bluuebunny/crossref_metadata_2025 huggingface dataset:
See, Hear, or Feel – to Speak: A Versatile Multiple-Choice Functional Near-Infrared Spectroscopy-Brain-Computer Interface Feasible With Visual, Auditory, or Tactile Instructions
Authors: Nagels-Coune Laurien , Riecke Lars , Benitez-Andonegui Amaia , Klinkhammer Simona , Goebel Rainer , De Weerd Peter , Lührs Michael , Sorger Bettina
Published: December 2021

Severely motor-disabled patients, such as those suffering from the so-called “locked-in” syndrome, cannot communicate naturally. They may benefit from brain-computer interfaces (BCIs) exploiting brain signals for communication and therewith circumventing the muscular system. One BCI technique that has gained attention recently is functional near-infrared spectroscopy (fNIRS). Typically, fNIRS-based BCIs allow for brain-based communication via voluntarily modulation of brain activity through mental task performance guided by visual or auditory instructions. While the development of fNIRS-BCIs has made great progress, the reliability of fNIRS-BCIs across time and environments has rarely been assessed. In the present fNIRS-BCI study, we tested six healthy participants across three consecutive days using a straightforward four-choice fNIRS-BCI communication paradigm that allows answer encoding based on instructions using various sensory modalities. To encode an answer, participants performed a motor imagery task (mental drawing) in one out of four time periods. Answer encoding was guided by either the visual, auditory, or tactile sensory modality. Two participants were tested outside the laboratory in a cafeteria. Answers were decoded from the time course of the most-informative fNIRS channel-by-chromophore combination. Across the three testing days, we obtained mean single- and multi-trial (joint analysis of four consecutive trials) accuracies of 62.5 and 85.19%, respectively. Obtained multi-trial accuracies were 86.11% for visual, 80.56% for auditory, and 88.89% for tactile sensory encoding. The two participants that used the fNIRS-BCI in a cafeteria obtained the best single- (72.22 and 77.78%) and multi-trial accuracies (100 and 94.44%). Communication was reliable over the three recording sessions with multi-trial accuracies of 86.11% on day 1, 86.11% on day 2, and 83.33% on day 3. To gauge the trade-off between number of optodes and decoding accuracy, averaging across two and three promising fNIRS channels was compared to the one-channel approach. Multi-trial accuracy increased from 85.19% (one-channel approach) to 91.67% (two-/three-channel approach). In sum, the presented fNIRS-BCI yielded robust decoding results using three alternative sensory encoding modalities. Further, fNIRS-BCI communication was stable over the course of three consecutive days, even in a natural (social) environment. Therewith, the developed fNIRS-BCI demonstrated high flexibility, reliability and robustness, crucial requirements for future clinical applicability.
The Relationship Between Hearing Loss and Cognitive Impairment in a Chinese Elderly Population: The Baseline Analysis
Authors: Fu Xinxing , Liu Bo , Wang Shuo , Eikelboom Robert H. , Jayakody Dona M. P.
Published: December 2021

Objectives: The objective of the study was to investigate the association between untreated age-related hearing loss and cognitive impairment in Mandarin-speaking older adults living in China.

Methods: Older adults (293; 111 males, M = 70.33 ± 4.90 years; 182 females, M = 69.02 ± 4.08 years) were recruited. All participants completed a pure tone audiometric hearing assessment, Hearing Impairment-Montreal Cognitive Assessment Test (HI-MoCA), and a computerized neuropsychology test battery (CANTAB). The Mandarin version of the De Jong Gierveld Loneliness Scale was used to measure the loneliness, and the Mandarin version of the 21-item Depression Anxiety Stress Scale (DASS-21) was used to measure the current severity of a range of symptoms common to depression, stress, and anxiety of the participants.

Results: A multiple stepwise regression analysis showed that the average of four mid-frequency thresholds in the better ear was related to CANTAB Paired Associates Learning (β = 0.20, p = 0.002), and the global cognitive function score (HI-MoCA) (β = −0.25, p < 0.001). The average of three high frequencies in the better ear was significantly associated with CANTAB Delayed Matching to Sample (β = −0.16, p = 0.008), and Spatial Working Memory (β = 0.17, p = 0.003).

Conclusion: The results revealed a significant relationship between age-related hearing loss and cognitive impairment in Mandarin-speaking older adults. These research outcomes have clinical implications specifically for hearing health care professionals in China and other populations that speak a tonal language, especially when providing hearing rehabilitation.
Adaptive Behavior, Emotional/Behavioral Problems and Parental Stress in Children With Autism Spectrum Disorder
Authors: Operto Francesca Felicia , Pastorino Grazia Maria Giovanna , Scuoppo Chiara , Padovano Chiara , Vivenzio Valentina , Pistola Ilaria , Belfiore Gilda , Rinaldi Rosetta , de Simone Valeria , Coppola Giangennaro
Published: December 2021

Background: The aim of our study was to compare adaptive skills, emotional/behavioral problems, and parental stress among children with different severity levels of Autism Spectrum Disorder (ASD) symptoms.

Methods: This study included a sample of 88 subjects with ASD (mean age = 6.00 ± 2.70). All subjects underwent standardized neuropsychological tests for the assessment of symptoms of the autism spectrum (Autism Diagnostic Observation Schedule-Second Edition), adaptive level (The Vineland Adaptive Behavior Scales, Survey Interview, 2nd edition), behavioral and emotional problems (Child Behavior CheckList CBCL), and parental stress (Parental Stress Index Short Form-PSI-SF). Non-parametric statistical methods (Kruskal-Wallis test and Mann-Whitney U-test for post hoc analysis) and linear regression analysis were used in this study.

Results:Children who had higher severity levels of ASD symptoms had less adaptive functioning; younger children showed more severe symptoms of ASD; older children had better communication skills. The presence of greater adaptive difficulties was related to a greater presence of internalizing problems. An increase in parental stress levels was related to an higher severity of ASD symptoms, fewer adaptive skills, and a greater presence of internalizing and externalizing problems.

Conclusion: This study suggests that the adaptive behavior should be considered in order to planning a habilitation intervention in children with autism. It is also important to monitor emotional/behavioral problems and parental stress levels in order to provide parenting support and improve the family quality of life.
Real-Time Cerebral Vessel Segmentation in Laser Speckle Contrast Image Based on Unsupervised Domain Adaptation
Authors: Chen Heping , Shi Yan , Bo Bin , Zhao Denghui , Miao Peng , Tong Shanbao , Wang Chunliang
Published: December 2021

Laser speckle contrast imaging (LSCI) is a full-field, high spatiotemporal resolution and low-cost optical technique for measuring blood flow, which has been successfully used for neurovascular imaging. However, due to the low signal–noise ratio and the relatively small sizes, segmenting the cerebral vessels in LSCI has always been a technical challenge. Recently, deep learning has shown its advantages in vascular segmentation. Nonetheless, ground truth by manual labeling is usually required for training the network, which makes it difficult to implement in practice. In this manuscript, we proposed a deep learning-based method for real-time cerebral vessel segmentation of LSCI without ground truth labels, which could be further integrated into intraoperative blood vessel imaging system. Synthetic LSCI images were obtained with a synthesis network from LSCI images and public labeled dataset of Digital Retinal Images for Vessel Extraction, which were then used to train the segmentation network. Using matching strategies to reduce the size discrepancy between retinal images and laser speckle contrast images, we could further significantly improve image synthesis and segmentation performance. In the testing LSCI images of rodent cerebral vessels, the proposed method resulted in a dice similarity coefficient of over 75%.
Methylation of BDNF and SLC6A4 Gene Promoters in Brazilian Patients With Temporal Lobe Epilepsy Presenting or Not Psychiatric Comorbidities
Authors: Bandeira Isabel Cristina , Giombelli Lucas , Werlang Isabel Cristina , Abujamra Ana Lucia , Secchi Thais Leite , Brondani Rosane , Bragatti José Augusto , Bizzi Jorge Wladimir Junqueira , Leistner-Segal Sandra , Bianchin Marino Muxfeldt
Published: December 2021

The relationship between epilepsy and psychiatric comorbidities has been recognized for centuries, but its pathophysiological mechanisms are still misunderstood. It is biologically plausible that genetic or epigenetic variations in genes that codify important neurotransmitters involved in epilepsy as well as in psychiatric disorders may influence the development of the latter in patients with epilepsy. However, this possibility remains poorly investigated. The aim of this study was to evaluate the methylation profile of the BDNF and SLC6A4, two genes importantly involved in neuroplasticity, in patients with temporal lobe epilepsy (TLE) regarding the development or not of psychiatric comorbidities. One hundred and thirty-nine patients with TLE, 90 females and 45 males, were included in the study. The mean age of patients was 44.0 (+12.0) years, and mean duration of epilepsy was 25.7 (+13.3) years. The Structured Clinical Interview for DSM-IV shows that 83 patients (59.7%) had neuropsychiatric disorders and 56 (40.3%) showed no psychiatric comorbidity. Mood disorders were the most common psychiatric disorder observed, being present in 64 (46.0%) of all 139 patients. Thirty-three (23.7%) patients showed anxiety disorders, 10 (7.2%) patients showed history of psychosis and 8 (5.8%) patients showed history of alcohol//drug abuse. Considering all 139 patients, 18 (12.9%) demonstrated methylation of the promoter region of both BDNF and SLC6A4 genes. A significant decreased methylation profile was observed only in TLE patients with mood disorders when compared with TLE patients without a history of mood disorders (O.R. = 3.45; 95% C.I. = 1.08–11.11; p = 0.04). A sub-analysis showed that TLE patients with major depressive disorder mostly account for this result (O.R. = 7.20; 95% C.I. = 1.01–56.16; p = 0.042). A logistic regression analysis showed that the independent factors associated with a history of depression in our TLE patients was female sex (O.R. = 2.30; 95% C.I. = 1.02–5.18; p = 0.044), not controlled seizures (O.R. = 2.51; 95% C.I. = 1.16–5.41; p = 0.019) and decreased methylation in BDNF and SLC6A4 genes (O.R. = 5.32; 95% C.I. = 1.14–25.00; p = 0.033). Our results suggest that BDNF or SLC6A4 genes profile methylation is independently associated with depressive disorders in patients with epilepsy. Further studies are necessary to clarify these matters.
Hybrid Systems to Boost EEG-Based Real-Time Action Decoding in Car Driving Scenarios
Authors: Vecchiato Giovanni
Published: December 2021

The complexity of concurrent cerebral processes underlying driving makes such human behavior one of the most studied real-world activities in neuroergonomics. Several attempts have been made to decode, both offline and online, cerebral activity during car driving with the ultimate goal to develop brain-based systems for assistive devices. Electroencephalography (EEG) is the cornerstone of these studies providing the highest temporal resolution to track those cerebral processes underlying overt behavior. Particularly when investigating real-world scenarios as driving, EEG is constrained by factors such as robustness, comfortability, and high data variability affecting the decoding performance. Hence, additional peripheral signals can be combined with EEG for increasing replicability and the overall performance of the brain-based action decoder. In this regard, hybrid systems have been proposed for the detection of braking and steering actions in driving scenarios to improve the predictive power of the single neurophysiological measurement. These recent results represent a proof of concept of the level of technological maturity. They may pave the way for increasing the predictive power of peripheral signals, such as electroculogram (EOG) and electromyography (EMG), collected in real-world scenarios when informed by EEG measurements, even if collected only offline in standard laboratory settings. The promising usability of such hybrid systems should be further investigated in other domains of neuroergonomics.
The Effects of Peanuts and Tree Nuts on Lipid Profile in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized, Controlled-Feeding Clinical Studies
Authors: Xia Jia-yue , Yu Jun-hui , Xu Deng-feng , Yang Chao , Xia Hui , Sun Gui-ju
Published: December 2021

Background: Type 2 diabetes mellitus was found to be associated with metabolic disorders, particularly abnormal glucose and lipid metabolism. Dietary food choices may have profound effects on blood lipids. The primary objective of this study was to examine the effects of peanuts and tree nuts intake on lipid profile in patients with type 2 diabetes.

Methods: According to preferred reporting items for systematic reviews and meta-analysis guidelines, we performed a systematic search of randomized controlled clinical trials and systematic reviews published in PubMed, Web of Science, Embase, Scopus, and Cochrane library, from inception through June 2021. Studies in populations with type 2 diabetes, which compare nuts or peanuts to a controlled-diet group were included. We used the mean difference with 95% CIs to present estimates for continuous outcomes from individual studies. In addition, we used the GRADEpro tool to evaluate the overall quality of evidence.

Results: Sixteen studies involving 1,041 participants were eligible for this review. The results showed that peanuts and tree nuts supplementation did not induce significant changes in low-density lipoprotein-cholesterol (LDL-C) (mean difference = −0.11; 95%CI: −0.25 – 0.03, p = 0.117) and high-density lipoprotein-cholesterol (HDL-C) (mean difference = 0.01; 95%CI: −0.01 – 0.04, p = 0.400) in patients with type 2 diabetics. In addition, we found that peanuts and tree nuts intake may cause a significantly reduction in total cholesterol (TC) (mean difference = −0.14; 95%CI: −0.26 – −0.02, p = 0.024) and triglyceride (TG) (mean difference = −0.10; 95%CI: −0.17 – −0.02, p = 0.010). In the subgroup analysis, a significantly greater reduction in TC was observed in studies which duration was <12 weeks (mean difference = −0.22; 95%CI: −0.37 – −0.08, p = 0.002). The quality of the body of evidence was “moderate” for TC and TG, the quality of evidence for LDL-C and HDL-C were “low.”

Conclusion: Our findings suggest that consuming peanuts and tree nuts might be beneficial to lower TC concentration and TG concentration in type 2 diabetics subjects. Furthermore, peanuts and tree nuts supplementation could be considered as a part of a healthy lifestyle in the management of blood lipids in patients with type 2 diabetes. Given some limits observed in the current studies, more well-designed trials are still needed.
A Systematic Review of Trans Fat Reduction Initiatives in the Eastern Mediterranean Region
Authors: Al-Jawaldeh Ayoub , Taktouk Mandy , Chatila Aya , Naalbandian Sally , Abdollahi Zahra , Ajlan Buthaina , Al Hamad Nawal , Alkhalaf Majid M. , Almamary Salima , Alobaid Rawan , Alyafei Salah Abdulla , Azizi Mohammad Hosein , Baqadir Nimah M. , Barham Rawhieh , Binsunaid Faisal F. , El Ammari Leila , El Ati Jalila , Hoteit Maha , Massad Hanan , Nejad Marzeyeh Soleymani , Nasreddine Lara
Published: December 2021

High intakes of trans fatty acids (TFA), particularly industrially-produced TFA, are implicated in the etiology of cardiovascular diseases, which represent the leading cause of mortality in the Eastern Mediterranean Region (EMR). This systematic review aims to document existing national TFA reduction strategies in the EMR, providing an overview of initiatives that are implemented by countries of the region, and tracking progress toward the elimination of industrially-produced TFA. A systematic review of published and gray literature was conducted using a predefined search strategy. A total of 136 peer-reviewed articles, gray literature documents, websites and references from country contacts were obtained, up until 2 August 2021. Randomized-control trials, case-control studies, and studies targeting unhealthy population groups were excluded. Only articles published after 1995, in English, Arabic or French, were included. Key characteristics of strategies were extracted and classified according to a pre-developed framework, which includes TFA intake assessment; determination of TFA levels in foods; strategic approach; implementation strategies (TFA bans/limits; consumer education, labeling, interventions in public institution settings, taxation), as well as monitoring and evaluation of program impact. Thirteen out of the 22 countries of the EMR (59%) have estimated TFA intake levels, 9 have determined TFA levels in foods (41%), and 14 (63.6%) have national TFA reduction initiatives. These initiatives were mainly led by governments, or by national multi-sectoral committees. The most common TFA reduction initiatives were based on TFA limits or bans (14/14 countries), with a mandatory approach being adopted by 8 countries (Bahrain, Iran, Jordan, KSA, Kuwait, Morocco, Oman and Palestine). Complementary approaches were implemented in several countries, including consumer education (10/14), food labeling (9/14) and interventions in specific settings (7/14). Monitoring activities were conducted by few countries (5/14), and impact evaluations were identified in only Iran and the UAE. The robustness of the studies, in terms of methodology and quality of assessment, as well as the lack of sufficient data in the EMR, remain a limitation that needs to be highlighted. Further action is needed to initiate TFA reduction programs in countries that are lagging behind, and to ensure rigorous implementation and evaluation of ongoing programs.
Dissolution Study on Grape Polyphenol Hard Gelatin Capsule Dietary Supplements
Authors: Lyu Weiting , Omar Thamer , Patel Harna , Rodriguez David , Ferruzzi Mario G. , Pasinetti Giulio M. , Murrough James W. , Muzzio Fernando J. , Simon James E. , Wu Qingli
Published: December 2021

Methods for a dissolution study by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC-QqQ/MS) analysis of grape polyphenol dietary supplements, namely, grape seed extract (GSE) and resveratrol (RSV) capsules, were developed following the guidance of United States Pharmacopeia (USP) <2040>. Two dissolution media, 0.1 N hydrochloric acid (pH 1.2) and 0.05 M acetate buffer (pH 4.6), were evaluated with dissolution apparatus (USP 1), 100 rpm rotation speed, and 900 ml dissolution medium volume. Dissolution profiling was performed over 120 min. Major phenolic compounds of gallic acid, catechin, epicatechin, and procyanidin B2 were quantitated to obtain the dissolution profile of GSE capsules, and trans-RSV was used for RSV capsules. Results indicated that the released trans-RSV for RSV capsules in both of the dissolution media meets the USP standards, and that for the GSE capsules, all the four marker compounds passed the dissolution test in the HCl medium but did not reach a 75% release within 60 min in the acetate buffer. These promising results suggest that the general USP dissolution protocols are adequate for the successful release of RSV capsules in HCl medium and acetate buffer and GSE capsules (in HCl medium), but may be inadequate for GSE capsules in acetate buffer. These results showed that under a low pH of 1.2 (simulated stomach environment), bioactive compounds were released on time from the GSE capsules and met the USP guidelines; however, under a higher pH of 4.6 (simulated duodenum environment), the same biomarkers failed, suggesting the need to further improve the dissolution of GSE over a wider range of pH environments to enhance bioavailability and efficacy.
Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options
Authors: Liu Zheran , Chen Ye , Su Yonglin , Hu Xiaolin , Peng Xingchen
Published: December 2021

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.
Curative Effect and Survival Assessment Comparing Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin and Cisplatin as Neoadjuvant Therapy for Bladder Cancer: A Systematic Review and Meta-Analysis
Authors: Wu Tiange , Wu Yuqing , Chen Shuqiu , Wu Jianping , Zhu Weidong , Liu Hui , Chen Ming , Xu Bin
Published: December 2021

Background

Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes than radical cystectomy or a cisplatin-based regimen. In the present study, we aimed to compare the two most commonly used cisplatin-based neoadjuvant chemotherapies, gemcitabine plus cisplatin and methotrexate plus vinblastine plus doxorubicin plus cisplatin, by summarizing and analyzing clinical data and outcomes of published research.

Methods

We searched for qualified studies that compared these two types of neoadjuvant chemotherapy, including 4 randomized controlled trials and 14 retrospective studies. Data and information on pathological responses and long-term survival studies were extracted and analyzed separately.

Results

A total of 18 studies with 3116 patients were selected from 1188 studies, which contained data on pathological complete response, pathological partial response, and overall survival. In contrast to the results of previous studies, there was no significant difference in pathological complete response (odds ratio, 0.97; 95% confidence interval, 0.81-1.15), pathological partial response (odds ratio, 0.85; 95% confidence interval, 0.72-1.14), and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.83-1.17) between GC and MVAC in this meta-analysis.

Conclusion

No significant differences were observed between GC and MVAC in the muscle-invasive bladder cancer treatment due to the similar curative effect and parallel long survival outcomes due to the similar curative effect and parallel long survival outcomes. The priority selection of GC or MVAC in the clinic should be guided by further investigation, and the clinical standard strategy still counts on the results of more randomized controlled trials in the future.
MRI-Based Bone Marrow Radiomics Nomogram for Prediction of Overall Survival in Patients With Multiple Myeloma
Authors: Li Yang , Liu Yang , Yin Ping , Hao Chuanxi , Sun Chao , Chen Lei , Wang Sicong , Hong Nan
Published: December 2021

Purpose

To develop and validate a radiomics nomogram for predicting overall survival (OS) in multiple myeloma (MM) patients.

Material and Methods

A total of 121 MM patients was enrolled and divided into training (n=84) and validation (n=37) sets. The radiomics signature was established by the selected radiomics features from lumbar MRI. The radiomics signature and clinical risk factors were integrated in multivariate Cox regression model for constructing radiomics nomogram to predict MM OS. The predictive ability and accuracy of the nomogram were evaluated by the index of concordance (C-index) and calibration curves, and compared with other four models including the clinical model, radiomics signature model, the Durie-Salmon staging system (D-S) and the International Staging System (ISS). The potential association between the radiomics signature and progression-free survival (PFS) was also explored.

Results

The radiomics signature, 1q21 gain, del (17p), and β2-MG≥5.5 mg/L showed significant association with MM OS. The predictive ability of radiomics nomogram was better than the clinical model, radiomics signature model, the D-S and the ISS (C-index: 0.793 vs. 0.733 vs. 0.742 vs. 0.554 vs. 0.671 in training set, and 0.812 vs. 0.799 vs.0.717 vs. 0.512 vs. 0.761 in validation set). The radiomics signature lacked the predictive ability for PFS (log-rank P=0.001 in training set and log-rank P=0.103 in validation set), whereas the 1-, 2- and 3-year PFS rates all showed significant difference between the high and low risk groups (P ≤ 0.05).

Conclusion

The MRI-based bone marrow radiomics may be an additional useful tool for MM OS prediction.
Comparison of the Accuracy and Clinical Parameters of Patient-Specific and Conventionally Bended Plates for Mandibular Reconstruction
Authors: Möllmann Henriette L. , Apeltrath Laura , Karnatz Nadia , Wilkat Max , Riedel Erik , Singh Daman Deep , Rana Majeed
Published: December 2021

Objectives

This retrospective study compared two mandibular reconstruction procedures—conventional reconstruction plates (CR) and patient-specific implants (PSI)—and evaluated their accuracy of reconstruction and clinical outcome.

Methods

Overall, 94 patients had undergone mandibular reconstruction with CR (n = 48) and PSI (n = 46). Six detectable and replicable anatomical reference points, identified via computer tomography, were used for defining the mandibular dimensions. The accuracy of reconstruction was assessed using pre- and postoperative differences.

Results

In the CR group, the largest difference was at the lateral point of the condyle mandibulae (D2) -1.56 mm (SD = 3.8). In the PSI group, the largest difference between preoperative and postoperative measurement was shown at the processus coronoid (D5) with +1.86 mm (SD = 6.0). Significant differences within the groups in pre- and postoperative measurements were identified at the gonion (D6) [t(56) = -2.217; p = .031 <.05]. In the CR group, the difference was 1.5 (SD = 3.9) and in the PSI group -1.04 (SD = 4.9). CR did not demonstrate a higher risk of plate fractures and post-operative complications compared to PSI.

Conclusion

For reconstructing mandibular defects, CR and PSI are eligible. In each case, the advantages and disadvantages of these approaches must be assessed. The functional and esthetic outcome of mandibular reconstruction significantly improves with the experience of the surgeon in conducting microvascular grafts and familiarity with computer-assisted surgery. Interoperator variability can be reduced, and training of younger surgeons involved in planning can be reaching better outcomes in the future.
Development and Validation of a Predictive Scoring System for Colorectal Cancer Patients With Liver Metastasis: A Population-Based Study
Authors: Cao Yinghao , Ke Songqing , Deng Shenghe , Yan Lizhao , Gu Junnan , Mao Fuwei , Xue Yifan , Zheng Changmin , Cai Wentai , Liu Hongli , Li Han , Shang Fumei , Sun Zhuolun , Wu Ke , Zhao Ning , Cai Kailin
Published: December 2021

Liver metastasis in colorectal cancer (CRC) is common and has an unfavorable prognosis. This study aimed to establish a functional nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer liver metastasis (CRCLM). A total of 9,736 patients with CRCLM from 2010 to 2016 were randomly assigned to training, internal validation, and external validation cohorts. Univariate and multivariate Cox analyses were performed to identify independent clinicopathologic predictive factors, and a nomogram was constructed to predict CSS and OS. Multivariate analysis demonstrated age, tumor location, differentiation, gender, TNM stage, chemotherapy, number of sampled lymph nodes, number of positive lymph nodes, tumor size, and metastatic surgery as independent predictors for CRCLM. A nomogram incorporating the 10 predictors was constructed. The nomogram showed favorable sensitivity at predicting 1-, 3-, and 5-year OS, with area under the receiver operating characteristic curve (AUROC) values of 0.816, 0.782, and 0.787 in the training cohort; 0.827, 0.769, and 0.774 in the internal validation cohort; and 0.819, 0.745, and 0.767 in the external validation cohort, respectively. For CSS, the values were 0.825, 0.771, and 0.772 in the training cohort; 0.828, 0.753, and 0.758 in the internal validation cohort; and 0.828, 0.737, and 0.772 in the external validation cohort, respectively. Calibration curves and ROC curves revealed that using our models to predict the OS and CSS would add more benefit than other single methods. In summary, the novel nomogram based on significant clinicopathological characteristics can be conveniently used to facilitate the postoperative individualized prediction of OS and CSS in CRCLM patients.
The Bioinformatics-Based Analysis Identifies 7 Immune-Related Genes as Prognostic Biomarkers for Colon Cancer
Authors: Pan Jie , Weng Zongqi , Xue Chaorong , Lin Bingqiang , Lin Mengxin
Published: December 2021

Colon cancer poses a great threat to human health. Currently, there is no effective treatment for colon cancer due to its complex causative factors. Immunotherapy has now become a new method for tumor treatment. In this study, 487 DEGs were screened from The Cancer Genome Atlas (TCGA) database and ImmPort database, and GeneOntology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Hierarchical clustering of all samples revealed a significant correlation between colon cancer and immunity. The weighted gene co-expression network analysis (WGCNA) algorithm was used to identify key gene modules associated with immunity in colon cancer, here, module grey60 showed the highest correlation. A protein-protein interaction (PPI) network was constructed using the STRING database to screen hub genes, and subsequently, 7 immune-related genes the most closely associated with colon cancer were identified by differential expression in cancer and paracancer. Finally, a risk prediction model was developed using least absolute shrinkage and selection operator (LASSO) COX analysis, and the accuracy of the model was validated by GSE14333. This study determined that IRF4 and TNFRSF17 were immune-related genes in colon cancer, providing immune-related prognostic biomarkers for colon cancer.
Radiation Treatment for Inoperable Local Relapse of Parathyroid Carcinoma With Symptomatic Hypercalcemia: A Case Report
Authors: Bollen Heleen , Decallonne Brigitte , Nuyts Sandra
Published: December 2021

Background

Parathyroid carcinoma (PC) is an extremely rare malignancy, characterized by slow progression, frequent recurrences and difficult-to-control hypercalcemia which is typically the main contributor to the morbidity and mortality of these patients. Patients often undergo repeated surgical resections, whether or not in combination with adjuvant radiation treatment. The role of radiation therapy within the symptomatic treatment of PC currently remains unclear.

Case description

We describe a 30-year-old male patient with an inoperable local relapse of PC and secondary symptomatic hypercalcemia, maximally pharmacologically treated. After a local radiation treatment to a total dose of 70 Gray in 35 fractions serum calcium and parathyroid hormone (PTH) levels decreased, accompanied by improvement of the severe gastro-intestinal disturbances.

Conclusion

For patients with inoperable symptomatic PC despite maximal medical treatment who are in a good overall condition, radiation treatment can be considered in well-defined cases to decrease symptoms and improve quality of life.
Tumor Budding Score Is a Strong and Independent Prognostic Factor in Patients With Pancreatic Ductal Adenocarcinoma: An Evaluation of Whole Slide Pathology Images of Large Sections
Authors: Jiang Hui , Yang Yelin , Qian Yuping , Shao Chengwei , Lu Jianping , Bian Yun , Zheng Jianming
Published: December 2021

Objective

We aimed to develop the tumor budding (TB) score and to explore the association between the TB score and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

In this retrospective study, 130 consecutive patients with PDAC underwent surgical resection between July 2016 and March 2019. The location and counts of TB were assessed based on the digitalized whole slide hematoxylin and eosin images. The TB score was achieved using the Cox regression equation. The cutoff point for the TB score was determined by X-tile. Univariate and multivariate Cox regression models were used to analyze the association between the TB score and OS.

Results

The TB score was 0.49 (range = 0–1.08), and the best cutoff for the TB score was 0.62. The duration of survival in individuals with a low TB score [median = 21.8 months, 95% confidence interval (CI) = 15.43–25.50] was significantly longer than that in those with a high TB score (median = 11.33 months, 95% CI = 9.8–14.22). Univariate analysis revealed that the TB score was significantly associated with OS [hazard ratio (HR) = 2.71, 95% CI = 1.48–4.96, p = 0.001]. Multivariate analysis revealed a strong and independent association between the TB score and OS (HR = 2.35, 95% CI = 1.27–4.33, p = 0.03). The high TB score group had a 2.14 times higher mortality than the low TB score group.

Conclusion

The TB score is strongly and independently associated with the risk of OS in PDAC.
Precise Identification of Recurrent Somatic Mutations in Oral Cancer Through Whole-Exome Sequencing Using Multiple Mutation Calling Pipelines
Authors: Lin Li-Han , Chou Chung-Hsien , Cheng Hui-Wen , Chang Kuo-Wei , Liu Chung-Ji
Published: December 2021

Understanding the genomic alterations in oral carcinogenesis remains crucial for the appropriate diagnosis and treatment of oral squamous cell carcinoma (OSCC). To unveil the mutational spectrum, in this study, we conducted whole-exome sequencing (WES), using six mutation calling pipelines and multiple filtering criteria applied to 50 paired OSCC samples. The tumor mutation burden extracted from the data set of somatic variations was significantly associated with age, tumor staging, and survival. Several genes (MUC16, MUC19, KMT2D, TTN, HERC2) with a high frequency of false positive mutations were identified. Moreover, known (TP53, FAT1, EPHA2, NOTCH1, CASP8, and PIK3CA) and novel (HYDIN, ALPK3, ASXL1, USP9X, SKOR2, CPLANE1, STARD9, and NSD2) genes have been found to be significantly and frequently mutated in OSCC. Further analysis of gene alteration status with clinical parameters revealed that canonical pathways, including clathrin-mediated endocytotic signaling, NFκB signaling, PEDF signaling, and calcium signaling were associated with OSCC prognosis. Defining a catalog of targetable genomic alterations showed that 58% of the tumors carried at least one aberrant event that may potentially be targeted by approved therapeutic agents. We found molecular OSCC subgroups which were correlated with etiology and prognosis while defining the landscape of major altered events in the coding regions of OSCC genomes. These findings provide information that will be helpful in the design of clinical trials on targeted therapies and in the stratification of patients with OSCC according to therapeutic efficacy.
Insulin Resistance and Metabolic Syndrome Increase the Risk of Relapse For Fertility Preserving Treatment in Atypical Endometrial Hyperplasia and Early Endometrial Cancer Patients
Authors: Li Xingchen , Fan Yuan , Wang Jiaqi , Zhou Rong , Tian Li , Wang Yiqin , Wang Jianliu
Published: December 2021

Objective

Fertility-sparing treatment for young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) is a difficult challenge. Insulin resistance (IR) and metabolic syndrome (MetS) are two potentially crucial, but currently enigmatic factors in the recurrence of AEH and early EC patients. In this study we attempt to elucidate these factors.

Methods

A retrospective study was conducted from January 2010 to December 2019. Risk factors for recurrence and complete remission time after recurrence (RCR time) were investigated. ROC curves were built to estimate the accuracy of the metabolic characteristics and Kaplan–Meier (K–M) analysis was used to calculate recurrence-free survival (RFS) for patients with various IR or MetS statuses.

Results

A total of 111 AEH or early EC patients met the criteria and were enrolled in our study. Univariate analysis found that BMI ≥25 kg/m2 (OR = 2.7, 95% CI: 1.1–6.4, P = 0.03), IR (OR = 9.5, 95% CI: 3.3–27.0, P <0.001), MetS (OR = 4.9, 95% CI:1.5–15.5, P = 0.008), IR+ and MetS+ (OR = 21.0, 95% CI: 4.8–92.7, P <0.001), histological type (OR = 3.5, 95% CI: 1.5–7.9, P = 0.003), and maintenance treatment (OR = 0.3, 95% CI: 0.1–0.6, P = 0.005) were all significantly associated with recurrence and longer RCR time. Among these factors, IR and MetS were determined to be two independent risk factors for recurrence. Moreover, using IR and MetS as markers significantly improved the diagnostic accuracy of recurrence for fertility-sparing treatment patients (AUC = 0.818, P <0.05) and may play synergistic roles in suppressing treatment. K–M analysis indicated both metabolic features played important roles in RFS (P <0.05).

Conclusion

Both IR and MetS were significantly associated with recurrence and longer RCR time in AEH and early EC patients receiving fertility-sparing treatment.
Cancer-Related Characteristics Associated With Invasive Mechanical Ventilation or In-Hospital Mortality in Patients With COVID-19 Admitted to ICU: A Cohort Multicenter Study
Authors: Caruso Pedro , Testa Renato Scarsi , Freitas Isabel Cristina Lima , Praça Ana Paula Agnolon , Okamoto Valdelis Novis , Santana Pauliane Vieira , Costa Ramon Teixeira , Kawasaki Alexandre Melo , Fumis Renata Rego Lins , Pino Illanes Wilber Antonio , Costa Eduardo Leite Vieira , Midega Thais Dias , Correa Thiago Domingos , de Carvalho Fabrício Rodrigo Torres , Ferreira Juliana Carvalho
Published: December 2021

Background

Coexistence of cancer and COVID-19 is associated with worse outcomes. However, the studies on cancer-related characteristics associated with worse COVID-19 outcomes have shown controversial results. The objective of the study was to evaluate cancer-related characteristics associated with invasive mechanical ventilation use or in-hospital mortality in patients with COVID-19 admitted to intensive care unit (ICU).

Methods

We designed a cohort multicenter study including adults with active cancer admitted to ICU due to COVID-19. Seven cancer-related characteristics (cancer status, type of cancer, metastasis occurrence, recent chemotherapy, recent immunotherapy, lung tumor, and performance status) were introduced in a multilevel logistic regression model as first-level variables and hospital was introduced as second-level variable (random effect). Confounders were identified using directed acyclic graphs.

Results

We included 274 patients. Required to undergo invasive mechanical ventilation were 176 patients (64.2%) and none of the cancer-related characteristics were associated with mechanical ventilation use. Approximately 155 patients died in hospital (56.6%) and poor performance status, measured with the Eastern Cooperative Oncology Group (ECOG) score was associated with increased in-hospital mortality, with odds ratio = 3.54 (1.60–7.88, 95% CI) for ECOG =2 and odds ratio = 3.40 (1.60–7.22, 95% CI) for ECOG = 3 to 4. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with in-hospital mortality.

Conclusions

In patients with active cancer and COVID-19 admitted to ICU, poor performance status was associated with in-hospital mortality but not with mechanical ventilation use. Cancer status, cancer type, metastatic tumor, lung cancer, and recent chemotherapy or immunotherapy were not associated with invasive mechanical ventilation use or in-hospital mortality.
Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma
Authors: Li Qinglin , Xia Liang , Sun Caixing , Zhang Huangjie , Zheng Mengying , Zhang Hongyan , Lu Hongyang , Wang Zeng
Published: December 2021

Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo. Furthermore, borneol markedly increased the number of autophagosomes in the glioma cells, which coincided with increased expression of beclin-1 and LC3. And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E. In addition, silencing mTORC1 and eIF4E upregulated Beclin-1 and LC3 and decreased the expression of HIF-1α, thereby inhibiting tumor cell proliferation. Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.
Does the Identification of a Minimum Number of Cases Correlate With Better Adherence to International Guidelines Regarding the Treatment of Penile Cancer? Survey Results of the European PROspective Penile Cancer Study (E-PROPS)
Authors: Lebentrau Steffen , Wakileh Gamal Anton , Schostak Martin , Schmid Hans-Peter , Suarez-Ibarrola Rodrigo , Merseburger Axel S. , Hutterer Georg C. , Necknig Ulrike H. , Rink Michael , Bögemann Martin , Kluth Luis Alex , Pycha Armin , Burger Maximilian , Brookman-May Sabine D. , Bründl Johannes , May Matthias
Published: December 2021

Background

Penile cancer represents a rare malignant disease, whereby a small caseload is associated with the risk of inadequate treatment expertise. Thus, we hypothesized that strict guideline adherence might be considered a potential surrogate for treatment quality. This study investigated the influence of the annual hospital caseload on guideline adherence regarding treatment recommendations for penile cancer.

Methods

In a 2018 survey study, 681 urologists from 45 hospitals in four European countries were queried about six hypothetical case scenarios (CS): local treatment of the primary tumor pTis (CS1) and pT1b (CS2); lymph node surgery inguinal (CS3) and pelvic (CS4); and chemotherapy neoadjuvant (CS5) and adjuvant (CS6). Only the responses from 206 head and senior physicians, as decision makers, were evaluated. The answers were assessed based on the applicable European Association of Urology (EAU) guidelines regarding their correctness. The real hospital caseload was analyzed based on multivariate logistic regression models regarding its effect on guideline adherence.

Results

The median annual hospital caseload was 6 (interquartile range (IQR) 3–9). Recommendations for CS1–6 were correct in 79%, 66%, 39%, 27%, 28%, and 28%, respectively. The probability of a guideline-adherent recommendation increased with each patient treated per year in a clinic for CS1, CS2, CS3, and CS6 by 16%, 7.8%, 7.2%, and 9.5%, respectively (each p < 0.05); CS4 and CS5 were not influenced by caseload. A caseload threshold with a higher guideline adherence for all endpoints could not be perceived. The type of hospital care (academic vs. non-academic) did not affect guideline adherence in any scenario.

Conclusions

Guideline adherence for most treatment recommendations increases with growing annual penile cancer caseload. Thus, the results of our study call for a stronger centralization of diagnosis and treatment strategies regarding penile cancer.
Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis
Authors: Tamihardja Jörg , Lutyj Paul , Kraft Johannes , Lisowski Dominik , Weick Stefan , Flentje Michael , Polat Bülent
Published: December 2021

Purpose

Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer.

Methods

338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition.

Results

Median follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%.

Conclusions

Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.