bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting Persistent Neuronal Activity During Covert Spatial Attention
Authors: Amengual Julian L. , Ben Hamed Suliann
Published: June 2021

Persistent activity has been observed in the prefrontal cortex (PFC), in particular during the delay periods of visual attention tasks. Classical approaches based on the average activity over multiple trials have revealed that such an activity encodes the information about the attentional instruction provided in such tasks. However, single-trial approaches have shown that activity in this area is rather sparse than persistent and highly heterogeneous not only within the trials but also between the different trials. Thus, this observation raised the question of how persistent the actually persistent attention-related prefrontal activity is and how it contributes to spatial attention. In this paper, we review recent evidence of precisely deconstructing the persistence of the neural activity in the PFC in the context of attention orienting. The inclusion of machine-learning methods for decoding the information reveals that attention orienting is a highly dynamic process, possessing intrinsic oscillatory dynamics working at multiple timescales spanning from milliseconds to minutes. Dimensionality reduction methods further show that this persistent activity dynamically incorporates multiple sources of information. This novel framework reflects a high complexity in the neural representation of the attention-related information in the PFC, and how its computational organization predicts behavior.
The Challenges and Perspectives of the Integration Between Virtual and Augmented Reality and Manual Therapies
Authors: Cerritelli Francesco , Chiera Marco , Abbro Marco , Megale Valentino , Esteves Jorge , Gallace Alberto , Manzotti Andrea
Published: June 2021

Virtual reality (VR) and augmented reality (AR) have been combined with physical rehabilitation and psychological treatments to improve patients' emotional reactions, body image, and physical function. Nonetheless, no detailed investigation assessed the relationship between VR or AR manual therapies (MTs), which are touch-based approaches that involve the manipulation of tissues for relieving pain and improving balance, postural stability and well-being in several pathological conditions. The present review attempts to explore whether and how VR and AR might be integrated with MTs to improve patient care, with particular attention to balance and to fields like chronic pain that need an approach that engages both mind and body. MTs rely essentially on touch to induce tactile, proprioceptive, and interoceptive stimulations, whereas VR and AR rely mainly on visual, auditory, and proprioceptive stimulations. MTs might increase patients' overall immersion in the virtual experience by inducing parasympathetic tone and relaxing the mind, thus enhancing VR and AR effects. VR and AR could help manual therapists overcome patients' negative beliefs about pain, address pain-related emotional issues, and educate them about functional posture and movements. VR and AR could also engage and change the sensorimotor neural maps that the brain uses to cope with environmental stressors. Hence, combining MTs with VR and AR could define a whole mind-body intervention that uses psychological, interoceptive, and exteroceptive stimulations for rebalancing sensorimotor integration, distorted perceptions, including visual, and body images. Regarding the technology needed to integrate VR and AR with MTs, head-mounted displays could be the most suitable devices due to being low-cost, also allowing patients to follow VR therapy at home. There is enough evidence to argue that integrating MTs with VR and AR could help manual therapists offer patients better and comprehensive treatments. However, therapists need valid tools to identify which patients would benefit from VR and AR to avoid potential adverse effects, and both therapists and patients have to be involved in the development of VR and AR applications to define truly patient-centered therapies. Furthermore, future studies should assess whether the integration between MTs and VR or AR is practically feasible, safe, and clinically useful.
Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability
Authors: Di Re Jessica , Hsu Wei-Chun J. , Kayasandik Cihan B. , Fularczyk Nickolas , James T. F. , Nenov Miroslav N. , Negi Pooran , Marosi Mate , Scala Federico , Prasad Saurabh , Labate Demetrio , Laezza Fernanda
Published: June 2021

The axon initial segment (AIS) is a highly regulated subcellular domain required for neuronal firing. Changes in the AIS protein composition and distribution are a form of structural plasticity, which powerfully regulates neuronal activity and may underlie several neuropsychiatric and neurodegenerative disorders. Despite its physiological and pathophysiological relevance, the signaling pathways mediating AIS protein distribution are still poorly studied. Here, we used confocal imaging and whole-cell patch clamp electrophysiology in primary hippocampal neurons to study how AIS protein composition and neuronal firing varied in response to selected kinase inhibitors targeting the AKT/GSK3 pathway, which has previously been shown to phosphorylate AIS proteins. Image-based features representing the cellular pattern distribution of the voltage-gated Na+ (Nav) channel, ankyrin G, βIV spectrin, and the cell-adhesion molecule neurofascin were analyzed, revealing βIV spectrin as the most sensitive AIS protein to AKT/GSK3 pathway inhibition. Within this pathway, inhibition of AKT by triciribine has the greatest effect on βIV spectrin localization to the AIS and its subcellular distribution within neurons, a phenotype that Support Vector Machine classification was able to accurately distinguish from control. Treatment with triciribine also resulted in increased excitability in primary hippocampal neurons. Thus, perturbations to signaling mechanisms within the AKT pathway contribute to changes in βIV spectrin distribution and neuronal firing that may be associated with neuropsychiatric and neurodegenerative disorders.
New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Authors: Wang Linqin , Hong Ruimin , Zhou Linghui , Ni Fang , Zhang Mingming , Zhao Houli , Wu Wenjun , Wang Yiyun , Ding Shuyi , Chang Alex H. , Hu Yongxian , Huang He
Published: June 2021

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.
The Complementary Relationship Between Echocardiography and Multi-Slice Spiral CT Coronary Angiography in the Diagnosis of Coronary Artery Thrombosis in Children With Kawasaki Disease
Authors: Xu Yun-ming , Chu Yan-qiu , Li Xue-mei , Wang Ce , Ma Quan-mei , Yu Xiao-na , Yu Xian-yi , Chen Rui , Xing Yan-lin , Yu Xue-xin , Sun Le , Cui Xiao-zhe , Wang Hong
Published: June 2021

Aim:To compare the diagnostic values by using transthoracic echocardiography (ECHO) and multi-slice spiral CT coronary angiography (CTCA) for identifying coronary artery thrombosis in children with Kawasaki disease (KD).

Methods:Total 97 KD children with coronary artery dilation complications in our hospital from June 2012 to December 2020 were included in the study. CTCA and ECHO were performed after over 1 month of illness.

Results:Coronary artery thrombosis was found in 14 out of 97 patients. Among them, 10 were identified as positive by CTCA, 9 were identified as positive by ECHO, and 5 were identified as positive by both CTCA and ECHO.

Conclusion:Both CTCA and ECHO can be used to diagnose coronary artery thrombosis. ECHO has advantage in identifying low-density thrombus, and CTCA is better for the clot in distal coronary artery. They can complement each other.
High-Frequency Deep Brain Stimulation of the Substantia Nigra Pars Reticulata Facilitates Extinction and Prevents Reinstatement of Methamphetamine-Induced Conditioned Place Preference
Authors: Zhang Libo , Meng Shiqiu , Chen Wenjun , Chen Yun , Huang Enze , Zhang Guipeng , Liang Yisen , Ding Zengbo , Xue Yanxue , Chen Yun , Shi Jie , Shi Yu
Published: June 2021

Persistent and stable drug memories lead to a high rate of relapse among addicts. A number of studies have found that intervention in addiction-related memories can effectively prevent relapse. Deep brain stimulation (DBS) exhibits distinct therapeutic effects and advantages in the treatment of neurological and psychiatric disorders. In addition, recent studies have also found that the substantia nigra pars reticulata (SNr) could serve as a promising target in the treatment of addiction. Therefore, the present study aimed to investigate the effect of DBS of the SNr on the reinstatement of drug-seeking behaviors. Electrodes were bilaterally implanted into the SNr of rats before training of methamphetamine-induced conditioned place preference (CPP). High-frequency (HF) or low-frequency (LF) DBS was then applied to the SNr during the drug-free extinction sessions. We found that HF DBS, during the extinction sessions, facilitated extinction of methamphetamine-induced CPP and prevented drug-primed reinstatement, while LF DBS impaired the extinction. Both HF and LF DBS did not affect locomotor activity or induce anxiety-like behaviors of rats. Finally, HF DBS had no effect on the formation of methamphetamine-induced CPP. In conclusion, our results suggest that HF DBS of the SNr could promote extinction and prevent reinstatement of methamphetamine-induced CPP, and the SNr may serve as a potential therapeutic target in the treatment of drug addiction.
Nitric Oxide System and Bronchial Epithelium: More Than a Barrier
Authors: Bayarri María Amparo , Milara Javier , Estornut Cristina , Cortijo Julio
Published: June 2021

Airway epithelium forms a physical barrier that protects the lung from the entrance of inhaled allergens, irritants, or microorganisms. This epithelial structure is maintained by tight junctions, adherens junctions and desmosomes that prevent the diffusion of soluble mediators or proteins between apical and basolateral cell surfaces. This apical junctional complex also participates in several signaling pathways involved in gene expression, cell proliferation and cell differentiation. In addition, the airway epithelium can produce chemokines and cytokines that trigger the activation of the immune response. Disruption of this complex by some inflammatory, profibrotic, and carcinogens agents can provoke epithelial barrier dysfunction that not only contributes to an increase of viral and bacterial infection, but also alters the normal function of epithelial cells provoking several lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or lung cancer, among others. While nitric oxide (NO) molecular pathway has been linked with endothelial function, less is known about the role of the NO system on the bronchial epithelium and airway epithelial cells function in physiological and different pathologic scenarios. Several data indicate that the fraction of exhaled nitric oxide (FENO) is altered in lung diseases such as asthma, COPD, lung fibrosis, and cancer among others, and that reactive oxygen species mediate uncoupling NO to promote the increase of peroxynitrite levels, thus inducing bronchial epithelial barrier dysfunction. Furthermore, iNOS and the intracellular pathway sGC-cGMP-PKG are dysregulated in bronchial epithelial cells from patients with lung inflammation, fibrosis, and malignancies which represents an attractive drug molecular target. In this review we describe in detail current knowledge of the effect of NOS-NO-GC-cGMP-PKG pathway activation and disruption in bronchial epithelial cells barrier integrity and its contribution in different lung diseases, focusing on bronchial epithelial cell permeability, inflammation, transformation, migration, apoptosis/necrosis, and proliferation, as well as the specific NO molecular pathways involved.
Evaluating the Aqueous Phase From Hydrothermal Carbonization of Cow Manure Digestate as Possible Fertilizer Solution for Plant Growth
Authors: Celletti Silvia , Lanz Maximilian , Bergamo Alex , Benedetti Vittoria , Basso Daniele , Baratieri Marco , Cesco Stefano , Mimmo Tanja
Published: June 2021

Improving the agronomic use of recycled nutrients derived from organic waste is one of the priorities within the measures adopted by the European community to reduce environmental issues but remains an unexplored area of research. This study focused on investigating the possibility of using innovative fertilizer solutions in hydroponic systems for the growth of agricultural plants. To this purpose, a liquid fraction [aqueous hydrothermal carbonization (HTC) liquid (AHL)] derived from HTC of cow manure digestate was chemically characterized (pH, electrical conductivity, mineral elements, and organic compounds such as phytotoxins), diluted with distilled water (1:30, 1:60, and 1:90, v/v) to reduce its potential phytotoxicity, and used to grow hydroponic maize (Zea maysL.) plants instead of the classical full-strength nutrient solution. The results indicated that the dilution ratio 1:30 of the AHL solution maintained a high level of toxicity for the plants (phytotoxic substances, especially Na and alkalinity), inducing the arrest of their growth. Differently, the two other dilution ratios (i.e., 1:60 and 1:90) seemed to considerably limit the levels of toxicity, since they allowed the plants to develop. However, these dilution ratios were poor in nutrient elements, inducing alteration in photosynthesis and an onset of deficiency symptoms such as pronounced leaf chlorosis. In view of an eco-friendly approach, future studies are, therefore, needed to identify the correct species-specific dilution ratio to supply both low levels of phytotoxins and adequate content of essential nutrients for appropriate plant growth and development. Furthermore, in order to lower specific Na phytotoxicity, treatments are of utmost importance before using AHL as a fertilizer solution.
Effects of Soil Type on Trace Element Absorption and Fruit Quality of Pepper
Authors: Liu Zhoubin , Huang Yu , Tan Fangjun , Chen Wenchao , Ou Lijun
Published: June 2021

The inbred “SJ11-3” pepper was cultured in yellow brown soil, paddy soil, fluvo-aquic soil, and pastoral soil, and the factors affecting the absorption of trace elements and fruit quality were analyzed. The results showed that the physicochemical properties of the soils were significantly different, which led to differences in the nutritional quality of pepper fruits. The pH value had a significant effect on the absorption of trace elements in pepper. The increase of pH promoted the absorption of magnesium and molybdenum but inhibited the absorption of zinc, copper, manganese, and iron. The stepwise multivariable regression analysis showed that the amount of molybdenum in soil was the main factor affecting the total amino acid content of pepper. Total nitrogen, zinc, and copper were the main factors that contributed to the soluble sugar content of pepper, and the available potassium was the major determinant of the vitamin C content of pepper. This study provides new insight on the pepper fruit quality grown on different types of soil with varying levels of trace elements.
Special Education Major or Attitudes to Predict Teachers' Self-Efficacy for Teaching in Inclusive Education
Authors: Alnahdi Ghaleb H. , Schwab Susanne
Published: June 2021

This study aimed to determine the predictors for Saudi Arabian teachers' self-efficacy to work in inclusive education. Five independent variables were tested in this study: attitudes toward inclusive education, participants' educational major, having relative with disability, working with students with disability and gender. Further, predictors of teachers' attitudes toward inclusive education were examined. The sample was 185 elementary-school teachers in Saudi Arabia. The Arabic version of the Teacher Efficacy for Inclusive Practices scale was used to measure self-efficacy. To assess attitudes toward inclusion an Arabic version of the Sentiments, Attitudes, and Concerns about Inclusive Education Revised subscale was used. Results showed teacher attitude toward inclusion are strongly linked with teachers' self-efficacy to work in inclusive classrooms. Further, participants with a relative with a disability showed more positive attitudes for inclusive education. Levels of self-efficacy were unaffected by gender, having a special education degree, or having a relative with a disability. In sum, this study highlighted the importance of teachers' attitudes toward inclusive education as a main predictor of teachers' self-efficacy.
Trajectories of Loneliness and Psychosocial Functioning
Authors: Hutten Elody , Jongen Ellen M. M. , Verboon Peter , Bos Arjan E. R. , Smeekens Sanny , Cillessen Antonius H. N.
Published: June 2021

The present study examined the relationship between developmental patterns of loneliness and psychosocial functioning among adolescents (9–21 years; N = 110, 52% male). Four-wave longitudinal data were obtained from the Nijmegen Longitudinal Study (NLS) on Infant and Child Development. Loneliness was measured at 9, 13, 16, and 21 years of age and anxiety, depression and self-esteem at 9 and 21 years of age. Using k-means cluster analysis, three trajectories of loneliness were identified as “stable low” (56% of the subjects), “high decreasing” (22% of the subjects), and “low increasing” (22% of the subjects). Importantly, trajectories of loneliness across adolescence significantly predicted psychosocial functioning in young adulthood. Both the “high-decreasing” and “low-increasing” loneliness clusters were associated with higher risk of depression and lower self-esteem compared to the “stable low” loneliness cluster. The “low-increasing” loneliness cluster was associated with higher risk of anxiety compared to the “stable low” loneliness cluster. These results indicate that loneliness in adolescence is a vulnerability that manifests itself in higher levels of anxiety and depression and lower self-esteem in young adulthood.
Massively Multiplayer Online Games and Well-Being: A Systematic Literature Review
Authors: Raith Lisa , Bignill Julie , Stavropoulos Vasileios , Millear Prudence , Allen Andrew , Stallman Helen M. , Mason Jonathan , De Regt Tamara , Wood Andrew , Kannis-Dymand Lee
Published: June 2021

Background: Massively multiplayer online games (MMOs) evolve online, whilst engaging large numbers of participants who play concurrently. Their online socialization component is a primary reason for their high popularity. Interestingly, the adverse effects of MMOs have attracted significant attention compared to their potential benefits.

Methods: To address this deficit, employing PRISMA guidelines, this systematic review aimed to summarize empirical evidence regarding a range of interpersonal and intrapersonal MMO well-being outcomes for those older than 13.

Results: Three databases identified 18 relevant English language studies, 13 quantitative, 4 qualitative and 1 mixed method published between January 2012 and August 2020. A narrative synthesis methodology was employed, whilst validated tools appraised risk of bias and study quality.

Conclusions: A significant positive relationship between playing MMOs and social well-being was concluded, irrespective of one's age and/or their casual or immersed gaming patterns. This finding should be considered in the light of the limited: (a) game platforms investigated; (b) well-being constructs identified; and (c) research quality (i.e., modest). Nonetheless, conclusions are of relevance for game developers and health professionals, who should be cognizant of the significant MMOs-well-being association(s). Future research should focus on broadening the well-being constructs investigated, whilst enhancing the applied methodologies.
Sounds of Silence in Times of COVID-19: Distress and Loss of Cardiac Coherence in People With Misophonia Caused by Real, Imagined or Evoked Triggering Sounds
Authors: Ferrer-Torres Antonia , Giménez-Llort Lydia
Published: June 2021

The extreme, unprecedented situations in the current COVID-19 pandemic are risk factors for psychosocial stress for the entire population. However, strict confinement had a particular impact on people suffering from misophonia and their families. Misophonia is a condition in which hearing certain sounds triggers intense anger, disgust and even severe autonomic nervous system responses. This prospective cohort study examined the impact of strict confinement (Spain, March 14–June 21, 2020) on a sample of 24 people (16 women and eight men) who had been diagnosed with moderate to extreme misophonia and were regularly attending a medical psychology center in Barcelona. The 3-month period of confinement caused general emotional maladjustment, distress, and a transitory crisis. Long-term biomonitoring of their heart variability rate (HRV) enabled to identify a significant increase in physiological arousal after the confinement period, which had already been recorded in a loss of cardiac coherence under basal rest/relaxation conditions. Certain auditory stimuli triggered adverse responses, lowered HRV scores, and an increased stress level and heart rate. Loss of cardiac coherence in their responses to these auditory stimuli (triggering mouth, nose and other sounds), as well as to non-triggering mouth, nose and other sounds was increased when compared to two assessments performed during the previous year. Despite the limited sample size, sex differences were observed in the incidence. Loss of cardiac coherence worsened with the severity of the misophonia. Most importantly, imagined or evoked triggering sounds, as well as real ones, were enough to cause the aversive responses, as displayed by the increased loss of cardiac coherence with respect to the at-rest basal level. A semi-structured interview revealed the exceptional nature of the situations, increased hyper-sensorial sensitivity, fear of being infected with or dying from COVID-19, the patients' coping strategies, and the difficulties and constraints they faced. Finally, the article gives recommendations for better management of misophonia. Improved knowledge of this disorder would help address the current lack of health and social care, hopefully preventing this shortfall's impact on social and affective relationships, which are particulary important for well-being now and in the coming periods of physical distancing measures.
Regulatory Measures' Effect on Gambling Participation: Experiences From Norway
Authors: Engebø Jonny , Torsheim Torbjørn , Pallesen Ståle
Published: June 2021

The purpose of gambling regulation can be to ensure revenue for the public, to prevent crime and gambling problems. One regulatory measure involves restriction of what games can be offered in a market. In this study, the effects of two regulatory market changes are investigated: First, a restriction of availability when slot machines were banned from the Norwegian market in 2007, and second the introduction of regulated online interactive games to the same market in 2014. Data collected from the general population in the period from 2005 through 2018, comprising 2,000 respondents every year, are used to investigate how participation in gambling changed over time. The respondents were asked if they took part in various games or lotteries. Logistic regression analyses were used to predict the proportion participating in five groups of games and if changes in participation coincided with major market changes. The first change was associated with a reduction in gambling on slot machines as well as a reduction in gambling participation overall. Following the slot machine ban, results show an increase in women participating in games offered in land-based bingo premises. A general increase in gambling on foreign websites was also seen, albeit much smaller than the reduction in slot machine gambling. The increases can partly be explained as substitution of one type of gambling with another. New regulated online interactive games were introduced in 2014. Despite the relatively large growth of such games internationally, Norway included, increased online gambling in general and an increased marketing of foreign gambling websites, the participation on foreign websites seemed stable. However, the overall participation in online interactive games increased. The introduction of the regulated alternative seems to have had a channelizing effect. Overall, the changes in gambling participation coinciding with two major regulatory changes can be explained by transformations of physical and social availability, and in terms of mechanisms outlined by the model of total consumption.
Virtual Reality in Fibromyalgia: Does Altering Visual Feedback Impact on Pain and Movement During Reaching?
Authors: Dagenais Marion , Brun Clémentine , Ohayon Alice , Mercier Catherine
Published: June 2021

People with fibromyalgia (FM) have movement-related fear impacting on daily activities. While virtual reality has been used as a distractor to promote exercise, it can be used to manipulate visual feedback (VF) about movement, potentially influencing pain and movement. Objectives: A. To determine whether altered VF modulates pain during movement; B. To compare adaptation to an altered VF between FM participants and healthy controls (HC); C. To explore relationships between adaptation, limb position sense, kinesiophobia and pain. 20 FM participants and 20 HC performed a reaching task during two sessions in a KINARM exoskeleton including a virtual reality interface allowing to replace their arm with a virtual arm. In one session, VF was altered to show GREATER movements while in the other it showed SMALLER movements (randomized order). Pain was assessed periodically using a numerical rating scale. Movement amplitude was assessed during exposure to altered VF (adaptation) and pre-/post-exposure (without VF; after-effects). Limb position sense was assessed with a KINARM task, and kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK-11). Pain intensity increased slightly with movement repetitions (p < 0.001), but did not differ between the VF conditions (GREATER vs. SMALLER). Both groups exhibited visuomotor adaptation, as shown by VF-dependent changes in movement amplitude and speed during exposure to altered VF, and by the presence of VF-dependent after-effects (p < 0.001 for all variables). However, no differences were observed across groups for any of these variables, despite the fact that FM had significantly more difficulty to correctly detect VF conditions than HC (p = 0.046). No clear limb position sense deficits were observed in FM participants, and no significant relationships were found between TSK-11 scores and changes in pain intensity during exposure to altered VF. Altering VF did not influence pain during a reaching task in the FM group. Surprisingly, both groups adapted similarly to altered VF. Visuomotor adaptation is therefore preserved in FM, despite impairments in sensory perception and the poor ability to detect VF alterations in the present study. Further research is warranted to clarify the relationship between sensory perceptions and motor control in FM.
Insight Into the Role of PGPR in Sustainable Agriculture and Environment
Authors: Mohanty Pratikhya , Singh Puneet Kumar , Chakraborty Debosmita , Mishra Snehasish , Pattnaik Ritesh
Published: June 2021

A multitude of roles is played by microbes in food and agriculture that include nutrient cycling and management, organic matter decomposition and fermentation. Plant growth promoting rhizobacteria (PGPR), representing microbial groups and with ability of colonizing plant roots, influence plant growth through various indirect and direct modes in order to promote its growth and/or protect it from diseases or damage due to insect attack. Thus, PGPR research has received renewed interest worldwide. Increasing number of crop-specific PGPR are being commercialized these days. Approaches like seed-inoculation and soil application either alone or in combination with bacterial culture/product for increased nutrient availability through phosphate solubilisation, potassium solubilisation, sulfur oxidation, nitrogen fixation, iron, and copper chelation are gaining popularity. Arbuscular mycorrhizal fungi (AMF) are root fungal symbiont that improve management of abiotic stress such as phosphorus deficiency. PGPR involves roles like production of indole acetic acid (IAA), ammonia (NH3), hydrogen cyanide (HCN), catalase, etc. PGPR also improve nutrient uptake by altering the level of plant hormone that enhances root surface area by increasing its girth and shape, thereby helping in absorbing more nutrients. PGPR facilitate seed germination, seedling growth and crop yield. An array of microbes includingPseudomonas, Azospirillum, Azotobacter, Klebsiella, Enterobacter, Alcaligenes, Arthrobacter, Burkholderia, Bacillus, andSerratiaenhance plant growth. VariousPseudomonassp. have demonstrated significant increase in germination, seedling growth and yield in different agricultural crops, including wheat. Hence, developing a successful crop-specific PGPR formulation, the candidate should possess characteristics like high rhizosphere competence, extensive competitive saprophytic ability, growth enhancing ability, ease of mass production, broad-spectrum action, safety toward the environment and compatibility with other partnering organisms.
COVID-19 Prediction Applying Supervised Machine Learning Algorithms with Comparative Analysis Using WEKA
Authors: Villavicencio Charlyn Nayve , Macrohon Julio Jerison Escudero , Inbaraj Xavier Alphonse , Jeng Jyh-Horng , Hsieh Jer-Guang
Published: June 2021

Early diagnosis is crucial to prevent the development of a disease that may cause danger to human lives. COVID-19, which is a contagious disease that has mutated into several variants, has become a global pandemic that demands to be diagnosed as soon as possible. With the use of technology, available information concerning COVID-19 increases each day, and extracting useful information from massive data can be done through data mining. In this study, authors utilized several supervised machine learning algorithms in building a model to analyze and predict the presence of COVID-19 using the COVID-19 Symptoms and Presence dataset from Kaggle. J48 Decision Tree, Random Forest, Support Vector Machine, K-Nearest Neighbors and Naïve Bayes algorithms were applied through WEKA machine learning software. Each model’s performance was evaluated using 10-fold cross validation and compared according to major accuracy measures, correctly or incorrectly classified instances, kappa, mean absolute error, and time taken to build the model. The results show that Support Vector Machine using Pearson VII universal kernel outweighs other algorithms by attaining 98.81% accuracy and a mean absolute error of 0.012.
Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes
Authors: Jillson Lauren K. , Yette Gabriel A. , Laajala Teemu D. , Tilley Wayne D. , Costello James C. , Cramer Scott D.
Published: June 2021

While many prostate cancer (PCa) cases remain indolent and treatable, others are aggressive and progress to the metastatic stage where there are limited curative therapies. Androgen receptor (AR) signaling remains an important pathway for proliferative and survival programs in PCa, making disruption of AR signaling a viable therapy option. However, most patients develop resistance to AR-targeted therapies or inherently never respond. The field has turned to PCa genomics to aid in stratifying high risk patients, and to better understand the mechanisms driving aggressive PCa and therapy resistance. While alterations to the AR gene itself occur at later stages, genomic changes at the primary stage can affect the AR axis and impact response to AR-directed therapies. Here, we review common genomic alterations in primary PCa and their influence on AR function and activity. Through a meta-analysis of multiple independent primary PCa databases, we also identified subtypes of significantly co-occurring alterations and examined their combinatorial effects on the AR axis. Further, we discussed the subsequent implications for response to AR-targeted therapies and other treatments. We identified multiple primary PCa genomic subtypes, and given their differing effects on AR activity, patient tumor genetics may be an important stratifying factor for AR therapy resistance.
Vocal Fold Leukoplakia: Which of the Classifications of White Light and Narrow Band Imaging Most Accurately Predicts Laryngeal Cancer Transformation? Proposition for a Diagnostic Algorithm
Authors: Pietruszewska Wioletta , Morawska Joanna , Rosiak Oskar , Leduchowska Agata , Klimza Hanna , Wierzbicka Małgorzata
Published: June 2021

The management of Vocal Fold Leukoplakia (VFL) remains problematic. There is no consensus on the indications or the timing for surgery. The objective was to select the most accurate classification for predicting low- and high-risk VFL in White Light Imaging (WLI) and Narrow Band Imaging (NBI) and to establish a diagnostic algorithm with a timely referral for treatment. A total of 259 VFL patients were included in the study; 186 lesions were classified as low-grade and 110 as high-grade dysplasia. The results of WLI acc. to the two-tier and the three-tier Chen 2019 classifications and NBI classifications: ELS, Ni 2011, and Ni 2019 with different cut-off points were compared with the pathological examination (HP). In WLI, the greatest agreement was obtained between type 3 of the three-tier classification and high-grade dysplasia (accuracy, specificity, and PPV: 80.4%, 92.0%, and 81.5%, respectively). Assessing VFL periphery in NBI, cut-off point 5 (Ni 2011 type V) demonstrated a higher accuracy, specificity, and PPV than 4 (83.1%, 93.6%, 85.5% and 77.4%, 74.9%, and 65.4%, respectively). In NBI, we observed higher accuracy, sensitivity, and PPV (84.1%, 93.0%, 85.2% vs. 80.7%, 81.3% and 71.3%, respectively) for cut-off point 5 (Ni 2019 type V and VI) in comparison to the cut-off point 4 group (type IV, V, and VI) (80.7%, 81.3%, 71.3%, respectively), and a higher kappa value (0.68 vs. 0.58) was obtained. We have shown that both the plaque image and the microvascular pattern on the leukoplakia periphery are critical in the diagnosis of high-risk VFL. The most accurate predictor of VFL malignant transformation in WLI is type 3 according to the Chen 2019 classification, while in NBI type V and VI according to the Ni 2019 classification.
Prediction of Myometrial Invasion in Stage I Endometrial Cancer by MRI: The Influence of Surgical Diagnostic Procedure
Authors: Chen Wei-Chun , Hsu Le-Tien , Huang Yu-Ting , Pan Yu-Bin , Ueng Shir-Hwa , Chou Hung-Hsueh , Chang Ting-Chang
Published: June 2021

Young women with endometrial cancer (EC) can choose fertility-sparing treatment for stage 1A disease without myometrial invasion (MI). The surgical diagnostic procedure (SDP) may affect the accuracy of magnetic resonance imaging (MRI) to assess MI. Here, we evaluated different SDP and compared the MI on MRI results with further pathologic results after hysterectomy. We retrospectively collected data on 263 patients with clinical stage IA EC diagnosed between January 2013 and December 2015. Patients were classified into four groups based on SDP, including diagnostic hysteroscopic biopsy (DHB, group 1), operative hysteroscopic partial resection (OHPR, group 2), operative hysteroscopic complete resection (OHCR, group 3), and cervical dilatation and fractional curettage (D&C, group 4). The sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value of MRI to assess MI were 73.1%, 46.7%, 63.9%, 71.8%, and 48.3%, respectively. Three hysteroscopic procedures (groups 1 to 3) had a trend with a higher odds ratio of discrepancy between MRI and histopathology (p = 0.068), especially in group 2 (odds ratio 2.268, p = 0.032). Here, we found MRI accuracy of MI was better in patients with EC diagnosed with D&C. Three diagnostic procedures using hysteroscopy might interfere with the diagnostic power of MI on MRI.
Radiobiological Evaluation of Combined Gamma Knife Radiosurgery and Hyperthermia for Pediatric Neuro-Oncology
Authors: Ghaderi Aram Morteza , Zanoli Massimiliano , Nordström Håkan , Toma-Dasu Iuliana , Blomgren Klas , Dobšíček Trefná Hana
Published: June 2021

Combining radiotherapy (RT) with hyperthermia (HT) has been proven effective in the treatment of a wide range of tumours, but the combination of externally delivered, focused heat and stereotactic radiosurgery has never been investigated. We explore the potential of such treatment enhancement via radiobiological modelling, specifically via the linear-quadratic (LQ) model adapted to thermoradiotherapy through modulating the radiosensitivity of temperature-dependent parameters. We extend this well-established model by incorporating oxygenation effects. To illustrate the methodology, we present a clinically relevant application in pediatric oncology, which is novel in two ways. First, it deals with medulloblastoma, the most common malignant brain tumour in children, a type of brain tumour not previously reported in the literature of thermoradiotherapy studies. Second, it makes use of the Gamma Knife for the radiotherapy part, thereby being the first of its kind in this context. Quantitative metrics like the biologically effective dose (BED) and the tumour control probability (TCP) are used to assess the efficacy of the combined plan.
COVID-19 Pandemic: Huge Stress Test for Health System Could Be a Great Opportunity to Update the Workflow in a Modern Surgical Pathology
Authors: Belfiore Antonino , Centonze Giovanni , Maisonneuve Patrick , Riva Carla , Morelli Daniele , Mangogna Alessandro , Sabella Giovanna , Pruneri Giancarlo , Milione Massimo
Published: June 2021

Background: On December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. This disease, characterized by the rapid human-to-human transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly in more than 200 countries. Northern Italy’s regions have been hit hard in terms of deaths. Here, we report the experience of the Pathology Department of the Fondazione IRCCS Istituto Nazionale Tumori (INT) in Milan, the first Italian public cancer center, in the period of the lockdown that took place in Lombardy from March to May 2020. Method: The variation in terms of exams was calculated in two different timeframes: December 2019–February 2020 (pre-COVID-19) and March–May 2020 (COVID-19). During these periods, Turn-Around-Time (TAT) metrics released by the Lombardy Region were calculated to assess if changes applied to guarantee the safeguarding of workers affected the average diagnosis time. Results: In the COVID-19 period, there was a decrease for all the performed exams. The most considerable decrease was observed for PAP tests (−81.6%), followed by biopsies (−48.8%), second opinions (−41.7%), and surgical (−31.5%), molecular (−29.4%) and cytological (−18.1%) tests. Measures applied within the Pathology Department, such as digital pathology, remote working, rotations and changes in operating procedures, improved the diagnostic performance as required by the guidelines of the Lombardy Region in terms of TAT. At the same time, the measures applied for the safeguarding of the personnel turned out to be feasible and did not affect the overall performance of the Pathology Department. Conclusions: The sharp slowdown in cancer screening during the first wave of COVID-19 could seriously endanger cancer prevention in the near future.
Prognostic Significance of CXCR4 in Colorectal Cancer: An Updated Meta-Analysis and Critical Appraisal
Authors: Ottaiano Alessandro , Santorsola Mariachiara , Del Prete Paola , Perri Francesco , Scala Stefania , Caraglia Michele , Nasti Guglielmo
Published: June 2021

Background: This study was conducted to provide an updated estimate of the prognostic power of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC), and analyze modalities of evaluating and reporting its expression. Methods: A systematic review with meta-analysis was performed and described according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were identified through PubMed and Google Scholar. The pooled hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS) with 95% confidence interval (CI) were estimated with the random-effect model. Results: Sixteen studies were selected covering a period from 2005 to 2020. An immunohistochemical evaluation of CXCR4 was performed in all studies. Only in three studies assessment of mRNA through RT–PCR was correlated with prognosis; in the remaining studies, the authors identified prognostic categories based on immunohistochemical expression. In pooled analyses, significant associations were found between positive or high or strong expression of CXCR4 and T stage ≥3 (P = 0.0001), and positive or high or strong expression of CXCR4 and left side primary tumor localization (P = 0.0186). The pooled HR for OS was 2.09 (95% CI: 1.30–2.88) in favor of high CXCR4 expression; for PFS, it was 1.42 (95% CI: 1.13–1.71) in favor of high CXCR4 expression. Conclusion: High CXCR4 expression is clearly associated with increased risk of death and progression in CRC. However, strong methodologic heterogeneity in CXCR4 assessment hinders direct translation into clinical practice; thus, a consensus to streamline detection and scoring of CXCR4 expression in CRC is indicated.
Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment
Authors: Lachowski Dariusz , Matellan Carlos , Cortes Ernesto , Saiani Alberto , Miller Aline F. , del Río Hernández Armando E.
Published: June 2021

The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).
The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy
Authors: Matarrese Paola , Mattia Gianfranco , Pagano Maria Teresa , Pontecorvi Giada , Ortona Elena , Malorni Walter , Carè Alessandra
Published: June 2021

The interplay between cancer cells and the tumor microenvironment (TME) has a fundamental role in tumor progression and response to therapy. The plethora of components constituting the TME, such as stroma, fibroblasts, endothelial and immune cells, as well as macromolecules, e.g., hormones and cytokines, and epigenetic factors, such as microRNAs, can modulate the survival or death of cancer cells. Actually, the TME can stimulate the genetically regulated programs that the cell puts in place under stress: apoptosis or, of interest here, autophagy. However, the implication of autophagy in tumor growth appears still undefined. Autophagy mainly represents a cyto-protective mechanism that allows cell survival but, in certain circumstances, also leads to the blocking of cell cycle progression, possibly leading to cell death. Since significant sex/gender differences in the incidence, progression and response to cancer therapy have been widely described in the literature, in this review, we analyzed the roles played by key components of the TME, e.g., estrogen and microRNAs, on autophagy regulation from a sex/gender-based perspective. We focused our attention on four paradigmatic and different forms of cancers—colon cancer, melanoma, lymphoma, and lung cancer—concluding that sex-specific differences may exert a significant impact on TME/cancer interaction and, thus, tumor growth.
Selective Antitumor Activity of Datelliptium toward Medullary Thyroid Carcinoma by Downregulating RET Transcriptional Activity
Authors: Alqahtani Tariq , Alswied Abdullah , Sun Daekyu
Published: June 2021

Medullary thyroid carcinoma (MTC) is a rare aggressive form of thyroid cancer with high rates of metastasis. Sporadic and hereditary MTC are strongly driven by somatic and germline mutations, respectively, in the transmembrane REarranged during Transfection (RET) proto-oncogene, which encodes a receptor tyrosine kinase. Our previous study identified datelliptium as a novel RET transcription inhibitor, which stabilizes the RET G-quadruplex structures and suppresses RET oncogene transcription. The present study aimed to elucidate the effect of datelliptium on the suppression of epithelial-to-mesenchymal transition (EMT) and metastasis-related behaviors of MTC cells, including cell migration and formation of cancer stem cells (CSCs). Our results demonstrated that datelliptium downregulated the expression of the mesenchymal markers, including N-cadherin, vimentin, slug, snail, and claudin-1. Compared to untreated cells, datelliptium significantly decreased the migration of TT cells in a dose-dependent manner in a wound healing assay. Additionally, datelliptium significantly reduced the size of preformed spheroids from TT cells over the time course. Finally, datelliptium inhibited approximately 75% of MTC xenograft growth with minimal systemic toxicity. In conclusion, datelliptium exerts its antitumor activity against MTC cells by reducing the EMT program, migratory ability, and self-renewal capacity of TT cells, thus preventing invasive and metastatic behavior of MTC.