bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype-phenotypic correlation of Peutz-Jeghers syndrome on the example of a series of clinical cases
Authors: Yanova T. I. , Bodunova N. A. , Khatkov I. E. , Tsukanov A. S. , Khodos N. G. , Pavlov I. A. , Nedoluzhko I. Yu. , Savelyeva T. A. , Danishevich A. M. , Polyakova V. V. 
Published: June 2022

Introduction: Peutz-Jeghers syndrome (PEUTZ-JEGHERS SYNDROME; PJS; OMIM#175200) is hereditary tumor syndrome and is characterized by the occurrence of hamartomatous polyps of gastrointestinal tract, melanocytic pigmentation of the skin and mucous membranes, as well as a high predisposition to malignant tumors of various locations. Despite the fact that the clinical features of PJS are currently well understood, the nature of the variability in the phenotypic manifestations of the disease has not been fully described. Aims: to determine the phenotypic and clinical features in patients with PJS depending on the type of mutation in the STK11 gene. Patients and methods: the clinical and genetic data of 3 patients aged 21, 28 and 39 years with clinical signs of PJS are presented. All patients underwent medical genetic counseling and molecular genetic diagnostics of the STK11 gene using NGS and MLPA methods. Results: large deletions of ex2-8 and ex1 in the STK11 gene were revealed in two patients, and one patient showed a splice site variant c.921-1G > A. The identified variant ex2-8 has not previously been described in international databases. When evaluating the clinical and genetic features, the most severe picture of the disease was in a patient with an extended deletion of exons 2-8, large number of polyps and surgical procedures in history. However, in this case, melanocytic pigmentation became less with age, in contrast to patients with a splice site mutation and a single exon deletion. No cancers were detected in the patients. Conclusion: the molecular genetic test made it possible to confirm the clinical diagnosis of PJS, based on various phenotypic features, and to work out the personalized plan for follow-up. Evaluation of the genotype-phenotype correlations will be possible with the development of a unified register of mutation carriers.
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.
Phaeohyphomycosis in China
Authors: He Yun , Zheng Hai-lin , Mei Huan , Lv Gui-xia , Liu Wei-da , Li Xiao-fang 
Published: June 2022

BackgroundDue 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
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

BackgroundThere 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).MethodsIn 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.ResultsWomen were found with significantly lower total EAT volumes (P &lt; 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.ConclusionWomen 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

BackgroundCoronary 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.MethodsAmong 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.ResultsFusion-FFR was strongly correlated with FFR (r = 0.836, P &lt; 0.001). Correlation between FFR and Fusion-FFR was stronger than that between FFR and CT-FFR (r = 0.682, P &lt; 0.001; z statistic, 5.42, P &lt; 0.001) and between FFR and OCT-FFR (r = 0.705, P &lt; 0.001; z statistic, 4.38, P &lt; 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 &lt; 0.001; 64.0%, P &lt; 0.001) and OCT-FFR (75.7%, P = 0.021; 73.5%, P = 0.020; 69.9%, P = 0.012).ConclusionCFD-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.
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

BackgroundInpatient 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.MethodsChildren 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.ResultsWe 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&lt;0.05). Additionally, aftercare attenders were younger than non-attenders (mean age, 13.4 ± 2.3 years vs 14.9 ± 2.0, p&lt;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&lt;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&lt;0.05) in multivariate linear regressions.ConclusionPatients 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

ObjectiveInsulin 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.DesignIt is a cross-sectional study conducted in an academic tertiary setting.PatientsThe patients comprised five hundred twenty-seven women diagnosed with PCOS by the 2003 Rotterdam criteria and 565 controls with regular vaginal bleeding.InterventionsThe interventions done for this study are medical history collection, physical examination, and blood sampling.Main outcome measuresThe main outcome measures are body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters.ResultsWomen 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.ConclusionsIn 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

PurposeGlioma 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.MethodsIn 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.ResultsBy 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.ConclusionWe 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

BackgroundThe 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.ObjectiveThis 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.DesignThis 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.ResultsBasal 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.ConclusionsThis 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.