bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging
Authors: Jin Wenyi , Liu Zilin , Zhang Yubiao , Che Zhifei , Gao Mingyong
Published: August 2021

Few longitudinal studies have systematically investigated whether or how individual musculoskeletal conditions (IMCs) convey risks for negative psychological health outcomes, and approaches to assess such risk in the older population are lacking. In this Irish nationally representative longitudinal prospective study of 6,715 individuals aged 50 and above, machine learning algorithms and various models, including mediation models, were employed to elaborate the underlying mechanisms of IMCs leading to depression and to develop an IMC-induced negative psychological risk (IMCPR) classification approach. Resultantly, arthritis [odds ratio (95% confidence interval): 2.233 (1.700–2.927)], osteoporosis [1.681 (1.133–2.421)], and musculoskeletal chronic pain [MCP, 2.404 (1.838–3.151)] were found to increase the risk of depression after 2 years, while fracture and joint replacement did not. Interestingly, mediation models further demonstrated that arthritisper sedid not increase the risk of depression; such risk was augmented only when arthritis-induced restrictions of activities (ARA) existed [proportion of mediation: 316.3% (ARA of usual), 213.3% (ARA of social and leisure), and 251.3% (ARA of sleep)]. The random forest algorithm attested that osteoarthritis, not rheumatoid arthritis, contributed the most to depressive symptoms. Moreover, bone mineral density was negatively associated with depressive symptoms. Systemic pain contributed the most to the increased risk of depression, followed by back, knee, hip, and foot pain (mean Gini-Index: 3.778, 2.442, 1.980, 1.438, and 0.879, respectively). Based on the aforementioned findings, the IMCPR classification approach was developed using an interpretable machine learning model, which stratifies participants into three grades. Among the IMCPR grades, patients with a grade of “severe” had higher odds of depression than those with a “mild” [odds ratio (95% confidence interval): 4.055 (2.907–5.498)] or “moderate” [3.584 (2.101–5.883)] grade. Females with a “severe” grade had higher odds of depression by 334.0% relative to those with a “mild” grade, while males had a relative risk of 258.4%. In conclusion, the present data provide systematic insights into the IMC-induced depression risk and updated the related clinical knowledge. Furthermore, the IMCPR classification approach could be used as an effective tool to evaluate this risk.
Modulating the Activity of the VMPFC With tDCS Alters the Social Framing Effect
Authors: Chen Yuyou , Lu Xinbo , Yu Ping , Zeng Lulu , Ye Hang , Shi Qing , Guo Wenmin
Published: August 2021

Numerous experimental studies have replicated the social framing effect-the observation that people’s decisions related to economic benefits and feelings depend on the method of presentation. Previous neuroimaging studies have shown that the ventromedial prefrontal cortex (VMPFC) plays a part in the influence of framing and how individuals think about the feelings of others. Based on this, we used transcranial direct current stimulation (tDCS) to modulate neuronal activity in the VMPFC to determine the likelihood of a direct association between VMPFC activity and the social framing effect. Subsequently, in three stimulation treatments, we assessed the presence of the social framing effect, as demonstrated by a disparity between harm degree and help degree. The findings revealed a social framing effect in the participants in the control group and the sham treatment but no social framing effect in the participants in the anodal or cathodal treatments. Furthermore, sex differences were observed in the sham treatment’s social framing effect, whereas no sex differences were observed in the anodal or cathodal treatments. The participants tended to harm the victim after receiving anodal or cathodal tDCS over the VMPFC and did not change their helping behaviour in any stimulations. Consequently, a clear causal link between the behaviour of the VMPFC and the social framing effect was found in the present research.
Cannabidiol Exposure During the Mouse Adolescent Period Is Without Harmful Behavioral Effects on Locomotor Activity, Anxiety, and Spatial Memory
Authors: Kaplan J. S. , Wagner J. K. , Reid K. , McGuinness F. , Arvila S. , Brooks M. , Stevenson H. , Jones J. , Risch B. , McGillis T. , Budinich R. , Gambell E. , Predovich B.
Published: August 2021

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid whose purported therapeutic benefits and impression of a high safety profile has promoted its increasing popularity. CBD’s popularity is also increasing among children and adolescents who are being administered CBD, off label, for the treatment of numerous symptoms associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, and depression. The relative recency of its use in the adolescent population has precluded investigation of its impact on the developing brain and the potential consequences that may present in adulthood. Therefore, there’s an urgency to identify whether prolonged adolescent CBD exposure has substantive impacts on the developing brain that impact behavioral and cognitive processes in adulthood. Here, we tested the effect of twice-daily intraperitoneal administrations of CBD (20 mg/kg) in male and female C57BL/6J mice during the adolescent period of 25–45 days on weight gain, and assays for locomotor behavior, anxiety, and spatial memory. Prolonged adolescent CBD exposure had no detrimental effects on locomotor activity in the open field, anxiety behavior on the elevated plus maze, or spatial memory in the Barnes Maze compared to vehicle-treated mice. Interestingly, CBD-treated mice had a faster rate of learning in the Barnes Maze. However, CBD-treated females had reduced weight gain during the exposure period. We conclude that prolonged adolescent CBD exposure in mice does not have substantive negative impacts on a range of behaviors in adulthood, may improve the rate of learning under certain conditions, and impacts weight gain in a sex-specific manner.
Literacy Level and Executive Control in Healthy Older Peruvian Adults
Authors: Soto-Añari Marcio , López Norman , Rivera-Fernández Claudia , Belón-Hercilla Verónica , Fernández-Guinea Sara
Published: August 2021

Introduction: Early-life educational experiences are associated with cognitive performance in aging. Early literacy seems to improve executive control mechanisms, however, it is not clear whether early education would still be an advantage in countries like Peru, where access to and quality of education is highly variable.

Aim: Our objective was to analyze the association of literacy level with executive control factors.

Method: We evaluated 93 healthy older adults with a clinical protocol that included the Mini-Mental State Examination, the Geriatric Depression Scale and Global Dementia Staging. We also used a neuropsychological executive function battery which included the Trail-Making Test parts A and B, the Stroop Test, phonological and semantic verbal fluency tasks, Forward and Backward Digits, Numbers and Letters of the Wechsler Scale, and the Go/No-Go task. We used a principal component analysis for the dimensional reduction of the variables. To measure the level of literacy we used the word accentuation test (WAT).

Results: We observed statistically significant correlations between the principal components (PCs) of working memory, cognitive flexibility and inhibitory control with the WAT scores. Furthermore, we observed that processing speed and WAT predict the scores on PCs factors better than years of education and age.

Conclusions: Literacy level correlates more closely with better cognitive performance than years of education and thus, might improve executive control factors that could compensate and protect against brain changes in cognitive decline and dementia.
Intestinal Permeability and Circulating CD161+CCR6+CD8+T Cells in Patients With Relapsing–Remitting Multiple Sclerosis Treated With Dimethylfumarate
Authors: Buscarinu Maria C. , Gargano Francesca , Lionetto Luana , Capi Matilde , Morena Emanuele , Fornasiero Arianna , Reniè Roberta , Landi Anna C. , Pellicciari Giulia , Romano Carmela , Mechelli Rosella , Romano Silvia , Borsellino Giovanna , Battistini Luca , Simmaco Maurizio , Fagnani Corrado , Salvetti Marco , Ristori Giovanni
Published: August 2021

Background: The changes of the gut-brain axis have been recently recognized as important components in multiple sclerosis (MS) pathogenesis.

Objectives: To evaluate the effects of DMF on intestinal barrier permeability and mucosal immune responses.

Methods: We investigated intestinal permeability (IP) and circulating CD161+CCR6+CD8+T cells in 25 patients with MS, who met eligibility criteria for dimethyl-fumarate (DMF) treatment. These data, together with clinical/MRI parameters, were studied at three time-points: baseline (before therapy), after one (T1) and 9 months (T2) of treatment.

Results: At baseline 16 patients (64%) showed altered IP, while 14 cases (56%) showed active MRI. During DMF therapy we found the expected decrease of disease activity at MRI compared to T0 (6/25 at T1, p = 0.035 and 3/25 at T2, p < 0.00), and a reduction in the percentage of CD161+CCR6+CD8+ T cells (16/23 at T2; p < 0.001). The effects of DMF on gut barrier alterations was variable, without a clear longitudinal pattern, while we found significant relationships between IP changes and drop of MRI activity (p = 0.04) and circulating CD161+CCr6+CD8+ T cells (p = 0.023).

Conclusions: The gut barrier is frequently altered in MS, and the CD161+ CCR6+CD8+ T cell-subset shows dynamics which correlate with disease course and therapy.
Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial
Authors: Kirzinger Bernadette , Stroux Andrea , Rackoll Torsten , Endres Matthias , Flöel Agnes , Ebinger Martin , Nave Alexander Heinrich
Published: August 2021

Background: Inflammatory markers, such as C-reactive Protein (CRP), Interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha and fibrinogen, are upregulated following acute stroke. Studies have shown associations of these biomarkers with increased mortality, recurrent vascular risk, and poor functional outcome. It is suggested that physical fitness training may play a role in decreasing long-term inflammatory activity and supports tissue recovery.

Aim: We investigated the dynamics of selected inflammatory markers in the subacute phase following stroke and determined if fluctuations are associated with functional recovery up to 6 months. Further, we examined whether exposure to aerobic physical fitness training in the subacute phase influenced serum inflammatory markers over time.

Methods: This is an exploratory analysis of patients enrolled in the multicenter randomized-controlled PHYS-STROKE trial. Patients within 45 days of stroke onset were randomized to receive either four weeks of aerobic physical fitness training or relaxation sessions. Generalized estimating equation models were used to investigate the dynamics of inflammatory markers and the associations of exposure to fitness training with serum inflammatory markers over time. Multiple logistic regression models were used to explore associations between inflammatory marker levels at baseline and three months after stroke and outcome at 3- or 6-months.

Results: Irrespective of the intervention group, high sensitive CRP (hs-CRP), IL-6, and fibrinogen (but not TNF-alpha) were significantly lower at follow-up visits when compared to baseline (p all ≤ 0.01). In our cohort, exposure to aerobic physical fitness training did not influence levels of inflammatory markers over time. In multivariate logistic regression analyses, increased baseline IL-6 and fibrinogen levels were inversely associated with worse outcome at 3 and 6 months. Increased levels of hs-CRP at 3 months after stroke were associated with impaired outcome at 6 months. We found no independent associations of TNF-alpha levels with investigated outcome parameters.

Conclusion: Serum markers of inflammation were elevated after stroke and decreased within 6 months. In our cohort, exposure to aerobic physical fitness training did not modify the dynamics of inflammatory markers over time. Elevated IL-6 and fibrinogen levels in early subacute stroke were associated with worse outcome up to 6-months after stroke.

Clinical Trial Registration:ClinicalTrials.gov, NCT01953549.
Influence of FMO3 and CYP3A4 Polymorphisms on the Pharmacokinetics of Teneligliptin in Humans
Authors: Park Jin-Woo , Kim Kyoung-Ah , Kim Jong-Min , Park In-Hwan , Park Ji-Young
Published: August 2021

Teneligliptin, a dipeptidyl peptidase-4 inhibitor, is used to treat type 2 diabetes mellitus. FMO3 and CYP3A4 metabolize teneligliptin into teneligliptin sulfoxide. This study examined the effects ofFMO3(rs909530, rs1800822, rs2266780, and rs2266782) andCYP3A4(rs2242480) polymorphisms on teneligliptin pharmacokinetics at a steady state among 23 healthy participants administered 20 mg teneligliptin daily for 6 days. Subjects withFMO3rs909530, rs2266780, and rs2266782 polymorphisms exhibited a significant gene dosage-dependent increase in maximum steady-state plasma drug concentration (Cmax,ss) and area under the drug concentration vs time curve (AUC) (p<0.05). However, the Cmaxvalues significantly decreased but the AUC values did not significantly vary in subjects withCYP3A4polymorphism (rs2242480). These results suggest thatFMO3andCYP3A4polymorphisms affect teneligliptin pharmacokinetics in humans. The findings of this study provide a scientific basis for the inter-individual variation in teneligliptin disposition.
Applied Improvisation Enhances the Effects of Behavioral Activation on Symptoms of Depression and PTSD in High School Students Affected by the Great East Japan Earthquake
Authors: Sugiyama Chikaze , Koseki Shunsuke , Niikawa Yoko , Ito Daisuke , Takahashi Fumito , Ishikawa Rie
Published: August 2021

Background

The education system can serve as a community-based resource to support the provision of long-term follow-up care after large-scale disasters. While school-based interventions conducted after a disaster have been confirmed to reduce symptoms of depression and posttraumatic stress disorder (PTSD), adolescents often exhibit low treatment motivation. Traditional methods used to encourage treatment motivation include fun activities, such as applied improv (AIM). This study evaluated the intervention effects and improved motivation of an intervention program combining AIM with the behavioral activation approach (BAA).

Methods

Participants were 253 tenth graders, who were in fifth grade at the time the Great East Japan Earthquake of 2011, and 239 students were included in the analyses. Participants were divided into two groups: the BAA and AIM + BAA groups. Students in each group participated in one class-wide intervention session, which lasted 60 min. Depression, PTSD symptoms, behavioral activation, avoidance, and resilience were evaluated using psychological scales. A participant’s evaluations of the intervention were confirmed using the impression sheet consisting of six items that measure comprehension, difficulty, efficacy, generalization, confirmation of a specific situation, and motivation.

Results

A two-way analysis of variance (ANOVA) conducted using data from the psychological scale did not reveal a significant effect from the intervention program. However, the Mann-Whitney U-test, which used data from the impression sheet, showed a significant effect on comprehension (p = 0.001), generalization (p = 0.023), and motivation (p = 0.025).

Conclusion

This study did not confirm the effectiveness of the BAA in reducing symptoms of depression and PTSD in adolescents. Regarding treatment motivation, the AIM + BAA group reported higher motivation than the BAA group. Thus, one session of AIM may contribute to improved treatment motivation in adolescents. AIM creates a safe environment and encourages engagement and participation in interventions. Treatment motivation is an important issue in adolescent therapy, and AIM may help solve this problem.
Opposites in Reasoning Processes: Do We Use Them More Than We Think, but Less Than We Could?
Authors: Branchini Erika , Capitani Elena , Burro Roberto , Savardi Ugo , Bianchi Ivana
Published: August 2021

Our aim in this paper is to contribute toward acknowledging the general role of opposites as an organizing principle in the human mind. We support this claim in relation to human reasoning by collecting evidence from various studies which shows that “thinking in opposites” is not only involved in formal logical thinking, but can also be applied in both deductive and inductive reasoning, as well as in problem solving. We also describe the results of a series of studies which, although they have been developed within a number of different theoretical frameworks based on various methodologies, all demonstrate that giving hints or training reasoners to think in terms of opposites improves their performance in tasks in which spontaneous thinking may lead to classic biases and impasses. Since we all possess an intuitive idea of what opposites are, prompting people to “think in opposites” is something which is undoubtedly within everyone's reach and in the final section, we discuss the potential of this strategy and suggest possible future research directions of systematic testing the benefits that might arise from the use of this technique in contexts beyond those tested thus far. Ascertaining the conditions in which reasoners might benefit will also help in terms of clarifying the underlying mechanisms from the point of view, for instance, of analytical, conscious processing vs. automatic, unconscious processing.
Future Expectations and Internet Addiction Among Adolescents: The Roles of Intolerance of Uncertainty and Perceived Social Support
Authors: Du Gang , Lyu Houchao
Published: August 2021

Internet addiction is a common and challenging problem among adolescents. Previous studies have shown that future time orientation is an important protective factor against internet addiction. In this study, the mediating effect of intolerance of uncertainty and the moderating role of perceived social support were examined on the association between future expectations, regarded as the “prospective life course” perspective of future time orientation, and internet addiction among adolescents. A total of 1,006 Chinese adolescents (54% male and 46% female; Mage = 15.42 years, SD = 1.32) recruited from middle schools completed questionnaires. Results indicated that future expectations were significantly negatively associated with internet addiction, and the link was mediated by intolerance to uncertainty in adolescents. Further, the latent moderated structural equation showed that perceived social support moderated the association between future expectations and intolerance of uncertainty. The association was significant only for adolescents with a higher level of perceived social support. The findings of this study provide specific guidelines for how to prevent adolescent internet addiction.
Underwater Crawling Robot With Hydraulic Soft Actuators
Authors: Tan Qinlin , Chen Yishan , Liu Jianhui , Zou Kehan , Yi Juan , Liu Sicong , Wang Zheng
Published: August 2021

Benthic operation plays a vital role in underwater applications, where crawling robots have advantages compared with turbine-based underwater vehicles, in locomotion accuracy, actuation efficiency, current resistance, and in carrying more payloads. On the other hand, soft robots are quickly trending in underwater robotic design, with their naturally sealed body structure and intrinsic compliance both desirable for the highly unstructured and corrosive underwater environment. However, the limitations resulting directly from the inherent compliance, in structural rigidity, actuation precision, and limited force exertion capability, have also restricted soft robots in underwater applications. To date soft robots are adopted mainly as grippers and manipulators for atraumatic sampling, rather than as locomotion platforms. In this work, we present a soft-robotic approach to designing underwater crawling robots, with three main innovations: 1) using rigid structural components to strategically reinforce the otherwise omni-directionally flexible soft actuators, drastically increasing their loading capability and actuation precision; 2) proposing a rigid–soft hybrid multi-joint leg design, with quasi-linear motion range and force exertion, while maintaining excellent passive impact compliance by exploiting the inherent flexibility of soft actuators; 3) developing a novel valve-free hydraulic actuation system with peristaltic pumps, achieving a compact, lightweight, and untethered underwater crawling robot prototype with a 5:1 payload-to-weight ratio and multi-gait capability. The prototype was tested for design verification and showcasing the advantages of the proposed hybrid mechanism and actuation approach.
Johne's Disease in Dairy Cattle: An Immunogenetic Perspective
Authors: Mallikarjunappa Sanjay , Brito Luiz F. , Pant Sameer D. , Schenkel Flavio S. , Meade Kieran G. , Karrow Niel A.
Published: August 2021

Johne's disease (JD), also known as paratuberculosis, is a severe production-limiting disease with significant economic and welfare implications for the global cattle industry. Caused by infection withMycobacterium aviumsubspeciesparatuberculosis(MAP), JD manifests as chronic enteritis in infected cattle. In addition to the economic losses and animal welfare issues associated with JD, MAP has attracted public health concerns with potential association with Crohn's disease, a human inflammatory bowel disease. The lack of effective treatment options, such as a vaccine, has hampered JD control resulting in its increasing global prevalence. The disease was first reported in 1895, but in recognition of its growing economic impact, extensive recent research facilitated by a revolution in technological approaches has led to significantly enhanced understanding of the immunological, genetic, and pathogen factors influencing disease pathogenesis. This knowledge has been derived from a variety of diverse models to elucidate host-pathogen interactions includingin vivoandin vitroexperimental infection models, studies measuring immune parameters in naturally-infected animals, and by studies conducted at the population level to enable the estimation of genetic parameters, and the identification of genetic markers and quantitative trait loci (QTL) putatively associated with susceptibility or resistance to JD. The main objectives of this review are to summarize these recent developments from an immunogenetics perspective and attempt to extract the principal and common findings emerging from this wealth of recent information. Based on these analyses, and in light of emerging technologies such as gene-editing, we conclude by discussing potential future avenues for effectively mitigating JD in cattle.
Towards Essential Hand Tremor Suppression via Pneumatic Artificial Muscles
Authors: Skaramagkas Vasileios , Andrikopoulos George , Manesis Stamatis
Published: August 2021

Essential tremor (ET) is one of the most common movement disorders and can occur unexpectedly and develop indefinitely to any population unit. According to the recorded statistics of people suffering from ET, the disorder affects 5% of people worldwide, thus creating an ever-increasing need to investigate ways for its suppression and treatment. In this article, we investigate the capability of Pneumatic Artificial Muscles (PAMs) to reduce or even suppress ET leading to the relief of the sufferers. In our work, we designed and constructed two iterations of a glovelike setup and attempted to explore the possibility of suppressing ET on different parts of the hand by exerting force on the index finger and metacarpal region. For both glove iterations, we established an experimental protocol based on the adjustment of a force controller. Finally, we evaluated exhaustively the performance of our setup under multiple motion scenarios with the participation of an ET-diagnosed volunteer.
Spatio-Temporal Analysis of Drought Variability in Myanmar Based on the Standardized Precipitation Evapotranspiration Index (SPEI) and Its Impact on Crop Production
Authors: Sein Zin Mie Mie , Zhi Xiefei , Ogou Faustin Katchele , Nooni Isaac Kwesi , Lim Kam Sian Kenny T. C. , Gnitou Gnim Tchalim
Published: August 2021

Drought research is an important aspect of drought disaster mitigation and adaptation. For this purpose, we used the Standardized Precipitation Evapotranspiration Index (SPEI) to investigate the spatial-temporal pattern of drought and its impact on crop production. Using monthly precipitation (Precip) and temperature (Temp) data from 1986–2015 for 39 weather stations, the drought index was obtained for the time scale of 3, 6, and 12 months. The Mann–Kendall test was used to determine trends and rates of change. Precip and Temp anomalies were investigated using the regression analysis and compared with the drought index. The link between drought with large-scale atmospheric circulation anomalies using the Pearson correlation coefficient (R) was explored. Results showed a non-uniform spatial pattern of dryness and wetness which varied across Myanmar agro-ecological zones and under different time scales. Generally, results showed an increasing trend for the SPEI in the three-time scales, signifying a high tendency of decreased drought from 1986–2015. The fluctuations in dryness/wetness might linked to reduction crop production between 1986–1999 and 2005, 2008, 2010, 2013 cropping years. Results show relationship between main crops production and climate (teleconnection) factors. However, the low correlation values (i.e., <0.49) indicate the extent of the relationship within the natural variability. However, readers are urged to interpret this result cautiously as reductions in crop production may also be affected by other factors. We have demonstrated droughts evolution and trends using weather stations, thus providing useful information to aid policymakers in developing spatially relevant climate change adaptation and mitigation management plans for Myanmar.
Multi-Trait Selection Indices for Identifying New Cassava Varieties Adapted to the Caribbean Region of Colombia
Authors: León Rommel , Rosero Amparo , García Jorge-Luis , Morelo Julio , Orozco Alfonso , Silva Gabriel , De la Ossa Víctor , Correa Ender , Cordero Carina , Villalba Leonardo , Belalcazar John , Ceballos Hernán
Published: August 2021

In Colombia, the highest cassava production comes from the semi-arid region of the Atlantic Coast with relatively low yield for fresh consumption (≤11 t/ha). Development of improved varieties is based on a plant ideotype which integrates a group of desirable traits independently measured in the field. However, selecting high performance genotypes for several traits simultaneously is a complex process. Sixteen genotypes were evaluated under four environmental conditions (localities) of the Colombian Caribbean region (Cereté, Carmen de Bolivar, Agustín Codazzi, and Sevilla), and two production cycles (2016/2017–2017/2018) in order to assess phenotypic expression of selected traits, their stability, and utility in genotype selection. Selection of promising genotypes should consider both their superiority and stability. Genotypes SM3106-14, GM1692-56, CM9456-12, and GM214-62 were selected based on their agronomic performance. In addition, frequency analysis of sensorial data showed that genotypes CM9456-12, SM1127-8, SM3553-27, and SM3562-32 were preferred by panelists who assessed, color, flavor, texture, and root shape. Determination of superiority through across-environments, multi-trait selection index allows identifying genotypes with superior performance. However, selection was improved when local multi-trait selection indices were included—phenotypic stability determination (through Lin and Binns index and AMMI model) supported an adequate selection of superior and stable cassava genotypes. The inclusion of palatability response and quality features determination in cassava genotypes can be recommended to identify genotypes with higher adoption rates by farmers and consumers.
Detection of Oxytetracycline in Citrus Phloem and Xylem Saps Using Europium-Based Method
Authors: Hijaz Faraj , Nehela Yasser , Batuman Ozgur , Killiny Nabil
Published: August 2021

Oxytetracycline (OTC) has been used for the control of several plant diseases and was recently approved for the control of Huanglongbing, the citrus greening disease. Huanglongbing is caused by the phloem limited ‘Candidatus Liberibacter asiaticus’. Determination of OTC in the xylem and phloem of citrus plants is of great interest as they are the main routes of translocation in citrus. In addition, the determination of the level of OTC in the phloem sap is necessary for the control of the ‘Ca. L. asiaticus’ pathogen, which resides in the phloem. Herein, we demonstrated that the level of OTC in the citrus phloem and xylem saps obtained using the centrifugation method can be successfully measured using the europium (Eu) method directly or with cleanup by solid-phase extraction (SPE). Recovery of OTC from spiked sap samples purified by solid-phase extraction (SPE) was higher than 90%, while recovery from saps without SPE cleanup were nearly 100%. The ‘Ca. L. asiaticus’-infected leaf and phloem sap samples showed higher inhibition of the fluorescence intensity of the OTC standard compared to non-infected control leaf and phloem samples. In agreement with this finding, the levels of phenols and flavonoids in ‘Ca. L. asiaticus’-infected leaves were higher than those controls and were shown to interfere with the Eu method. Therefore, the SPE cleanup step only improved OTC recovery from leaf samples containing the interfering compounds. The Eu method was then used to determine OTC levels in the phloem and xylem sap of OTC-treated plants, and the results were similar whether measured directly or after SPE. Visualization under ultraviolet light (400 nm) showed the presence of OTC in citrus xylem and phloem saps with and without the use of SPE.
Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Pseudomonas aeruginosa Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis
Authors: Dughbaj Mansour A. , Jayne Jordanna G. , Park A Young J. , Bensman Timothy J. , Algorri Marquerita , Ouellette Andre J. , Selsted Michael E. , Beringer Paul M.
Published: August 2021

Vicious cycles of chronic airway obstruction, lung infections with Pseudomonas aeruginosa, and neutrophil-dominated inflammation contribute to morbidity and mortality in cystic fibrosis (CF) patients. Rhesus theta defensin-1 (RTD-1) is an antimicrobial macrocyclic peptide with immunomodulatory properties. Our objective was to investigate the anti-inflammatory effect of RTD-1 in a murine model of chronic P. aeruginosa lung infection. Mice received nebulized RTD-1 daily for 6 days. Bacterial burden, leukocyte counts, and cytokine concentrations were evaluated. Microarray analysis was performed on bronchoalveolar lavage fluid (BALF) cells and lung tissue homogenates. In vitro effects of RTD-1 in THP-1 cells were assessed using quantitative reverse transcription PCR, enzyme-linked immunosorbent assays, immunoblots, confocal microscopy, enzymatic activity assays, and NF-κB-reporter assays. RTD-1 significantly reduced lung white blood cell counts on days 3 (−54.95%; p = 0.0003) and 7 (−31.71%; p = 0.0097). Microarray analysis of lung tissue homogenates and BALF cells revealed that RTD-1 significantly reduced proinflammatory gene expression, particularly inflammasome-related genes (nod-like receptor protein 3, Mediterranean fever gene, interleukin (IL)-1α, and IL-1β) relative to the control. In vitro studies demonstrated NF–κB activation was reduced two-fold (p ≤ 0.0001) by RTD-1 treatment. Immunoblots revealed that RTD-1 treatment inhibited proIL-1β biosynthesis. Additionally, RTD-1 treatment was associated with a reduction in caspase-1 activation (FC = −1.79; p = 0.0052). RTD-1 exhibited potent anti-inflammatory activity in chronically infected mice. Importantly, RTD-1 inhibits inflammasome activity, which is possibly a downstream effect of NF-κB modulation. These findings support that this immunomodulatory peptide may be a promising therapeutic for CF-associated lung disease.
Phytochemicals: A Promising Weapon in the Arsenal against Antibiotic-Resistant Bacteria
Authors: Khameneh Bahman , Eskin N. A. Michael , Iranshahy Milad , Fazly Bazzaz Bibi Sedigheh
Published: August 2021

The extensive usage of antibiotics and the rapid emergence of antimicrobial-resistant microbes (AMR) are becoming important global public health issues. Many solutions to these problems have been proposed, including developing alternative compounds with antimicrobial activities, managing existing antimicrobials, and rapidly detecting AMR pathogens. Among all of them, employing alternative compounds such as phytochemicals alone or in combination with other antibacterial agents appears to be both an effective and safe strategy for battling against these pathogens. The present review summarizes the scientific evidence on the biochemical, pharmacological, and clinical aspects of phytochemicals used to treat microbial pathogenesis. A wide range of commercial products are currently available on the market. Their well-documented clinical efficacy suggests that phytomedicines are valuable sources of new types of antimicrobial agents for future use. Innovative approaches and methodologies for identifying plant-derived products effective against AMR are also proposed in this review.
High-Carbohydrate Diet Alleviates the Oxidative Stress, Inflammation and Apoptosis of Megalobrama amblycephala Following Dietary Exposure to Silver Nanoparticles
Authors: Chen Fang , Zhao Cai-Yuan , Guan Jun-Feng , Liu Xiao-Cheng , Li Xiang-Fei , Xie Di-Zhi , Xu Chao
Published: August 2021

A 12-week feeding trial was performed to evaluate the effects of high-carbohydrate diet on oxidative stress, inflammation and apoptosis induced by silver nanoparticles (Ag-NPs) in M. amblycephala. Fish (20.12 ± 0.85 g) were randomly fed four diets (one control diet (C, 30% carbohydrate), one control diet supplemented with 100 mg kg−1 Ag-NPs (CS), one high-carbohydrate diet (HC, 45% carbohydrate) and one HC diet supplemented with 100 mg kg−1 Ag-NPs (HCS)). The results indicated that weight gain rate (WGR), specific growth rate (SGR), antioxidant enzyme (SOD and CAT) activities and expression of Trx, Cu/Zn-SOD, Mn-SOD, CAT and GPx1 of fish fed CS diet were all remarkably lower than those of other groups, whereas the opposite was true for plasma IL 1β and IL 6 levels, liver ROS contents, hepatocytes apoptotic rate, AMP/ATP ratio, AMPKα, P 53 and caspase 3 protein contents and mRNA levels of AMPKα 1, AMPKα 2, TXNIP, NF-κB, TNFα, IL 1β, IL 6, P 53, Bax and caspase 3. However, high-carbohydrate diet remarkably increased WGR, SGR, liver SOD and CAT activities, AMPKα protein content and mRNA levels of antioxidant genes (Cu/Zn-SOD, Mn-SOD, CAT and GPx1), anti-inflammatory cytokines (IL 10) and anti-apoptotic genes (Bcl 2) of fish facing Ag-NPs compared with the CS group, while the opposite was true for liver ROS contents, hepatocytes apoptotic rate, P 53 and caspase 3 protein contents, as well as mRNA levels of TXNIP, NF-κB, TNFα, IL 1β, IL 6, P 53, Bax and caspase 3. Overall, high-carbohydrate diet could attenuate Ag-NPs-induced hepatic oxidative stress, inflammation and apoptosis of M. amblycephala through AMPK activation.
Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells
Authors: Polat Ibrahim H. , Tarrado-Castellarnau Míriam , Benito Adrian , Hernandez-Carro Claudia , Centelles Josep , Marin Silvia , Cascante Marta
Published: August 2021

Nucleotide pools need to be constantly replenished in cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of cancer cells. Enhanced glutamine metabolism and increased glucose 6-phosphate dehydrogenase (G6PD) expression have been related to a malignant phenotype in tumors. However, the association between G6PD overexpression and glutamine consumption in cancer cell proliferation is still incompletely understood. In this study, we demonstrated that both inhibition of G6PD and glutamine deprivation decrease the proliferation of colon cancer cells and induce cell cycle arrest and apoptosis. Moreover, we unveiled that glutamine deprivation induce an increase of G6PD expression that is mediated through the activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2). This crosstalk between G6PD and glutamine points out the potential of combined therapies targeting oxidative PPP enzymes and glutamine catabolism to combat colon cancer.
Plant-Based Antioxidant Extracts and Compounds in the Management of Oral Cancer
Authors: Prakash Suraj , Radha  , Kumar Manoj , Kumari Neeraj , Thakur Mamta , Rathour Sonia , Pundir Ashok , Sharma Abhishek Kumar , Bangar Sneh Punia , Dhumal Sangram , Singh Surinder , Thiyagarajan Anitha , Sharma Anshu , Sharma Munisha , Changan Sushil , Sasi Minnu , Senapathy Marisennayya , Pradhan Prakash Chandra , Garg Nitin Kumar , Ilakiya Tamilselvan , Nitin Mukesh , Abdel-Daim Mohamed M. , Puri Sunil , Natta Suman , Dey Abhijit , Amarowicz Ryszard , Mekhemar Mohamed
Published: August 2021

Oral cancer continues to be a leading cause of death worldwide, and its prevalence is particularly high in developing countries, where people chew tobacco and betel nut on a regular basis. Radiation-, chemo-, targeted-, immuno-, and hormone-based therapies along with surgery are commonly used as part of a treatment plan. However, these treatments frequently result in various unwanted short- to long-term side effects. As a result, there is an urgent need to develop treatment options for oral cancer that have little or no adverse effects. Numerous bioactive compounds derived from various plants have recently attracted attention as therapeutic options for cancer treatment. Antioxidants found in medicinal plants, such as vitamins E, C, and A, reduce damage to the mucosa by neutralizing free radicals found in various oral mucosal lesions. Phytochemicals found in medicinal plants have the potential to modulate cellular signalling pathways that alter the cellular defence mechanisms to protect normal cells from reactive oxygen species (ROS) and induce apoptosis in cancer cells. This review aims to provide a comprehensive overview of various medicinal plants and phytoconstituents that have shown the potential to be used as oral cancer therapeutics.
Microalgal Co-Cultivation Prospecting to Modulate Vitamin and Bioactive Compounds Production
Authors: Pistelli Luigi , Mondo Angelo Del , Smerilli Arianna , Corato Federico , Piscitelli Concetta , Pellone Paola , Carbone Dora Allegra , Sansone Clementina , Brunet Christophe
Published: August 2021

Microalgal biotechnology is gaining importance. However, key issues in the pipeline from species selection towards large biomass production still require improvements to maximize the yield and lower the microalgal production costs. This study explores a co-cultivation strategy to improve the bioactive compounds richness of the harvested microalgal biomass. Based on their biotechnological potential, two diatoms (Skeletonema marinoi, Cyclotella cryptica) and one eustigmatophyte (Nannochloropsis oceanica) were grown alone or in combination. Concentrations of ten vitamins (A, B1, B2, B6, B12, C, D2, D3, E and H), carotenoids and polyphenols, together with total flavonoids, sterols, lipids, proteins and carbohydrates, were compared. Moreover, antioxidant capacity and chemopreventive potential in terms inhibiting four human tumor-derived and normal cell lines proliferation were evaluated. Co-cultivation can engender biomass with emergent properties regarding bioactivity or bioactive chemical profile, depending on the combined species. The high vitamin content of C. cryptica or N. oceanica further enhanced (until 10% more) when co-cultivated, explaining the two-fold increase of the antioxidant capacity of the combined C. cryptica and N. oceanica biomass. Differently, the chemopreventive activity was valuably enhanced when coupling the two diatoms C. cryptica and S. marinoi. The results obtained in this pilot study promote microalgal co-cultivation as a valuable strategy aiming to boost their application in eco-sustainable biotechnology.
Machine Learning Prediction Models for Mitral Valve Repairability and Mitral Regurgitation Recurrence in Patients Undergoing Surgical Mitral Valve Repair
Authors: Penso Marco , Pepi Mauro , Mantegazza Valentina , Cefalù Claudia , Muratori Manuela , Fusini Laura , Gripari Paola , Ghulam Ali Sarah , Caiani Enrico G. , Tamborini Gloria
Published: August 2021

Background: Mitral valve regurgitation (MR) is the most common valvular heart disease and current variables associated with MR recurrence are still controversial. We aim to develop a machine learning-based prognostic model to predict causes of mitral valve (MV) repair failure and MR recurrence. Methods: 1000 patients who underwent MV repair at our institution between 2008 and 2018 were enrolled. Patients were followed longitudinally for up to three years. Clinical and echocardiographic data were included in the analysis. Endpoints were MV repair surgical failure with consequent MV replacement or moderate/severe MR (>2+) recurrence at one-month and moderate/severe MR recurrence after three years. Results: 817 patients (DS1) had an echocardiographic examination at one-month while 295 (DS2) also had one at three years. Data were randomly divided into training (DS1: n = 654; DS2: n = 206) and validation (DS1: n = 164; DS2 n = 89) cohorts. For intra-operative or early MV repair failure assessment, the best area under the curve (AUC) was 0.75 and the complexity of mitral valve prolapse was the main predictor. In predicting moderate/severe recurrent MR at three years, the best AUC was 0.92 and residual MR at six months was the most important predictor. Conclusions: Machine learning algorithms may improve prognosis after MV repair procedure, thus improving indications for correct candidate selection for MV surgical repair.
Synergistic Antioxidant and Antibacterial Advantages of Essential Oils for Food Packaging Applications
Authors: Basavegowda Nagaraj , Baek Kwang-Hyun
Published: August 2021

The development of food-borne and infectious diseases has increased globally at an anomalous rate and is combined with emerging social and economic problems. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action at regular intervals. Some chemical or artificial food additives are considered harmful if they are used beyond their permissible levels. Today, consumers are demanding alternative, green, safer, and natural food additives to increase the shelf life of food. Essential oils (EOs) are concentrated liquid mixtures of volatile compounds with antioxidant and antibacterial properties that can be used as natural, eco-friendly, renewable, and cost-effective additives. The use of combinations of different EOs and their components is a promising strategy to increase the synergistic and additive effects of EOs in foods. In this article, we review the recent literature on EOs concerning the chemical constituents, extraction methods, antioxidant and antibacterial activities, and their mechanisms of action. Additionally, we discuss the synergistic interaction of different EOs and their components, challenges, and future directions of EOs as natural food preservatives, with special emphasis on shelf life extension and applications in the packaging of food products.
Is a High HDL-Cholesterol Level Always Beneficial?
Authors: Franczyk Beata , Rysz Jacek , Ławiński Janusz , Rysz-Górzyńska Magdalena , Gluba-Brzózka Anna
Published: August 2021

The specific interest concerning HDL cholesterol (HDL-C) is related to its ability to uptake and return surplus cholesterol from peripheral tissues back to the liver and, therefore, to its role in the prevention of cardiovascular diseases, such as atherosclerosis and myocardial infarction, but also transient ischemic attack and stroke. Previous epidemiological studies have indicated that HDL-C concentration is inversely associated with the risk of cardiovascular disease and that it can be used for risk prediction. Some genetic disorders are characterized by markedly elevated levels of HDL-C; however, they do not translate into diminished cardiovascular risk. The search of the potential causative relationship between HDL-C and adverse events has shifted the attention of researchers towards the composition and function of the HDL molecule/subfractions. HDL possesses various cardioprotective properties. However, currently, it appears that higher HDL-C is not necessarily protective against cardiovascular disease, but it can even be harmful in extremely high quantities.
Associations of Dietary Lipid-Soluble Micronutrients with Hepatic Steatosis among Adults in the United States
Authors: Chai Weiwen , Eaton Sarah , Rasmussen Heather E. , Tao Meng-Hua
Published: August 2021

Lipid-soluble micronutrients may be beneficial to non-alcoholic fatty liver disease due to their important roles in metabolism and maintaining tissue functions. Utilizing 2017–2018 National Health and Nutrition Examination Survey, this study examined the potential overall and race/ethnicity-specific (black, Hispanic and white) associations of dietary lipid-soluble micronutrients (α-tocopherol, retinol, vitamin D, β-carotene and total carotenoids) with hepatic steatosis. The analysis included 4376 adults (1037 blacks, 981 Hispanics, 1549 whites) aged ≥20 years who completed the transient elastography examination with dietary data available. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regressions. The age-adjusted prevalence of steatosis was 20.9% for blacks, 34.0% for Hispanics and 28.7% for whites. Overall, dietary α-tocopherol was inversely associated with steatosis (highest vs. lowest quartile: OR = 0.51, 95%CI = 0.35–0.74, Ptrend = 0.0003). The associations remained significant among blacks (highest vs. lowest tertile: OR = 0.45, 95%CI = 0.26–0.77, Ptrend = 0.002) and whites (highest vs. lowest tertile: OR = 0.56, 95%CI = 0.33–0.94, Ptrend = 0.02). Higher α-tocopherol intake was associated with lower odds of steatosis among all (Ptrend = 0.016) and black participants (Ptrend = 0.003) classified as never/rare/occasional alcohol drinkers. There was a trend suggesting higher β-carotene intake with lower odds of steatosis (Ptrend = 0.01). Our results suggest potential protective effects of dietary vitamin E as α-tocopherol on steatosis particularly among blacks.
T-cell Redirecting Therapies for the Treatment of B-cell Lymphomas: Recent Advances
Authors: Messéant Ondine , Houot Roch , Manson Guillaume
Published: August 2021

T-cell specificity can be redirected against tumor antigens either ex vivo using engineered chimeric antigen receptor (CAR) T-cells or in vivo by bridging natural T-cells and tumor cells with bispecific T-cell engager (TCE) antibodies. Currently, four CAR T-cells have been approved by the FDA for the treatment of B-cell lymphomas, including diffuse large B cell lymphomas (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). No TCE have yet been approved for the treatment of B-cell lymphomas. However, at least four of them are in clinical development and show promising activity. Here, we review the most recent advances of CAR T-cells and TCE in the treatment of B-cell lymphomas.