bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric Analysis of Birt-Hogg-Dubé Syndrome From 2001 to 2021
Authors: Liu Shixu , Xia Kun , Liu Xiaohong , Duan Yuanyuan , Hu Mu , Xia Hongsheng , Lv Jiayu , Zhang Lili , Liu Yanyi , Xia Xiao , Li Guangxi , Cui Xiangning
Published: April 2022

Background

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disorder caused by germline mutations in folliculin (FLCN). Despite our significantly evolved understanding of BHD over the past decades, no bibliometric analyses have been conducted in this field. This study aimed to analyze and visualize the characteristics of publication outputs, the research hotspots, and scientific frontiers about BHD using bibliometric analysis.

Methods

All relevant literature on BHD was culled from the Web of Science Core Collection (WoSCC) database. Valid data were extracted from the articles and visually analyzed using CiteSpace and VOSviewer.

Results

A total of 751 qualifying papers were included. Publication outputs concerning BHD increased over time. The dominant position of the United States and Japan in BHD research field was evident. National Cancer Institute (the USA) and Yokohama City University (Japan) were the two most productive organizations. W. Marston Linehan exerted a considerable publication impact and had made the most remarkable contributions in the field of BHD. Plos One was the journal with the highest publication outputs, and half of the top 10 journals and co-cited journals belonged to Q1 or Q2. Keyword citation bursts revealed that management, tumor suppressor, flcn gene, spectrum, diagnosis, risk, computed tomography were the emerging research hotspots.

Conclusion

Research on BHD is prosperous. International cooperation between countries and organizations is also expected to deepen and strengthen in the future. Our results indicated that FLCN-associated pathways involved in the pathogenesis of BHD, specific options for early diagnosis, and molecular-targeting therapies will remain research hotspots in the future.
Effects of Early Physical Therapy and Follow-Up in Acute Severe Coronavirus Disease 2019 Pneumonia: A Retrospective Observational Study
Authors: Bordas-Martínez Jaume , Luzardo-González Ana , Arencibia Alejandro , Tormo Franco , Matéu Lluís , Vicens-Zygmunt Vanesa , Bermudo Guadalupe , Santos Salud , Molina-Molina María , Planas Rosa , Suarez-Cuartín Guillermo
Published: April 2022

Background

Rehabilitation in subjects with severe coronavirus disease 2019 (COVID-19) pneumonia has been widely recommended. However, data regarding the starting time of rehabilitation, subjects and healthcare workers’ safety, as well as rehabilitation program features are limited. We aimed to assess the safety and characterize the effect of early and non-early physiotherapy on severe COVID-19 pneumonia subjects.

Methods

A retrospective cohort study, including a consecutive sample of surviving subjects admitted to an acute care hospital due to severe COVID-19 pneumonia from March 13th to May 15th of 2020, is made. Subjects were separated into three groups: non-physical therapy, early physiotherapy (onset <7 days of admission), and non-early physiotherapy. Subject and therapist safety and length of hospital stay were the main evaluated outcomes.

Results

A total of 159 subjects were included (72% men; median age 62 years). Rehabilitation was performed on 108 subjects (32 early and 76 non-early physiotherapies). The length of hospital stay was 19 [interquartile range (IQR) 36.25] and 34 days (IQR 27.25) (p = 0.001) for early and non-early physiotherapy groups, respectively. No physiotherapist was infected and no subject adverse effect was identified. Multivariate analysis of subjects receiving physiotherapy during admission identified obesity [odds ratio (OR) 3.21; p-value 0.028], invasive mechanical ventilation (OR 6.25; p-value <0.001), and non-early physiotherapy (OR 3.54; p-value 0.017) as independent factors associated with a higher risk of prolonged hospital stay. Survivors’ follow-up after hospital discharge at 8 weeks was completed by 54% of subjects.

Conclusion

Rehabilitation in acute severe COVID-19 pneumonia is safe for subjects and healthcare workers and could reduce the length of hospitalization stay, especially in those that may start early.
Could Artificial Intelligence/Machine Learning and Inclusion of Diet-Gut Microbiome Interactions Improve Disease Risk Prediction? Case Study: Coronary Artery Disease
Authors: Vilne Baiba , Ķibilds Juris , Siksna Inese , Lazda Ilva , Valciņa Olga , Krūmiņa Angelika
Published: April 2022

Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems. Therefore, timely and precise identification of people at high risk of CAD is urgently required. Most current CAD risk prediction approaches are based on a small number of traditional risk factors (age, sex, diabetes, LDL and HDL cholesterol, smoking, systolic blood pressure) and are incompletely predictive across all patient groups, as CAD is a multi-factorial disease with complex etiology, considered to be driven by both genetic, as well as numerous environmental/lifestyle factors. Diet is one of the modifiable factors for improving lifestyle and disease prevention. However, the current rise in obesity, type 2 diabetes (T2D) and CVD/CAD indicates that the “one-size-fits-all” approach may not be efficient, due to significant variation in inter-individual responses. Recently, the gut microbiome has emerged as a potential and previously under-explored contributor to these variations. Hence, efficient integration of dietary and gut microbiome information alongside with genetic variations and clinical data holds a great promise to improve CAD risk prediction. Nevertheless, the highly complex nature of meals combined with the huge inter-individual variability of the gut microbiome poses several Big Data analytics challenges in modeling diet-gut microbiota interactions and integrating these within CAD risk prediction approaches for the development of personalized decision support systems (DSS). In this regard, the recent re-emergence of Artificial Intelligence (AI) / Machine Learning (ML) is opening intriguing perspectives, as these approaches are able to capture large and complex matrices of data, incorporating their interactions and identifying both linear and non-linear relationships. In this Mini-Review, we consider (1) the most used AI/ML approaches and their different use cases for CAD risk prediction (2) modeling of the content, choice and impact of dietary factors on CAD risk; (3) classification of individuals by their gut microbiome composition into CAD cases vs. controls and (4) modeling of the diet-gut microbiome interactions and their impact on CAD risk. Finally, we provide an outlook for putting it all together for improved CAD risk predictions.
Emergence and Evolution of Novel Canine-Avian Reassortant H3N2 Influenza A Viruses in Duck in Leizhou Peninsula, China
Authors: Yao Qiucheng , Mai Wenhong , Lian Yuexiao , Zhang Mengdi , Yao Qiang , Huang Caiyun , Ge Ye , Zhao Zhihui
Published: April 2022

Avian-to-mammal transmission and mammalian adaptation of avian influenza virus (AIV) are threats to public health and of great concern. The H3 subtype of influenza virus has low pathogenicity and is widely distributed in humans, canines, equines and avians. In 2018–2019, we isolated six H3N2 subtype influenza viruses from 329 samples acquired from ducks on the Leizhou Peninsula, China, as part of an ongoing virus surveillance program. All viruses were analyzed by whole-genome sequencing with subsequent genetic comparison and phylogenetic analysis. Phylogenetic analysis demonstrated that reassortment of these viruses has occurred among different hosts and subtypes. Some of the H3 AIV isolates have similar genes as subtypes H5 and H7 of highly pathogenic avian influenza viruses (HPAIVs). Most importantly, one strain of H3N2 virus is a novel reassortant influenza virus containing HA and PB2 segments from canine H3N2 virus. The time of most recent common ancestor (tMRCA) data indicated that this reassortant H3N2 virus might have emerged in 2011–2018. The findings suggest that the viruses studied here have undergone multiple reassortment events. Our results provide a framework for understanding the molecular basis of host-range shifts of influenza viruses and we should pay more attention to canine which lived with avian together.
Inhibitory Control of Saccadic Eye Movements and Cognitive Impairment in Mild Cognitive Impairment
Authors: Opwonya Julius , Wang Changwon , Jang Kyoung-Mi , Lee Kunho , Kim Joong Il , Kim Jaeuk U.
Published: April 2022

Background

Mild cognitive impairment (MCI) may occur due to several forms of neurodegenerative diseases and non-degenerative conditions and is associated with cognitive impairment that does not affect everyday activities. For a timely diagnosis of MCI to prevent progression to dementia, a screening tool of fast, low-cost and easy access is needed. Recent research on eye movement hints it a potential application for the MCI screening. However, the precise extent of cognitive function decline and eye-movement control alterations in patients with MCI is still unclear.

Objective

This study examined executive control deficits and saccade behavioral changes in patients with MCI using comprehensive neuropsychological assessment and interleaved saccade paradigms.

Methods

Patients with MCI (n = 79) and age-matched cognitively healthy controls (HC) (n = 170) completed four saccadic eye-movement paradigms: prosaccade (PS)/antisaccade (AS), Go/No-go, and a battery of neuropsychological tests.

Results

The findings revealed significantly longer latency in patients with MCI than in HC during the PS task. Additionally, patients with MCI had a lower proportion of correct responses and a marked increase in inhibition errors for both PS/AS and Go/No-go tasks. Furthermore, when patients with MCI made errors, they failed to self-correct many of these inhibition errors. In addition to the increase in inhibition errors and uncorrected inhibition errors, patients with MCI demonstrated a trend toward increased correction latencies. We also showed a relationship between neuropsychological scores and correct and error saccade responses.

Conclusion

Our results demonstrate that, similar to patients with Alzheimer’s dementia (AD), patients with MCI generate a high proportion of erroneous saccades toward the prepotent target and fail to self-correct many of these errors, which is consistent with an impairment of inhibitory control and error monitoring.

Significance

The interleaved PS/AS and Go/No-go paradigms are sensitive and objective at detecting subtle cognitive deficits and saccade changes in MCI, indicating that these saccadic eye movement paradigms have clinical potential as a screening tool for MCI.
Research and Application of Fine-Grained Image Classification Based on Small Collar Dataset
Authors: Chengcheng Huang , Jian Yuan , Xiao Qin
Published: April 2022

With the rapid development of apparel e-commerce, the variety of apparel is increasing, and it becomes more and more important to classify the apparel according to its collar design. Traditional image processing methods have been difficult to cope with the increasingly complex image backgrounds. To solve this problem, an EMRes-50 classification algorithm is proposed to solve the problem of garment collar image classification, which is designed based on the ECA-ResNet50 model combined with the MC-Loss loss function method. Applying the improved algorithm to the Coller-6 dataset, and the classification accuracy obtained was 73.6%. To further verify the effectiveness of the algorithm, it was applied to the DeepFashion-6 dataset, and the classification accuracy obtained was 86.09%. The experimental results show that the improved model has higher accuracy than the existing CNN model, and the model has better feature extraction ability, which is helpful to solve the problem of the difficulty of fine-grained collar classification and promote the further development of clothing product image classification.
Visceral Adiposity and Risk of Stroke: A Mendelian Randomization Study
Authors: Xu Ran , Hu Xinzhi , Wang Tao , Yang Yutong , Jiang Nan , Luo Jichang , Zhang Xiao , Patel Aman B. , Dmytriw Adam A. , Jiao Liqun
Published: April 2022

Purpose

In recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.

Methods

Based on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.

Results

VAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; P = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, P = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, P = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, P = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, P = 2.59E-02).

Conclusions

This study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.
Analysis of ERBB4 Variants in Amyotrophic Lateral Sclerosis Within a Chinese Cohort
Authors: Wang Fan , Liu Xiangyi , He Ji , Zhang Nan , Chen Lu , Tang Lu , Fan Dongsheng
Published: April 2022

ERBB4 is related to amyotrophic lateral sclerosis (ALS) in patients with a family history and is thought to cause ALS-19. We screened 448 ALS patients, including 364 sporadic ALS (sALS) and 84 familial ALS (fALS) patients with ERBB4 variants, in a Chinese cohort. In total, 12 missense variants were identified in this study. Of these, 3 (p.Arg106His, p.Gln164Pro, and p.Val212Leu) were absent from the in-house healthy control cohort and population databases and predicted to be likely pathogenic. Genetic burden analysis did not reveal an increase in damaging variants of the ERBB4 gene. We considered that most of the missense variants in ERBB4 were not pathogenic, but certain variants, such as p.Arg106His, p.Gln164Pro, and p.Val212Leu, were likely pathogenic. The phenotype of these three patients carrying ERBB4 variants revealed the typical clinical manifestations of ALS without cognitive dysfunction. We concluded that ERBB4 likely pathogenic variants account for ~0.67% of ALS patients in China. It is necessary to interpret the relationship between the disease and variants carefully for ALS patients with ERBB4 gene variants.
Predicting Ecological Momentary Assessments in an App for Tinnitus by Learning From Each User's Stream With a Contextual Multi-Armed Bandit
Authors: Shahania Saijal , Unnikrishnan Vishnu , Pryss Rüdiger , Kraft Robin , Schobel Johannes , Hannemann Ronny , Schlee Winny , Spiliopoulou Myra
Published: April 2022

Ecological Momentary Assessments (EMA) deliver insights on how patients perceive tinnitus at different times and how they are affected by it. Moving to the next level, an mHealth app can support users more directly by predicting a user's next EMA and recommending personalized services based on these predictions. In this study, we analyzed the data of 21 users who were exposed to an mHealth app with non-personalized recommendations, and we investigate ways of predicting the next vector of EMA answers. We studied the potential of entity-centric predictors that learn for each user separately and neighborhood-based predictors that learn for each user separately but take also similar users into account, and we compared them to a predictor that learns from all past EMA indiscriminately, without considering which user delivered which data, i.e., to a “global model.” Since users were exposed to two versions of the non-personalized recommendations app, we employed a Contextual Multi-Armed Bandit (CMAB), which chooses the best predictor for each user at each time point, taking each user's group into account. Our analysis showed that the combination of predictors into a CMAB achieves good performance throughout, since the global model was chosen at early time points and for users with few data, while the entity-centric, i.e., user-specific, predictors were used whenever the user had delivered enough data—the CMAB chose itself when the data were “enough.” This flexible setting delivered insights on how user behavior can be predicted for personalization, as well as insights on the specific mHealth data. Our main findings are that for EMA prediction the entity-centric predictors should be preferred over a user-insensitive global model and that the choice of EMA items should be further investigated because some items are answered more rarely than others. Albeit our CMAB-based prediction workflow is robust to differences in exposition and interaction intensity, experimentators that design studies with mHealth apps should be prepared to quantify and closely monitor differences in the intensity of user-app interaction, since users with many interactions may have a disproportionate influence on global models.
Effect of a High Fat Diet vs. High Carbohydrate Diets With Different Glycemic Indices on Metabolic Parameters in Male Endurance Athletes: A Pilot Trial
Authors: Zdzieblik Denise , Friesenborg Hilke , Gollhofer Albert , König Daniel
Published: April 2022

Consuming low glycemic carbohydrates leads to an increased muscle fat utilization and preservation of intramuscular glycogen, which is associated with improved flexibility to metabolize either carbohydrates or fats during endurance exercise. The purpose of this trial was to investigate the effect of a 4-week high fat low carbohydrate (HFLC-G: ≥65% high glycemic carbohydrates per day; n = 9) vs. high carbohydrate low glycemic (LGI-G: ≥65% low glycemic carbohydrates daily; n = 10) or high glycemic (HGI-G: ≥65% fat, ≤ 50 g carbohydrates daily; n = 9) diet on fat and carbohydrate metabolism at rest and during exercise in 28 male athletes. Changes in metabolic parameters under resting conditions and during cycle ergometry (submaximal and with incremental workload) from pre- to post-intervention were determined by lactate diagnostics and measurements of the respiratory exchange ratio (RER). Additionally, body composition and perceptual responses to the diets [visual analog scale (VAS)] were measured. A significance level of α = 0.05 was considered. HFLC-G was associated with markedly decreased lactate concentrations during the submaximal (−0.553 ± 0.783 mmol/l, p = 0.067) and incremental cycle test [−5.00 ± 5.71 (mmol/l) × min; p = 0.030] and reduced RER values at rest (−0.058 ± 0.108; p = 0.146) during the submaximal (−0.078 ± 0.046; p = 0.001) and incremental cycle test (−1.64 ± 0.700 RER × minutes; p < 0.001). In the HFLC-G, fat mass (p < 0.001) decreased. In LGI-G lactate, concentrations decreased in the incremental cycle test [−6.56 ± 6.65 (mmol/l) × min; p = 0.012]. In the LGI-G, fat mass (p < 0.01) and VAS values decreased, indicating improved levels of gastrointestinal conditions and perception of effort during training. The main findings in the HGI-G were increased RER (0.047 ± 0.076; p = 0.117) and lactate concentrations (0.170 ± 0.206 mmol/l, p = 0.038) at rest. Although the impact on fat oxidation in the LGI-G was not as pronounced as following the HFLC diet, the adaptations in the LGI-G were consistent with an improved metabolic flexibility and additional benefits regarding exercise performance in male athletes.
Molecular Mechanisms of Iron Mediated Programmed Cell Death and Its Roles in Eye Diseases
Authors: Zhang Jie , Sheng Shuai , Wang Wenting , Dai Jiazhen , Zhong Yifan , Ren Jiantao , Jiang Keke , Li Shuchan , Bian Xiaoyan , Liu Lei
Published: April 2022

Ferroptosis, a newly identified, iron-dependent type of programmed cell death, is active in several diseases, such as heart disease, brain damage, and cancer. Its main characteristics commonly involve excess iron accumulation, elevated lipid peroxides and reactive oxygen species, and reduced levels of glutathione and glutathione peroxidase 4 levels. The effects of ferroptosis in eye diseases cannot be underestimated, with ferroptosis becoming a research target in ocular disorders and emerging evidence from a series of in vivo and in vitro researches into ferroptosis revealing its role in eye conditions. However, no report provides comprehensive information on the pathophysiology of ferroptosis in eye diseases and its possible treatments. In the current review, we present an up-to-date overview of ferroptosis biology and its involvement in the pathological processes of ocular diseases. Furthermore, we pose several outstanding questions and areas for future research in this topic. We deem ferroptosis-associated cell death a pivotal new field of scientific study in ocular diseases and consider it a new therapeutic target in the treatment of some eye disorders.
Implementation of a Case Presentation Program for Clinical Nutrition Students
Authors: Shahbazi Shaahin , Vahdat Shariatpanahi Maryam , Vahdatshariatpanahi Saba , Shahbazi Erfan , Vahdat Shariatpanahi Zahra
Published: April 2022

Background and Aims

To implement a training method increase clinical nutritionists' knowledge and make doctors more familiar with this specialty.

Methods

The study was conducted in an internship course of all third semester clinical nutrition students. At first, conventional training was presented for students, and then, in the same duration, case presentation training program was implemented. The presentations were filmed and uploaded to the Internet, and the link was placed on the hospital's website. At the end of the 2 phases, the students were asked to answer the survey questionnaire. Additionally, consultation report sheets were evaluated and scored by 2 physicians. Number of consultation requests was also recorded in 2 study phases.

Results

The mean satisfaction score was statistically higher in the case presentation training program than in the conventional program. All the students recommended similar case report program courses for the students in the future. Although the mean consultation report score was not statistically different between the two training programs, case presentation program resulted in significantly better scores in 4 items of nutrition focused physical examinations, assessment of malnutrition, assessment of related laboratory tests, and food-drug interactions. Number of consultation requests was significantly increased during the case presentation program training compared to the conventional training from 194 to 272 (P < 0.001).

Conclusion

From the students' perspective, the case-based learning report was preferred to the conventional method. From the physicians' viewpoint, the answer to the counseling sheets was more complete and helpful.
Prognostic Effect of Primary Recurrence Patterns in Squamous Cervical Carcinoma After Radical Surgery
Authors: Zhang Zongkai , Jiang Long , Bi Rui , Wu Xiaohua , Ke Guihao , Zhu Jun
Published: April 2022

Objective

To examine the effect of primary recurrence patterns on the prognosis of squamous cervical cancer after initial treatment.

Methods

Primary recurrence patterns and prognostic factors were examined in stage IB-IIA cervical cancer patients after initial treatment. Recurrence site (locoregional recurrence and distant metastasis or in-field and out-field recurrence for patients receiving adjuvant radiotherapy) and subtype (nodal and organ recurrence) were examined. Clinicopathological characteristics and survival rates were evaluated to generate a prognostic nomogram.

Results

A total of 472 patients were included. The median follow-up period, 5-year overall (OS) rate, and median OS were 59.1 months, 33.7%, and 24.0 months, respectively. Overall, 38.8% and 61.2% of the patients had locoregional recurrence and distant metastasis, respectively, and survival rates were comparable in these groups. Patients with nodal recurrence had better OS than those with organ recurrence (38.3% vs 30.7%, respectively; P = 0.001). Patients not receiving adjuvant radiotherapy had increased risk of pelvic recurrence [odds ratio (OR) = 0.148; 95% confidence interval[(CI): 0.075–0.291, P = 0.000]. Positive lymph-vascular space invasion (OR= 1.928; 95% CI: 1.151–3.229, P = 0.013) and no chemotherapy (OR = 0.521; 95% CI: 0.317–0.733, P = 0.040) increased the risk of distant metastasis. Positive lymph node status after initial treatment were associated with nodal recurrence (OR = 3.729; 95% CI: 1.838–7.563, P = 0.000), while elevated preoperative squamous cell carcinoma antigen (SCC-Ag) levels were associated with organ recurrence (OR = 1.642; 95% CI: 1.325–2.265, P = 0.002). Recurrence subtype, therapy for relapse, the International Federation of Gynecology and Obstetrics stage, adjuvant radiotherapy, preoperative SCC-Ag levels, and risk subgroup were independently associated with OS.

Conclusions

Primary recurrence patterns were associated with specific clinicopathological characteristics of cervical cancer. Recurrent cervical cancer prognosis was mainly affected by recurrence location and subtype.
Case Report: Olaparib Shows Satisfactory Clinical Outcomes Against Small Cell Esophageal Carcinoma With ATM Mutation
Authors: Wang Weiwei , Zhang Xiaoyan , Fang Yu , He Jia , Huang Jingjing , Li Shanqing , Ma Tonghui , Li Li
Published: April 2022

Small cell esophageal carcinoma (SCEC) is a rare, undifferential type of cancer, with a high degree of malignancy and early systemic metastasis. Radio-chemotherapy and surgery have been used as the primary treatment strategies for SCEC, but they both result in poor prognosis. There is need to develop an optimal standard treatment for the disease to improve prognosis and limit the related mortality. In this study, we described identification of driver mutations in ATM, a gene involved in homologous recombination deficiency (HRD) pathway, using next-generation sequencing on primary lesion and peripheral blood of a SCEC patient, who experienced recurrence after resection and radio-chemotherapy. In addition, we subjected the patient to olaparib, a PARP inhibitor, for the treatment of tumor with HRD and obtained a partial response. This is the first evidence implicating olaparib in successful treatment of SCEC with ATM mutation. The findings suggest that targeting mutations in HRD genes using olaparib or actionable genetic mutations using corresponding drugs, may be an effective therapeutic option for SCEC, although this requires further investigation.
Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis
Authors: Gallenga Carla Enrica , Franco Elena , Adamo Ginevra Giovanna , Violanti Sara Silvia , Tassinari Paolo , Tognon Mauro , Perri Paolo
Published: April 2022

Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.
Cancer Progression Gene Expression Profiling Identifies the Urokinase Plasminogen Activator Receptor as a Biomarker of Metastasis in Cutaneous Squamous Cell Carcinoma
Authors: Minaei Elahe , Mueller Simon A. , Ashford Bruce , Thind Amarinder Singh , Mitchell Jenny , Perry Jay R. , Genenger Benjamin , Clark Jonathan R. , Gupta Ruta , Ranson Marie
Published: April 2022

Cutaneous squamous cell carcinoma (cSCC) of the head and neck region is the second most prevalent skin cancer, with metastases to regional lymph nodes occurring in 2%–5% of cases. To further our understanding of the molecular events characterizing cSCC invasion and metastasis, we conducted targeted cancer progression gene expression and pathway analysis in non-metastasizing (PRI-) and metastasizing primary (PRI+) cSCC tumors of the head and neck region, cognate lymph node metastases (MET), and matched sun-exposed skin (SES). The highest differentially expressed genes in metastatic (MET and PRI+) versus non-metastatic tumors (PRI-) and SES included PLAU, PLAUR, MMP1, MMP10, MMP13, ITGA5, VEGFA, and various inflammatory cytokine genes. Pathway enrichment analyses implicated these genes in cellular pathways and functions promoting matrix remodeling, cell survival and migration, and epithelial to mesenchymal transition, which were all significantly activated in metastatic compared to non-metastatic tumors (PRI-) and SES. We validated the overexpression of urokinase plasminogen activator receptor (uPAR, encoded by PLAUR) in an extended patient cohort by demonstrating higher uPAR staining intensity in metastasizing tumors. As pathway analyses identified epidermal growth factor (EGF) as a potential upstream regulator of PLAUR, the effect of EGF on uPAR expression levels and cell motility was functionally validated in human metastatic cSCC cells. In conclusion, we propose that uPAR is an important driver of metastasis in cSCC and represents a potential therapeutic target in this disease.
Restored CD8+PD-1+ T Cells Facilitate the Response to Anti-PD-1 for Patients With Pancreatic Ductal Adenocarcinoma
Authors: Zhu Qian , Qiao Guoliang , Huang Lefu , Xu Chang , Guo Deliang , Wang Shuo , Zhao Jing , Song Yuguang , Liu Bing , Chen Zheng , Yang Zhiyong , Yuan Yufeng
Published: April 2022

Purpose

We aimed to investigate the restoration of CD8+PD-1+ T cells through adoptive T-cell therapy (ACT) in relation to the prognosis and the therapeutic response to anti-PD-1 in patients with advanced pancreatic cancer (APC).

Methods

A total of 177 adult patients who underwent tumor resection as initial treatment for pancreatic ductal adenocarcinoma (PDAC) from February 2013 to July 2019 at Zhongnan Hospital of Wuhan University were enrolled in this study. Another cohort of 32 patients with APC was prospectively enrolled from Capital Medical University Cancer Center between June 1, 2013, and May 30, 2019.

Results

Of the 177 patients who received tumor resection, 67 tumor samples showed overexpression of PD-L1 and 110 patients with low expression of PD-L1. We found that overexpressed PD-L1 was a significant prognostic factor related to overall survival (OS). Furthermore, we tested the percentage of peripheral CD8+PD-1+ T cells in all patients and found that it was significantly correlated with the PD-L1 expression and the prognosis of patients with PDAC. The peripheral blood T lymphocyte subtypes were tracked for 30 months, and CD8+PD-1+ cells were shown to decrease. After that, we performed ACT for patients with APC in another cancer center. We found that the ratios of posttreatment of ACT/pre-ACT CD8+PD-1+ T cells were significantly related to the prognosis of patients with APC. Moreover, patients with combined treatment of ACT with anti-PD-1 had significantly favorable OS.

Conclusions

This study showed that the CD8+PD-1+ T-cell level was related to the expression of PD-L1. Restoring CD8+PD-1+ T cells in patients with APC by treatment of ACT significantly benefits the prognosis and facilitates the response to anti-PD-1.
Dosimetric Impact of Inter-Fraction Variability in the Treatment of Breast Cancer: Towards New Criteria to Evaluate the Appropriateness of Online Adaptive Radiotherapy
Authors: Iezzi Martina , Cusumano Davide , Piccari Danila , Menna Sebastiano , Catucci Francesco , D’Aviero Andrea , Re Alessia , Di Dio Carmela , Quaranta Flaviovincenzo , Boschetti Althea , Marras Marco , Piro Domenico , Tomei Flavia , Votta Claudio , Valentini Vincenzo , Mattiucci Gian Carlo
Published: April 2022

Purpose

As a discipline in its infancy, online adaptive RT (ART) needs new ontologies and ad hoc criteria to evaluate the appropriateness of its use in clinical practice. In this experience, we propose a predictive model able to quantify the dosimetric impact due to daily inter-fraction variability in a standard RT breast treatment, to identify in advance the treatment fractions where patients might benefit from an online ART approach.

Methods

The study was focused on right breast cancer patients treated using standard adjuvant RT on an artificial intelligence (AI)-based linear accelerator. Patients were treated with daily CBCT images and without online adaptation, prescribing 40.05 Gy in 15 fractions, with four IMRT tangential beams. ESTRO guidelines were followed for the delineation on planning CT (pCT) of organs at risk and targets. For each patient, all the CBCT images were rigidly aligned to pCT: CTV and PTV were manually re-contoured and the original treatment plan was recalculated. Various radiological parameters were measured on CBCT images, to quantify inter-fraction variability present in each RT fraction after the couch shifts compensation. The variation of these parameters was correlated with the variation of V95% of PTV (ΔV95%) using the Wilcoxon Mann–Whitney test. Fractions where ΔV95% > 2% were considered as adverse events. A logistic regression model was calculated considering the most significant parameter, and its performance was quantified with a receiver operating characteristic (ROC) curve.

Results

A total of 75 fractions on 5 patients were analyzed. The body variation between daily CBCT and pCT along the beam axis with the highest MU was identified as the best predictor (p = 0.002). The predictive model showed an area under ROC curve of 0.86 (95% CI, 0.82–0.99) with a sensitivity of 85.7% and a specificity of 83.8% at the best threshold, which was equal to 3 mm.

Conclusion

A novel strategy to identify treatment fractions that may benefit online ART was proposed. After image alignment, the measure of body difference between daily CBCT and pCT can be considered as an indirect estimator of V95% PTV variation: a difference larger than 3 mm will result in a V95% decrease larger than 2%. A larger number of observations is needed to confirm the results of this hypothesis-generating study.
Cervical Carcinoma: Evaluation Using Diffusion MRI With a Fractional Order Calculus Model and its Correlation With Histopathologic Findings
Authors: Shao Xian , An Li , Liu Hui , Feng Hui , Zheng Liyun , Dai Yongming , Yu Bin , Zhang Jin
Published: April 2022

Objective

The objective of the study is to investigate the feasibility of using the fractional order calculus (FROC) model to reflect tumor subtypes and histological grades of cervical carcinoma.

Methods

Sixty patients with untreated cervical carcinoma underwent multi-b-value diffusion-weighted imaging (DWI) at 3.0T magnetic resonance imaging (MRI). The mono-exponential and the FROC models were fitted. The differences in the histological subtypes and grades were evaluated by the Mann–Whitney U test. Receiver operating characteristic (ROC) analyses were performed to assess the diagnostic performance and to determine the best predictor for both univariate analysis and multivariate analysis. Differences between ROC curves were tested using the Hanley and McNeil test, while the sensitivity, specificity, and accuracy were compared using the McNemar test. P-value <0.05 was considered as significant difference. The Bonferroni corrections were applied to reduce problems associated with multiple comparisons.

Results

Only the parameter β, derived from the FROC model could differentiate cervical carcinoma subtypes (P = 0.03) and the squamous cell carcinoma (SCC) lesions exhibited significantly lower β than that in the adenocarcinoma (ACA) lesions. All the individual parameters, namely, ADC, β, D, and μ derived from the FROC model, could differentiate low-grade cervical carcinomas from high-grade ones (P = 0.022, 0.009, 0.004, and 0.015, respectively). The combination of all the FROC parameters showed the best overall performance, providing the highest sensitivity (81.2%) and AUC (0.829).

Conclusion

The parameters derived from the FROC model were able to differentiate the subtypes and grades of cervical carcinoma.
Women With Ovarian Cancer and With Fertility Preservation: A Survival Analysis Using the Surveillance, Epidemiology, and End Results Database and Construction of Nomograms to Predict Cancer-Specific Survival
Authors: Hou Yue-min , Yu Hui , Hao Jia-tao , Feng Fang , An Rui-fang
Published: April 2022

Objective

This study aimed to determine the risk and prognostic factors of ovarian cancer (OC) in women having fertility-sparing surgery, as well as survival outcomes of those with stage I epithelial ovarian cancer (EOC). We also determined the effect of chemotherapy in OC treatment and used multiple independent risk factors to establish a prognostic nomogram model for patients with stage I EOC.

Patients and Methods

Individuals with OC and with fertility-sparing surgery (FSS) between 1998 and 2016 were identified in the SEER database. Univariate and multivariate logistic regression was performed to identify the distributions of patient characteristics according to chemotherapy. Cancer-specific survival (CSS) was assessed using Kaplan–Meier curves and log-rank tests. Univariate and multivariate Cox regression was conducted to determine the independent prognostic factors for CSS. Cox analysis was used to construct a nomogram model. The C-index and calibration plots showed the performance evaluation results.

Results

A total of 1,839 women with OC with FSS were identified in the SEER database. Factors associated with significantly higher odds of undergoing chemotherapy included younger age, being unmarried, having grades 2–4, stages II–III, or clear cell and non-epithelial histologic type following a multivariate logistic regression analysis. Multivariate Cox regression analysis confirmed that age, marital status, chemotherapy, histologic type, grade, and the International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for CSS. In stage I EOC, the prognosis in patients with stage IA/IB-grade 3 (5-year CSS 85.3%) or stage IC (5-year CSS 80.6%) was worse than that in those with stage IA/IB-grade 1 (5-year CSS 95.2%), or stage IA/IB-grade 2 (5-year CSS 94.7%). However, chemotherapy improved the survival of patients with stage IA/IB-grade 3 (5-year CSS 78.1% vs. 94.6%, p = 0.024) or stage IC (5-year CSS 75.1% vs. 86.7%, p = 0.170).

Discussion

The study provided population-based estimates of risk factors and prognoses in patients with OC and with FSS as well as the survival outcomes of patients with stage I EOC and the effect of chemotherapy. The constructed nomograms exhibited superior prognostic discrimination and survival prediction for patients with stage I EOC.
Surgical Treatment for Esophageal Leiomyoma: 13 Years of Experience in a High-Volume Tertiary Hospital
Authors: A-Lai Gu-Ha , Hu Jian-Rong , Yao Peng , Lin Yi-Dan
Published: April 2022

Background

Esophageal leiomyoma is the most common benign tumor in the esophagus. Thoracotomy and thoracoscopy are both elective for esophageal leiomyoma enucleation. This study aimed at presenting surgical experience in our center and exploring more suitable surgical methods for different situations.

Methods

We conducted this retrospective study by collecting data from patients who underwent esophageal leiomyoma enucleation through thoracotomy or thoracoscopy from January 2009 to November 2021 at West China Hospital Sichuan University.

Results

A total of 34 patients were enrolled for analysis. All patients were diagnosed with a single esophageal leiomyoma. There were 25 men and 9 women. The mean age was 44.41 years (range, 18–72 years), the mean longest diameter was 4.99 cm (range, 1.4–10 cm), and the esophagus was thoroughly circled with leiomyoma in 10 patients, 10 patients underwent thoracotomy to enucleate leiomyoma, while others underwent thoracoscopic enucleation. No perioperative deaths occurred. Between the thoracotomy group and thoracoscopy group, baseline characteristics were comparable except for gastric tube status (p = 0.034). Patients were inclined to undergo the left lateral surgery approach (p = 0.001) and suffered esophagus completely encircled by leiomyoma (p = 0.002). Multivariable logistic regression analysis demonstrated that the left lateral surgery approach (p = 0.014) and esophagus completely encircled by leiomyoma (p = 0.042) were risk factors for thoracotomy of leiomyoma enucleation, while a larger tumor size demonstrated no risk. The median follow-up time was 63.5 months, and no deaths or recurrence occurred during the follow-up period.

Conclusion

Thoracotomy enucleation of the leiomyoma was recommended when the esophagus was thoroughly encircled by the leiomyoma and the left lateral surgery approach was needed. However, tumor size demonstrated less value for selecting a surgical approach.
Identification of a 12-Gene Signature and Hub Genes Involved in Kidney Wilms Tumor via Integrated Bioinformatics Analysis
Authors: Huang Guoping , Mao Jianhua
Published: April 2022

Wilms tumor (WT), also known as nephroblastoma, is a rare primary malignancy in all kinds of tumor. With the development of second-generation sequencing, the discovery of new tumor markers and potential therapeutic targets has become easier. This study aimed to explore new WT prognostic biomarkers. In this study, WT-miRNA datasets GSE57370 and GSE73209 were selected for expression profiling to identify differentially expressed genes. The key gene miRNA, namely hsa-miR-30c-5p, was identified by overlapping, and the target gene of candidate hsa-miR-30c-5p was predicted using an online database. Furthermore, 384 genes were obtained by intersecting them with differentially expressed genes in the TARGET-WT database, and the genes were analyzed for pathway and functional enrichment. Kaplan–Meier survival analysis of the 384 genes yielded a total of 25 key genes associated with WT prognosis. Subsequently, a prediction model with 12 gene signatures (BCL6, CCNA1, CTHRC1, DGKD, EPB41L4B, ERRFI1, LRRC40, NCEH1, NEBL, PDSS1, ROR1, and RTKN2) was developed. The model had good predictive power for the WT prognosis at 1, 3, and 5 years (AUC: 0.684, 0.762, and 0.774). Finally, ERRFI1 (hazard ratios [HR] = 1.858, 95% confidence intervals [CI]: 1.298–2.660) and ROR1 (HR = 0.780, 95% CI: 0.609–0.998) were obtained as independent predictors of prognosis in WT patients by single, multifactorial Cox analysis.
Cardiovascular Health at Age 5 Years: Distribution, Determinants, and Association With Neurodevelopment
Authors: Climie Rachel E. , Tafflet Muriel , Sloten Thomas van , Lauzon-Guillain Blandine de , Bernard Jonathan Y. , Dargent-Molina Patricia , Plancoulaine Sabine , Lioret Sandrine , Jouven Xavier , Charles Marie-Alines , Heude Barbara , Empana Jean-Philippe
Published: April 2022

Background

Early childhood may represent an opportune time to commence primordial prevention of cardiovascular disease (CVD, i.e., prevention of risk factors onset), but epidemiological evidence is scarce. We aimed to examine the distribution and parental and early life determinants of ideal cardiovascular health (CVH) in children up to 5 years and to compare the level of cognitive development between children with and without ideal CVH at age 5 years.

Methods

Using data from the Etude sur les déterminants pré et post natals précoces du Développement psychomoteur et de la santé de l'Enfant (EDEN) study, a French population-based mother–child cohort study, CVH was examined in children at 5 years of age based on the American Heart Association CVH metrics (ideal body mass index, physical activity, diet, blood pressure, cholesterol and glucose levels, and passive smoking, considered in sensitivity analysis only). Children were categorized as having ideal (five to six ideal metrics) or non-ideal CVH (<5 ideal metrics). Intelligence quotient (IQ) at age 5 years was assessed using the French version of the Wechsler Preschool and Primary Scale of Intelligence.

Results

Among the 566 children (55% boys), only 34% had ideal CVH. In fully adjusted logistic regression, boys compared to girls (OR = 1.77, 95% CI 1.13–2.78), children with intermediate (1.77, 1.05–2.98) or ideal (2.58, 1.38–4.82) behavioral CVH at age 3 years and children who spent < 30 min/day watching television (1.91, 1.09–3.34) at age 3 years were more likely to have ideal CVH at age 5 years. At age 5 years, there was a significant 2.98-point difference (95% CI 0.64–5.32) in IQ between children with and without ideal biological CVH after adjusting for confounders.

Conclusion

This study highlights that only a third of children aged 5 years had ideal CVH and identified modifiable determinants of ideal CVH and is suggestive of an association between CVH and neurodevelopment at a young age.
Scaling Beyond Cities
Authors: Prieto Curiel Rafael , Cabrera-Arnau Carmen , Bishop Steven Richard
Published: April 2022

City population size is a crucial measure when trying to understand urban life. Many socio-economic indicators scale superlinearly with city size, whilst some infrastructure indicators scale sublinearly with city size. However, the impact of size also extends beyond the city’s limits. Here, we analyse the scaling behaviour of cities beyond their boundaries by considering the emergence and growth of nearby cities. Based on an urban network from African continental cities, we construct an algorithm to create the region of influence of cities. The number of cities and the population within a region of influence are then analysed in the context of urban scaling. Our results are compared against a random permutation of the network, showing that the observed scaling power of cities to enhance the emergence and growth of cities is not the result of randomness. By altering the radius of influence of cities, we observe three regimes. Large cities tend to be surrounded by many small towns for small distances. For medium distances (above 114 km), large cities are surrounded by many other cities containing large populations. Large cities boost urban emergence and growth (even more than 190 km away), but their scaling power decays with distance.