bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic risk variants for multiple sclerosis are linked to differences in alternative pre-mRNA splicing
Authors: Putscher Elena , Hecker Michael , Fitzner Brit , Boxberger Nina , Schwartz Margit , Koczan Dirk , Lorenz Peter , Zettl Uwe Klaus
Published: October 2022

Background

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system to which a genetic predisposition contributes. Over 200 genetic regions have been associated with increased disease risk, but the disease-causing variants and their functional impact at the molecular level are mostly poorly defined. We hypothesized that single-nucleotide polymorphisms (SNPs) have an impact on pre-mRNA splicing in MS.

Methods

Our study focused on 10 bioinformatically prioritized SNP–gene pairs, in which the SNP has a high potential to alter alternative splicing events (ASEs). We tested for differential gene expression and differential alternative splicing in B cells from MS patients and healthy controls. We further examined the impact of the SNP genotypes on ASEs and on splice isoform expression levels. Novel genotype-dependent effects on splicing were verified with splicing reporter minigene assays.

Results

We were able to confirm previously described findings regarding the relation of MS-associated SNPs with the ASEs of the pre-mRNAs from GSDMB and SP140. We also observed an increased IL7R exon 6 skipping when comparing relapsing and progressive MS patients to healthy subjects. Moreover, we found evidence that the MS risk alleles of the SNPs rs3851808 (EFCAB13), rs1131123 (HLA-C), rs10783847 (TSFM), and rs2014886 (TSFM) may contribute to a differential splicing pattern. Of particular interest is the genotype-dependent exon skipping of TSFM due to the SNP rs2014886. The minor allele T creates a donor splice site, resulting in the expression of the exon 3 and 4 of a short TSFM transcript isoform, whereas in the presence of the MS risk allele C, this donor site is absent, and thus the short transcript isoform is not expressed.

Conclusion

In summary, we found that genetic variants from MS risk loci affect pre-mRNA splicing. Our findings substantiate the role of ASEs with respect to the genetics of MS. Further studies on how disease-causing genetic variants may modify the interactions between splicing regulatory sequence elements and RNA-binding proteins can help to deepen our understanding of the genetic susceptibility to MS.
An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance
Authors: Han Yanxun , Shi Yangyang , Chen Bangjie , Wang Jianpeng , Liu Yuchen , Sheng Shuyan , Fu Ziyue , Shen Chuanlu , Wang Xinyi , Yin Siyue , Li Haiwen
Published: October 2022

Purpose

Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients.

Methods

Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry.

Results

We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments.

Conclusion

The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.
Ocean observation system design of mooring buoy and benthic node with electro-optical-mechanical cable
Authors: Zhang Shaowei , Tian Chuan , Zhou Fenghua
Published: October 2022

We designed a hybrid system named Mooring Buoys Observation System with Benthic Electro-optical-mechanical Cable (MBOSBC) for long-term seafloor and sea surface multi-parameter ocean observation. The electro-optical-mechanical (EOM) cable connects a sea surface buoy and a seafloor junction box so as to establish a transmission link of information and power between the sea surface and the seafloor. The EOM cable also plays the role of mooring tether to the MBOSBC and has to withstand the rigorous marine environment—experiencing mooring loads under complex marine environmental conditions for long periods of time. The data transmission of the system includes the EOM, satellite communication, wireless radio, and acoustic communication. The system power is generated by a wind turbine and solar panels and is transmitted to the seafloor junction box. An acoustic communication instrument is used to gather the sample data from other benthic nodes, such as seafloor landers, AUVs, and underwater gliders. MBOSBC is designed to operate from shallow water to deep sea, and to simultaneously monitor sea surface hydrology, meteorology, and water quality, as well as benthic temperature, pressure, salinity, currents, and seafloor video. We provide the MBOSBC architecture design, including the mechanical design, control, power, data transmission, and EOM cable. Finally, we describe the launch and recovery process of MBOSBC, as well as experimental results.
Modeling of temperature dependence of Λ-graded InGaN solar cells for both strained and relaxed features
Authors: Sarollahi Mirsaeid , Zamani-Alavijeh Mohammad , Aldawsari Manal A. , Allaparthi Rohith , Maruf Md Helal Uddin , Refaei Malak , Alhelais Reem , Mazur Yuriy I. , Ware Morgan E.
Published: October 2022

The temperature dependence of Λ-graded InGaN solar cells is studied through simulation using nextnano software. Λ-Graded structures have been designed by increasing and then decreasing the indium composition in epitaxial InGaN layers. Due to polarization doping, layers of p-type and n-type doping arise without the need for impurity doping. Different individual structures are designed by varying the indium alloy profile from GaN to maximum indium concentrations, xmax, ranging from 20% to 90% pseudomorphically strained to a GaN substrate and from 20% to 100% for completely strain-relaxed materials and linearly decreases back to GaN. For InxGa1-xN with x>∼0.9, if the material is strained to the GaN lattice constant, it is predicted to have a negative band gap. So this case is not considered here. The temperature dependence of the electrical and optical properties as they relate to the solar efficiency of the Λ-graded structures under relaxed and strained conditions are studied. Additionally, the dimensionless absorption coefficients are fitted and plotted as functions of the band gap under both strained and relaxed conditions at different temperatures. As a result, the generation rates as functions of the penetration depth within a cell can be calculated in order to obtain the solar cell parameters including efficiency for each Λ-graded structure at different temperatures. Under the strained condition, the xmax, where the solar cell efficiency reaches its maximum for each temperature, decreases as the temperature increases. At the same time, under the relaxed condition, at low temperatures (T = 100–400 K), xmax is 100%, that is, grading to InN results in maximum efficiency, while at higher temperatures (T = 500–800 K), xmax decreases with the increasing temperature.
Chemical composition optimization of nanocomposites used for shed and core of outdoor composite insulators
Authors: Gafti Abdolah , Taherian Reza , Kiahoseini Seyed Rahim
Published: October 2022

Outdoor 24-kV power transmission insulators include two main pieces, namely, the shed and core. In this study, these pieces were manufactured separately by roll/hot pressing and hand lay-up methods, respectively. Both shed and core were formed from polymer-based composites due to their low weight, high strength-to-weight ratio, and higher moisture and pollution resistance compared to those of ceramic and glass sheds. The sheds were made from silicone rubber as the matrix and alumina trihydrate (ATH) and TiO2 as additives in single- and double-filler composites. The characterization tests of the sheds included variable (max stability voltage) and constant (dry, wet, and notched max endurance voltage, as well as erosion) voltage tests, in addition to contact angle tests. The results of these analyses demonstrated that silicone rubber reinforced with 5 wt.% TiO2 was the best shed material based on its hydrophobicity. The core of the insulator was made of epoxy reinforced with different glass fiber percentages (10, 13, and 15 wt.%). The manufacturing method was hand lay-up. Tensile strength and scanning electron microscopy (SEM) were used for characterization.
Case report: Successful management of Parvimonas micra pneumonia mimicking hematogenous Staphylococcus aureus pneumonia
Authors: Feng Yanmei , Wu Chunxia , Huang Xiaohui , Huang Xia , Peng Li , Guo Rui
Published: October 2022

Parvimonas micra is an anaerobic Gram-positive coccus frequently found in the oral cavity and gastrointestinal tract, but rarely in the lung. Therefore, pneumonia caused by P. micra is also rare. Although there are some reports of P. micra related pneumonia due to aspiration or blood-borne infection with definite remote infection source, there are no reported cases of hematogenous P. micra pneumonia in healthy adults lacking a remote source of infection. Herein, we described the intact disease of P. micra-related pneumonia mimicking hematogenous Staphylococcus aureus pneumonia in terms of chest imagery and diagnosed via metagenomic next-generation sequencing (mNGS). Interestingly, there was no clear remote pathogenic source identified in the patient. Microbiome analysis revealed dysbiosis of the oral flora possibly related to poor oral hygiene and a long history of smoking. The patient was treated with moxifloxacin for 3 months. Ultimately, computed tomography (CT) of the chest showed total resolution of the lung lesion. Clinicians need to update the etiology of community-acquired pneumonia. When antibiotic therapy is not effective, pathogen examination becomes very important. New methods of pathogen detection such as mNGS should be employed to this end. For the treatment of P. micra pneumonia, no standardized course of treatment was reported. Imaging absorption of lung infections may provide a more objective guidance for the duration of antibiotics in P. micra pneumonia.
The role of extracellular vesicles in vascular calcification in chronic kidney disease
Authors: Zhao Huan , Liu Haojie , Liu Yueming , Jin Juan , He Qiang , Lin Bo
Published: October 2022

Widespread vascular calcification (VC) in patients with chronic kidney disease (CKD) is the pathological basis for the development of cardiovascular disease, and VC has been identified as an independent risk factor for increased cardiovascular mortality in cases of CKD. While VC was earlier thought to be a passive deposition process following calcium and phosphorus supersaturation, recent studies have suggested that it is an active, modifiable, biological process similar to bone development. The involvement of extracellular vesicles (EVs) in the process of VC has been reported as an important transporter of material transport and intercellular communication. This paper reviews the mechanism of the role of EVs, especially exosomes, in VC and the regulation of VC by stem cell-derived EVs, and discusses the possible and promising application of related therapeutic targets in the clinical setting.
In vitro and in vivo synergistic effect of chrysin in combination with colistin against Acinetobacter baumannii
Authors: Zhao Yining , Liu Yan , Feng Luozhu , Xu Mengxin , Wen Hong , Yao Zhuocheng , Shi Shiyi , Wu Qing , Zhou Cui , Cao Jianming , Zhou Tieli
Published: October 2022

Acinetobacter baumannii is an opportunistic pathogen that is primarily associated with nosocomial infections. With the rise in cases of acquired drug resistance, A. baumannii is gaining resistance to conventional antimicrobial drugs and even to the last line of antibiotics, such as colistin. Hence, the application of the synergistic combination of an antibiotic and a non-antibacterial agent is being contemplated as a new alternative therapeutic approach. Chrysin is a component of honey with anti-inflammatory and antioxidant properties. In this study, we evaluated the antibacterial activity of chrysin in combination with colistin against A. baumannii both in vitro and in vivo, as well as the cytotoxicity of chrysin with or without colistin. Our results revealed that chrysin and colistin exerted synergistic effects against A. baumannii by damaging the extracellular membrane and modifying the bacterial membrane potential. The chrysin/colistin combination group demonstrated an inhibitory effect on biofilm formation. In conclusion, it is expected that the synergy between these drugs can allow the use of a lower concentration of colistin for the treatment of A. baumannii infections, thereby reducing dose-dependent side effects. Thus, a combination therapy of chrysin/colistin may provide a new therapeutic option for controlling A. baumannii infections.
A putative bifunctional CPD/ (6-4) photolyase from the cyanobacteria Synechococcus sp. PCC 7335 is encoded by a UV-B inducible operon: New insights into the evolution of photolyases
Authors: Fernández María Belén , Latorre Lucas , Correa-Aragunde Natalia , Cassia Raúl
Published: October 2022

Photosynthetic organisms are continuously exposed to solar ultraviolet radiation-B (UV-B) because of their autotrophic lifestyle. UV-B provokes DNA damage, such as cyclobutane pyrimidine dimers (CPD) or pyrimidine (6-4) pyrimidone photoproducts (6-4 PPs). The cryptochrome/photolyase family (CPF) comprises flavoproteins that can bind damaged or undamaged DNA. Photolyases (PHRs) are enzymes that repair either CPDs or 6-4 PPs. A natural bifunctional CPD/(6-4)- PHR (PhrSph98) was recently isolated from the UV-resistant bacteria Sphingomonas sp. UV9. In this work, phylogenetic studies of bifunctional CPD/(6-4)- photolyases and their evolutionary relationship with other CPF members were performed. Amino acids involved in electron transfer and binding to FAD cofactor and DNA lesions were conserved in proteins from proteobacteria, planctomycete, bacteroidete, acidobacteria and cyanobacteria clades. Genome analysis revealed that the cyanobacteria Synechococcus sp. PCC 7335 encodes a two-gene assembly operon coding for a PHR and a bifunctional CPD/(6-4) PHR- like. Operon structure was validated by RT-qPCR analysis and the polycistronic transcript accumulated after 15 min of UV-B irradiation. Conservation of structure and evolution is discussed. This study provides evidence for a UV-B inducible PHR operon that encodes a CPD/(6-4)- photolyase homolog with a putative bifunctional role in the repair of CPDs and 6-4 PPs damages in oxygenic photosynthetic organisms.
Astrocytes exhibit diverse Ca2+ changes at subcellular domains during brain aging
Authors: Ding Fusheng , Liang Shanshan , Li Ruijie , Yang Zhiqi , He Yong , Yang Shaofan , Duan Qingtian , Zhang Jianxiong , Lyu Jing , Zhou Zhenqiao , Huang Mingzhu , Wang Haoyu , Li Jin , Yang Chuanyan , Wang Yuxia , Gong Mingyue , Chen Shangbin , Jia Hongbo , Chen Xiaowei , Liao Xiang , Fu Ling , Zhang Kuan
Published: October 2022

Astrocytic Ca2+transients are essential for astrocyte integration into neural circuits. These Ca2+transients are primarily sequestered in subcellular domains, including primary branches, branchlets and leaflets, and endfeet. In previous studies, it suggests that aging causes functional defects in astrocytes. Until now, it was unclear whether and how aging affects astrocytic Ca2+transients at subcellular domains. In this study, we combined a genetically encoded Ca2+sensor (GCaMP6f) andin vivotwo-photon Ca2+imaging to determine changes in Ca2+transients within astrocytic subcellular domains during brain aging. We showed that aging increased Ca2+transients in astrocytic primary branches, higher-order branchlets, and terminal leaflets. However, Ca2+transients decreased within astrocytic endfeet during brain aging, which could be caused by the decreased expressions of Aquaporin-4 (AQP4). In addition, aging-induced changes of Ca2+transient types were heterogeneous within astrocytic subcellular domains. These results demonstrate that the astrocytic Ca2+transients within subcellular domains are affected by aging differently. This finding contributes to a better understanding of the physiological role of astrocytes in aging-induced neural circuit degeneration.
Repetitively burst-spiking neurons in reeler mice show conserved but also highly variable morphological features of layer Vb-fated “thick-tufted” pyramidal cells
Authors: Staiger Jochen F. , Sachkova Alexandra , Möck Martin , Guy Julien , Witte Mirko
Published: October 2022

Reelin is a large extracellular glycoprotein that is secreted by Cajal-Retzius cells during embryonic development to regulate neuronal migration and cell proliferation but it also seems to regulate ion channel distribution and synaptic vesicle release properties of excitatory neurons well into adulthood. Mouse mutants with a compromised reelin signaling cascade show a highly disorganized neocortex but the basic connectional features of the displaced excitatory principal cells seem to be relatively intact. Very little is known, however, about the intrinsic electrophysiological and morphological properties of individual cells in the reeler cortex. Repetitive burst-spiking (RB) is a unique property of large, thick-tufted pyramidal cells of wild-type layer Vb exclusively, which project to several subcortical targets. In addition, they are known to possess sparse but far-reaching intracortical recurrent collaterals. Here, we compared the electrophysiological properties and morphological features of neurons in the reeler primary somatosensory cortex with those of wild-type controls. Whereas in wild-type mice, RB pyramidal cells were only detected in layer Vb, and the vast majority of reeler RB pyramidal cells were found in the superficial third of the cortical depth. There were no obvious differences in the intrinsic electrophysiological properties and basic morphological features (such as soma size or the number of dendrites) were also well preserved. However, the spatial orientation of the entire dendritic tree was highly variable in the reeler neocortex, whereas it was completely stereotyped in wild-type mice. It seems that basic quantitative features of layer Vb-fated RB pyramidal cells are well conserved in the highly disorganized mutant neocortex, whereas qualitative morphological features vary, possibly to properly orient toward the appropriate input pathways, which are known to show an atypical oblique path through the reeler cortex. The oblique dendritic orientation thus presumably reflects a re-orientation of dendritic input domains toward spatially highly disorganized afferent projections.
Chronic treatment with corticosterone increases the number of tyrosine hydroxylase-expressing cells within specific nuclei of the brainstem reticular formation
Authors: Busceti Carla Letizia , Bucci Domenico , Scioli Mariarosaria , Di Pietro Paola , Nicoletti Ferdinando , Puglisi-Allegra Stefano , Ferrucci Michela , Fornai Francesco
Published: October 2022

Cushing's syndrome is due to increased glucocorticoid levels in the body, and it is characterized by several clinical alterations which concern both vegetative and behavioral functions. The anatomical correlates of these effects remain largely unknown. Apart from peripheral effects induced by corticosteroids as counter-insular hormones, only a few reports are available concerning the neurobiology of glucocorticoid-induced vegetative and behavioral alterations. In the present study, C57 Black mice were administered daily a chronic treatment with corticosterone in drinking water. This treatment produces a significant and selective increase of TH-positive neurons within two nuclei placed in the lateral column of the brainstem reticular formation. These alterations significantly correlate with selective domains of Cushing's syndrome. Specifically, the increase of TH neurons within area postrema significantly correlates with the development of glucose intolerance, which is in line with the selective control by area postrema of vagal neurons innervating the pancreas. The other nucleus corresponds to the retrorubral field, which is involved in the behavioral activity. In detail, the retrorubral field is likely to modulate anxiety and mood disorders, which frequently occur following chronic exposure to glucocorticoids. To our knowledge, this is the first study that provides the neuroanatomical basis underlying specific symptoms occurring in Cushing's syndrome.
Cerebral venous sinus thrombosis with an acute subdural hematoma treated with endovascular intervention: A case report
Authors: Crouch Miranda , Quig Nathan , Yap Edward , Lau Winnie
Published: October 2022

We report two cases of endovascular intervention for management of cerebral venous sinus thrombosis complicated by an acute intracranial hemorrhage during treatment with therapeutic anticoagulation. The first patient developed an acute subdural hematoma with progressive enlargement and was subsequently managed with venous sinus thrombectomy. The second patient developed an intraparenchymal and subdural hematoma and was treated with middle meningeal embolization. Anticoagulation is the primary treatment for cerebral venous sinus thrombosis but also contraindicated in an acute intracranial hemorrhage. In these cases, after endovascular intervention both patients resumed therapeutic anticoagulation without further hematoma expansion or additional invasive interventions. Both patients made an excellent neurological recovery and returned to their baseline functional independent status. Given the need for anticoagulation, endovascular intervention in the form of thrombectomy or middle meningeal artery embolization may be a viable adjuvant to anticoagulation in select patients.
Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory
Authors: Erdinger Susanne , Amrein Irmgard , Back Michaela , Ludewig Susann , Korte Martin , von Engelhardt Jakob , Wolfer David P. , Müller Ulrike C.
Published: October 2022

The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer’s disease.
Psychotic-like experiences in the lonely predict conspiratorial beliefs and are associated with the diet during COVID-19
Authors: Terenzi Damiano , Muth Anne-Katrin , Losecaat Vermeer Annabel , Park Soyoung Q.
Published: October 2022

The COVID-19 pandemic has increased the occurrence of conspiracy theories. It has been suggested that a greater endorsement of these theories may be associated with psychotic-like experiences (PLEs), as well as with social isolation. In this preregistered study, we investigated whether both PLEs and measures of social isolation (e.g., loneliness) can predict conspiratorial beliefs and, if so, which of these variables can mediate the association with conspiratorial beliefs. Furthermore, based on previous studies on schizophrenia, we explored whether the diet is associated with PLEs and conspiratorial beliefs. Participants (N = 142) completed online questionnaires measuring PLEs, social isolation, mental well-being, and conspiratorial beliefs. They also submitted their daily food intake for a week using a smartphone app. We found that loneliness predicted the endorsement of conspiracy theories during the COVID-19 lockdown. Strikingly, the proneness to experience subclinical psychotic symptoms played an underlying mediating role. In addition, these subclinical symptoms were associated with lower fruit, carbohydrate, and iron intakes, as well as with higher fat intake. Our results add insights into how conspiratorial beliefs can affect individuals’ mental health and relationships. Moreover, these results open the avenue for potential novel intervention strategies to optimize food intake in individuals with PLEs.
Comprehensive review of composition distribution and advances in profiling of phenolic compounds in oilseeds
Authors: Zhang Yao , Xiao Huaming , Lv Xin , Wang Dan , Chen Hong , Wei Fang
Published: October 2022

A wide range of phenolic compounds participate in oilseed growth, regulate oxidative stability of corresponding vegetable oil, and serve as important minor food components with health-promoting effects. Composition distribution of phenolic compounds varied in oilseeds. Isoflavones, sinapic acid derivatives, catechin and epicatechin, phenolic alcohols, chlorogenic acid, and lignans were the main phenolic compounds in soybean, rapeseed, peanut skin, olive, sunflower seed, sesame and flaxseed, respectively. Among which, the total isoflavones content in soybean seeds reached from 1,431 to 2,130 mg/100 g; the main phenolic compound in rapeseed was sinapine, representing 70–90%; chlorogenic acid as the predominant phenolic compound in sunflower kernels, represented around 77% of the total phenolic content. With the rapid development of analytical techniques, it is becoming possible for the comprehensive profiling of these phenolic compounds from oilseeds. This review aims to provide recently developments about the composition distribution of phenolic compounds in common oilseeds, advanced technologies for profiling of phenolic compounds by the metabolomics approaches based on mass spectrometry. As there is still limited research focused on the comprehensive extraction and determination of phenolics with different bound-forms, future efforts should take into account the non-targeted, pseudo-targeted, and spatial metabolomic profiling of phenolic compounds, and the construction of phenolic compound database for identifying and quantifying new types of phenolic compounds in oilseeds and their derived products.
Use of radiomics containing an effective peritumoral area to predict early recurrence of solitary hepatocellular carcinoma ≤5 cm in diameter
Authors: Wang Fang , Cheng Ming , Du Binbin , Li Li-ming , Huang Wen-peng , Gao Jian-bo
Published: October 2022

Background

Hepatocellular carcinoma (HCC) is the sixth leading type of cancer worldwide. We aimed to develop a preoperative predictive model of the risk of early tumor recurrence after HCC treatment based on radiomic features of the peritumoral region and evaluate the performance of this model against postoperative pathology.

Method

Our model was developed using a retrospective analysis of imaging and clinicopathological data of 175 patients with an isolated HCC ≤5 cm in diameter; 117 patients were used for model training and 58 for model validation. The peritumoral area was delineated layer-by-layer for the arterial and portal vein phase on preoperative dynamic enhanced computed tomography images. The volume area of interest was expanded by 5 and 10 mm and the radiomic features of these areas extracted. Lasso was used to select the most stable features.

Results

The radiomic features of the 5-mm area were sufficient for prediction of early tumor recurrence, with an area under the curve (AUC) value of 0.706 for the validation set and 0.837 for the training set using combined images. The AUC of the model using clinicopathological information alone was 0.753 compared with 0.786 for the preoperative radiomics model (P >0.05).

Conclusions

Radiomic features of a 5-mm peritumoral region may provide a non-invasive biomarker for the preoperative prediction of the risk of early tumor recurrence for patients with a solitary HCC ≤5 cm in diameter. A fusion model that combines the radiomic features of the peritumoral region and postoperative pathology could contribute to individualized treatment of HCC.
Cause of death during upper tract urothelial carcinoma survivorship: A contemporary, population-based analysis
Authors: Peng Fu-Sheng , Wu Wan-Ting , Zhang Lu , Shen Jia-Hua , Yu Dong-Dong , Mao Li-Qi
Published: October 2022

Background

Very few studies have been published on the causes of death of upper tract urothelial carcinoma (UTUC). We sought to explore the mortality patterns of contemporary UTUC survivors.

Methods

We performed a retrospective cohort study involving patients with upper urinary tract carcinoma from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2000 and 2015). We used standardized mortality ratios (SMRs) to compare death rates among patients with UTUC in the general population and excess absolute risks (EARs) to quantify the disease-specific death burden.

Results

A total of 10,179 patients with UTUC, including 7,133 who died, were included in our study. In total, 302 (17.17%) patients with the localized disease died of UTUC; however, patients who died from other causes were 4.8 times more likely to die from UTUC (n = 1,457 [82.83%]). Cardiovascular disease was the most common non-cancer cause of death (n = 393 [22.34% of all deaths]); SMR, 1.22; 95% confidence intervals [CI], 1.1–1.35; EAR, 35.96). A total of 4,046 (69.99%) patients with regional stage died within their follow-up, 1,413 (34.92%) of whom died from UTUC and 1,082 (26.74%) of whom died from non-cancer causes. UTUC was the main cause of death (SMR, 242.48; 95% CI, 230–255.47; EAR, 542.47), followed by non-tumor causes (SMR, 1.18; 95% CI, 1.11–1.25; EAR, 63.74). Most patients (94.94%) with distant stage died within 3 years of initial diagnosis. Although UTUC was the leading cause of death (n = 721 [54.29%]), these patients also had a higher risk of death from non-cancer than the general population (SMR, 2.08; 95% CI, 1.67–2.56; EAR, 288.26).

Conclusions

Non-UTUC deaths accounted for 82.48% of UTUC survivors among those with localized disease. Patients with regional/distant stages were most likely to die of UTUC; however, there is an increased risk of dying from non-cancer causes that cannot be ignored. These data provide the latest and most comprehensive assessment of the causes of death in patients with UTUC.
Liver resection, radiofrequency ablation, and radiofrequency ablation combined with transcatheter arterial chemoembolization for very-early- and early-stage hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis for comparison of efficacy
Authors: Zhang Yunlong , Qin Yunlong , Dong Peng , Ning Houfa , Wang Guangzhi
Published: October 2022

Objective

To compare the efficacy of liver resection (LR), radiofrequency ablation (RFA), and radiofrequency ablation combined with transcatheter arterial chemoembolization (RFA+TACE) in the treatment of very-early- and early-stage hepatocellular carcinoma (HCC).

Methods

We systemically searched the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) and observational analyses with propensity score-matched cohort analyses (PSMs) comparing any two of the three treatments were included in this study. The primary result was overall survival (OS) and the secondary result was recurrence-free survival (RFS), which were analyzed by calculating the hazard ratio (HR) and 95% confidence intervals (CI).

Results

A total of 25 studies (4249 patients), including 10 RCTs and 15 PSM observational studies, met the inclusion criteria. Although there was no significant difference between LR and RFA in terms of one-year OS, though LR showed superior performance for three- and five-year OS (at three years, HR: 0.74, 95% CI: 0.56-0.96; at five years, HR: 0.73, 95% CI: 0.55-0.94). In addition, significantly higher rates of RFS at one-, three- and five-year follow-up were found for LR than for RFA alone (at one year, HR: 0.68, 95% CI: 0.51-0.92; at three years, HR: 0.67, 95% CI: 0.55-0.81; at five years, HR: 0.61, 95% CI: 0.48-0.78). The combination of RFA+TACE was superior to RFA alone based on one-year RFS (HR: 0.57, 95% CI: 0.34-0.96), while there were no significant differences in OS at one, three, and five years, and in RFS at three and five years.

Conclusions

For very-early- and early-stage HCC, this systematic review and network meta-analysis showed that the efficacy of LR is superior to that of RFA alone, regardless of whether the evaluation is based on either OS or RFS. The advantages of RFA+TACE compared to RFA alone are limited, and further studies are needed to determine whether combination therapy is necessary, i.e., results in significantly improved outcomes.

Systematic Review Registration

The study was registered with http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022299269
Cost-utility analysis of empagliflozin in heart failure patients with reduced and preserved ejection fraction in China
Authors: Tang Yi , Sang Haiqiang
Published: October 2022

Objective: EMPEROR-Reduced and EMPEROR-Preserved studies showed the benefits of empagliflozin along with a reduction in cardiovascular death or hospitalisation for heart failure (HF). Our aim was to evaluate the economics and effectiveness of adding empagliflozin to the standard therapy for HF with reduced ejection fraction (HFrEF) and HF preserved ejection fraction (HFpEF) in China.

Methods: A multistate Markov model was constructed to yield the clinical and economic outcomes of adding empagliflozin to the standard therapy for 65-year-old patients with HFrEF and HFpEF. A cost-utility analysis was conducted, mostly derived from the EMPEROR-Reduced study, EMPEROR-Preserved study, and national statistical database. All costs and outcomes were discounted at the rate of 5% per annum. The primary outcomes were total and incremental costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were also performed.

Results: In the HFrEF population, the 10-year incremental cost was $827.52 and the 10-year incremental QALY was 0.15 QALYs, resulting in an ICER of $5,612.06/QALY, which was below the WTP of $12,652.5/QALY. In the HFpEF population, compared with the control group, the incremental cost was $1,271.27, and the incremental QALY was 0.11 QALYs, yielding an ICER of 11,312.65 $/QALY, which was also below the WTP of $12,652.5/QALY. In the HFrEF and HFpEF populations, the results of a one-way sensitivity analysis showed that the risk of cardiovascular death in both groups was the most influential parameter. In the HFrEF population, a probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,652.5/QALY and $37,957.5/QALY, the probabilities of being cost-effective with empagliflozin as an add-on were 59.4% and 72.6%, respectively. In the HFpEF population, the PSA results revealed that the probabilities of being cost-effective with empagliflozin as an add-on were 53.1% and 72.2%, respectively.

Conclusion: Considering that the WTP threshold was $12,652.5/QALY, adding empagliflozin to standard therapy was proven to be a slightly more cost-effective option for the treatment of HFrEF and HFpEF from a Chinese healthcare system perspective, which promoted the rational use of empagliflozin for HF.
Crohn’s disease patients with L4-esophagogastroduodenal phenotype is associated with a better prognosis: A retrospective cohort study
Authors: Weng Jingrong , Lin Xutao , Chen Xi , Liang Yu-fan , Xu Yu-cheng , Cai Jia-wei , Lu Peng-cheng , Rong Yuming , Zou Yifeng , Zhu Lixin
Published: October 2022

Background: In the Montreal classification, L4 Crohn’s disease (CD) is defined as an ileal disease, including L4-esophagogastric duodenum (EGD), L4-jejunum, and L4-proximal ileal involvement. According to the previous studies, the prognosis of L4 disease was worse than that of non-L4 disease. Among L4 diseases, the phenotypes of L4-jejunum and L4-proximal ileum indicated that the risk of abdominal surgery was higher. However, the prognosis of L4-esophagogastroduodenal remains largely elusive. Therefore, we aim to investigate whether the prognosis differs between CD patients with and without esophagogastroduodenal involvement.

Methods: In this study, patients with L4-EGD phenotype (n = 74) who underwent gastroscopy, ileocolonoscopy, biopsies, and CTE from 2018 to 2020 were compared with L4 non-EGD controls (n = 148) who were randomly selected at a ratio of 1:2 in the same period. Demographic information inclusive of disease conduct and location, important points of the surgery, and hospitalization have been collected. The distinction between L4-EGD patients and non-L4-EGD patients was identified by way of multivariable logistic regression analysis. The Kaplan–Meier technique was used to consider the possibility of abdominal surgical operation and complications, observed by means of Cox percentage hazard fashions to decide if L4 EGD independently estimated the endpoints inclusive of the abdominal surgery and the occurrences of complications.

Results: L4-EGD group (n = 74) had a lower proportion of intestinal fistula than the control group (n = 148) (17.6% versus 34.5%; p = 0.009), and the probabilities of requiring abdominal surgery and multiple abdominal surgeries were also lower (21.6% versus 36.5%; p = 0.025), (6.8% versus 18.9%; p = 0.016), respectively. The frequency of hospitalization was lower in the L4-EGD group than in the control group (3-7 versus 4–9; p = 0.013). L4-EGD phenotype was found to be an independent protective factor for abdominal surgery and intestinal fistula in the Cox regression model, with HRs of 0.536 (95%CI: 0.305–0.940; p = 0.030) and 0.478 (95%CI: 0.259–0.881; p = 0.018), respectively.

Conclusion: Our data suggest that the L4-EGD phenotype may have a better prognosis compared to the Non-L4-EGD phenotype. Our data may advocate a revision of the Montreal classification including separate designations for L4-EGD disease.
Terpene-Enriched CBD oil for treating autism-derived symptoms unresponsive to pure CBD: Case report
Authors: Raz Noa , Heller Iso , Lombardi Titti , Marino Giorgio , Davidson Elyad M. , Eyal Aharon M.
Published: October 2022

Cannabidiol (CBD) rich products are successfully used in some countries for treating symptoms associated with autism spectrum disorder (ASD). Yet, CBD provides insufficient intervention in some individuals, or for some characterizing symptoms of ASD, raising the need for improved compositions. The current study presents a case wherein pure CBD was sufficient for treating ASD during childhood and early adolescence. However, it became insufficient during puberty accompanied by increased hyperactivity, agitation, and frequent severe aggressive behavior. Increasing the CBD dose did not result in significant improvement. Enriching the pure CBD with a carefully selected blend of anxiolytic and calming terpenes, resulted in gradual elimination of those aggressive events. Importantly, this was achieved with a significantly reduced CBD dose, being less than one-half the amount used when treating with pure CBD. This case demonstrates a strong improvement in efficacy due to terpene enrichment, where pure CBD was not sufficient. Combined with terpenes’ high safety index and the ease with which they can be incorporated into cannabinoid-containing products, terpene-enriched CBD products may provide a preferred approach for treating ASD and related conditions. The careful selection of terpenes to be added enables maximizing the efficacy and tailoring the composition to particular and changing needs of ASD subjects, e.g., at different times of the day (daytime vs nighttime products).
Low FNDC5/Irisin expression is associated with aggressive phenotypes in gastric cancer
Authors: Xu Luyun , Ye Yan , Sun Yuqin , Zhong Wenting , Chi Liangjie , Lin Youyu , Liu Hongxia , Li ShengZhao , Chen Hui , Li Chengcheng , Lin Yuxuan , Wang Qingshui , Xue Fangqin , Lin Yao
Published: October 2022

Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown.

Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients.

Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients.

Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.
Non-degenerate rogue waves and multiple transitions in systems of three-wave resonant interaction
Authors: Wu Yu-Han , Liu Chong , Yang Zhan-Ying , Yang Wen-Li
Published: October 2022

Non-degenerate rogue waves (RWs) and multiple transitions between RWs and solitons arising from vector three-wave resonant interaction are studied analytically and numerically. In contrast to the conventional degenerate RWs, such non-degenerate RWs consist of two fundamental RWs each with individual Lax spectral parameter. We show distinctive continuous transitions from bright (dark) RWs to four-petal RWs to dark (bright) solitons as the relative frequency between the wave components increases. The underlying mechanism of such processes is the non-monotonic variation of the energy exchanges between different components of the waves. We further reveal the transition dynamics of non-degenerate RWs. Finally, we confirm numerically the robustness of the transition dynamics in the presence of spontaneous modulation instability induced by white noise. Our results provide insights into the RW formation and the multiple transitions in systems with three-wave resonant interaction, and may offer the possibility of experimental observations in multi-component resonant processes.
OsDREB2B, an AP2/ERF transcription factor, negatively regulates plant height by conferring GA metabolism in rice
Authors: Ma Ziming , Jin Yong-Mei , Wu Tao , Hu Lanjuan , Zhang Ying , Jiang Wenzhu , Du Xinglin
Published: October 2022

The AP2/ERF family is a large group of plant-specific transcription factors that play an important role in many biological processes, such as growth, development, and abiotic stress responses. OsDREB2B, a dehydration responsive factor (DRE/CRT) in the DREB subgroup of the AP2/ERF family, is associated with abiotic stress responses, such as cold, drought, salt, and heat stress, in Arabidopsis or rice. However, its role in regulating plant growth and development in rice is unclear. In this study, we reported a new function of OsDREB2B, which negatively regulates plant height in rice. Compared with wild type (WT), OsDREB2B-overexpressing (OE) rice exhibited dwarf phenotypes, such as reduction in plant height, internode length, and seed length, as well as grain yield, while the knockout mutants developed by CRISPR/Cas9 technology exhibited similar phenotypes. Spatial expression analysis revealed that OsDREB2B was highly expressed in the leaf sheaths. Under exogenous GA3 application, OsDREB2B expression was induced, and the length of the second leaf sheath of the OsDREB2B-OE lines recovered to that of the WT. OsDREB2B localized to the nucleus of the rice protoplast acted as a transcription activator and upregulated OsAP2-39 by directly binding to its promoter. OsDREB2B-OE lines reduced endogenous bioactive GA levels by downregulating seven GA biosynthesis genes and upregulating eight GA deactivation genes but not GA signaling genes. The yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that OsDREB2B interacted with OsWRKY21. In summary, our study suggests that OsDREB2B plays a negative role in rice growth and development by regulating GA metabolic gene expression, which is mediated by OsAP2-39 and OsWRKY21, thereby reducing GA content and rice plant height.