bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoadjuvant chemotherapy without radiation therapy for rectal cancer with negative prognosis
Authors: Nevolskikh A. A. , Avdeenko V. A. , Belohvostova A. S. , Zibirov R. F. , Mihaleva Yu. Yu. , Pochuev T. P. , Berezovskaya T. P. , Daineko Ya. A. , Petrov L. O. , Ivanov S. A. , Kaprin A. D.
Published: June 2022

Aim: to assess the effectiveness of neo-CT in the FOLFOX6 regimen in patients with mid- and upper rectal cancer (RC)associated with poor prognosis.   Patients and methods: fifty-two patients were included into study. All had neo-CT with subsequent surgical treat-ment between 2017 and 2021. Of them 94.2% had stage III and 5.8% had stage II. An extramural vascular invasionwas detected by MRI in 33 (63.5%) patients. The distance between the tumor and the mesorectal fascia was ≤ 2 mmin 17%. All patients had 4 cycles of neo-CT in FOLFOX6 regimen followed by surgery.   Results: the compliance (≥ 4 cycles of neo-CT) was 82.7 % (n = 43). The overall toxicity rate was 35.6 %. Sphincter-saving surgery was performed in 51 (98.1 %) patients. Postoperative morbidity was 25.0 %. Final pathology revealed stage III in 29 (55.8 %) patients, stage 0 — stage II — in 22 (42.3 %). In accordance with the degree of pathomorphosis (CAP, 2019), 12 (23.1 %) patients showed a partial response. In one patient (1.9 %) no signs of residual tumor were detected. Downstaging of the T stage compared with MRI data before neo-CT was noted in 23 (44.2 %) patients, N stage — in 29 (55.8 %). With a mean follow-up of 31 (3-54) months, local recurrences were detected in 5 (9.6 %) patients, and distant metastases in 4 (7.7 %). The cumulative 3-year recurrence rate was 11.3 ± 4.8 %. The three-year overall and recurrence-free survival rate was 88.2 ± 5.8 % and 76.4 ± 7.4 %, respectively.

   Conclusion: the multimodal approach for RC with adverse prognostic factors using neo-CT in the FOLFOX6 regimenis well tolerated by patients, has a small toxicity and postoperative morbidity as well. It is necessary to develop newpathology criteria for tumor response to neo-CT.
Analysis of Omics Data Reveals Nucleotide Excision Repair-Related Genes Signature in Highly-Grade Serous Ovarian Cancer to Predict Prognosis
Authors: Dai Danian , Li Qiang , Zhou Pengfei , Huang Jianjiang , Zhuang Hongkai , Wu Hongmei , Chen Bo
Published: June 2022

Most of the high-grade serous ovarian cancers (HGSOC) are accompanied by P53 mutations, which are related to the nucleotide excision repair (NER) pathway. This study aims to construct a risk signature based on NER-related genes that could effectively predict the prognosis for advanced patients with HGSOC. In our study, we found that two clusters of HGSOC with significantly different overall survival (OS) were identified by consensus clustering and principal component analysis (PCA). Then, a 7-gene risk signature (DDB2, POLR2D, CCNH, XPC, ERCC2, ERCC4, and RPA2) for OS prediction was developed subsequently based on TCGA cohort, and the risk score-based signature was identified as an independent prognostic indicator for HGSOC. According to the risk score, HGSOC patients were divided into high-risk group and low-risk group, in which the distinct OS and the predictive power were also successfully verified in the GEO validation sets. Then we constructed a nomogram, including the risk signature and clinical-related risk factors (age and treatment response) that predicted an individual’s risk of OS, which can be validated by assessing calibration curves. Furthermore, GSEA showed that the genes in the high-risk group were significantly enriched in cancer-related pathways, such as “MAPK signaling pathway”, “mTOR signaling pathway”, “VEGF signaling pathway” and so on. In conclusion, our study has developed a robust NER-related genes-based molecular signature for prognosis prediction, and the nomogram could be used as a convenient tool for OS evaluation and guidance of therapeutic strategies in advanced patients with HGSOC.
A Data-Driven Semi-Supervised Soft-Sensor Method: Application on an Industrial Cracking Furnace
Authors: Ma Fangyuan , Wang Jingde , Sun Wei
Published: June 2022

The cracking furnace is the key equipment of the ethylene unit. Coking in furnace tubes results from the generation of coke during cracking, which will compromise the heat transfer efficiency and lead to shape change of tubes. In order to keep the cracking furnace operating economically and safely, the engineers need to decoke according to the surface temperature of the furnace tube. However, the surface temperature of the furnace tube is difficult to obtain in practice. Due to redundant instrumentation and the high level of process control in cracking furnaces, a large number of operation data have been collected, which makes it possible to predict the surface temperature of furnace tubes based on autocorrelation and cross correlation within and among variables. Traditional prediction methods rely on labeled data samples for training, ignoring the process information contained in a vast amount of unlabeled data. In this work, a data-driven semi-supervised soft-sensor method is proposed. Considering the nonlinear and dynamic relationship among variables, long short-term memory network (LSTM) autoencoder (AE), a deep neural network suitable for the feature extraction of long-term nonlinear series, is used for pre-training to extract process data features from unlabeled and labeled data. Then, principal component analysis (PCA) and mutual information (MI) are applied to remove feature correlation and select features related to target variables, respectively. Finally, the selected data features are utilized to establish a soft-sensor model based on artificial neural network (ANN). Data from an industrial cracking furnace of an ethylene unit is considered to validate the performance of the proposed method. The results show that the prediction error of furnace tube surface temperature is about 1% and successfully aid engineers in determining the optimal time for decoking.
Canine Adenovirus 1 Isolation Bioinformatics Analysis of the Fiber
Authors: Wang Ben , Wang Minchun , Zhang Hongling , Xu Jinfeng , Hou Jinyu , Zhu Yanzhu
Published: June 2022

Canine adenovirus type 1 (CAdV-1) is a double-stranded DNA virus, which is the causative agent of fox encephalitis. The Fiber protein is one of the structural proteins in CAdV-1, which mediates virion binding to the coxsackievirus and adenovirus receptor on host cells. The suspected virus was cultured in the MDCK cells, and it was determined through the cytopathic effects, sequencing and electron microscopy. The informatics analysis of the Fiber was done using online bioinformatics servers. The CAdV-1-JL2021 strain was isolated successfully, and were most similar to the CAdV-1 strain circulating in Italy. The occurrence of negative selection and recombination were found in the CAdV-1-JL2021 and CAdV-2-AC_000020.1. Host cell membrane was its subcellular localization. The CAdV-1-JL2021 Fiber (ON164651) had 6 glycosylation sites and 107 phosphorylation sites, exerted adhesion receptor-mediated virion attachment to host cell, which was the same as CAdV-2-AC_000020.1 Fiber. The Fiber tertiary structure of the CAdV-1-JL2021 and CAdV-2-AC_000020.1 was different, but they had the same coxsackievirus and adenovirus receptor. “VATTSPTLTFAYPLIKNNNH” were predicted to be the potential CAdV-1 B cell linear epitope. The MHC-I binding peptide “KLGVKPTTY” were both presented in the CAdV-1-JL2021 and CAdV-2-AC_000020.1 Fiber and it is useful to design the canine adenovirus vaccine.
Phaeohyphomycosis in China
Authors: He Yun , Zheng Hai-lin , Mei Huan , Lv Gui-xia , Liu Wei-da , Li Xiao-fang
Published: June 2022

Background

Due to more attentions paid to melanized fungi over the past few decades and under the background of the global coronavirus disease 2019 pandemic (COVID-19) the fact that the virus itself and the immunosuppressive agents such as glucocorticoids can further increase the risk of infections of deep mycoses, the number of patients with phaeohyphomycosis (PHM) has a substantial increase. Their spectrum is broad and the early diagnosis and treatments are extremely sticky. This study aims to more comprehensively understand the clinical features of phaeohyphomycosis in China over 35 years and to establish a more applicable systematical classification and severity grades of lesions to guide treatments and prognosis.

Methods

We reviewed 174 cases of proven phaeohyphomycosis reported in Chinese and English language literature from 1987 to 2021 and we also made the accurate classification definitions and detailed information about the epidemiology, species of clinical dematiaceous fungi, minimum inhibitory concentration values, clinical features, treatments, and prognosis.

Results

The mortality of cerebral, disseminated and pulmonary phaeohyphomycosis are 55%, 36%, and 25%. Nearly 19% of patients had poor quality of life caused by the complications such as disability, disfigurements, and blindness. The overall misdiagnosis rate of phaeohyphomycosis was 74%. Moderate to severe rashes are accounting for 82% of subcutaneous phaeohyphomycosis. The areas of the head and face are mostly affected accounting for 16% of severe rashes. Nearly 30% of invasive infections of phaeohyphomycosis are triggered by recurrent lesions. Voriconazole, itraconazole, amphotericin B deoxycholate (AmB-DOC), and terbinafine were most commonly used but diagnosis and treatments of phaeohyphomycosis remain challenging in reality.

Conclusions

Our classifications are likely to be more practical and easier to popularize, and there are still also plenty of characteristics in these non-specific lesions. There’re no significant variations in cure rates, or death rates between three grades of lesions. But patients with severe rashes have longer courses and lower effective rates.
Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study
Authors: Ueha Rumi , Ito Toshihiro , Furukawa Ryutaro , Kitabatake Masahiro , Ouji-Sageshima Noriko , Ueha Satoshi , Koyama Misaki , Uranaka Tsukasa , Kondo Kenji , Yamasoba Tatsuya
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause long-lasting anosmia, but the impact of SARS-CoV-2 infection, which can spread to the nasal cavity via the oral route, on the olfactory receptor neuron (ORN) lineage and olfactory bulb (OB) remains undetermined. Using Syrian hamsters, we explored whether oral SARS-CoV-2 inoculation can lead to nasal viral infection, examined how SARS-CoV-2 affects the ORN lineage by site, and investigated whether SARS-CoV-2 infection can spread to the OB and induce inflammation. On post-inoculation day 7, SARS-CoV-2 presence was confirmed in the lateral area (OCAM-positive) but not the nasal septum of NQO1-positive and OCAM-positive areas. The virus was observed partially infiltrating the olfactory epithelium, and ORN progenitor cells, immature ORNs, and mature ORNs were fewer than in controls. The virus was found in the olfactory nerve bundles to the OB, suggesting the nasal cavity as a route for SARS-CoV-2 brain infection. We demonstrated that transoral SARS-CoV-2 infection can spread from the nasal cavity to the central nervous system and the possibility of central olfactory dysfunction due to SARS-CoV-2 infection. The virus was localized at the infection site and could damage all ORN-lineage cells.
Sex Differences in Epicardial Adipose Tissue: Association With Atrial Fibrillation Ablation Outcomes
Authors: Zhu Jing , Zhuo Kaimin , Zhang Bo , Xie Zhen , Li Wenjia
Published: June 2022

Background

There are significant differences in the prevalence and prognosis of atrial fibrillation (AF) between sexes. Epicardial adipose tissue (EAT) has been found as a risk factor for AF. This study aimed to evaluate whether sex-based EAT differences were correlated with AF recurrence and major adverse cardiovascular events (MACE).

Methods

In this study, postmenopausal women and age, BMI, and type of AF matched men who had received first catheter ablation were included. EAT volume was quantified based on the pre-ablation cardiac computed tomography (CT) images. Clinical, CT, and echocardiographic variables were compared by sex groups. The predictors of AF recurrence and MACE were determined through Cox proportional hazards regression.

Results

Women were found with significantly lower total EAT volumes (P < 0.001) but higher periatrial/total (P/T) EAT ratios (P = 0.009). The median follow-up duration was 444.5 days. As revealed by the result of the Kaplan-Meier survival analysis, the women were found to have a significantly higher prevalence of AF recurrence (log rank, P = 0.011) but comparable MACE (log rank, P = 0.507) than men. Multivariate analysis demonstrated that female gender (HR: 1.88 [95% CI: 1.03, 4.15], P = 0.032), persistent AF (HR: 2.46 [95% CI: 1.19, 5.05], P = 0.015), left atrial (LA) dimension (HR: 1.47 [95% CI: 1.02, 2.13], P = 0.041), and P/T EAT ratio (HR: 1.73 [95% CI: 1.12, 2.67], P = 0.013) were found as the independent predictors of AF recurrence. Sex-based subgroup multivariable analysis showed that the P/T EAT ratio was an independent predictor of AF recurrence in both men (HR: 1.13 [95% CI: 1.01, 1.46], P = 0.047) and women (HR: 1.37 [95% CI: 1.11, 1.67], P = 0.028). While age (HR: 1.81 [95% CI: 1.18, 2.77], P = 0.007), BMI (HR: 1.44 [95% CI: 1.02, 2.03], P = 0.038), and periatrial EAT volume (HR: 1.31 [95% CI: 1.01, 1.91], P = 0.046) were found to be independent of MACE.

Conclusion

Women had a higher P/T EAT ratio and AF post-ablation recurrence but similar MACE as compared with men. Female gender and P/T EAT ratio were found to be independent predictors of AF recurrence, whereas age and periatrial EAT volume were found to be independent predictors of MACE.
Computational Fractional Flow Reserve From Coronary Computed Tomography Angiography—Optical Coherence Tomography Fusion Images in Assessing Functionally Significant Coronary Stenosis
Authors: Lee Yong-Joon , Kim Young Woo , Ha Jinyong , Kim Minug , Guagliumi Giulio , Granada Juan F. , Lee Seul-Gee , Lee Jung-Jae , Cho Yun-Kyeong , Yoon Hyuck Jun , Lee Jung Hee , Kim Ung , Jang Ji-Yong , Oh Seung-Jin , Lee Seung-Jun , Hong Sung-Jin , Ahn Chul-Min , Kim Byeong-Keuk , Chang Hyuk-Jae , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo , Lee Joon Sang , Kim Jung-Sun
Published: June 2022

Background

Coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) provide additional functional information beyond the anatomy by applying computational fluid dynamics (CFD). This study sought to evaluate a novel approach for estimating computational fractional flow reserve (FFR) from coronary CTA-OCT fusion images.

Methods

Among patients who underwent coronary CTA, 148 patients who underwent both pressure wire-based FFR measurement and OCT during angiography to evaluate intermediate stenosis in the left anterior descending artery were included from the prospective registry. Coronary CTA-OCT fusion images were created, and CFD was applied to estimate computational FFR. Based on pressure wire-based FFR as a reference, the diagnostic performance of Fusion-FFR was compared with that of CT-FFR and OCT-FFR.

Results

Fusion-FFR was strongly correlated with FFR (r = 0.836, P < 0.001). Correlation between FFR and Fusion-FFR was stronger than that between FFR and CT-FFR (r = 0.682, P < 0.001; z statistic, 5.42, P < 0.001) and between FFR and OCT-FFR (r = 0.705, P < 0.001; z statistic, 4.38, P < 0.001). Area under the receiver operating characteristics curve to assess functionally significant stenosis was higher for Fusion-FFR than for CT-FFR (0.90 vs. 0.83, P = 0.024) and OCT-FFR (0.90 vs. 0.83, P = 0.043). Fusion-FFR exhibited 84.5% accuracy, 84.6% sensitivity, 84.3% specificity, 80.9% positive predictive value, and 87.5% negative predictive value. Especially accuracy, specificity, and positive predictive value were superior for Fusion-FFR than for CT-FFR (73.0%, P = 0.007; 61.4%, P < 0.001; 64.0%, P < 0.001) and OCT-FFR (75.7%, P = 0.021; 73.5%, P = 0.020; 69.9%, P = 0.012).

Conclusion

CFD-based computational FFR from coronary CTA-OCT fusion images provided more accurate functional information than coronary CTA or OCT alone.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT03298282].
Testing Site Amplification Curves in Hybrid Broadband Ground Motion Simulations of M6.0, 24 August 2016 Amatrice Earthquake, Italy
Authors: Pischiutta Marta , Akinci Aybige , Felicetta Chiara , Pacor Francesca , Morasca Paola
Published: June 2022

This research focuses on predicting and assessing earthquake impact due to future scenarios regarding the ground motion seismic hazard by accounting mainly for site effect in the Central Apennines. To this end, we produced synthetic broadband seismograms by adopting a hybrid simulation technique for the Mw6.0 Amatrice earthquake, Central Italy, on 24 August 2016, accounting for site conditions by means of amplification curves, computed with different approaches. Simulations were validated by comparing with data recorded at 57 strong-motion stations, the majority installed in urban areas. This station sample was selected among stations recording the Amatrice earthquake within an epicentral distance of 150 km and potentially prone to experience site amplification effects because of lying in particular site conditions (sedimentary basins, topographic irregularities, and fault zones). The evaluation of amplification curves best suited to describe local effects is of great importance because many towns and villages in central Italy are built in very different geomorphological conditions, from valleys and sedimentary basins to topographies. In order to well reproduce observed ground motions, we accounted for the site amplification effect by testing various generic and empirical amplification curves such as horizontal-to-vertical spectral ratios (calculated from Fourier spectra using both earthquake, HVSR, and ambient noise, HVNSR, recordings) and those derived from the generalized inversion technique (GIT). The site amplifications emanated from GIT improve the match between observed and simulated data, especially in the case of stations installed in sedimentary basins, where the empirical amplification curve effectively reproduces spectral peaks. On the contrary, the worst performances are for the spectral ratios between components, even compared to the generic site amplification, although the latter ignores the strong bedrock/soil seismic impedance contrasts. At sites on topography, we did not observe any systematic behavior, the use of empirical curves ameliorating the fit only in a small percentage of cases. These results may provide a valuable framework for developing ground motion models for earthquake seismic hazard assessment and risk mitigation, especially in urban areas located in the seismically active central Italy region.
Discourse Moves and Emotion in Knowledge Building Discourse and Metadiscourse
Authors: Zhu Gaoxia , Scardamalia Marlene , Moreno Matthew , Martins Michael , Nazeem Raadiyah , Lai Zhixin
Published: June 2022

This paper explores the possibility that knowledge building metadiscourse-discourse about knowledge building-can produce a positive feedback loop, with positive emotional state and knowledge advancement serving to increase each other. Grades 2 and 3 students’ utterances over several months were analyzed as a unit of study, starting with identification of each discourse move and corresponding emotion, defined as a state. These states were then analyzed over time, with a focus on metadiscourse sessions in which students reflected on earlier discourse to identify questions and ideas to be pursued in greater depth. Each discourse move-emotional state was analyzed to determine frequency, transition from one state to another, and spread of each state such as “reflection and positive” and “proposing new directions for inquiry and curiosity.” These two states were among the most frequently occurring in the metadiscourse sessions and virtually absent in other discourse sessions. Transition rates indicated that reflection tended to trigger more reflection, and proposing a new direction led to more proposals for new directions. Sequential pattern analysis suggested sub-sequences specific to metadiscourse sessions. Overall, results indicate that engaging in metadiscourse contributes to students’ productive KB and positive emotions.
The Predictive Value of Adipokines and Metabolic Risk Factors for Dropouts and Treatment Outcomes in Children With Obesity Treated in a Pediatric Rehabilitation Center
Authors: Vermeiren Eline , Van Eyck Annelies , Van De Maele Karolien , Ysebaert Marijke , Makhout Sanae , De Guchtenaere Ann , Van Helvoirt Maria , Tanghe Ann , Naets Tiffany , Vervoort Leentje , Braet Caroline , Bruyndonckx Luc , De Winter Benedicte , Verhulst Stijn , Van Hoorenbeeck Kim
Published: June 2022

Background

Inpatient pediatric obesity treatments are highly effective, although dropouts and weight regain threaten long-term results. Preliminary data indicate that leptin, adiponectin, and cardiometabolic comorbidities might predict treatment outcomes. Previous studies have mainly focused on the individual role of adipokines and comorbidities, which is counterintuitive, as these risk factors tend to cluster. This study aimed to predict the dropouts and treatment outcomes by pre-treatment patient characteristics extended with cardiometabolic comorbidities (individually and in total), leptin, and adiponectin.

Methods

Children aged 8–18 years were assessed before, immediately after and 6 months after a 12-month inpatient obesity treatment. Anthropometric data were collected at each visit. Pre-treatment lipid profiles; glucose, insulin, leptin, and adiponectin levels; and blood pressure were measured. The treatment outcome was evaluated by the change in body mass index (BMI) standard deviation score (SDS) corrected for age and sex.

Results

We recruited 144 children with a mean age of 14.3 ± 2.2 years and a mean BMI of 36.7 ± 6.2 kg/m2 corresponding to 2.7 ± 0.4 BMI SDS. The 57 patients who dropped out during treatment and the 44 patients who dropped out during aftercare had a higher pre-treatment BMI compared to the patients who completed the treatment (mean BMI, 38.3 ± 6.8 kg/m2 vs 35.7 ± 5.5 kg/m2) and those who completed aftercare (mean BMI, 34.6 ± 5.3 kg/m2 vs 37.7 ± 6.3 kg/m2) (all p<0.05). Additionally, aftercare attenders were younger than non-attenders (mean age, 13.4 ± 2.3 years vs 14.9 ± 2.0, p<0.05).

Patients lost on average 1.0 ± 0.4 SDS during treatment and regained 0.4 ± 0.3 SDS post-treatment corresponding to regain of 43 ± 27% (calculated as the increase in BMI SDS post-treatment over the BMI SDS lost during treatment). A higher BMI and more comorbidities inversely predicted BMI SDS reduction in linear regression (all p<0.05).

The absolute BMI SDS increase after returning home was predicted by pre-treatment leptin and systolic blood pressure, whereas the post-treatment BMI SDS regain was predicted by pre-treatment age, leptin, and adiponectin levels (all p<0.05) in multivariate linear regressions.

Conclusion

Patients who need treatment the most are at increased risk for dropouts and weight regain, emphasizing the urgent need for interventions to reduce dropout and support inpatients after discharge. Furthermore, this study is the first to report that pre-treatment leptin and adiponectin levels predict post-treatment BMI SDS regain, requiring further research.
The Degree of Menstrual Disturbance Is Associated With the Severity of Insulin Resistance in PCOS
Authors: Li Xiaojia , Yang Dongyong , Pan Ping , Azziz Ricardo , Yang Dongzi , Cheng Yanxiang , Zhao Xiaomiao
Published: June 2022

Objective

Insulin resistance (IR) is an important determinant of the phenotype and morbidity of the polycystic ovary syndrome (PCOS). In this study, we aimed to figure out the association between the degree of menstrual disturbance and the severity of IR in women with PCOS.

Design

It is a cross-sectional study conducted in an academic tertiary setting.

Patients

The patients comprised five hundred twenty-seven women diagnosed with PCOS by the 2003 Rotterdam criteria and 565 controls with regular vaginal bleeding.

Interventions

The interventions done for this study are medical history collection, physical examination, and blood sampling.

Main outcome measures

The main outcome measures are body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters.

Results

Women with PCOS had a higher level of BMI, HOMA-IR, and HOMA-β than controls, with a decreased level of sex hormone-binding globulin and QUICK I index. The luteinizing hormone (LH)/follicle-stimulating hormone (FSH), testosterone (T), antral follicle count (AFC), dehydroepiandrosterone sulfate, free androgen index, modified Ferriman–Gallwey score, and the incidence of delayed insulin peak increased with the degree of menstrual disturbance, although there was no significance for the latter four parameters. Women with vaginal bleeding intervals of 45–90 days had a relatively higher level of HOMA-IR and HOMA-β, although it was adjusted with age and BMI than the other two groups. Similar results were observed in AUCI (area under the curve of insulin) and I/G [the ratio of AUCI and AUCG (area under the curve of glucose)]. Anovulatory women with vaginal bleeding episodes of less than 45 days tended to have higher glucose and insulin levels, area under the curve of glucose (AUCG), area under the curve of insulin (AUCI), HOMA-IR, and HOMA-β but decreased QUICK I and Matsuda index than those who were ovulatory. Women with vaginal bleeding intervals of longer than 45 days who had hyperandrogenism (HA) showed a higher level of glucose, insulin, HOMA-IR, and HOMA-β but lower QUICK I and Matsuda Index.

Conclusions

In women with PCOS, the severity of IR, the LH/FSH ratio, and androgen level increased with a higher degree of disturbance in menstrual cyclicity (i.e., the vaginal bleeding intervals). Subgroup analysis indicated that the situation of HA may aggravate the disorder of glucose metabolism in women with PCOS. Overall, the interval between episodes of vaginal bleeding may be useful as a ready measure for predicting the severity of IR in PCOS.
Glioma Subtypes Based on the Activity Changes of Immunologic and Hallmark Gene Sets in Cancer
Authors: Chen Sihan
Published: June 2022

Purpose

Glioma is the most common primary cranial brain tumor that arises from the cancelation of glial cells (which can be in the brain or spinal cord). It is due to innate genetic risk factors or induced by a carcinogenic environment. If left untreated, the disease has a poor prognosis.

Methods

In this study, we downloaded glioma data from TCGA database and GEO (GSE4412). The GSEA database was used to screen tumor microenvironment-related gene sets. Cancer subtypes were classified by GSVA enrichment method.

Results

By GSVA enrichment analysis, we obtain three Gliomas cancer subtypes. After further survival prognosis analysis and biological function analysis, we obtained 13 tumor microenvironment gene sets and 14 core genes that affect patients’ survival prognosis, and these genes have the potential to become targets for targeted therapies and disease detection.

Conclusion

We screened a total of 13 gene sets through a series of enrichment analyses, statistical and prognostic analyses, etc. Among them, 14 core genes were identified, namely: TOP2A, TPX2, BUB1, AURKB, AURKA, CDK1, BUB1B, CCNA2, CCNB2, CDCA8, CDC20, KIF11, KIF20A and KIF2C.
GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature
Authors: Apel Anja , Iliev Daniel I. , Urban Christina , Weber Karin , Schweizer Roland , Blumenstock Gunnar , Pasche Sarah , Nieratschker Vanessa , Binder Gerhard
Published: June 2022

Background

The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed.

Objective

This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied.

Design

This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples.

Results

Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment.

Conclusions

This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.
Robust Strong Structural Controllability of Complex Power Systems
Authors: Sun Yunhe , Yang Dongsheng , Gao Xiaoting , Qin Jia
Published: June 2022

Ensuring the control of power systems is crucial for their safe operation. This paper analyses the robust controllability of complex power systems from the structural sighta structural point of view. Stressing the dominant role of generators in the control of power systems, we propose three kinds of controllable networks by generator nodes. Additionally, the satisfied conditions and the relevant proof of zero forcing set in the controllable networks by generator nodes and extra nodes are given. Besides, tThe satisfied conditions and the relevant proofs of the largest set of removable edges that have no -effect on the strong structural controllability in three kinds of controllable networks by generator nodes are also proposed. Finally, the robustness of strong structural controllability of IEEE 39 bus system and IEEE 14 bus system have been analyzed. The zero-forcing set and the largest set of removable edges of IEEE 39 bus system and IEEE 14 bus system are provided.
Below Average Midsummer to Early Autumn Precipitation Evolved Into the Main Driver of Sudden Scots Pine Vitality Decline in the Swiss Rhône Valley
Authors: Hunziker Stefan , Begert Michael , Scherrer Simon C. , Rigling Andreas , Gessler Arthur
Published: June 2022

The vitality of Scots pine (Pinus sylvestris L.) is declining since the 1990s in many European regions. This was mostly attributed to the occurrence of hotter droughts, other climatic changes and secondary biotic stressors. However, it is still not well understood which specific atmospheric trends and extremes caused the observed spatio-temporal dieback patterns. In the Swiss Rhône valley, we identified negative precipitation anomalies between midsummer and early autumn as the main driver of sudden vitality decline and dieback events. Whereas climate change from 1981 to 2018 did not lead to a reduced water input within this time of the year, the potential evapotranspiration strongly increased in spring and summer. This prolonged and intensified the period of low soil moisture between midsummer and autumn, making Scots pines critically dependent on substantial precipitation events which temporarily reduce the increased water stress. Thus, local climate characteristics (namely midsummer to early autumn precipitation minima) are decisive for the spatial occurrence of vitality decline events, as the lowest minima outline the most affected regions within the Swiss Rhône valley. Mortality events will most likely spread to larger areas and accelerate the decline of Scots pines at lower elevations, whereas higher altitudes may remain suitable Scots pine habitats. The results from our regional study are relevant on larger geographic scales because the same processes seem to play a key role in other European regions increasingly affected by Scots pine dieback events.
Allopurinol-Induced Stevens–Johnson Syndrome in Javanese Men With Positive HLA‐B*58:01
Authors: Ferdiana Astri , Fachiroh Jajah , Oktarina Dyah Ayu Mira , Irwanto Astrid , Mahendra Caroline , Febriana Sri Awalia , Soebono Hardyanto
Published: June 2022

Background: Allopurinol is the most commonly used drug for the treatment of gout arthritis. However, the use of allopurinol is associated with severe cutaneous adverse reactions (SCARs) and life-threatening immune-mediated reactions that include Stevens–Johnson syndrome (SJS). SJS induced by allopurinol is strongly linked with the presence of HLA-B*58:01 in the Asian population. Such a study has not been conducted in Indonesia. We present two cases with clinical diagnosis of SJS. These patients had Javanese ethnicity, for which evidence on the genetic predisposition of allopurinol-induced SJS/TEN had not been established. Testing for the presence of the HLA-B∗58:01 allele was positive in both cases. Our case report confirms findings from studies in Asian countries that link HLA-B*58:01 and allopurinol-induced SJS/TEN. A larger study is needed to elicit evidence that the HLA-B*58:01 allele can potentially be used as a genetic marker for allopurinol-induced SCARs among different ethnicities in Indonesia.
Biomolecular Prospecting, Informative Gaps, and the Cancer Clinic: A Qualitative Fieldwork and an Epistemological, Historical and Ethical Analysis of Informed Consent for Clinical Trials for Monoclonal Antibodies and Biobank Research
Authors: D’Abramo Flavio , Bont Annemieke , Nüßlein Lisa
Published: June 2022

What happens to patients with cancer engaged in biomedical research when intellectual property regimes and ethical regimes intersect? This qualitative historical study addresses this question by situating the experiences, hopes, and reasons of patients to enter clinical trials within the historical trajectory of informed consent and monoclonal antibodies, the biotechnology underpinning many targeted drugs used in oncological clinical trials and biobank research. Based on fieldwork we undertook in a German university hospital where we interviewed patients and the medical personnel, a historical review, and an ethical analysis we inquire into the effects that financial, legal, and technological changes connected to the relevant pharmaceutical research and commerce have on cancer patients engaged in clinical trials and biobank research. We find that the controversial aspects of monoclonal antibodies, especially those related to the commercial interests at stake, enter the informed consent process mainly in the form of informative gaps. We highlight how a qualitative analysis of the clinic, especially when it is situated against the backdrop of the history of related technological advancements and patent regime, it can serve the purpose of giving voice to subjects who are silenced by regimes of an ethical, epistemic, and commercial kind while pointing to informed consent as an unhelpful device for addressing risks arising from the commercial purposes of biomedical products and infrastructure.
Cardiovascular Abnormalities and Gene Mutations in Children With Noonan Syndrome
Authors: Sun Ling , Xie Yu-mei , Wang Shu-shui , Zhang Zhi-wei
Published: June 2022

Background: Common cardiac abnormalities in Noonan syndrome (NS) include congenital heart diseases (CHD), pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Molecular diagnoses are enabling earlier and more precise diagnosis of patients who have a subtle or atypical presentation. The aims of this study were to investigate genotype-phenotype associations with respect to Noonan syndrome (NS)-associated cardiac abnormalities and catheter or surgery-based interventions conditions.

Methods: From January 2019 to December 2021, 22 children with a confirmed molecular diagnosis of NS combined with cardiovascular abnormalities were consecutively enrolled into the current study. A comprehensive review was carried out of echocardiography and electrocardiogram results, second-generation whole-exome sequencing results and catheter or surgery-based interventions conditions.

Results: The main manifestations of electrocardiogram abnormalities were QTc prolongation, abnormal Q wave in the precordial lead and limb lead, right ventricular hypertrophy and left or right deviation of the electrical axis. The most commonly detected abnormality was pulmonary valve dysplasia with stenosis, seen in 15 (68.2%) patients, followed by atrial septal defect in 11 (50%) patients. Seven genes (RAF1, RIT1, SOS1, PTPN11, BRAF, SOS2, and LZTR1) were found to contain disease-associated variants. The most commonly observed genetic mutations were PTPN11 (27%) and RAF1 (27%). Each genotype was associated with specific phenotypic findings. RIT1, SOS1, PTPN11, and SOS2 had common echocardiography features characterized by pulmonary valve stenosis, while RAF1 was characterized by HCM. Interestingly, patients with BRAF mutations were not only characterized by HCM, but also by pulmonary valve stenosis. In the cohort there was only one patient carrying a LZTR1 mutation characterized by left ventricle globose dilation. Ten cases underwent catheter or surgery-based interventions. All the operations had immediate results and high success rates. However, some of the cases had adverse outcomes during extended follow-up. Based on the genotype-phenotype associations observed during follow-up, BRAF and RAF1 genotypes seem to be poor prognostic factors, and multiple interventions may be required for NS patients with severe pulmonary stenosis or myectomy for HCM.

Conclusions: The identification of causal genes in NS patients has enabled the evaluation of genotype-cardiac phenotype relationships and prognosis of the disease. This may be beneficial for the development of therapeutic approaches.
Transcriptional Basis for Haustorium Formation and Host Establishment in Hemiparasitic Psittacanthus schiedeanus Mistletoes
Authors: Ibarra-Laclette Enrique , Venancio-Rodríguez Carlos Ariel , Vásquez-Aguilar Antonio Acini , Alonso-Sánchez Alexandro G. , Pérez-Torres Claudia-Anahí , Villafán Emanuel , Ramírez-Barahona Santiago , Galicia Sonia , Sosa Victoria , Rebollar Eria A. , Lara Carlos , González-Rodríguez Antonio , Díaz-Fleisher Francisco , Ornelas Juan Francisco
Published: June 2022

The mistletoe Psittacanthus schiedeanus, a keystone species in interaction networks between plants, pollinators, and seed dispersers, infects a wide range of native and non-native tree species of commercial interest. Here, using RNA-seq methodology we assembled the whole circularized quadripartite structure of P. schiedeanus chloroplast genome and described changes in the gene expression of the nuclear genomes across time of experimentally inoculated seeds. Of the 140,467 assembled and annotated uniGenes, 2,000 were identified as differentially expressed (DEGs) and were classified in six distinct clusters according to their expression profiles. DEGs were also classified in enriched functional categories related to synthesis, signaling, homoeostasis, and response to auxin and jasmonic acid. Since many orthologs are involved in lateral or adventitious root formation in other plant species, we propose that in P. schiedeanus (and perhaps in other rootless mistletoe species), these genes participate in haustorium formation by complex regulatory networks here described. Lastly, and according to the structural similarities of P. schiedeanus enzymes with those that are involved in host cell wall degradation in fungi, we suggest that a similar enzymatic arsenal is secreted extracellularly and used by mistletoes species to easily parasitize and break through tissues of the host.
Differential Contribution of NF-κB Signaling Pathways to CD4+ Memory T Cell Induced Activation of Endothelial Cells
Authors: Jeucken Kim C. M. , van Rooijen Charlotte C. N. , Kan Yik Y. , Kocken Lotte A. , Jongejan Aldo , van Steen Abraham C. I. , van Buul Jaap D. , Olsson Henric K. , van Hamburg Jan Piet , Tas Sander W.
Published: June 2022

Endothelial cells (ECs) are important contributors to inflammation in immune-mediated inflammatory diseases (IMIDs). In this study, we examined whether CD4+ memory T (Tm) cells can drive EC inflammatory responses. Human Tm cells produced ligands that induced inflammatory responses in human umbilical vein EC as exemplified by increased expression of inflammatory mediators including chemokines and adhesion molecules. NF-κB, a key regulator of EC activation, was induced by Tm cell ligands. We dissected the relative contribution of canonical and non-canonical NF-κB signaling to Tm induced EC responses using pharmacological small molecule inhibitors of IKKβ (iIKKβ) or NF-κB inducing kinase (iNIK). RNA sequencing revealed substantial overlap in IKKβ and NIK regulated genes (n=549) that were involved in inflammatory and immune responses, including cytokines (IL-1β, IL-6, GM-CSF) and chemokines (CXCL5, CXCL1). NIK regulated genes were more restricted, as 332 genes were uniquely affected by iNIK versus 749 genes by iIKKβ, the latter including genes involved in metabolism, proliferation and leukocyte adhesion (VCAM-1, ICAM-1). The functional importance of NIK and IKKβ in EC activation was confirmed by transendothelial migration assays with neutrophils, demonstrating stronger inhibitory effects of iIKKβ compared to iNIK. Importantly, iIKKβ – and to some extent iNIK - potentiated the effects of currently employed therapies for IMIDs, like JAK inhibitors and anti-IL-17 antibodies, on EC inflammatory responses. These data demonstrate that inhibition of NF-κB signaling results in modulation of Tm cell-induced EC responses and highlight the potential of small molecule NF-κB inhibitors as a novel treatment strategy to target EC inflammatory responses in IMIDs.
Case Report: Tocilizumab Treatment for VEXAS Syndrome With Relapsing Polychondritis: A Single-Center, 1-Year Longitudinal Observational Study In Japan
Authors: Kunishita Yosuke , Kirino Yohei , Tsuchida Naomi , Maeda Ayaka , Sato Yuichiro , Takase-Minegishi Kaoru , Yoshimi Ryusuke , Nakajima Hideaki
Published: June 2022

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic variants in the UBA1 gene that lead to severe systemic inflammation and myelodysplastic syndrome. Although no standard therapy has been established yet, azacitidine and bone marrow transplantation have been reported to be promising possibilities; however, the indications for these treatments are problematic and not necessarily applicable to all patients. We previously reported the results of short-term treatment with tocilizumab (TCZ) and glucocorticoids in three patients with VEXAS syndrome. In this paper, we report that the combination of TCZ and glucocorticoids allowed the patients to continue treatment for at least one year without significant disease progression. Glucocorticoids were able to be reduced from the start of TCZ. Adverse events were herpes zoster, skin ulceration after cellulitis, and decreased blood counts. The results suggest the significance of this treatment as a bridge therapy for the development of future therapies.
A Whole Exon Screening-Based Score Model Predicts Prognosis and Immune Checkpoint Inhibitor Therapy Effects in Low-Grade Glioma
Authors: Luo Cheng , Wang Songmao , Shan Wenjie , Liao Weijie , Zhang Shikuan , Wang Yanzhi , Xin Qilei , Yang Tingpeng , Hu Shaoliang , Xie Weidong , Xu Naihan , Zhang Yaou
Published: June 2022

Objective

This study aims to identify prognostic factors for low-grade glioma (LGG) via different machine learning methods in the whole genome and to predict patient prognoses based on these factors. We verified the results through in vitro experiments to further screen new potential therapeutic targets.

Method

A total of 940 glioma patients from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) were included in this study. Two different feature extraction algorithms – LASSO and Random Forest (RF) – were used to jointly screen genes significantly related to the prognosis of patients. The risk signature was constructed based on these screening genes, and the K-M curve and ROC curve evaluated it. Furthermore, we discussed the differences between the high- and low-risk groups distinguished by the signature in detail, including differential gene expression (DEG), single-nucleotide polymorphism (SNP), copy number variation (CNV), immune infiltration, and immune checkpoint. Finally, we identified the function of a novel molecule, METTL7B, which was highly correlated with PD-L1 expression on tumor cell, as verified by in vitro experiments.

Results

We constructed an accurate prediction model based on seven genes (AUC at 1, 3, 5 years= 0.91, 0.85, 0.74). Further analysis showed that extracellular matrix remodeling and cytokine and chemokine release were activated in the high-risk group. The proportion of multiple immune cell infiltration was upregulated, especially macrophages, accompanied by the high expression of most immune checkpoints. According to the in vitro experiment, we preliminarily speculate that METTL7B affects the stability of PD-L1 mRNA by participating in the modification of m6A.

Conclusion

The seven gene signatures we constructed can predict the prognosis of patients and identify the potential benefits of immune checkpoint inhibitors (ICI) therapy for LGG. More importantly, METTL7B, one of the risk genes, is a crucial molecule that regulates PD-L1 and could be used as a new potential therapeutic target.
Knowledge Mapping of Necroptosis From 2012 to 2021: A Bibliometric Analysis
Authors: Zhang Jie , Song Luxia , Jia Jundi , Tian Wende , Lai Runmin , Zhang Zihao , Li Jingen , Ju Jianqing , Xu Hao
Published: June 2022

Background

Necroptosis, a recently discovered programmed cell death, has been pathologically linked to various diseases and is thus a promising target for treating diseases. However, a comprehensive and objective report on the current status of entire necroptosis research is lacking. Therefore, this study aims to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of necroptosis research in the last decade.

Methods

Articles were acquired from the Web of Science Core Collection database. We used two bibliometric tools (CiteSpace and VOSviewer) to quantify and identify the individual impact and cooperation information by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Afterwards, we identified the trending research areas of necroptosis by analyzing the co-occurrence and burst of keywords and co-cited references.

Results

From 2012 to 2021, a total of 3,111 research articles on necroptosis were published in 786 academic journals by 19,687 authors in 885 institutions from 82 countries/regions. The majority of publications were from China and the United States, of which the United States maintained the dominant position in necroptosis research; meanwhile, the Chinese Academy of Sciences and Ghent University were the most active institutions. Peter Vandenabeele published the most papers, while Alexei Degterev had the most co-citations.Cell Death & Diseasepublished the most papers on necroptosis, whileCellwas the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. High-frequency keywords mainly included those that are molecularly related (MLKL, TNF-alpha, NF-κB, RIPK3, RIPK1), pathological process related (cell-death, apoptosis, necroptosis, necrosis, inflammation), and disease related (cancer, ischemia/reperfusion injury, infection, carcinoma, Alzheimer’s disease).

Conclusion

Necroptosis research had a stable stepwise growth in the past decade. Current necroptosis studies focused on its cross-talk with other types of cell death, potential applications in disease treatment, and further mechanisms. Among them, the synergy with ferroptosis, further RIPK1/RIPK3/MLKL studies, its association with inflammation and oxidative stress and translational applications, and the therapeutic potential to treat cancer and neurodegenerative diseases are the trending research area. These might provide ideas for further research in the necroptosis field.