bluuebunny/crossref_metadata_2025 huggingface dataset:
The Deterioration of Agronomical Traits of the Continuous Cropping of Stevia Is Associated With the Dynamics of Soil Bacterial Community
Authors: Xu Xinjuan , Luo Qingyun , Wei Qichao , Jiang Shangtao , Dong Caixia , Faruque Mohammad Omar , Huang Zhongwen , Xu Zhenghua , Yin Changxi , Zhu Zaibiao , Hu Xuebo
Published: June 2022

Stevia rebaudiana Bertoni is grown worldwide as an important, natural sweetener resource plant. The yield of steviol glycosides (SVglys) is greatly influenced by continuous cropping. In this study, we collected the roots, rhizosphere soils, and bulk soils from 2 years of continuous cropping (Y2) and 8 years of continuous cropping (Y8). A high-throughput sequencing technology based on Illumina Hiseq 2500 platform was used to study the structure and diversity of bacterial communities in the roots and soils of stevia with different years of continuous cropping. The results demonstrated that although the content of a group of SVglys was significantly increased in stevia of long-term continuous cropping, it inhibited the growth of plants and lowered the leaf dry weight; as a result, the total amount of SVglys was significantly decreased. Meanwhile, continuous cropping changed the physicochemical properties and the bacterial composition communities of soil. The different sampling sources of the root, rhizosphere soil, and bulk soil had no impact on the richness of bacterial communities, while it exhibited obvious effects on the diversity of bacterial communities. Continuous cropping had a stronger effect on the bacterial community composition in rhizosphere soil than in root and bulk soil. Based on linear discriminant analysis effect size (LEfSe), in the rhizosphere soil of Y8, the relative abundance of some beneficial bacterial genera of Sphingomonas, Devosia, Streptomyces, and Flavobacterium decreased significantly, while the relative abundance of Polycyclovorans, Haliangium, and Nitrospira greatly increased. Moreover, the soil pH and nutrient content, especially the soil organic matter, were correlated with the relative abundance of predominant bacteria at the genus level. This study provides a theoretical basis for uncovering the mechanism of obstacles in continuous stevia cropping and provides guidance for the sustainable development of stevia.
Environmental and Anthropogenic Factors Shape the Snow Microbiome and Antibiotic Resistome
Authors: Sanchez-Cid Concepcion , Keuschnig Christoph , Torzewski Karol , Stachnik Łukasz , Kępski Daniel , Luks Bartłomiej , Nawrot Adam , Niedzielski Przemysław , Vogel Timothy M. , Larose Catherine
Published: June 2022

Winter tourism can generate environmental pollution and affect microbial ecology in mountain ecosystems. This could stimulate the development of antibiotic resistance in snow and its dissemination through the atmosphere and through snow melting. Despite these potential impacts, the effect of winter tourism on the snow antibiotic resistome remains to be elucidated. In this study, snow samples subjected to different levels of anthropogenic activities and surrounding forest were obtained from the Sudety Mountains in Poland to evaluate the impact of winter tourism on snow bacteria using a metagenomic approach. Bacterial community composition was determined by the sequencing of the V3-V4 hypervariable region of the 16S rRNA gene and the composition of the antibiotic resistome was explored by metagenomic sequencing. Whereas environmental factors were the main drivers of bacterial community and antibiotic resistome composition in snow, winter tourism affected resistome composition in sites with similar environmental conditions. Several antibiotic resistance genes (ARGs) showed a higher abundance in sites subjected to human activities. This is the first study to show that anthropogenic activities may influence the antibiotic resistome in alpine snow. Our results highlight the need to survey antibiotic resistance development in anthropogenically polluted sites.
Metabolic Mechanisms Connecting Alzheimer’s and Parkinson’s Diseases: Potential Avenues for Novel Therapeutic Approaches
Authors: Colca Jerry R. , Finck Brian N.
Published: June 2022

Alzheimer’s (AD) and Parkinson’s Diseases (PD) are common neurodegenerative disorders growing in incidence and prevalence and for which there are no disease-modifying treatments. While there are considerable complexities in the presentations of these diseases, the histological pictures of these pathologies, as well as several rare genetic predispositions for each, point to the involvement of maladaptive protein processing and inflammation. Importantly, the common presentations of AD and PD are connected to aging and to dysmetabolism, including common co-diagnosis of metabolic syndrome or diabetes. Examination of anti-diabetic therapies in preclinical models and in some observational clinical studies have suggested effectiveness of the first generation insulin sensitizer pioglitazone in both AD and PD. Recently, the mitochondrial pyruvate carrier (MPC) was shown to be a previously unrecognized target of pioglitazone. New insulin sensitizers are in development that can be dosed to full engagement of this previously unappreciated mitochondrial target. Here we review molecular mechanisms that connect modification of pyruvate metabolism with known liabilities of AD and PD. The mechanisms involve modification of autophagy, inflammation, and cell differentiation in various cell types including neurons, glia, macrophages, and endothelium. These observations have implications for the understanding of the general pathology of neurodegeneration and suggest general therapeutic approaches to disease modification.
The Association of CSF sTREM2 With Cognitive Decline and Its Dynamic Change in Parkinson's Disease: Analysis of the PPMI Cohort
Authors: Qin Qixiong , Wan Hengming , Wang Danlei , Li Jingyi , Qu Yi , Zhao Jingwei , Li Jiangting , Xue Zheng
Published: June 2022

Background

Soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is a biomarker of microglial activation and increased in several neurodegenerative diseases. However, the role of sTREM2 in Parkinson's diseases (PDs) remains unclear. This study aims to investigate whether CSF sTREM2 is changed during the pathology of PD and its association with cognitive decline.

Methods

We recruited 219 de novo patients with PD and 100 healthy controls from Parkinson's Progression Markers Initiative (PPMI). Cross-sectional and longitudinal associations between cognition and CSF sTREM2 were evaluated using multivariable-adjusted models. To assess the changes in CSF sTREM2 during the pathology of PD, patients were classified through the A/T classification framework with addition of α-synuclein (α-syn), which we implemented based on the CSF amyloid β-peptide 1−42 (A) and phosphorylated tau (T) and α-syn (S).

Results

The CSF sTREM2 did not differ between healthy controls and patients with PD or between PD clinical subgroups (p > 0.05). However, higher baseline CSF sTREM2 predicted greater global cognitive decline in patients with PD (β = −0.585, p = 0.039). Moreover, after a mean follow-up of 5.51 ± 1.31 years, baseline CSF sTREM2 that elevated in the middle tertile (HR = 2.426, 95% CI: 1.023–5.754, p = 0.044) and highest tertile (HR = 2.833, 95% CI: 1.226–6.547, p = 0.015) were associated with a future high risk of cognitive decline. Additionally, CSF sTREM2 decreased in abnormal Aβ pathology (A+) and α-syn pathology (S+) but normal tau pathology, while increased in abnormal phosphorylated tau (T+) (p < 0.05).

Conclusion

CSF sTREM2 may be a promising predictor for the cognitive decline in PD rather than a diagnostic biomarker. The dynamic change in CSF sTREM2 in PD may help to the monitor of neuronal injury and microglial activity.
Tai Chi Quan Versus Physical Therapy on Pain and Cognitive Performance for Elderly People With Chronic Low Back Pain: Study Protocol for a Randomized Controlled Trial
Authors: Wang Rui , Zhu Dong , Wang Lin , Liu Jing , Zou Jun , Sun Yang , Jiang Yan , Hu Hao-Yu , Deng Zhi-Wei , Weng Lin-Man , Zheng Kang-Yong , Kiartivich Suparata , Wang Xue-Qiang
Published: June 2022

Objectives

Chronic low back pain has become a major cause of global disability and caused a huge economic burden to society. Physical therapy is a vital strategy for rehabilitation of chronic low back pain. Although several trials have shown that Tai Chi Quan is a beneficial treatment, the comparative effectiveness of Tai Chi Quan versus physical therapy is unknown. We are conducting a randomized controlled trial to assess the effectiveness of Tai Chi Quan versus that of physical therapy in treating chronic low back pain.

Methods

We will perform a single-blind randomized controlled trial on elderly people with chronic low back pain. 138 participants will be randomly assigned to the Tai Chi Quan group (60-min classes, three times per week for 12 weeks) or physical therapy group (10 min of evaluation and warm-up, 40 min of therapist-directed exercise therapy, and 10 min of relaxation, three times per week for 12 weeks) with an allocation of 1:1. The participants will be followed up for 40 weeks for the study of long-term effects. The primary outcomes include pain intensity and back-related function at 12 weeks. Secondary outcomes include lumbar quantitative sensory testing, balance, cognitive function, psychosocial function, cost-effectiveness, compliance and adverse events. We will perform the intention-to-treat analysis for withdrawal and missing data.

Discussion

The study will be the first randomized trial with comparative-effectiveness of Tai Chi Quan and physical therapy for chronic low back pain. Standardized protocol, large sample size, and comprehensive outcomes are important features in this trial. This study aims to determine the feasibility and effectiveness of Tai Chi Quan for low back pain. The results of this study will be beneficial for elderly people with low back pain and medical rehabilitation personnel.

Clinical Trial Registration

www.chictr.org.cn, identifier ChiCTR2000029723.
Clinical Features and Potential Mechanisms Relating Neuropathological Biomarkers and Blood-Brain Barrier in Patients With Alzheimer’s Disease and Hearing Loss
Authors: Zhang Wei-jiao , Li Dan-ning , Lian Teng-hong , Guo Peng , Zhang Ya-nan , Li Jing-hui , Guan Hui-ying , He Ming-yue , Zhang Wen-jing , Zhang Wei-jia , Luo Dong-mei , Wang Xiao-min , Zhang Wei
Published: June 2022

Background

The aim of this study was to explore clinical features and potential mechanisms relating neuropathological biomarkers and blood-brain barrier (BBB) in Alzheimer’s disease (AD) and hearing loss (HL).

Materials and Methods

A total of 65 patients with AD were recruited and auditory function was assessed by threshold of pure tone audiometry (PTA). Patients were divided into AD with HL (AD-HL) and AD with no HL (AD-nHL) groups based on the standard of World Health Organization. Clinical symptoms were assessed by multiple rating scales. The levels of neuropathological biomarkers of β amyloid1-42 (Aβ1–42) and multiple phosphorylated tau (P-tau), and BBB factors of matrix metalloproteinases (MMPs), receptor of advanced glycation end products, glial fibrillary acidic protein, and low-density lipoprotein receptor related protein 1 were measured.

Results

(1) Compared with AD-nHL group, AD-HL group had significantly impaired overall cognitive function and cognitive domains of memory, language, attention, execution, and activities of daily living (ADL) reflected by the scores of rating scales (P < 0.05). PTA threshold was significantly correlated with the impairments of overall cognitive function and cognitive domains of memory and language, and ADL in patients with AD (P < 0.05). (2) P-tau (S199) level was significantly increased in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD. (3) MMP-3 level was significantly elevated in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD (P < 0.05). (4) In AD-HL group, P-tau (S199) level was significantly and positively correlated with the levels of MMP-2 and MMP-3 in CSF (P < 0.05).

Conclusion

AD-HL patients have severely compromised overall cognitive function, multiple cognitive domains, and ADL. The potential mechanisms of AD-HL involve elevations of AD neuropathological biomarker of P-tau (S199) and BBB factor of MMP-3, and close correlations between P-tau (S199) and MMP-2/MMP-3 in CSF. Findings from this investigation highly suggest significance of early evaluation of HL for delaying AD progression, and indicate new directions of drug development by inhibiting neuropathological biomarkers of AD and protecting BBB.
Recent Trends in Non-invasive Neural Recording Based Brain-to-Brain Synchrony Analysis on Multidisciplinary Human Interactions for Understanding Brain Dynamics: A Systematic Review
Authors: Nazneen Tahnia , Islam Iffath Binta , Sajal Md. Sakibur Rahman , Jamal Wasifa , Amin M. Ashraful , Vaidyanathan Ravi , Chau Tom , Mamun Khondaker A.
Published: June 2022

The study of brain-to-brain synchrony has a burgeoning application in the brain-computer interface (BCI) research, offering valuable insights into the neural underpinnings of interacting human brains using numerous neural recording technologies. The area allows exploring the commonality of brain dynamics by evaluating the neural synchronization among a group of people performing a specified task. The growing number of publications on brain-to-brain synchrony inspired the authors to conduct a systematic review using the PRISMA protocol so that future researchers can get a comprehensive understanding of the paradigms, methodologies, translational algorithms, and challenges in the area of brain-to-brain synchrony research. This review has gone through a systematic search with a specified search string and selected some articles based on pre-specified eligibility criteria. The findings from the review revealed that most of the articles have followed the social psychology paradigm, while 36% of the selected studies have an application in cognitive neuroscience. The most applied approach to determine neural connectivity is a coherence measure utilizing phase-locking value (PLV) in the EEG studies, followed by wavelet transform coherence (WTC) in all of the fNIRS studies. While most of the experiments have control experiments as a part of their setup, a small number implemented algorithmic control, and only one study had interventional or a stimulus-induced control experiment to limit spurious synchronization. Hence, to the best of the authors' knowledge, this systematic review solely contributes to critically evaluating the scopes and technological advances of brain-to-brain synchrony to allow this discipline to produce more effective research outcomes in the remote future.
Young COVID-19 Patients Show a Higher Degree of Microglial Activation When Compared to Controls
Authors: Matschke Jakob , Lahann Henri , Krasemann Susanne , Altmeppen Hermann , Pfefferle Susanne , Galliciotti Giovanna , Fitzek Antonia , Sperhake Jan-Peter , Ondruschka Benjamin , Busch Miriam , Rotermund Natalie , Schulz Kristina , Lohr Christian , Dottermusch Matthias , Glatzel Markus
Published: June 2022

The severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) is the cause of human coronavirus disease 2019 (COVID-19). Since its identification in late 2019 SARS-CoV-2 has spread rapidly around the world creating a global pandemic. Although considered mainly a respiratory disease, COVID-19 also encompasses a variety of neuropsychiatric symptoms. How infection with SARS-CoV-2 leads to brain damage has remained largely elusive so far. In particular, it has remained unclear, whether signs of immune cell and / or innate immune and reactive astrogliosis are due to direct effects of the virus or may be an expression of a non-specific reaction of the brain to a severe life-threatening disease with a considerable proportion of patients requiring intensive care and invasive ventilation activation. Therefore, we designed a case-control-study of ten patients who died of COVID-19 and ten age-matched non-COVID-19-controls to quantitatively assess microglial and astroglial response. To minimize possible effects of severe systemic inflammation and / or invasive therapeutic measures we included only patients without any clinical or pathomorphological indication of sepsis and who had not been subjected to invasive intensive care treatment. Our results show a significantly higher degree of microglia activation in younger COVID-19 patients, while the difference was less and not significant for older COVID-19 patients. The difference in the degree of reactive gliosis increased with age but was not influenced by COVID-19. These preliminary data warrants further investigation of larger patient cohorts using additional immunohistochemical markers for different microglial phenotypes.
Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study
Authors: Lazzeri Giulia , Franco Giulia , Difonzo Teresa , Carandina Angelica , Gramegna Chiara , Vergari Maurizio , Arienti Federica , Naci Anisa , Scatà Costanza , Monfrini Edoardo , Dias Rodrigues Gabriel , Montano Nicola , Comi Giacomo P. , Saetti Maria Cristina , Tobaldini Eleonora , Di Fonzo Alessio
Published: June 2022

Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.
Behavioral Studies Using Large-Scale Brain Networks – Methods and Validations
Authors: Liu Mengting , Amey Rachel C. , Backer Robert A. , Simon Julia P. , Forbes Chad E.
Published: June 2022

Mapping human behaviors to brain activity has become a key focus in modern cognitive neuroscience. As methods such as functional MRI (fMRI) advance cognitive scientists show an increasing interest in investigating neural activity in terms of functional connectivity and brain networks, rather than activation in a single brain region. Due to the noisy nature of neural activity, determining how behaviors are associated with specific neural signals is not well-established. Previous research has suggested graph theory techniques as a solution. Graph theory provides an opportunity to interpret human behaviors in terms of the topological organization of brain network architecture. Graph theory-based approaches, however, only scratch the surface of what neural connections relate to human behavior. Recently, the development of data-driven methods, e.g., machine learning and deep learning approaches, provide a new perspective to study the relationship between brain networks and human behaviors across the whole brain, expanding upon past literatures. In this review, we sought to revisit these data-driven approaches to facilitate our understanding of neural mechanisms and build models of human behaviors. We start with the popular graph theory approach and then discuss other data-driven approaches such as connectome-based predictive modeling, multivariate pattern analysis, network dynamic modeling, and deep learning techniques that quantify meaningful networks and connectivity related to cognition and behaviors. Importantly, for each topic, we discuss the pros and cons of the methods in addition to providing examples using our own data for each technique to describe how these methods can be applied to real-world neuroimaging data.
Classification of Electrophysiological Signatures With Explainable Artificial Intelligence: The Case of Alarm Detection in Flight Simulator
Authors: Massé Eva , Bartheye Olivier , Fabre Ludovic
Published: June 2022

Relevant sounds such as alarms are sometimes involuntarily ignored, a phenomenon called inattentional deafness. This phenomenon occurs under specific conditions including high workload (i.e., multitasking) and/or cognitive fatigue. In the context of aviation, such an error can have drastic consequences on flight safety. This study uses an oddball paradigm in which participants had to detect rare sounds in an ecological context of simulated flight. Cognitive fatigue and cognitive load were manipulated to trigger inattentional deafness, and brain activity was recorded via electroencephalography (EEG). Our results showed that alarm omission and alarm detection can be classified based on time-frequency analysis of brain activity. We reached a maximum accuracy of 76.4% when the algorithm was trained on all participants and a maximum of 90.5%, on one participant, when the algorithm was trained individually. This method can benefit from explainable artificial intelligence to develop efficient and understandable passive brain–computer interfaces, improve flight safety by detecting such attentional failures in real time, and give appropriate feedback to pilots, according to our ambitious goal, providing them with reliable and rich human/machine interactions.
Cerebellum Involvement in Dystonia During Associative Motor Learning: Insights From a Data-Driven Spiking Network Model
Authors: Geminiani Alice , Mockevičius Aurimas , D’Angelo Egidio , Casellato Claudia
Published: June 2022

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. Although dystonia is traditionally associated with basal ganglia dysfunction, recent evidence has been pointing to a role of the cerebellum, a brain area involved in motor control and learning. Cerebellar abnormalities have been correlated with dystonia but their potential causative role remains elusive. Here, we simulated the cerebellar input-output relationship with high-resolution computational modeling. We used a data-driven cerebellar Spiking Neural Network and simulated a cerebellum-driven associative learning task, Eye-Blink Classical Conditioning (EBCC), which is characteristically altered in relation to cerebellar lesions in several pathologies. In control simulations, input stimuli entrained characteristic network dynamics and induced synaptic plasticity along task repetitions, causing a progressive spike suppression in Purkinje cells with consequent facilitation of deep cerebellar nuclei cells. These neuronal processes caused a progressive acquisition of eyelid Conditioned Responses (CRs). Then, we modified structural or functional local neural features in the network reproducing alterations reported in dystonic mice. Either reduced olivocerebellar input or aberrant Purkinje cell burst-firing resulted in abnormal learning curves imitating the dysfunctional EBCC motor responses (in terms of CR amount and timing) of dystonic mice. These behavioral deficits might be due to altered temporal processing of sensorimotor information and uncoordinated control of muscle contractions. Conversely, an imbalance of excitatory and inhibitory synaptic densities on Purkinje cells did not reflect into significant EBCC deficit. The present work suggests that only certain types of alterations, including reduced olivocerebellar input and aberrant PC burst-firing, are compatible with the EBCC changes observed in dystonia, indicating that some cerebellar lesions can have a causative role in the pathogenesis of symptoms.
An Alkaline Protease-Digestion of Silkworm Powder Enhances Its Effects Over Healthspan, Autophagy, and Mitochondria Function in a Rotenone-Induced Drosophila Model
Authors: Mai Linh Xuan , Kang Sang-Kug , Jo You-Young , Nguyen Phuong , Kim A-Young , Kim Kee-Young , Kim Nam-Suk , Koh Young Ho
Published: June 2022

Background

Recent studies have reported that steamed and freeze-dried mature silkworms, also known as HongJam, have various health-promoting effects.

Objective

The goal of this study was to elucidate changes in the various health-promoting effects of HongJam, after its digestion with a food-grade protease.

Materials and Methods

We examined whether healthspan-promotion and rotenone-induced loss of motor-control prevention effects were enhanced in Drosophila fed with food-grade alkaline protease-digested HongJam compared to those fed with non-digested HongJam. The differences in mitochondrial functions, chemical susceptibilities, and activations of signal transduction pathways between Drosophila supplemented with various feed were examined to elucidate the molecular and biochemical basis of healthspan-promotion and locomotor-improvement effects of protease-digested HongJam.

Results

We first found that the healthspan-promotion effect of HongJam digested with a food-grade protease was different depending on the silkworm variety used for its production. Digestion with food-grade protease into White-Jade HongJam (WJ) as prepared from the White-Jade silkworm variety that spins white cocoons did not enhance its functionality. However, compared to Golden-Silk HongJam (GS), a food-grade protease-digested Golden-Silk HongJam (GSD) produced from the Golden-Silk silkworm variety that spins yellow cocoons, it further promoted the healthspan in a Drosophila model. By conducting a series of studies to reveal the molecular and biochemical basis for healthspan-promoting effects, we found that GS and GSD similarly enhanced mitochondrial activity, but GSD activated autophagy signaling more than GS. In addition, GSD feed (GSDf)-, GSD supernatant feed (GSDsupf)-, and GSD precipitate feed (GSDprecf)-reared Drosophila were also found to have increased resistance to an autophagy inhibitor compared to that of normal feed- or GS feed-reared Drosophila. Furthermore, we found that the rotenone-induced loss of motor control prevention effect was superior for GSDsup compared to GS, GSD, or GSDprec. This result may have occurred because GSDsup has more phenolic compounds and antioxidant activities than other samples.

Conclusion

GSDsup contained more digested small peptides and free phytochemicals than other samples due to the digestion of proteins with a food-grade protease. Thus, GSDsup leads to further healthspan-promoting and locomotor-improvement effects than GS, GSD, or GSDprec.
Psychological, Physiological, and Physical Effects of Resistance Training and Personalized Diet in Celiac Women
Authors: Martínez-Rodríguez Alejandro , Loaiza-Martínez Daniela Alejandra , Sánchez-Sánchez Javier , Rubio-Arias Jacobo Á. , Alacid Fernando , Prats-Moya Soledad , Martínez-Olcina María , Yáñez-Sepúlveda Rodrigo , Asencio-Mas Nuria , Marcos-Pardo Pablo J.
Published: June 2022

Background

Gluten intolerance is a systemic process of autoimmune nature; it develops in genetically predisposed subjects with gluten ingestion. The only treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). This study was designed to evaluate adherence to a GFD, risk of an eating disorder, and nutritional status in adult CD patients undergoing different interventions.

Methods

A total of 28 Spanish women, aged 40 years or more, took part in a randomized controlled trial. Each group received a different intervention: group 1, gluten-free nutrition plan + exercise (GFD + E); group 2, gluten-free nutrition plan (GFD); group 3, celiac controls (NO-GFD); and group 4, non-celiac controls (CONTROL). The training was prescribed by a sport scientist. It was based on resistance training with elastic bands; beforehand a warm-up was performed and the resistance was increased progressively. The variables studied were adherence to the GFD, risk of eating disorders, blood values, and body composition.

Results

Celiac women with personalized nutritional planning presented greater adherence to a gluten-free diet (p < 0.001). Regarding leukocytes, significant differences were observed between the GFD and control groups (p = 0.004). Perimeters and folds did not decrease significantly.

Conclusion

Women with celiac disease who follow an adapted and personalized diet have a better adherence to a GFD compared to those who follow a non-professional diet, and therefore have a better immune system status (blood leukocytes).
Evaluating the Effects of Wheat Cultivar and Extrusion Processing on Nutritional, Health-Promoting, and Antioxidant Properties of Flour
Authors: Bangar Sneh Punia , Sandhu Kawaljit Singh , Rusu Alexandru , Trif Monica , Purewal Sukhvinder Singh
Published: June 2022

Wheat has been considered one of the most important staple foods for thousands of years. It is one of the largest suppliers of calories in the daily diet, which is added to many different products. Wheat is also a good source of health-benefiting antioxidants. This study aims toinvestigate the changes in the antioxidant properties, such as total phenol content, 2,2-diphenyl-1-picrylhydrazyl (DPPH), metal chelating activity, 2,2′-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid) diammonium salt (ABTS+) scavenging activity, and color intensity, during the extrusion processing of six different wheat cultivars. The extrusion factors evaluated were 15% feed moisture and two extrusion temperatures (150 and 180°C). Extrusion processing increased antioxidant activity (DPPH, metal chelating activity, and ABTS+ scavenging activity), whereas total flavonoids content and total phenolic content were decreased. The L* values of wheat flours increased significantly (p < 0.05) after extrusion at 150 and 180°C, 15% mc. Furthermore, redness was decreased from control wheat cultivars (range: 0.17–0.21) to extrusion at 150°C (range: 0.14–0.17) and 180°C (range: 0.1–0.14). The study suggests that extruded wheat could improve the antioxidant potential in food products.
The Preventive Effects of Fermented and Germinated Foxtail Millet Whole Grain on Kidney Damage in a Diabetic Mouse Model
Authors: Liu Xia , Qiu Bin , Liu Wei , Zhang Yuhan , Wang Xianshu , Li Xingang , Li Lingfei , Zhang Di
Published: June 2022

Diabetic kidney disease (DKD) is an important complication of diabetes. The prevention of DKD can effectively reduce the mortality rate of diabetic patients and improve their quality of life. The present study examined the effects of fermented and germinated foxtail millet whole grain (FG-FM) on kidney lesions in a diabetic mouse model (Db/Db mice). The results proved that the FG-FM consumption significantly alleviated the kidney tissue damage in the diabetic mouse model. The transcriptome analysis of kidney tissues demonstrated that the overactivation of signaling pathways related to inflammation and immunity in the diabetic mouse model was significantly inhibited with the FG-FM intake. Moreover, the consumption of the FG-FM diet effectively elevated the bacterial diversity, increased the relative abundance of probiotics and decreased the relative abundance of previously reported DKD-related bacteria in the gut microbiota of diabetic mice. Our study confirmed foxtail millet as a potential source of functional food for the non-pharmacological intervention of DKD.
Genomic Features of Solid Tumor Patients Harboring ALK/ROS1/NTRK Gene Fusions
Authors: Dai Yinghuan , Liu Ping , He Wenlong , Yang Lizhen , Ni Yang , Ma Xuejiao , Du Furong , Song Chao , Liu Yang , Sun Yi
Published: June 2022

The fusions of receptor tyrosine kinase (RTK) involving anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neurotrophic receptor tyrosine kinase (NTRK) represent the potential targets of therapeutic intervention for various types of solid tumors. Here, the genomic features of 180 Chinese solid tumor patients with ALK, ROS1, and NTRK fusions by next generation sequencing (NGS) were comprehensively characterized, and the data from 121 patients in Memorial Sloan Kettering Cancer Center (MSKCC) database were used to compare. We found that ALK, ROS1, and NTRK fusions were more common in younger female patients (p<0.001) and showed a higher expression of programmed death ligand 1 (PD-L1). The gene-intergenic fusion and the fusion with rare formation directions accounted for a certain proportion in all samples and 62 novel fusions were discovered. Alterations in TP53 and MUC16 were common in patients with RTK fusions. The mutational signatures of patients were mainly distributed in COSMIC signature 1, 2, 3, 15 and 30, while had a higher frequency in copy number variations (CNVs) of individual genes, such as IL-7R. In the MSKCC cohort, patients with fusions and CNVs showed shorter overall survival than those with only fusions. Furthermore, the differentially mutated genes between fusion-positive and -negative patients mainly concentrated on MAPK signaling and FOXO signaling pathways. These results may provide genomic information for the personalized clinical management of solid tumor patients with ALK, ROS1, and NTRK fusions in the era of precision medicine.
Financial Burden and Mental Health Among LGBTQIA+ Adolescent and Young Adult Cancer Survivors During the COVID-19 Pandemic
Authors: Waters Austin R. , Bybee Sara , Warner Echo L. , Kaddas Heydon K. , Kent Erin E. , Kirchhoff Anne C.
Published: June 2022

Background

In the United States, the cost of cancer treatment can lead to severe financial burden for cancer survivors. The economic impacts of the COVID-19 pandemic compound cancer survivors’ financial challenges. Financial burden may be particularly challenging for lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexual and gender minority (LGBTQIA+) survivors. LGBTQIA+ survivors who are adolescent and young adults (AYA) may face elevated financial burden due to multiple, intersecting identities.

Methods

An explanatory sequential mixed methods design was applied, beginning with a survey of AYA cancer survivors in the Mountain West region of the United States. Survey measures included demographics, COVID-19 impacts, the COmprehensive Score for financial Toxicity (COST), Perceived Stress Scale-4 (PSS-4), and PROMIS anxiety and depression scales. Two-way t-tests were used to analyze differences in outcomes between LGBTQIA+ and non-LGBTQIA+ AYAs. All LGBTQIA+ survey participants were invited to complete an interview, and those who agreed participated in descriptive interviews about financial burden due to cancer, COVID-19, and LGBTQIA+ identity. Interviews were audio recorded, transcribed, and analyzed using Dedoose.

Results

Survey participants (N=325) were LGBTQIA+ (n=29, 8.9%), primarily female (n= 197, 60.6%), non-Hispanic White (n= 267, 82.2%), and received treatment during COVID-19 (n= 174, 54.0%). LGBTQIA+ interview participants (n=9, 100%) identified as a sexual minority and (n=2, 22.2%) identified as a gender minority. Most were non-Hispanic White (n=6, 66.7%) and had received treatment during COVID-19 (n=7, 77.8%). Statistical analyses revealed that LGBTQIA+ AYAs reported significantly worse COST scores than non-LGBTQIA+ AYAs (p=0.002). LGBTQIA+ AYAs also reported significantly higher PSS-4 (p=0.001), PROMIS anxiety (p=0.002) and depression scores (p<0.001) than non-LGBTQIA+ AYAs, reflecting worse mental health outcomes. High costs of cancer treatment and employment disruptions due to COVID-19 contributed to substantial financial stress, which exacerbated existing mental health challenges and introduced new ones.

Conclusions

LGBTQIA+ AYA survivors reported substantial financial burden and psychological distress exacerbated by cancer, the COVID-19 pandemic, and LGBTQIA+ stigma. Given their multiple intersecting identities and potential for marginalization, LGBTQIA+ AYA survivors deserve prioritization in research to reduce financial burden and poor mental health.
A Comprehensive Prognostic Model for Colorectal Cancer Liver Metastasis Recurrence After Neoadjuvant Chemotherapy
Authors: Zhou Zhenyuan , Han Xin , Sun Diandian , Liang Zhiying , Wu Wei , Ju Haixing
Published: June 2022

Background

For patients with colorectal cancer liver metastases (CRLMs), it is important to stratify patients according to the risk of recurrence. This study aimed to validate the predictive value of some clinical, imaging, and pathology biomarkers and develop an operational prognostic model for patients with CRLMs with neoadjuvant chemotherapy (NACT) before the liver resection.

Methods

Patients with CRLMs accompanied with primary lesion and liver metastases lesion resection were enrolled into this study. A nomogram based on independent risk factors was identified by Kaplan–Meier analysis and multivariate Cox proportional hazard analysis. The predictive ability was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Calibration plot were also used to explore the consistency between prediction and reality.

Results

A total of 118 patients were enrolled into the study. Multivariable Cox analysis found that histopathological growth patterns (HGPs) [Hazard Rate (HR) = 2.130], radiology response (stable disease vs. partial response, HR = 2.207; progressive disease vs. partial response, HR = 3.824), lymph node status (HR = 1.442), and age (HR = 0.576) were independent risk factors for disease-free survival (DFS) (p < 0.05). Corresponding nomogram was constructed on the basis of the above factors, demonstrating that scores ranging from 5 to 11 presented better prognosis than the scores of 0–4 (median DFS = 14.3 vs. 4.9 months, p < 0.0001). The area under ROC curves of the model for 1-, 2-, and 3-year DFS were 0.754, 0.705, and 0.666, respectively, and DCA confirmed that the risk model showed more clinical benefits than clinical risk score. Calibration plot for the probability of DFS at 1 or 3 years verified an optimal agreement between prediction and actual observation. In the course of our research, compared with pure NACT, a higher proportion of desmoplastic HGP (dHGP) was detected in patients treated with NACT plus cetuximab (p = 0.030), and the use of cetuximab was an independent factor for decreased replacement HGP (rHGP) and increased dHGP (p = 0.049).

Conclusion

Our model is concise, comprehensive, and high efficient, which may contribute to better predicting the prognosis of patients with CRLMs with NACT before the liver resection. In addition, we observed an unbalanced distribution of HGPs as well.
Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis
Authors: Hatipoğlu Tevfik , Esmeray Sönmez Esra , Hu Xiaozhou , Yuan Hongling , Danyeli Ayça Erşen , Şeyhanlı Ahmet , Önal-Süzek Tuğba , Zhang Weiwei , Akman Burcu , Olgun Aybüke , Özkal Sermin , Alacacıoğlu İnci , Özcan Mehmet Ali , You Hua , Küçük Can
Published: June 2022

Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.
SEMA3C Supports Pancreatic Cancer Progression by Regulating the Autophagy Process and Tumor Immune Microenvironment
Authors: Zhang Dalin , Lindstrom Aaron , Kim Edward J , Hwang Chang-il , Hall Madison Lee , Lin Tzu-Yin , Li Yuanpei
Published: June 2022

To date, driver genes for pancreatic cancer treatment are difficult to pursue therapeutically. Targeting mutated KRAS, the most renowned driver gene in pancreatic cancer, is an active area of study. We discovered a gene named SEMA3C was highly expressed in pancreatic cancer cell lines and patients with a G12D mutation in KRAS. High expression of SEMA3C in patients was significantly associated with the decreased survival of pancreatic cancer patients based on the TCGA database. In pancreatic cancer cells, SEMA3C knockdown or inhibition exhibited growth/colony inhibition and cell cycle arrest. In addition, SEMA3C inhibition sensitized KRAS or MEK1/2 inhibition in pancreatic cancer cells. Overexpression of SEMA3C resulted in the induction of autophagy, whereas depletion of SEMA3C compromised induction of autophagy. SEMA3C modified the PD-L1 expression in tumor and immune cells and is correlated with the M2-like macrophage marker ARG1/CD163 expression, which could reshape the tumor microenvironment. Inhibition of SEMA3C decreased tumor formation in the xenograft model in vivo. Taken together, our data suggest that SEMA3C plays a substantial role in promoting cancer cell survival by regulating the autophagy process and impacting the tumor environment immune response. SEMA3C can be used as a novel target or marker with therapeutic or diagnostic potential in pancreatic cancer especially in tumors harboring the specific KRAS G12D mutation.
A Nomogram to Predict Survival in Patients With Locoregional Recurrent Nasopharyngeal Carcinoma Receiving Comprehensive Treatment
Authors: Wei Ying-Hong , Wang Ying , Li He , Wang Chi-jie , Liu Song-Ran , Huang Zi-Lu , Wang Guan-Nan , Tao Ya-Lan , Xia Yun-Fei
Published: June 2022

Objective

This study aimed to establish a prognostic stratified model of chemotherapy-based comprehensive treatment for patients with locoregional recurrent nasopharyngeal carcinoma (lrNPC), to help individualized treatment decision-making.

Materials and Methods

This study retrospectively reviewed patients with lrNPC who received chemotherapy-based comprehensive treatment from January 1, 2010, to December 31, 2018. A total of 422 eligible patients were divided into test (n = 338) and validation (n = 84) cohorts. A LASSO cox regression model was used to identify significant prognostic factors for overall survival (OS) in the test cohort. A nomogram was then developed based on a combined consideration of clinically meaningful prognostic factors and statistically significant prognostic factors. The performance of the nomogram was assessed with Harrell’s concordance index (C-index) and calibration plots.

Results

Five significant factors were identified: age, albumin (ALB), T stage after recurrent (rT), neutrophil to lymphocyte ratio (NLR), and systematic immune-inflammation index (SII). The nomogram was established with these five factors. C-index was 0.636 in the test cohort and 0.610 in the validation cohort. The calibration curves for the OS rate at 3, and 5 years showed an excellent agreement in both cohorts. In addition, the corresponding risk classification system successfully classified patients into low- and high-risk groups and performed well in stratification (P < 0.001).

Conclusions

The nomogram shows well prognostic performance for lrNPC patients receiving chemotherapy-based comprehensive treatment.
Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma
Authors: Dai Qingqing , Ain Quratul , Rooney Michael , Song Fei , Zipprich Alexander
Published: June 2022

IQ motif-containing GTPase-activating proteins (IQGAPs) are a class of scaffolding proteins, including IQGAP1, IQGAP2, and IQGAP3, which govern multiple cellular activities by facilitating cytoskeletal remodeling and cellular signal transduction. The role of IQGAPs in cancer initiation and progression has received increasing attention in recent years, especially in hepatocellular carcinoma (HCC), where the aberrant expression of IQGAPs is closely related to patient prognosis. IQGAP1 and 3 are upregulated and are considered oncogenes in HCC, while IQGAP2 is downregulated and functions as a tumor suppressor. This review details the three IQGAP isoforms and their respective structures. The expression and role of each protein in different liver diseases and mainly in HCC, as well as the underlying mechanisms, are also presented. This review also provides a reference for further studies on IQGAPs in HCC.