bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic adaption of cancer cells toward autophagy: Is there a role for ER-phagy?
Authors: Gentile Debora , Esposito Marianna , Grumati Paolo
Published: August 2022

Autophagy is an evolutionary conserved catabolic pathway that uses a unique double-membrane vesicle, called autophagosome, to sequester cytosolic components, deliver them to lysosomes and recycle amino-acids. Essentially, autophagy acts as a cellular cleaning system that maintains metabolic balance under basal conditions and helps to ensure nutrient viability under stress conditions. It is also an important quality control mechanism that removes misfolded or aggregated proteins and mediates the turnover of damaged and obsolete organelles. In this regard, the idea that autophagy is a non-selective bulk process is outdated. It is now widely accepted that forms of selective autophagy are responsible for metabolic rewiring in response to cellular demand. Given its importance, autophagy plays an essential role during tumorigenesis as it sustains malignant cellular growth by acting as a coping-mechanisms for intracellular and environmental stress that occurs during malignant transformation. Cancer development is accompanied by the formation of a peculiar tumor microenvironment that is mainly characterized by hypoxia (oxygen < 2%) and low nutrient availability. Such conditions challenge cancer cells that must adapt their metabolism to survive. Here we review the regulation of autophagy and selective autophagy by hypoxia and the crosstalk with other stress response mechanisms, such as UPR. Finally, we discuss the emerging role of ER-phagy in sustaining cellular remodeling and quality control during stress conditions that drive tumorigenesis.
Suppression of crosstalk in multielectrode arrays with local shielding
Authors: Naughton J. R. , Varela J. A. , Connolly T. J. , Shepard S. , Dodge T. E. , Kempa K. , Burns M. J. , Christianson J. P. , Naughton M. J.
Published: August 2022

Electrical crosstalk can constrain the performance of multielectrode arrays in electro- and neurophysiology, in terms of both stimulation and recording. This is especially so at high electrode density, desirable for spatiotemporal mapping of bioelectrical signals from multiple cells. Channel interference due to crosstalk is currently only partially addressed, via continuous interleaved sampling or post-data acquisition spike sorting. Here, we show that a locally-shielded electrode architecture significantly suppresses crosstalk, and enables multi-site recording at high electrode density without the need for spike sorting. Arrays of shielded electrodes, prepared by micro- and nanofabrication techniques in a vertically-oriented coaxial geometry, demonstrate at least a 400 times improvement in spatial density over the unshielded case.
Angiotensin-(1-7) improves cognitive function and reduces inflammation in mice following mild traumatic brain injury
Authors: Bruhns Ryan P. , Sulaiman Maha Ibrahim , Gaub Michael , Bae Esther H. , Davidson Knapp Rachel B. , Larson Anna R. , Smith Angela , Coleman Deziree L. , Staatz William D. , Sandweiss Alexander J. , Joseph Bellal , Hay Meredith , Largent-Milnes Tally M. , Vanderah Todd W.
Published: August 2022

Introduction

Traumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model.

Materials and methods

Male mice (n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) (n = 12) or vehicle (n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1–5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury.

Results

Administration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control.

Discussion

These are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries.
Evaluation of phase-locking to parameterized speech envelopes
Authors: David Wouter , Gransier Robin , Wouters Jan
Published: August 2022

Humans rely on the temporal processing ability of the auditory system to perceive speech during everyday communication. The temporal envelope of speech is essential for speech perception, particularly envelope modulations below 20 Hz. In the literature, the neural representation of this speech envelope is usually investigated by recording neural phase-locked responses to speech stimuli. However, these phase-locked responses are not only associated with envelope modulation processing, but also with processing of linguistic information at a higher-order level when speech is comprehended. It is thus difficult to disentangle the responses into components from the acoustic envelope itself and the linguistic structures in speech (such as words, phrases and sentences). Another way to investigate neural modulation processing is to use sinusoidal amplitude-modulated stimuli at different modulation frequencies to obtain the temporal modulation transfer function. However, these transfer functions are considerably variable across modulation frequencies and individual listeners. To tackle the issues of both speech and sinusoidal amplitude-modulated stimuli, the recently introduced Temporal Speech Envelope Tracking (TEMPEST) framework proposed the use of stimuli with a distribution of envelope modulations. The framework aims to assess the brain's capability to process temporal envelopes in different frequency bands using stimuli with speech-like envelope modulations. In this study, we provide a proof-of-concept of the framework using stimuli with modulation frequency bands around the syllable and phoneme rate in natural speech. We evaluated whether the evoked phase-locked neural activity correlates with the speech-weighted modulation transfer function measured using sinusoidal amplitude-modulated stimuli in normal-hearing listeners. Since many studies on modulation processing employ different metrics and comparing their results is difficult, we included different power- and phase-based metrics and investigate how these metrics relate to each other. Results reveal a strong correspondence across listeners between the neural activity evoked by the speech-like stimuli and the activity evoked by the sinusoidal amplitude-modulated stimuli. Furthermore, strong correspondence was also apparent between each metric, facilitating comparisons between studies using different metrics. These findings indicate the potential of the TEMPEST framework to efficiently assess the neural capability to process temporal envelope modulations within a frequency band that is important for speech perception.
Whole-volume ADC histogram of the brain as an image biomarker in evaluating disease severity of neonatal hypoxic-ischemic encephalopathy
Authors: Wang Ruizhu , Xi Yanli , Yang Ming , Zhu Meijiao , Yang Feng , Xu Huafeng
Published: August 2022

Purpose

To examine the diagnostic significance of the apparent diffusion coefficient (ADC) histogram in quantifying neonatal hypoxic ischemic encephalopathy (HIE).

Methods

An analysis was conducted on the MRI data of 90 HIE patients, 49 in the moderate-to-severe group, and the other in the mild group. The 3D Slicer software was adopted to delineate the whole brain region as the region of interest, and 22 ADC histogram parameters were obtained. The interobserver consistency of the two radiologists was assessed by the interclass correlation coefficient (ICC). The difference in parameters (ICC > 0.80) between the two groups was compared by performing the independent sample t-test or the Mann–Whitney U test. In addition, an investigation was conducted on the correlation between parameters and the neonatal behavioral neurological assessment (NBNA) score. The ROC curve was adopted to assess the efficacy of the respective significant parameters. Furthermore, the binary logistic regression was employed to screen out the independent risk factors for determining the severity of HIE.

Results

The ADCmean, ADCmin, ADCmax,10th−70th, 90th percentile of ADC values of the moderate-to-severe group were smaller than those of the mild group, while the group's variance, skewness, kurtosis, heterogeneity, and mode-value were higher than those of the mild group (P < 0.05). All the mentioned parameters, the ADCmean, ADCmin, and 10th−70th and 90th percentile of ADC displayed positive correlations with the NBNA score, mode-value and ADCmax displayed no correlations with the NBNA score, the rest showed negative correlations with the NBNA score (P < 0.05). The area under the curve (AUC) of variance was the largest (AUC = 0.977; cut-off 972.5, sensitivity 95.1%; specificity 87.8%). According to the logistic regression analysis, skewness, kurtosis, variance, and heterogeneity were independent risk factors for determining the severity of HIE (OR > 1, P < 0.05).

Conclusions

The ADC histogram contributes to the HIE diagnosis and is capable of indicating the diffusion information of the brain objectively and quantitatively. It refers to a vital method for assessing the severity of HIE.
Qualitative and quantitative detectability of hypertrophic olivary degeneration in T2, FLAIR, PD, and DTI: A prospective MRI study
Authors: Steidl Eike , Rauch Maximilian , Hattingen Elke , Breuer Stella , Schüre Jan Rüdiger , Grapengeter Marike , Shrestha Manoj , Foerch Christian , Schaller-Paule Martin A.
Published: August 2022

Purpose:

Hypertrophic olivary degeneration (HOD) is a pathology of the inferior olivary nucleus (ION) that occurs after injuries to the Guillain-Mollaret triangle (GMT). Lacking a diagnostic gold standard, diagnosis is usually based on T2 or FLAIR imaging and expert rating. To facilitate precise HOD diagnosis in future studies, we assessed the reliability of this rater-based approach and explored alternative, quantitative analysis.

Methods

Patients who had suffered strokes in the GMT and a matched control group prospectively underwent an MRI examination including T2, FLAIR, and proton density (PD). Diffusion tensor imaging (DTI) was additionally performed in the patient group. The presence of HOD was assessed on FLAIR, T2, and PD separately by 3 blinded reviewers. Employing an easily reproducible segmentation approach, relative differences in intensity, fractional anisotropy (FA), and mean diffusivity (MD) between both IONs were calculated.

Results

In total, 15 patients were included in this study. The interrater reliability was best for FLAIR, followed by T2 and PD (Fleiss κ = 0.87 / 0.77 / 0.65). The 3 raters diagnosed HOD in 38–46% (FLAIR), 40–47% (T2), and 53–67% (PD) of patients. False-positive findings in the control group were less frequent in T2 than in PD and FLAIR (2.2% / 8.9% / 6.7%). In 53% of patients, the intensity difference between both IONs on PD was significantly increased in comparison with the control group. These patients also showed significantly decreased FA and increased MD.

Conclusion

While the rater-based approach yielded the best performance on T2 imaging, a quantitative, more sensitive HOD diagnosis based on ION intensities in PD and DTI imaging seems possible.
Slow Firing Single Units Are Essential for Optimal Decoding of Silent Speech
Authors: Ganesh Ananya , Cervantes Andre J. , Kennedy Philip R.
Published: August 2022

The motivation of someone who is locked-in, that is, paralyzed and mute, is to find relief for their loss of function. The data presented in this report is part of an attempt to restore one of those lost functions, namely, speech. An essential feature of the development of a speech prosthesis is optimal decoding of patterns of recorded neural signals during silent or covert speech, that is, speaking “inside the head” with output that is inaudible due to the paralysis of the articulators. The aim of this paper is to illustrate the importance of both fast and slow single unit firings recorded from an individual with locked-in syndrome and from an intact participant speaking silently. Long duration electrodes were implanted in the motor speech cortex for up to 13 years in the locked-in participant. The data herein provide evidence that slow firing single units are essential for optimal decoding accuracy. Additional evidence indicates that slow firing single units can be conditioned in the locked-in participant 5 years after implantation, further supporting their role in decoding.
Mitigating negative emotions through virtual reality and embodiment
Authors: Sansoni Maria , Scarzello Giovanni , Serino Silvia , Groff Elena , Riva Giuseppe
Published: August 2022

Oncological treatments are responsible for many of the physical changes (aesthetic and functional) associated with cancer. Because of this, cancer patients are at high risk of developing mental health problems. The aim of this study is to propose an innovative Virtual Reality (VR) training that uses a somatic technique (i.e., embodiment) to create a bridge with the bodily dimension of cancer. After undergoing a psycho-educational procedure, a combination of exposure, out-of-body experience, and body swapping will gradually train the patient to cope with cancer-related difficulties, increasing stress tolerance, and patient empowerment. The most engaging step of this advanced form of Stress Inoculation Training is the body swapping experience, which will guide the patient in embodying a resilient cancer patient who is facing similar difficulties. Through the VR ability to simulate the human brain functioning, and the potential of embodiment to hook to the somatic dimension of illness, we expect that once the concepts endured through the patient’s experience of resilience are triggered, the patient will be more prone to implement functional coping strategies in real life, reaching empowerment and adjusting to the post-treatment difficulties. When the scenarios are built and the training tested, our intervention could be used to support patients with different oncological diseases and who are treated in different cancer hospitals, as well as patients with other non-oncological problems (e.g., social anxiety). Future research should focus on using our paradigm for other clinical populations, and supporting cancer patients in coping with different distressing situations.
Improved classification performance of EEG-fNIRS multimodal brain-computer interface based on multi-domain features and multi-level progressive learning
Authors: Qiu Lina , Zhong Yongshi , He Zhipeng , Pan Jiahui
Published: August 2022

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) have potentially complementary characteristics that reflect the electrical and hemodynamic characteristics of neural responses, so EEG-fNIRS-based hybrid brain-computer interface (BCI) is the research hotspots in recent years. However, current studies lack a comprehensive systematic approach to properly fuse EEG and fNIRS data and exploit their complementary potential, which is critical for improving BCI performance. To address this issue, this study proposes a novel multimodal fusion framework based on multi-level progressive learning with multi-domain features. The framework consists of a multi-domain feature extraction process for EEG and fNIRS, a feature selection process based on atomic search optimization, and a multi-domain feature fusion process based on multi-level progressive machine learning. The proposed method was validated on EEG-fNIRS-based motor imagery (MI) and mental arithmetic (MA) tasks involving 29 subjects, and the experimental results show that multi-domain features provide better classification performance than single-domain features, and multi-modality provides better classification performance than single-modality. Furthermore, the experimental results and comparison with other methods demonstrated the effectiveness and superiority of the proposed method in EEG and fNIRS information fusion, it can achieve an average classification accuracy of 96.74% in the MI task and 98.42% in the MA task. Our proposed method may provide a general framework for future fusion processing of multimodal brain signals based on EEG-fNIRS.
Hyperexcitability: From Normal Fear to Pathological Anxiety and Trauma
Authors: Rosen Jeffrey B. , Schulkin Jay
Published: August 2022

Hyperexcitability in fear circuits is suggested to be important for development of pathological anxiety and trauma from adaptive mechanisms of fear. Hyperexcitability is proposed to be due to acquired sensitization in fear circuits that progressively becomes more severe over time causing changing symptoms in early and late pathology. We use the metaphor and mechanisms of kindling to examine gains and losses in function of one excitatory and one inhibitory neuropeptide, corticotrophin releasing factor and somatostatin, respectively, to explore this sensitization hypothesis. We suggest amygdala kindling induced hyperexcitability, hyper-inhibition and loss of inhibition provide clues to mechanisms for hyperexcitability and progressive changes in function initiated by stress and trauma.
Classification of chinese fragrant rapeseed oil based on sensory evaluation and gas chromatography-olfactometry
Authors: Guo Fei , Ma Mingjuan , Yu Miao , Bian Qi , Hui Ju , Pan Xin , Su Xiaoxia , Wu Jihong
Published: August 2022

Fragrant rapeseed oils and traditional pressed oils are increasingly popular in China owing to their sensory advantages. Many fragrant rapeseed oils are labeled by different fragrance types; however, the scientific basis for these differences is lacking. To identify the distinctive aroma and achieve fragrance classification, the sensory characteristics and aroma components of nine different fragrant rapeseed oils were analyzed via sensory evaluation and gas-chromatography-mass spectrometry-olfactometry. A total of 35 aroma compounds were found to contribute to the overall aroma. By using chemometrics methods, rapeseed oils were categorized into three fragrance styles: “strong fragrance,” “umami fragrance,” and “delicate fragrance.” In total, 10 aroma compounds were predicted to be the most effective compounds for distinguishing sensory characteristics of fragrant rapeseed oil. According to our results, this approach has excellent potential for the fragrance classification and quality control of rapeseed oil.
Germplasm variability-assisted near infrared reflectance spectroscopy chemometrics to develop multi-trait robust prediction models in rice
Authors: John Racheal , Bhardwaj Rakesh , Jeyaseelan Christine , Bollinedi Haritha , Singh Neha , Harish G. D. , Singh Rakesh , Nath Dhrub Jyoti , Arya Mamta , Sharma Deepak , Singh Satyapal , John K Joseph , Latha M. , Rana Jai Chand , Ahlawat Sudhir Pal , Kumar Ashok
Published: August 2022

Rice is a major staple food across the world in which wide variations in nutrient composition are reported. Rice improvement programs need germplasm accessions with extreme values for any nutritional trait. Near infrared reflectance spectroscopy (NIRS) uses electromagnetic radiations in the NIR region to rapidly measure the biochemical composition of food and agricultural products. NIRS prediction models provide a rapid assessment tool but their applicability is limited by the sample diversity, used for developing them. NIRS spectral variability was used to select a diverse sample set of 180 accessions, and reference data were generated using association of analytical chemists and standard methods. Different spectral pre-processing (up to fourth-order derivatization), scatter corrections (SNV-DT, MSC), and regression methods (partial least square, modified partial least square, and principle component regression) were employed for each trait. Best-fit models for total protein, starch, amylose, dietary fiber, and oil content were selected based on high RSQ, RPD with low SEP(C) in external validation. All the prediction models had ratio of prediction to deviation (RPD) > 2 amongst which the best models were obtained for dietary fiber and protein with R2 = 0.945 and 0.917, SEP(C) = 0.069 and 0.329, and RPD = 3.62 and 3.46. A paired sample t-test at a 95% confidence interval was performed to ensure that the difference in predicted and laboratory values was non-significant.
Research progress on extraction technology and biomedical function of natural sugar substitutes
Authors: Lei Pengyu , Chen Haojie , Ma Jiahui , Fang Yimen , Qu Linkai , Yang Qinsi , Peng Bo , Zhang Xingxing , Jin Libo , Sun Da
Published: August 2022

Improved human material living standards have resulted in a continuous increase in the rate of obesity caused by excessive sugar intake. Consequently, the number of diabetic patients has skyrocketed, not only resulting in a global health problem but also causing huge medical pressure on the government. Limiting sugar intake is a serious problem in many countries worldwide. To this end, the market for sugar substitute products, such as artificial sweeteners and natural sugar substitutes (NSS), has begun to rapidly grow. In contrast to controversial artificial sweeteners, NSS, which are linked to health concepts, have received particular attention. This review focuses on the extraction technology and biomedical function of NSS, with a view of generating insights to improve extraction for its large-scale application. Further, we highlight research progress in the use of NSS as food for special medical purpose (FSMP) for patients.
Chicken skin-derived collagen peptides chelated zinc promotes zinc absorption and represses tumor growth and invasion in vivo by suppressing autophagy
Authors: Liu Tengfei , Zou Lifang , Ji Xiaowen , Xiao Guiran
Published: August 2022

To improve the utilization value of chicken by-products, we utilized the method of step-by-step hydrolysis with bromelain and flavourzyme to prepare low molecular weight chicken skin collagen peptides (CCP) (<5 kDa) and characterized the amino acids composition of the CCP. Then, we prepared novel CCP-chelated zinc (CCP–Zn) by chelating the CCP with ZnSO4. We found that the bioavailability of CCP–Zn is higher than ZnSO4. Besides, CCP, ZnSO4, or CCP–Zn effectively repressed the tumor growth, invasion, and migration in a Drosophila malignant tumor model. Moreover, the anti-tumor activity of CCP–Zn is higher than CCP or ZnSO4. Furthermore, the functional mechanism studies indicated that CCP, ZnSO4, or CCP–Zn inhibits tumor progression by reducing the autonomous and non-autonomous autophagy in tumor cells and the microenvironment. Therefore, this research provides in vivo evidence for utilizing chicken skin in the development of zinc supplements and cancer treatment in the future.
Evaluation of the effect of Loigolactobacillus coryniformis K8 CECT 5711 consumption in health care workers exposed to COVID-19
Authors: Rodriguez-Blanque Raquel , Sánchez-García Juan Carlos , Cobos-Vargas Ángel , Aguilar Quesada Ana , Maldonado-Lobón Jose A. , Olivares Mónica , Blanco-Rojo Ruth
Published: August 2022

Following the spread of the SARS-CoV-2 coronavirus, an unprecedented burden has been placed on health care systems, with health care workers (HCWs) being most at risk of COVID-19 infection. The effect of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on frontline HCWs exposed to the virus was studied in a randomized, double-blind, placebo controlled trial. Parameters related to the incidence and severity of COVID-19 as well as the immune response and the side effects of the COVID-19 vaccine were evaluated. For 2 months, a group of 250 front-line HCWs over the age of 20 was randomly allocated to receive either L. coryniformis K8 or a placebo daily. SARS-CoV-2 infection incidence was verified via PCR or antigen test. In those volunteers who were vaccinated during the intervention, serum levels of specific IgG were analyzed at the end of the study. The incidence of COVID-19 infection was very low [IR (SD) = 0.016 (0.011)], and no significant difference was found between the groups [IRR (95% CI): 1.008 (0.140–7.268), p = 0.994]. For immune response analysis, the total sample was divided according to the days between the first dose and the antibody analysis (cutoff points were set at ≤ 56, 57–80 and ≥ 81 days). The specific IgG level decreased over time (p > 0.001). However, in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, the specific IgG levels were significantly higher in the those that took the L. coryniformis K8 [7.12 (0.21)] than in the control group [6.48 (0.19)] (P = 0.040). Interestingly, the subjects who started probiotic consumption before the first dose reported significantly fewer side effects (of any kind) at the 1st dose of the vaccine (OR: 0.524, p = 0.043), specifically less arm pain (OR: 0.467, p = 0.017). In conclusion, the administration of L. coryniformis K8 CECT 5711 to HCWs helps to extend the immune protection generated by the COVID-19 vaccine over time.
Glucagon and other proglucagon-derived peptides in the pathogenesis of obesity
Authors: Holst Jens Juul
Published: August 2022

Because of differential processing of the hormone precursor, proglucagon, numerous peptide products are released from the pancreatic alpha cells and the intestinal L-cells in which the (pro)glucagon gene is expressed. Of particular interest in relation to obesity are glucagon from the pancreas and oxyntomodulin and GLP-1 from the gut, all of which inhibit food intake, but the other products are also briefly discussed, because knowledge about these is required for selection and evaluation of the methods for measurement of the hormones. The distal intestinal L-cells also secrete the appetite-inhibiting hormone PYY. Characteristics of the secretion of the pancreatic and intestinal products are described, and causes of the hypersecretion of glucagon in obesity and type 2 diabetes are discussed. In contrast, the secretion of the products of the L-cells is generally impaired in obesity, raising questions about their role in the development of obesity. It is concluded that the impairment probably is secondary to obesity, but the lower plasma levels may contribute to the development.
A strategy for accurately and sensitively quantifying free and esterified fatty acids using liquid chromatography mass spectrometry
Authors: Feng Xiaohui , Wang Juan , Tang Zhonghai , Chen Bingyao , Hou Xinhua , Li Jing , Feng Shengnan , Li Peng , Meng Qingshi
Published: August 2022

Fatty acid (FA) composition of foods dictates a diversity of aspects regarding food quality, ranging from product shelf life, sensory properties to nutrition. There is a challenge to quantitate FAs using liquid chromatography-mass spectrometry due to poor ionization efficiency and matrix effects. Here, an isotopic-tagged derivatization strategy was established to accurately and sensitively quantify free and esterified FAs. After derivatization reaction, the detection sensitivity of FAs was remarkably improved and the limit of quantitation was lower than 100 ng/L. The quantitative errors caused by matrix effects were diminished benefiting from isotope-derivatized internal standards. The established quantitation strategy was successfully applied to verify both free and esterified FA contents in meat after different post-harvest procedures, finding that free polyunsaturated FAs increased significantly during freezing process.
The reporting of uveal melanoma cases to the cancer registry in North Carolina
Authors: Gordon Kathleen G. , Carvajal Richard D. , Graham Sharnee’ L. , Houghton Odette M.
Published: August 2022

Objective

To ascertain the completeness of reporting of uveal melanoma cases in North Carolina to the state’s cancer registry.

Methods

This was a retrospective chart review performed at a single institution analyzing the completeness of information reported to the North Carolina Cancer Registry between 2010 and 2015. A list of all patients with uveal melanoma diagnosed, treated and/or followed at UNC-Chapel Hill between 2010-2015 was compared to the list of patients with uveal melanoma reported to the North Carolina Central Cancer registry during the same time frame.

Results

Based on ICD 9 and 10 codes, there were 66 patients with ciliary body or choroidal melanomas diagnosed, followed and/or treated at UNC between 2010 and 2015. Of those, 41 (62%) were on the list of cases reported through the UNC Cancer Registry to the NCCCR. A chart review of the excluded cases was performed and the following barriers to reporting of uveal melanoma were identified: lack of diagnostic imaging results, lack of histopathologic confirmation, inconsistent language used to communicate diagnosis, and lack of implementation of the North American Association of Central Cancer Registries’ National Interstate Data Exchange Agreement.

Conclusion

The diagnosis and treatment of uveal melanoma is unique when compared to other types of cancers. Diagnosis is based on clinical features and characteristic findings on ophthalmic imaging and ultrasound. There is often no pathology report or radiologic imaging which makes it difficult for hospital registrars to recognize and confirm cases of uveal melanoma. This creates significant barriers to reporting cases to state and national cancer registries. The incomplete data makes it difficult to detect changes in the incidence of uveal melanoma in North Carolina. The development of a national uveal melanoma registry should be seriously considered.
Efficacy and safety of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for locally advanced stages of esophageal cancer: A systematic review and meta-analysis
Authors: Wu Jing , Deng Rong , Ni Tingting , Zhong Qin , Tang Fei , Li Yan , Zhang Yu
Published: August 2022

Background

Radiotherapy (RT)/Chemoradiotherapy (CRT) are important treatments for all stages of esophageal cancer (EC). The combination of immune checkpoint inhibitors (ICIs) with RT/CRT seems to be promising avenue for the treatment of EC. Therefore, a systematic review and meta-analysis was performed in order to assess the safety and efficacy of RT/CRT and ICI combination therapy for EC patients.

Methods

PubMed and several other databases were searched (according to specific criteria) to find relevant studies published prior to the 31st of December 2021.

Results

1962 articles were identified for screening, and six trials containing 668 patients were identified and pooled to determine the one- and two-year overall survival (OS), which were 84.5% (95% confidence interval (CI): 69.9%-100%) and 68.3% (95% CI: 49.0%-95.1%), respectively. Additionally, the rate of pooled grade 3-5 adverse reactions was 41.0% (95% CI: 31.2%-51.2%). The rate of specific grade 3-5 adverse reactions are as follows: lymphopenia (36.8%-60%), esophagitis (20%), anastomotic leakage (18%), esophageal fistula (10%), pain (10%), leukopenia (5.3%-10%), esophageal hemorrhage (2.5%-5%), chyle leakage (3%), fatigue (5%), cough (2.7%-5%), diarrhea (2.7%), pulmonary embolism (2.5%) and allergic reaction (2.5%). The pooled rate of pneumonitis of grade 3-5 and grade 1-5 was 0.8% (95% CI: 0.1%-0.16%, I2: 0%) and 5.4% (95% CI: 2.0%-14.2%, I2: 82%). For thoracic complication, esophagitis was 63.6% (95% CI: 42.4%-80.6%), which appeared to be more frequent with the combination of ICIs to RT/CRT (12%-37.7%). Other thoracic complications include esophageal hemorrhage (2.5%-10%), esophageal fistula (6%-10%) and anastomotic leakage (6%-21%). Additionally, some of the trials did not report cardiac related adverse reactions. The subgroup analyses also revealed that the pooled rate patients with grade 3-5 pneumonitis was higher for CRT/RT with concurrent and sequential ICI treatment (1.9%) than other groups (0.8%).

Conclusion

This study suggests that the addition of ICIs to RT/CRT for EC patients may be both safe and feasible. However, larger randomized studies are needed to confirm these results.
High risk and early onset of cancer in Chinese patients with Peutz-Jeghers syndrome
Authors: Wang Zhiqing , Wang Zhi , Wang Ying , Wu Jianhua , Yu Zonglin , Chen Chudi , Chen Junsheng , Wu Baoping , Chen Ye
Published: August 2022

Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with a predisposition to a variety of cancers. Previous studies that have evaluated the cancer spectrum and risk of this rare disease have primarily been based on small data sets or heterogeneous cohorts from different countries. Here, we report the results of a large homogeneous cohort of Chinese PJS patients who were followed prospectively from 2006 to July 2021, and clinical data before 2006 were retrospectively collected. A total of 412 PJS patients (56.55% males) from 208 families were enrolled, contributing 12,798 person-years of follow-up. A total of 113 cancers were diagnosed in 109 patients (26.46%). The median age at the first cancer diagnosis was 40 years. In particular, patients born after the 1980s were diagnosed with cancer at an earlier median age of 30.5 years. The cumulative cancer risk was sharply increased to 30.9% at age 40 years; this high cancer risk age was 10 years earlier than that reported in previous Western studies, and increased to 76.2% at an age of 60 years. The most common cancer was gastrointestinal (GI) cancer (64.6%), in which colorectal cancer constituted a significantly larger proportional distribution (32.74%), when compared with previous investigations (11.1%−20.83%). There was some evidence that overrepresentation point variants in domain XI of STK11 may be associated with GI cancers. Furthermore, the incidences of gynecological and lung cancers were second only to that of GI cancer in this cohort. These results may provide novel insight for justifying surveillance to detect cancers at an earlier phase to improve clinical outcomes. Furthermore, the potential STK11 genotype-phenotype association could be the basis for future genetic counseling.
Reparative properties of human glioblastoma cells after single exposure to a wide range of X-ray doses
Authors: Pavlova Galina , Belyashova Alexandra , Savchenko Ekaterina , Panteleev Dmitri , Shamadykova Dzhirgala , Nikolaeva Anna , Pavlova Svetlana , Revishchin Alexander , Golbin Denis , Potapov Alexander , Antipina Natalia , Golanov Andrey
Published: August 2022

Radiation therapy induces double-stranded DNA breaks in tumor cells, which leads to their death. A fraction of glioblastoma cells repair such breaks and reinitiate tumor growth. It was necessary to identify the relationship between high radiation doses and the proliferative activity of glioblastoma cells, and to evaluate the contribution of DNA repair pathways, homologous recombination (HR), and nonhomologous end joining (NHEJ) to tumor-cell recovery. We demonstrated that the GO1 culture derived from glioblastoma cells from Patient G, who had previously been irradiated, proved to be less sensitive to radiation than the Sus\fP2 glioblastoma culture was from Patient S, who had not been exposed to radiation before. GO1 cell proliferation decreased with radiation dose, and MTT decreased to 35% after a single exposure to 125 Gγ. The proliferative potential of glioblastoma culture Sus\fP2 decreased to 35% after exposure to 5 Gγ. At low radiation doses, cell proliferation and the expression of RAD51 were decreased; at high doses, cell proliferation was correlated with Ku70 protein expression. Therefore, HR and NHEJ are involved in DNA break repair after exposure to different radiation doses. Low doses induce HR, while higher doses induce the faster but less accurate NHEJ pathway of double-stranded DNA break repair.
Anticancer effect of Indanone-based thiazolyl hydrazone derivative on p53 mutant colorectal cancer cell lines: An in vitro and in vivo study
Authors: Narayanan Silpa , Teng Qiu-Xu , Wu Zhuo-Xun , Nazim Urooj , Karadkhelkar Nishant , Acharekar Nikita , Yoganathan Sabesan , Mansoor Najia , Ping Feng-Feng , Chen Zhe-Sheng
Published: August 2022

Colorectal cancer is a major health problem, and it is the third most diagnosed cancer in the United States. The current treatment for colorectal cancer includes irinotecan, a topoisomerase I inhibitor, and other targeted drugs, such as bevacizumab and regorafenib. The low response rates and incidence of high toxicity caused by these drugs instigated an evaluation of the anticancer efficacy of a series of 13 thiazolyl hydrazone derivatives of 1-indanone, and four compounds among them show favorable anticancer activity against some of the tested colorectal cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that one of the indanone-based thiazolyl hydrazone (ITH) derivatives, N-Indan-1-ylidene-N’-(4-Biphenyl-4-yl-thiazol-2-yl)-hydrazine (ITH-6), has a better cytotoxicity profile against p53 mutant colorectal cancer cells HT-29, COLO 205, and KM 12 than a p53 wild-type colorectal cancer cell line, such as HCT 116. Mechanistic studies show that ITH-6 arrests these three cancer cell lines in the G2/M phase and induces apoptosis. It also causes a rise in the reactive oxygen species level with a remarkable decrease in the glutathione (GSH) level. Moreover, ITH-6 inhibits the expression of NF-κB p65 and Bcl-2, which proves its cytotoxic action. In addition, ITH-6 significantly decreased tumor size, growth rate, and tumor volume in mice bearing HT-29 and KM 12 tumor xenografts. Moreover, CRISPR/Cas9 was applied to establish an NF-κB p65 gene knockout HT-29 cell line model to validate the target of ITH-6. Overall, the results suggest that ITH-6 could be a potential anticancer drug candidate for p53 mutant colorectal cancers.
Segmentation of the cervical lesion region in colposcopic images based on deep learning
Authors: Yu Hui , Fan Yinuo , Ma Huizhan , Zhang Haifeng , Cao Chengcheng , Yu Xuyao , Sun Jinglai , Cao Yuzhen , Liu Yuzhen
Published: August 2022

Background

Colposcopy is an important method in the diagnosis of cervical lesions. However, experienced colposcopists are lacking at present, and the training cycle is long. Therefore, the artificial intelligence-based colposcopy-assisted examination has great prospects. In this paper, a cervical lesion segmentation model (CLS-Model) was proposed for cervical lesion region segmentation from colposcopic post-acetic-acid images and accurate segmentation results could provide a good foundation for further research on the classification of the lesion and the selection of biopsy site.

Methods

First, the improved Faster Region-convolutional neural network (R-CNN) was used to obtain the cervical region without interference from other tissues or instruments. Afterward, a deep convolutional neural network (CLS-Net) was proposed, which used EfficientNet-B3 to extract the features of the cervical region and used the redesigned atrous spatial pyramid pooling (ASPP) module according to the size of the lesion region and the feature map after subsampling to capture multiscale features. We also used cross-layer feature fusion to achieve fine segmentation of the lesion region. Finally, the segmentation result was mapped to the original image.

Results

Experiments showed that on 5455 LSIL+ (including cervical intraepithelial neoplasia and cervical cancer) colposcopic post-acetic-acid images, the accuracy, specificity, sensitivity, and dice coefficient of the proposed model were 93.04%, 96.00%, 74.78%, and 73.71%, respectively, which were all higher than those of the mainstream segmentation model.

Conclusion

The CLS-Model proposed in this paper has good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnostic level.
Robot-assisted vs. laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis based on comparative studies
Authors: Ji Ruoyu , He Zhangyuting , Fang Shiyuan , Yang Wenjie , Wei Mengchao , Dong Jie , Xu Weifeng , Ji Zhigang
Published: August 2022

Background

Robot-assisted nephroureterectomy (RANU) and laparoscopic nephroureterectomy (LNU) are two minimally invasive surgical management for upper urinary tract urothelial carcinomas (UTUC). Though more high-tech, it remains largely unclear whether RANU provides additional benefits over LNU. We aimed to quantitatively compare the perioperative and oncologic outcomes between RANU and LNU.

Methods

The systematic review was performed based on a registered protocol (registration number CRD42022319086). We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2022) for comparative studies reporting perioperative and oncologic outcomes independently in RANU and LNU groups. Selection of studies and data extraction were performed independently by two researchers. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD) or Odds ratio (OR), as appropriate. Subgroup and univariate meta-regression analyses were performed to identify interstudy heterogeneities.

Results

The review included 8470 patients undergoing RANU and 19872 patients undergoing LNU from 12 comparative original studies. RANU was associated with fewer overall complications (OR=0.71, 95%CI: 0.62 to 0.81), longer operative time (MD=27.70, 95%CI: 0.83 to 54.60) and shorter length of stay (MD=-0.53, 95%CI: -0.98 to -0.07) compared to LNU. In addition, patients receiving RANU were more likely to have lymph node dissected (OR=2.61, 95%CI: 1.86 to 3.65). Recurrence and survival outcomes did not differ between two surgical procedures. Sample size, types of LNU and world region were major sources of heterogeneity.

Conclusion

For UTUC patients, RANU offers fewer complications and shorter hospitalization. However, RANU requires longer operative time and shares similar oncologic outcomes compared to LNU. Further randomized designed studies are warranted.

Systematic Review Registration

www.crd.york.ac.uk/prospero/, identifier CRD42022319086.
An exploratory study on the checkout rate of circulating tumor cells and the prediction of efficacy of neoadjuvant therapy and prognosis in patients with HER-2-positive early breast cancer
Authors: Zhou Jinmei , Wu Jiangling , Hao Xiaopeng , Li Ping , Zhang Huiqiang , Wu Xuexue , Chen Jiaxin , Liu Jiawei , Xiao Jinyi , Zhang Shaohua , Jiang Zefei , Yang Yanlian , Hu Zhiyuan , Wang Tao
Published: August 2022

Background

Neoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain.

Methods

The study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy.

Results

The sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods.

Conclusions

Our study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.
Oncogenic circular RNA circ_0007534 contributes to paclitaxel resistance in endometrial cancer by sponging miR-625 and promoting ZEB2 expression
Authors: Yi Hanjie , Han Yongqing , Li Shanfeng
Published: August 2022

Circular RNAs (circRNAs) and epithelial to mesenchymal transition (EMT) have been implicated in the development of human cancer and paclitaxel resistance. CircRNA circ_0007534 has been described as a key oncogenic circular RNA that is upregulated in a variety of cancer tissues. However, whether circ_0007534 causes EMT and paclitaxel resistance in endometrial cancer is still unknown. In this work, we revealed that circ_0007534 levels were significantly higher in endometrial cancer tissues, and that high circ_0007534 expression was associated with poor differentiation, advanced tumor stage, cancer invasion, cancer metastasis, and poor prognosis in endometrial cancer patients. Overexpression of circ_0007534 boosted endometrial cancer cell proliferation, invasion, EMT, and paclitaxel resistance. Knockdown of circ_0007534 restored paclitaxel sensitivity and reversed EMT in endometrial cancer cells. We also showed that circ_0007534 enhanced endometrial cancer aggressiveness, progression, and paclitaxel resistance by sponging microRNA-625 (miR-625) and subsequently increasing the expression of the miR-625 target gene ZEB2. Our cell functional studies demonstrated that inhibiting miR-625 or increasing ZEB2 mimicked the effects of circ_0007534 overexpression. Consequently, our data show that circ_0007534 plays a crucial role in EMT and paclitaxel resistance through miR-625/ZEB2 signaling. Targeting the circ_0007534/miR-625/ZEB2 pathway might be an effective strategy for overcoming paclitaxel resistance in endometrial cancer.