stress.

Conclusion

Improvements in cortisol levels were seen in the intervention group at 4 months but did not persist until the end of the study. This indicates that dance and yoga could have a stress-reducing effect during the ongoing intervention.
Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations
Authors: Abduljalil Khaled , Gardner Iain , Jamei Masoud
Published: May 2022

Perinatal pharmacology is influenced by a myriad of physiological variables that are changing dynamically. The influence of these covariates has not been assessed systemically. The objective of this work was to use theophylline as a model drug and to predict its pharmacokinetics before, during (including prediction of the umbilical cord level), and after pregnancy as well as in milk (after single and multiple doses) and in neonates using a physiological-based pharmacokinetic (PBPK) model. Neonatal theophylline exposure from milk consumption was projected in both normal term and preterm subjects. Predicted infant daily doses were calculated using theophylline average and maximum concentration in the milk as well as an estimate of milk consumption. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted theophylline concentrations in non-pregnant and pregnant populations at different gestational weeks were within 2-fold of the observations and the observed concentrations fell within the 5th−95th prediction interval from the PBPK simulations. The PBPK model predicted an average cord-to-maternal plasma ratio of 1.0, which also agrees well with experimental observations. Predicted postpartum theophylline concentration profiles in milk were also in good agreement with observations with a predicted milk-to-plasma ratio of 0.68. For an infant of 2 kg consuming 150 ml of milk per day, the lactation model predicted a relative infant dose (RID) of 12 and 17% using predicted average (Cavg,ss) and maximum (Cmax,ss) concentration in milk at steady state. The maximum RID of 17% corresponds to an absolute infant daily dose of 1.4 ± 0.5 mg/kg/day. This dose, when administered as 0.233 mg/kg every 4 h, to resemble breastfeeding frequency, resulted in plasma concentrations as high as 3.9 (1.9–6.8) mg/L and 2.8 (1.3–5.3) (5th−95th percentiles) on day 7 in preterm (32 GW) and full-term neonatal populations.