bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of COVID-19 Induced Respiratory Failure and Typical ARDS: Similarities and Differences
Authors: Lu Sen , Huang Xiaobo , Liu Rongan , Lan Yunping , Lei Yu , Zeng Fan , Tang Xuemei , He Hongli
Published: June 2022

Coronavirus disease 2019 (COVID-19) is a predominantly respiratory infectious disease caused by novel coronavirus infection (SARS-CoV-2), respiratory failure is the main clinical manifestation and the leading cause of death. Even though it can meet the acute respiratory distress syndrome (ARDS) Berlin definition, only some clinical features of COVID-19 are consistent with typical ARDS, and which has its own peculiar phenotypes. When compared with typical ARDS, in addition to the typical diffuse alveolar injury, COVID-19 has unique pathological and pathophysiological features, such as endothelial injury, extensive microthrombus, and pulmonary capillary hyperplasia. The clinical features of patients with respiratory failure caused by COVID-19 are heterogeneous and can be generally divided into two phenotypes: progressive respiratory distress and unique “silent hypoxemia”. The “H-type” characteristics of reduced lung volume, decreased lung compliance, and unmatched ventilator-perfusion ratio. While some patients may have close to normal lung compliance, that is “L-type”. Identifying the exact phenotype in whom are suffered with COVID-19 is crucial to guide clinicians to adopt appropriate treatment strategies. This review discussed the similarities and differences in the pathogenesis, pathophysiology, clinical features and treatment strategies of COVID-19 induced acute respiratory failure and typical ARDS.
Student and Educator Perspectives of Adapting to Remote Health Professions Education: A Mixed-Methods Study
Authors: Sarkar Mahbub , Liu Karen , Kumar Arunaz , Ilic Dragan , Morphet Julia , Maloney Stephen , Davis Elizabeth , Palermo Claire
Published: June 2022

During the COVID-19 pandemic, universities across the world transitioned rapidly to remote education. Engaging with a curriculum that has been transitioned from in-person to remote education mode is likely to impact how students and educators adapt to the changes and uncertainties caused by the pandemic. There is limited knowledge about individual differences in students' and educators' adaptability to remote education in response to the pandemic. This paper explored healthcare students' and educators' adaptability experiences to remote education. Drawing on pragmatism, a convergent mixed-methods design was adopted. Data were collected between May and August in 2020 using an online survey, followed by interviews with students and educators of five large health courses at an Australian research-intensive University. Data included 476 surveys and seven focus group interviews with 26 students, and 95 surveys and 17 individual interviews with educators. Results were interpreted through an integration of quantitative and qualitative elements from student and educator experiences. Findings indicated that students were less adaptable than educators. Whilst remote learning was less appealing than in-person learning, some students adapted well to the new learning environment. Limited social learning, transmissive pedagogy, and lack of technical and non-technical skills were identified as factors that impacted upon the experience of students and educators. Navigating the challenges associated with remote education provided students and educators with a unique opportunity to improve adaptability—an attribute critical for future uncertainties in healthcare practice.
Case Report: Malignant Melanoma Associated With COVID-19: A Coincidence or a Clue?
Authors: Leis A. Arturo , Montesi Anna Peyton , Khan Sariya Maryam , Montesi Michael
Published: June 2022

Following SARS-CoV-2 infection in humans, there is upregulation of proinflammatory molecules S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), osteopontin (OPN), tumor necrosis factor alpha (TNF-α), and other cytokines that promote hyperinflammation. The same immunoregulatory proteins that fuel the COVID-19 “cytokine storm” are also produced by melanoma cells and various other cancers to promote tumorigenesis. We report three cases of malignant melanoma (MM) associated with severe COVID-19, the first two with amelanotic melanoma and the third with hypopigmented melanoma. It is noteworthy that we did not search for these cases. Patient 1 is a personal acquaintance and cases 2 and 3 were hospitalized and worked at our rehabilitation center, respectively. We hypothesize that SARS-CoV-2 induced inflammatory tumorigenic proteins in the microenvironment that may have contributed to the de novo development (case 1), aggressive growth (case 2), or recurrence (case 3) of these malignant tumors. Moreover, high concentrations of the same proinflammatory proteins found in the “cytokine storm” associated with COVID-19, including TNF-α, interleukin (IL)-1α, IL-1β, IL-6, and ferritin, also induce skin depigmentation or hypopigmentation by interfering with tyrosinase synthesis, the enzyme that catalyzes the rate-limiting step of pigmentation. Hence, the marked elevation of the biological effectors that decrease skin pigmentation may also reduce pigmentation in MMs, resulting in amelanotic or hypopigmented lesions. Although it is certainly possible that the occurrence of melanoma following COVID-19 is coincidental, the ability of SARS-CoV-2 to increase expression of proinflammatory and tumorigenic molecules warrants further investigations to determine if there is an association between these disease processes or implications for patients with melanoma or other cancers who develop COVID-19.
A Genetic Association Test Accounting for Skewed X-Inactivation With Application to Biotherapy Immunogenicity in Patients With Autoimmune Diseases
Authors: Hässler Signe , Camilleri-Broët Sophie , Allez Matthieu , Deisenhammer Florian , Fogdell-Hahn Anna , Mariette Xavier , Pallardy Marc , Broët Philippe
Published: June 2022

Despite being assayed on commercialized DNA chips, the X chromosome is commonly excluded from genome-wide association studies (GWAS). One of the reasons is the complexity to analyze the data taking into account the X-chromosome inactivation (XCI) process in women and in particular the XCI process with a potentially skewed pattern. This is the case when investigating the role of X-linked genetic variants in the occurrence of anti-drug antibodies (ADAs) in patients with autoimmune diseases treated by biotherapies. In this context, we propose a novel test statistic for selecting loci of interest harbored by the X chromosome that are associated with time-to-event data taking into account skewed X-inactivation (XCI-S). The proposed statistic relies on a semi-parametric additive hazard model and is straightforward to implement. Results from the simulation study show that the test provides higher power gains than the score tests from the Cox model (under XCI process or its escape) and the Xu et al.'s XCI-S likelihood ratio test. We applied the test to the data from the real-world observational multicohort study set-up by the IMI-funded ABIRISK consortium for identifying X chromosome susceptibility loci for drug immunogenicity in patients with autoimmune diseases treated by biotherapies. The test allowed us to select two single nucleotide polymorphisms (SNPs) with high linkage disequilibrium (rs5991366 and rs5991394) located in the cytoband Xp22.2 that would have been overlooked by the Cox score tests and the Xu et al.'s XCI-S likelihood ratio test. Both SNPs showed a similar protective effect for drug immunogenicity without any occurrence of ADA positivity for the homozygous females and hemizygous males for the alternative allele. To our knowledge, this is the first study to investigate the association between X chromosome loci and the occurrence of anti-drug antibodies. We think that more X-Chromosome GWAS should be performed and that the test is well-suited for identifying X-Chromosome SNPs, while taking into account all patterns of the skewed X-Chromosome inactivation process.
Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response
Authors: Jacquier Marine , Binquet Christine , Manoha Catherine , Audia Sylvain , Simonet-Lamm Anne-Laure , Casenaz Alice , Sow Amadou-Khalilou , Piroth Lionel , Blot Mathieu
Published: June 2022

Introduction

While QuantiFERON-TB gold (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known.

Methods

Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative [interferon (IFN)-γ ≤ 0.5 IU/ml, official threshold] or weak (0.5–2 IU/ml) mitogen response, and one group of controls with normal (>2 IU/ml) mitogen response.

Results

A total of 872 patients were included. An ongoing infection was independently associated with both a negative (RR = 4.34; 95% CI = 2.94–6.41) and a weak mitogen response (RR = 2.44; 95% CI = 1.66–3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (3–13), 11 (5–21) and 15 (10–30) days; p < 0.001] and increasing hospital mortality (3, 7, and 15%; p < 0.001).

Conclusion

Clinicians should take notice of the mitogen response since IFN-γ concentrations lower than <2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.
Tuberculous Thoracic Aortic Pseudoaneurysm Associated With Spinal Tuberculosis: A Case Report and Literature Review
Authors: Chen Yurou , Sheng Bo , Li Jia , Lv Furong
Published: June 2022

Background

Thoracic aortic pseudoaneurysm associated with spinal tuberculosis is a rare but fatal condition. The risk of pseudoaneurysm rupture is extremely high and this disease needs greater awareness. The present study reported a case of thoracic aortic pseudoaneurysm caused by paravertebral cold abscess with spinal tuberculosis.

Case presentation

A 35-year-old woman with back pain was diagnosed with thoracic aortic pseudoaneurysm with spinal tuberculosis, and endovascular aneurysm repair (EVAR) was performed. The patient's symptoms disappeared after EVAR, following which she was discharged.

Conclusions

The case highlighted that in cases where non-enhanced computed tomography (CT) revealed that the aortic vessel was surrounded by a paravertebral abscess, magnetic resonance imaging (MRI) should be performed to confirm whether the presence of a pseudoaneurysm. Upon diagnosis of pseudoaneurysm, surgery should be performed immediately. In recent times, EVAR has emerged as a promising alternative to open surgery.
Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics
Authors: Munoz Flor M. , Cutland Clare L. , Jones Christine E. , Kampmann Beate , Khalil Asma , Sevene Esperança , Stergachis Andy , Swamy Geeta K. , Voss Gerald , Sobanjo-ter Meulen Ajoke
Published: June 2022

Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal Immunization Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.
Analysis of Microbial Community Structure and Diversity in Burial Soil of Yangguanzhai Cemetery
Authors: Wei Xiaoyang , Ling Xue , Yang Liping , Zhang Jun , Cui Menghe , He Zhang , Zhao Xichen , Sun Manli
Published: June 2022

As one of the common physical remains in archaeological discoveries, human bones are important bases for studying the history of human development, which is of great significance for exploring the evolution law of ancient human, reconstructing ancient human society, and tracking the development of human civilization. However, in the process of human bone burial, in addition to being affected by physical and chemical factors, it will also be affected by microorganisms in the buried soil, resulting in a variety of diseases. According to the determination and analysis of the microbial community structure and diversity in the burial soil of Yangguanzhai Site in Gaoling District in Xi’an city, Shaanxi Province, this paper attempts to explore the influence of microorganisms in the burial environment on human bones, in order to provide scientific proof for the microbial prevention and control of bone relics in the archaeological excavation site. For the first time, Illumina NovaSeq high-throughput sequencing technology was used to analyze the microbial community structure in the burial soil. At the phylum level, there were 8 dominant bacteria species in the soil samples of tombs, which were Firmicutes, Actinobacteriota, Actinobacteria, Proteobacteria, Acidobacteriota, Methylomirabilota, Chloroflexi, Bacteroidota. At the genus level, there were 12 dominant species in the soil samples of tombs, including MIZ17, MND1, Gaiella, oc32, Kroppenstedtia, Halomonas, Bacteroides, Dongia, Faecalibacterium, Nocardioides, Pseudomonas, Pseudonocardia. The overall microorganisms in the soil of Yangguanzhai Cemetery were relatively well-distributed, and the microbial community structure near human bones is the most abundant and diverse. Therefore, it is necessary to take some measures to control microorganisms and protect human bones.
Changes in Higher-Order Chromosomal Structure of Klebsiella pneumoniae Under Simulated Microgravity
Authors: Wang Yahao , Shen Wenlong , Yin Man , Huang Wenhua , Ye Bingyu , Li Ping , Shi Shu , Bai Ge , Guo Xinjie , Jin Yifei , Lin Kailin , Zhang Yan , Jiang Yongqiang , Wang Junfeng , Han Yanping , Zhao Zhihu
Published: June 2022

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.
Molecular Characterization of Predominant Serotypes, Drug Resistance, and Virulence Genes of Streptococcus pneumoniae Isolates From East China
Authors: Huang Li-Dan , Yang Mei-Juan , Huang Yan-Ying , Jiang Ke-Yi , Yan Jie , Sun Ai-Hua
Published: June 2022

Streptococcus pneumoniae is a common diplococcus pathogen found worldwide. The characterization of predominant serotypes, drug resistance, and virulence genes of S. pneumoniae isolates prevailing in different areas and countries is clinically important for choice of antibiotics and improvement of vaccines. In this study, pneumonia (78.7%) and meningitis (37.0%) were the predominant diseases observed in the 282 (children) and 27 (adults) S. pneumoniae-infected patients (p < 0.05) from seven hospitals in different areas of East China. Of the 309 pneumococcal isolates, 90.3% were classified by PCR into 15 serotypes, with serotypes 19F (27.2%) and the 6A/B (19.1%) being most predominant (p < 0.05). Importantly, serotypes 15A and 15B/C combined for a total of 10.4% of the isolates, but these serotypes are not included in the 13-valent pneumococcal capsule conjugate vaccine used in China. Antimicrobial susceptibility analysis by the E-test showed that >95% of the 309 pneumococcal isolates were susceptible to moxifloxacin and levofloxacin, as well as 18.4, 85.8, and 81.6% of the isolates displayed susceptibility to penicillin, cefotaxime, and imipenem, respectively. A significant correlation between the prevalence of predominant serotypes and their penicillin resistance was observed (p < 0.05). In particular, >95% of all the pneumococcal isolates showed resistance to erythromycin and azithromycin. Of the nine detected virulence genes, the lytA, ply, hysA, and nanA were the most common with 95–100% positive rates in the 309 pneumococcal isolates, while the pavA and psaA genes displayed a significant correlation with pneumococcal bacteremia and meningitis (p < 0.05). Overall, our data suggested that the predominant serotypes, drug resistance, and virulence genes of the S. pneumoniae isolates prevailing in East China are distinct from those observed in other areas of China and adjacent countries.
CABGen: A Web Application for the Bioinformatic Analysis of Bacterial Genomes
Authors: Duré Felicita Mabel , Silveira Melise Chaves , Rocha-de-Souza Cláudio Marcos , Leão Robson Souza , de Oliveira Santos Ivson Cassiano , Albano Rodolpho Mattos , Marques Elizabeth Andrade , D’Alincourt Carvalho-Assef Ana Paula , da Silva Fabricio Alves Barbosa
Published: June 2022

Due to recent developments in NGS technologies, genome sequencing is generating large volumes of new data containing a wealth of biological information. Understanding sequenced genomes in a biologically meaningful way and delineating their functional and metabolic landscapes is a first-level challenge. Considering the global antimicrobial resistance (AMR) problem, investments to expand surveillance and improve existing genome analysis technologies are pressing. In addition, the speed at which new genomic data is generated surpasses our capacity to analyze it with available bioinformatics methods, thus creating a need to develop new, user-friendly and comprehensive analytical tools. To this end, we propose a new web application, CABGen,1 developed with open-source software. CABGen allows storing, organizing, analyzing, and interpreting bioinformatics data in a friendly, scalable, easy-to-use environment and can process data from bacterial isolates of different species and origins. CABGen has three modules: Upload Sequences, Analyze Sequences, and Verify Results. Functionalities include coverage estimation, species identification, de novo genome assembly, and assembly quality, genome annotation, MLST mapping, searches for genes related to AMR, virulence, and plasmids, and detection of point mutations in specific AMR genes. Visualization tools are also available, greatly facilitating the handling of biological data. The reports include those results that are clinically relevant. To illustrate the use of CABGen, whole-genome shotgun data from 181 bacterial isolates of different species collected in 5 Brazilian regions between 2018 and 2020 were uploaded and submitted to the platform’s modules.
Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule
Authors: Grinkevich Vera V. , Vema Aparna , Fawkner Karin , Issaeva Natalia , Andreotti Virginia , Dickinson Eleanor R. , Hedström Elisabeth , Spinnler Clemens , Inga Alberto , Larsson Lars-Gunnar , Karlén Anders , Wilhelm Margareta , Barran Perdita E. , Okorokov Andrei L. , Selivanova Galina , Zawacka-Pankau Joanna E.
Published: June 2022

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.
Structural Characterization of Mycobacterium abscessus Phosphopantetheine Adenylyl Transferase Ligand Interactions: Implications for Fragment-Based Drug Design
Authors: Thomas Sherine E. , McCarthy William J. , El Bakali Jamal , Brown Karen P. , Kim So Yeon , Blaszczyk Michal , Mendes Vítor , Abell Chris , Floto R. Andres , Coyne Anthony G. , Blundell Tom L.
Published: June 2022

Anti-microbial resistance is a rising global healthcare concern that needs urgent attention as growing number of infections become difficult to treat with the currently available antibiotics. This is particularly true for mycobacterial infections like tuberculosis and leprosy and those with emerging opportunistic pathogens such as Mycobacterium abscessus, where multi-drug resistance leads to increased healthcare cost and mortality. M. abscessus is a highly drug-resistant non-tuberculous mycobacterium which causes life-threatening infections in people with chronic lung conditions such as cystic fibrosis. In this study, we explore M. abscessus phosphopantetheine adenylyl transferase (PPAT), an enzyme involved in the biosynthesis of Coenzyme A, as a target for the development of new antibiotics. We provide structural insights into substrate and feedback inhibitor binding modes of M. abscessus PPAT, thereby setting the basis for further chemical exploration of the enzyme. We then utilize a multi-dimensional fragment screening approach involving biophysical and structural analysis, followed by evaluation of compounds from a previous fragment-based drug discovery campaign against M. tuberculosis PPAT ortholog. This allowed the identification of an early-stage lead molecule exhibiting low micro molar affinity against M. abscessus PPAT (Kd 3.2 ± 0.8 µM) and potential new ways to design inhibitors against this enzyme. The resulting crystal structures reveal striking conformational changes and closure of solvent channel of M. abscessus PPAT hexamer providing novel strategies of inhibition. The study thus validates the ligandability of M. abscessus PPAT as an antibiotic target and identifies crucial starting points for structure-guided drug discovery against this bacterium.
Comparison of Electroencephalography in Patients With Seizures Caused by Neurosyphilis and Viral Encephalitis
Authors: Zheng Li-Li , Chen Jing-Zhen , Zhuang Xiao-Rong , Miao Jia-Yin
Published: June 2022

Background

Neurosyphilis (NS) lacks specificity in clinical and imaging features, and patients are frequently misdiagnosed as viral encephalitis when they present with seizures. This study aimed to compare electroencephalography (EEG) in patients with seizures resulting from the two diseases and provide guidance for differential diagnosis.

Methods

A retrospective study on patients diagnosed with neurosyphilis and viral encephalitis with seizures in the Department of Neurology, Zhongshan Hospital, Xiamen University from 2012 to 2020.

Results

A total of 39 patients with seizures caused by neurosyphilis and 40 patients with seizures caused by viral encephalitis were included. Chi-square test analysis showed that compared with patients with viral encephalitis, patients with neurosyphilis mainly developed in middle-aged and elderly people (p < 0.001), were more likely to have temporal epileptiform discharges (p < 0.001), and less likely to have status epilepticus (SE) (p = 0.029). There was difference between two groups in the EEG performance of lateralized periodic discharges (LPDs) (p = 0.085). The two groups were matched for age and sex by case-control matching, and 25 cases in each group were successfully matched. Patients with neurosyphilis were more likely to have temporal epileptiform discharges than those with viral encephalitis (p = 0.002), and there were no significant differences in LPDs (p = 0.077) and SE (p = 0.088) between two groups.

Conclusion

When EEG shows temporal epileptiform discharges, especially in the form of LPDs, we should consider the possibility of neurosyphilis.
Increased Magnetic Susceptibility in the Deep Gray Matter Nuclei of Wilson's Disease: Have We Been Ignoring Atrophy?
Authors: Jing Xiao-Zhong , Yuan Xiang-Zhen , Li Gai-Ying , Chen Jia-Lin , Wu Rong , Yang Ling-Li , Zhang Shu-Yun , Wang Xiao-Ping , Li Jian-Qi
Published: June 2022

Background

Histopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls.

Methods

Quantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility.

Results

Mean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively.

Conclusion

Brain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.
Study Protocol of tDCS Based Pain Modulation in Head and Neck Cancer Patients Under Chemoradiation Therapy Condition: An fNIRS-EEG Study
Authors: de Souza Moura Brenda , Hu Xiao-Su , DosSantos Marcos F. , DaSilva Alexandre F.
Published: June 2022

Background

Multiple therapeutic strategies have been adopted to reduce pain, odynophagia, and oral mucositis in head and neck cancer patients. Among them, transcranial direct current stimulation (tDCS) represents a unique analgesic modality. However, the details of tDCS mechanisms in pain treatment are still unclear.

Aims

(1) to study the analgesic effects of a protocol that encompassed supervised-remote and in-clinic tDCS sessions applied in head and neck patients undergoing chemoradiation therapy; (2) to explore the underlining brain mechanisms of such modulation process, using a novel protocol that combined functional near-infrared spectroscopy (fNIRS), and electroencephalograph (EEG), two distinct neuroimaging methods that bring information regarding changes in the hemodynamic as well as in the electrical activity of the brain, respectively.

Methods

This proof-of-concept study was performed on two subjects. The study protocol included a 7-week-long tDCS stimulation procedure, a pre-tDCS baseline session, and two post-tDCS follow-up sessions. Two types of tDCS devices were used. One was used in the clinical setting and the other remotely. Brain imaging was obtained in weeks 1, 2, 5, 7, 8, and after 1 month.

Results

The protocol implemented was safe and reliable. Preliminary results of the fNIRS analysis in weeks 2 and 7 showed a decrease in functional connections between the bilateral prefrontal cortex (PFC) and the primary sensory cortex (S1) (p < 0.05, FDR corrected). Changes in EEG power spectra were found in the PFC when comparing the seventh with the first week of tDCS.

Conclusion

The protocol combining remote and in-clinic administered tDCS and integrated fNIRS and EEG to evaluate the brain activity is feasible. The preliminary results suggest that the mechanisms of tDCS in reducing the pain of head and neck cancer patients may be related to its effects on the connections between the S1 and the PFC.
Fructose Induces Pulmonary Fibrotic Phenotype Through Promoting Epithelial-Mesenchymal Transition Mediated by ROS-Activated Latent TGF-β1
Authors: Xu Xiaoxiao , Ma Chuang , Wu Hang , Ma Yuanqiao , Liu Zejin , Zhong Peijie , Jin Chaolei , Ning Wenjuan , Wu Xiao , Zhang Yijie , Han Jichang , Wang Junpeng
Published: June 2022

Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
Malnutrition Is Highly Prevalent in Patients With Chronic Pancreatitis and Characterized by Loss of Skeletal Muscle Mass but Absence of Impaired Physical Function
Authors: Wiese Mats L. , Gärtner Simone , von Essen Nele , Doller Julia , Frost Fabian , Tran Quang Trung , Weiss Frank Ulrich , Meyer Fatuma , Valentini Luzia , Garbe Leif-A. , Metges Cornelia C. , Bannert Karen , Sautter Lea Franziska , Ehlers Luise , Jaster Robert , Lamprecht Georg , Steveling Antje , Lerch Markus M. , Aghdassi Ali A.
Published: June 2022

Background/Aims

Patients with chronic pancreatitis (CP) have an increased risk of malnutrition, a condition linked to reduced muscle mass and physical performance. We have investigated the risk factors, phenotypic presentation, and health implications associated with malnutrition in CP.

Materials and Methods

In a multicenter cross-sectional study we recruited patients with confirmed CP and healthy volunteers as a control group. Malnutrition was diagnosed according to the criteria proposed by the Global Leadership Initiative on Malnutrition. We performed detailed examinations of body composition and physical function as well as testing of routine blood parameters and markers of inflammation.

Results

We included 66 patients [mean (±SD) age: 56.0 (±14.5) years; 51 males] and an equal number of age- and sex-matched controls. Moderate malnutrition was diagnosed in 21% (n = 14) and severe malnutrition in 42% (n = 28) of patients. Besides weight loss malnourished patients showed lower fat and skeletal muscle mass compared to both non-malnourished subjects and healthy controls. Only in severe malnutrition, blood parameters reflected elevated inflammation and reduced muscle reserves. Handgrip strength in patients did not differ by nutritional status but there was a significant correlation (rho = 0.705, p < 0.001) with skeletal muscle mass. Although 20 patients (30%) had pathologically reduced skeletal muscle mass, only two individuals (3%) had sarcopenia with concomitantly reduced handgrip strength.

Conclusion

Malnutrition is a frequent complication of CP characterized by loss of skeletal muscle mass. As this condition becomes evident only at an advanced stage, regular testing for altered body composition is recommended. Suitable biomarkers and the link between loss of muscle mass and physical function require further investigation.

Clinical Trial Registration

[https://clinicaltrials.gov/ct2/show/NCT04474743], identifier [NCT04474743].
Biocompatible Polyelectrolyte Complex Nanoparticles for Lycopene Encapsulation Attenuate Oxidative Stress-Induced Cell Damage
Authors: Zhang Dongjing , Jiang Yun , Xiang Ming , Wu Fen , Sun Min , Du XianFeng , Chen Lei
Published: June 2022

In this study, lycopene was successfully encapsulated in polyelectrolyte complex nanoparticles (PEC NPs) fabricated with a negatively charged polysaccharide, TLH-3, and a positively charged sodium caseinate (SC) via electrostatic interactions. Results showed that the lycopene-loaded PEC NPs were spherical in shape, have a particle size of 241 nm, have a zeta potential of −23.6 mV, and have encapsulation efficiency of 93.6%. Thus, lycopene-loaded PEC NPs could serve as effective lycopene carriers which affected the physicochemical characteristics of the encapsulated lycopene and improved its water dispersibility, storage stability, antioxidant capacity, and sustained release ability in aqueous environments when compared with the free lycopene. Moreover, encapsulated lycopene could enhance the cells' viability, prevent cell apoptosis, and protect cells from oxidative damage through the Nrf2/HO-1/AKT signalling pathway, via upregulation of antioxidase activities and downregulation of MDA and ROS levels. Therefore, the biocompatible lycopene-loaded PEC NPs have considerable potential use for the encapsulation of hydrophobic nutraceuticals in the food and pharmaceutical industries.
Edible Insects in Latin America: A Sustainable Alternative for Our Food Security
Authors: Abril Silvana , Pinzón Mariana , Hernández-Carrión María , Sánchez-Camargo Andrea del Pilar
Published: June 2022

Nowadays, the food industry faces paramount challenges in different areas, since worldwide consumers are increasing every day, and at the same time, they are demanding new convenient products. Recent studies show that the current food production system is unsustainable over time and therefore is necessary to create new alternatives of production. New food trends are focused on the consumption of natural products, that have an eco-friendly production approach, and a beneficial nutritional profile for the consumer’s health. Hence, products are being created to not only have good organoleptic characteristics, but also to contain a wide variety of micro and macronutrients, and to be sustainable within their production. For this reason, the use of raw materials that satisfy the needs previously mentioned is being implemented. For instance, the use of insects as raw material, because they have a high protein content comparable to animal-based foods. Specifically, ants and crickets can contain between 9 and 77% protein of dry weight, while beef contains between 25 and 28%. On the other hand, insects present an ease and sustainable production system, compared to livestock farming, since some of them feed with food waste generated by humans. In addition, require less food for their upbringing; insects can convert 2 kg of feed into 1 kg of insect mass, while cattle use 8 kg of feed to produce 1 kg of body weight. On the other hand, there is evidence that insects produce fewer greenhouse gases during their production, for example, pigs produce between 10 and 100 times more greenhouse gases per kg of weight. United States, Mexico, Chile, Peru, and Argentina have begun to develop and consume these products; thus, promoting different and new ventures. Large-scale production of insect-based food products could help solve or even prevent the looming food problem and contribute to the sustainable development goals set by the United Nations. Thus, the aim of this review work was to compile and investigate the edible insect’s alternatives in Latin America, as well as the commercially available or potential derivative products. We discussed the nutritional value of edible insects, and how they could contribute to food security.
The Genetics of Early-Stage Melanoma in a Veteran Population
Authors: Cheung Kevin , Bossler Aaron D. , Mott Sarah L. , Zeisler Megan , McKillip Julie , Zakharia Yousef , Swick Brian L. , Powers Jennifer G.
Published: June 2022

To improve understanding of the genetic signature of early-stage melanomas in Veterans, hotspot mutation profiling using next-generation sequencing (NGS) was performed on melanoma tissue samples from patients at the Iowa City Veterans Affairs Medical Center (VAMC). Genetic analysis identified BRAF (36.3%), TP53 (25.9%), NRAS (19.3%), CDKN2A (11.1%), KIT (8.1%), and BAP1 (7.4%) mutations with the highest prevalence. Although common variants in BRAF were detected at lower rates than what is reported for the general population, 55.6% of cases showed activating mutations in the RAS/RAF pathways. Variants in TP53 and KIT were detected at higher rates than in the general population. Veterans with prior history of melanoma were at significantly higher odds of having TP53 mutation (OR = 2.67, p = 0.04). This suggests that TP53 may be a marker for recurrent melanoma and possibly alternative exposures in the military population. This study provides new information regarding the genetics of melanoma in a Veteran population and early-stage melanomas, highlighting risk factors unique to this population and contributing to the conversation about preventing melanoma deaths in US Military personnel.
Quality Assessment of Cancer Pain Clinical Practice Guidelines
Authors: Zhang Zhigang , Cao Xiao , Wang Qi , Yang Qiuyu , Sun Mingyao , Ge Long , Tian Jinhui
Published: June 2022

Introduction

Several clinical practice guidelines (CPGs) for cancer pain have been published; however, the quality of these guidelines has not been evaluated so far. The purpose of this study was to evaluate the quality of CPGs for cancer pain and identify gaps limiting knowledge.

Methods

We systematically searched seven databases and 12 websites from their inception to July 20, 2021, to include CPGs related to cancer pain. We used the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist to assess the methodology and reporting quality of eligible CPGs. The overall agreement among reviewers with the intraclass correlation coefficient (ICC) was calculated. The development methods of CPGs, strength of recommendations, and levels of evidence were determined.

Results

Eighteen CPGs published from 1996 to 2021 were included. The overall consistency of the reviewers in each domain was acceptable (ICC from 0.76 to 0.95). According to the AGREE II assessment, only four CPGs were determined to be recommended without modifications. For reporting quality, the average reporting rates for all seven domains of CPGs was 57.46%, with the highest domain in domain 3 (evidence, 68.89%) and the lowest domain in domain 5 (review and quality assurance, 33.3%).

Conclusion

The methodological quality of cancer pain CPGs fluctuated widely, and the complete reporting rate in some areas is very low. Researchers need to make greater efforts to provide high-quality guidelines in this field to clinical decision-making.
Investigating the Anticancer Potential of Salvicine as a Modulator of Topoisomerase II and ROS Signaling Cascade
Authors: Dey Dipta , Hasan Mohammad Mehedi , Biswas Partha , Papadakos Stavros P. , Rayan Rehab A. , Tasnim Sabiha , Bilal Muhammad , Islam Mohammod Johirul , Arshe Farzana Alam , Arshad Efat Muhammad , Farzana Maisha , Rahaman Tanjim Ishraq , Baral Sumit Kumar , Paul Priyanka , Bibi Shabana , Rahman Md. Ataur , Kim Bonglee
Published: June 2022

Salvicine is a new diterpenoid quinone substance from a natural source, specifically in a Chinese herb. It has powerful growth-controlling abilities against a broad range of human cancer cells in both in vitro and in vivo environments. A significant inhibitory effect of salvicine on multidrug-resistant (MDR) cells has also been discovered. Several research studies have examined the activities of salvicine on topoisomerase II (Topo II) by inducing reactive oxygen species (ROS) signaling. As opposed to the well-known Topo II toxin etoposide, salvicine mostly decreases the catalytic activity with a negligible DNA breakage effect, as revealed by several enzymatic experiments. Interestingly, salvicine dramatically reduces lung metastatic formation in the MDA-MB-435 orthotopic lung cancer cell line. Recent investigations have established that salvicine is a new non-intercalative Topo II toxin by interacting with the ATPase domains, increasing DNA–Topo II interaction, and suppressing DNA relegation and ATP hydrolysis. In addition, investigations have revealed that salvicine-induced ROS play a critical role in the anticancer-mediated signaling pathway, involving Topo II suppression, DNA damage, overcoming multidrug resistance, and tumor cell adhesion suppression, among other things. In the current study, we demonstrate the role of salvicine in regulating the ROS signaling pathway and the DNA damage response (DDR) in suppressing the progression of cancer cells. We depict the mechanism of action of salvicine in suppressing the DNA–Topo II complex through ROS induction along with a brief discussion of the anticancer perspective of salvicine.
Videomics of the Upper Aero-Digestive Tract Cancer: Deep Learning Applied to White Light and Narrow Band Imaging for Automatic Segmentation of Endoscopic Images
Authors: Azam Muhammad Adeel , Sampieri Claudio , Ioppi Alessandro , Benzi Pietro , Giordano Giorgio Gregory , De Vecchi Marta , Campagnari Valentina , Li Shunlei , Guastini Luca , Paderno Alberto , Moccia Sara , Piazza Cesare , Mattos Leonardo S. , Peretti Giorgio
Published: June 2022

Introduction

Narrow Band Imaging (NBI) is an endoscopic visualization technique useful for upper aero-digestive tract (UADT) cancer detection and margins evaluation. However, NBI analysis is strongly operator-dependent and requires high expertise, thus limiting its wider implementation. Recently, artificial intelligence (AI) has demonstrated potential for applications in UADT videoendoscopy. Among AI methods, deep learning algorithms, and especially convolutional neural networks (CNNs), are particularly suitable for delineating cancers on videoendoscopy. This study is aimed to develop a CNN for automatic semantic segmentation of UADT cancer on endoscopic images.

Materials and Methods

A dataset of white light and NBI videoframes of laryngeal squamous cell carcinoma (LSCC) was collected and manually annotated. A novel DL segmentation model (SegMENT) was designed. SegMENT relies on DeepLabV3+ CNN architecture, modified using Xception as a backbone and incorporating ensemble features from other CNNs. The performance of SegMENT was compared to state-of-the-art CNNs (UNet, ResUNet, and DeepLabv3). SegMENT was then validated on two external datasets of NBI images of oropharyngeal (OPSCC) and oral cavity SCC (OSCC) obtained from a previously published study. The impact of in-domain transfer learning through an ensemble technique was evaluated on the external datasets.

Results

219 LSCC patients were retrospectively included in the study. A total of 683 videoframes composed the LSCC dataset, while the external validation cohorts of OPSCC and OCSCC contained 116 and 102 images. On the LSCC dataset, SegMENT outperformed the other DL models, obtaining the following median values: 0.68 intersection over union (IoU), 0.81 dice similarity coefficient (DSC), 0.95 recall, 0.78 precision, 0.97 accuracy. For the OCSCC and OPSCC datasets, results were superior compared to previously published data: the median performance metrics were, respectively, improved as follows: DSC=10.3% and 11.9%, recall=15.0% and 5.1%, precision=17.0% and 14.7%, accuracy=4.1% and 10.3%.

Conclusion

SegMENT achieved promising performances, showing that automatic tumor segmentation in endoscopic images is feasible even within the highly heterogeneous and complex UADT environment. SegMENT outperformed the previously published results on the external validation cohorts. The model demonstrated potential for improved detection of early tumors, more precise biopsies, and better selection of resection margins.