bluuebunny/crossref_metadata_2025 huggingface dataset:
Offering Biofeedback Assisted Relaxation Training in a Virtual World: Considerations and Future Directions
Authors: Schaefer Megan , Iskander Jeannette , Tams Sean , Butz Catherine
Published: February 2021

Objective: As the landscape of health care continues to shift, providing mental health and pain management services via telehealth is becoming an ideal option to increase accessibility of care. Research demonstrates the benefit of biofeedback-assisted relaxation training (BART) for children. During the COVID-19 pandemic, clinicians required to use telehealth needed an alternative to provide ongoing services. This commentary seeks to illustrate the benefits of offering BART virtually with discussing considerations and future directions. Method: An existing BART protocol was modified for telehealth delivery. Variations to the approach included increased psychoeducation, more parental engagement, and a greater focus on mobile applications (apps) in treatment. Mobile apps were used to introduce relaxation strategies, encourage practice outside of session, and obtain physiological measurements pre- and postpractice of relaxation strategies. Results: Clinicians quickly pivoted their approach and provided services without interruption. Protocol changes illustrated the need for more thorough description of treatment sessions, increased focus on privacy and ethical considerations, and age-related factors. Conclusions: As the uncertainty of the pandemic continues, it is important for clinicians to innovate to provide effective remote clinical interventions for patients and families. Future research studies examining the provision of BART via telehealth and its impact on pain and overall functioning are warranted.

Implications for Impact Statement

Identifying innovative modalities to offer biofeedback assisted relaxation training (BART) to pediatric populations with chronic medical conditions is critical in increasing accessibility of care. Clinicians may consider modifying their BART protocols to offer this intervention via telehealth or in a hybrid manner.
LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival
Authors: Lee Yu Geon , Kim Hui Won , Nam Yeji , Shin Kyeong Jin , Lee Yu Jin , Park Do Hong , Rhee Hyun-Woo , Seo Jeong Kon , Chae Young Chan
Published: February 2021

Mitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival. LONP1 and ClpP genes closely localized on chromosome 19 and were co-expressed at high levels in most human cancers. Depletion of both genes synergistically attenuated cancer cell growth and induced cell death due to impaired mitochondrial functions and increased oxidative stress. Using mitochondrial matrix proteomic analysis with an engineered peroxidase (APEX)-mediated proximity biotinylation method, we identified the specific target substrates of these proteases, which were crucial components of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and amino acid and lipid metabolism. Furthermore, we found that LONP1 and ClpP shared many substrates, including serine hydroxymethyltransferase 2 (SHMT2). Inhibition of both LONP1 and ClpP additively increased the amount of unfolded SHMT2 protein and enhanced sensitivity to SHMT2 inhibitor, resulting in significantly reduced cell growth and increased cell death under metabolic stress. Additionally, prostate cancer patients with higher LONP1 and ClpP expression exhibited poorer survival. These results suggest that interventions targeting the mitochondrial proteostasis network via LONP1 and ClpP could be potential therapeutic strategies for cancer.
Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase
Authors: Lee Su-Hyun , Kim Okhwa , Kim Hyo-Jin , Hwangbo Cheol , Lee Jeong-Hyung
Published: February 2021

Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in proliferation and epithelial–mesenchymal transition (EMT) of cancer cells, but much less is understood about their contribution to interactions with other signaling events. Recent studies have indicated that crosstalk between TGF-β and Ras signaling makes a contribution to TGF-β-mediated EMT. Here, we demonstrate that Jumonji domain containing-3 (JMJD3 also called KDM6B) promotes TGF-β-mediated Smad activation and EMT in Ras-activated lung cancer cells. JMJD3 in lung cancer patients was significantly increased and JMJD3 expression in lung tumor tissues was correlated with expression of K-Ras or H-Ras in particular, and its expression was regulated by Ras activity in lung cancer cells. JMJD3 promotes TGF-β-induced Smad activation and EMT in Ras-activated lung cancer cells through the induction of syntenin, a protein that regulates TGF-β receptor activation upon ligand binding. Tissue array and ChIP analysis revealed that JMJD3 epigenetically induces syntenin expression by directly regulating H3K27 methylation levels. Mechanical exploration identified a physical and functional association of JMJD3 with syntenin presiding over the TGF-β in Ras-activated lung cancer cells. Taken together, these findings provide new insight into the mechanisms by which JMJD3 promotes syntenin expression resulting in oncogenic Ras cooperation with TGF-β to promote EMT.
MYB oncoproteins: emerging players and potential therapeutic targets in human cancer
Authors: Cicirò Ylenia , Sala Arturo
Published: February 2021

MYB transcription factors are highly conserved from plants to vertebrates, indicating that their functions embrace fundamental mechanisms in the biology of cells and organisms. In humans, theMYBgene family is composed of three members:MYB,MYBL1andMYBL2, encoding the transcription factors MYB, MYBL1, and MYBL2 (also known as c-MYB, A-MYB, and B-MYB), respectively. A truncated version of MYB, the prototype member of the MYB family, was originally identified as the product of the retroviral oncogenev-myb, which causes leukaemia in birds. This led to the hypothesis that aberrant activation of vertebrate MYB could also cause cancer. Despite more than three decades have elapsed since the isolation of v-myb, only recently investigators were able to detectMYBgenes rearrangements and mutations, smoking gun evidence of the involvement ofMYBfamily members in human cancer. In this review, we will highlight studies linking the activity ofMYBfamily members to human malignancies and experimental therapeutic interventions tailored forMYB-expressing cancers.
Development of a nanobody-based immunoassay for the sensitive detection of fibrinogen-like protein 1
Authors: Zhang Wan-ting , Liu Ting-ting , Wu Man , Chen Xiao-chen , Han Li , Shi Zhen-zhong , Li Yu-ying , Li Xi-yang , Xu Hai-xing , Gong Li-kun , Xu Pei-hu , Geng Yong
Published: February 2021

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625–2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.
Effects of oral moisturizing gel containing propolis following head and neck radiotherapy: randomized controlled pilot trial
Authors: Nakao Ryoma , Ueno Takao
Published: February 2021

Aim

Topical administration of oral gel may reduce radiotherapy-related oral complications. The aim of this study was to examine clinical and microbiological effects of self-administration of different gel formulations to oral mucosa in head and neck cancer patients.

Materials and methods

Twenty-seven subjects were recruited from outpatients who underwent radiotherapy of at least 50 Gy to the head and neck area. They were randomly assigned to oral gel with the following different ingredients: placebo, chlorhexidine, curry leaf, propolis, and turmeric. Before and after intervention, oral symptoms were evaluated, and nine oral pathogens in saliva were also quantified using real-time PCR.

Results

Twenty-five subjects completed the study and their data were analyzed. The number of Porphyromonas gingivalis in saliva significantly decreased after treatment with propolis gel, but not after any other treatments. Propolis gel treatment also relieved oral pain in all subjects who had oral pain at the baseline.

Conclusions

Topical administration with propolis gel may not only reduce P. gingivalis carriage in saliva, but also relieve oral pain.

Discussion

A future larger-scale clinical trial of oral propolis gel is needed to determine its clinical efficacy in radiotherapy-related oral complications of head and neck cancer patients.
The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study
Authors: Tramonti Fantozzi Maria Paola , Lazzarini Giulia , De Cicco Vincenzo , Briganti Angela , Argento Serena , De Cicco Davide , Barresi Massimo , Cataldo Enrico , Bruschini Luca , d’Ascanio Paola , Pirone Andrea , Lenzi Carla , Vannozzi Iacopo , Miragliotta Vincenzo , Faraguna Ugo , Manzoni Diego
Published: February 2021

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input.
BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression
Authors: Li Yu , Wang Yuantao , Zhang Wanpeng , Wang Xinchen , Chen Lu , Wang Shuping
Published: February 2021

Poly (ADP-ribose) polymerase (PARP) inhibitors offer a significant clinical benefit for triple-negative breast cancers (TNBCs) with BRCA1/2 mutation. However, the narrow clinical indication limits the development of PARP inhibitors. Phosphoinositide 3-kinase (PI3K) inhibition sensitizes BRCA-proficient TNBC to PARP inhibition, which broadens the indication of PARP inhibitors. Previously researches have reported that PI3K inhibition induced the defect of homologous recombination (HR) mediated repair by downregulating the expression of BRCA1/2 and Rad51. However, the mechanism for their synergistic effects in the treatment of TNBC is still unclear. Herein, we focused on DNA damage, DNA single-strand breaks (SSBs) repair and DNA double-strand breaks (DSBs) repair three aspects to investigate the mechanism of dual PI3K and PARP inhibition in DNA damage response. We found that dual PI3K and PARP inhibition with BKM120 and olaparib significantly reduced the proliferation of BRCA-proficient TNBC cell lines MDA-MB-231 and MDA231-LM2. BKM120 increased cellular ROS to cause DNA oxidative damage. Olaparib resulted in concomitant gain of PARP1, forkhead box M1 (FOXM1) and Exonuclease 1 (Exo1) while inhibited the activity of PARP. BKM120 downregulated the expression of PARP1 and PARP2 to assist olaparib in blocking PARP mediated repair of DNA SSBs. Meanwhile, BKM120 inhibited the expression of BRAC1/2 and Rad51/52 to block HR mediated repair through the PI3K/Akt/NFκB/c-Myc signaling pathway and PI3K/Akt/ FOXM1/Exo1 signaling pathway. BKM120 induced HR deficiency expanded the application of olaparib to HR proficient TNBCs. Our findings proved that PI3K inhibition impaired the repair of both DNA SSBs and DNA DSBs. FOXM1 and Exo1 are novel therapeutic targets that serves important roles in DNA damage response.
Repair of full-thickness articular cartilage defects using IEIK13 self-assembling peptide hydrogel in a non-human primate model
Authors: Dufour Alexandre , Lafont Jérôme E. , Buffier Marie , Verset Michaël , Cohendet Angéline , Contamin Hugues , Confais Joachim , Sankar Sharanya , Rioult Marika , Perrier-Groult Emeline , Mallein-Gerin Frédéric
Published: February 2021

Articular cartilage is built by chondrocytes which become less active with age. This declining function of the chondrocytes, together with the avascular nature of the cartilage, impedes the spontaneous healing of chondral injuries. These lesions can progress to more serious degenerative articular conditions as in the case of osteoarthritis. As no efficient cure for cartilage lesions exist yet, cartilage tissue engineering has emerged as a promising method aiming at repairing joint defects and restoring articular function. In the present work, we investigated if a new self-assembling peptide (referred as IEIK13), combined with articular chondrocytes treated with a chondrogenic cocktail (BMP-2, insulin and T3, designated BIT) could be efficient to restore full-thickness cartilage defects induced in the femoral condyles of a non-human primate model, the cynomolgus monkey. First, in vitro molecular studies indicated that IEIK13 was efficient to support production of cartilage by monkey articular chondrocytes treated with BIT. In vivo, cartilage implant integration was monitored non-invasively by contrast-enhanced micro-computed tomography, and then by post-mortem histological analysis and immunohistochemical staining of the condyles collected 3 months post-implantation. Our results revealed that the full-thickness cartilage injuries treated with either IEIK13 implants loaded with or devoid of chondrocytes showed similar cartilage-characteristic regeneration. This pilot study demonstrates that IEIK13 can be used as a valuable scaffold to support the in vitro activity of articular chondrocytes and the repair of articular cartilage defects, when implanted alone or with chondrocytes.
Impact of cigarette versus electronic cigarette aerosol conditioned media on aortic endothelial cells in a microfluidic cardiovascular model
Authors: Makwana Om , Smith Gina A. , Flockton Hannah E. , Watters Gary P. , Lowe Frazer , Breheny Damien
Published: February 2021

Atherosclerosis is a complex process involving progressive pathological events, including monocyte adhesion to the luminal endothelial surface. We have developed a functional in vitro adhesion assay using BioFlux microfluidic technology to investigate THP-1 (human acute monocytic leukaemia cell) monocyte adhesion to human aortic endothelial cells (HAECs). The effect of whole smoke conditioned media (WSCM) generated from University of Kentucky reference cigarette 3R4F, electronic cigarette vapour conditioned media (eVCM) from an electronic nicotine delivery system (ENDS) product (Vype ePen) and nicotine on monocyte adhesion to HAECs was evaluated. Endothelial monolayers were grown in microfluidic channels and exposed to 0–1500 ng/mL nicotine or nicotine equivalence of WSCM or eVCM for 24 h. Activated THP-1 cells were perfused through the channels and a perfusion, adhesion period and wash cycle performed four times with increasing adhesion period lengths (10, 20, 30 and 40 min). THP-1 cell adhesion was quantified by counting adherent cells. WSCM induced dose-dependent increases in monocyte adhesion compared to vehicle control. No such increases were observed for eVCM or nicotine. Adhesion regulation was linked to increased ICAM-1 protein expression. Staining of ICAM-1 in HAECs and CD11b (MAC-1) in THP-1 cells demonstrated adhesion molecule co-localisation in BioFlux plates. The ICAM-1 adhesion response to WSCM was downregulated by transfecting HAECs with ICAM-1 siRNA. We conclude that the BioFlux system is able to model human monocyte adhesion to primary human endothelial cells in vitro and WSCM drives the greatest increase in monocyte adhesion via a mechanism involving endothelial ICAM-1 expression.
Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Metselaar Paula I. , Mendoza-Maldonado Lucero , Li Yim Andrew Yung Fong , Abarkan Ilias , Henneman Peter , te Velde Anje A. , Schönhuth Alexander , Bosch Jos A. , Kraneveld Aletta D. , Lopez-Rincon Alejandro
Published: February 2021

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disorder characterized by disabling fatigue. Several studies have sought to identify diagnostic biomarkers, with varying results. Here, we innovate this process by combining both mRNA expression and DNA methylation data. We performed recursive ensemble feature selection (REFS) on publicly available mRNA expression data in peripheral blood mononuclear cells (PBMCs) of 93 ME/CFS patients and 25 healthy controls, and found a signature of 23 genes capable of distinguishing cases and controls. REFS highly outperformed other methods, with an AUC of 0.92. We validated the results on a different platform (AUC of 0.95) and in DNA methylation data obtained from four public studies on ME/CFS (99 patients and 50 controls), identifying 48 gene-associated CpGs that predicted disease status as well (AUC of 0.97). Finally, ten of the 23 genes could be interpreted in the context of the derailed immune system of ME/CFS.
Reappraisal of the incidence, various types and risk factors of malignancies in patients with dermatomyositis and polymyositis in Taiwan
Authors: Hsu Jung-Lung , Liao Ming-Feng , Chu Chun-Che , Kuo Hung-Chou , Lyu Rong-Kuo , Chang Hong-Shiu , Chen Chiung-Mei , Wu Yih-Ru , Chang Kuo-Hsuan , Weng Yi-Ching , Chang Chun-Wei , Chiang Hsing-I. , Cheng Chih-Kuang , Lee Pai-Wei , Huang Chin-Chang , Ro Long-Sun
Published: February 2021

Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40–59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.
Disentangling the role of environment in cross-taxon congruence of species richness along elevational gradients
Authors: Ramos Carolina S. , Picca Pablo , Pocco Martina E. , Filloy Julieta
Published: February 2021

Spatial patterns of species richness have been found to be positively associated, a phenom called cross-taxon congruence. This may be explained by a common response to environment or by ecological interactions between taxa. Spatial changes in species richness are related to energy and environmental heterogeneity but their roles in cross-taxon congruence remain poorly explored. Elevational gradients provide a great opportunity to shed light on the underlying drivers of species richness patterns. We study the joint influence of environment and biotic interactions in shaping the cross-taxon congruence of plants and orthopterans species richness, along three elevational gradients in Sierras Grandes, central Argentina. Elevational patterns of species richness of orthopterans and plants were congruent, being temperature the best single predictor of both patterns supporting the energy-related hypotheses. Using a structural equation model, we found that temperature explained plant richness directly and orthopteran richness indirectly via orthopteran abundance. Cross-taxon congruence is likely due to a common response of both taxa to temperature although via different theoretical mechanisms, possibly, range limitations for plants and foraging activity for orthopterans. We disentangled the role of temperature in determining the cross-taxon congruence of plants and orthopterans by showing that a common response to the environment may mask different mechanisms driving the diversity of different taxonomic groups.
Human ophthalmic artery as a sensor for non-invasive intracranial pressure monitoring: numerical modeling and in vivo pilot study
Authors: Lucinskas Paulius , Deimantavicius Mantas , Bartusis Laimonas , Zakelis Rolandas , Misiulis Edgaras , Dziugys Algis , Hamarat Yasin
Published: February 2021

Intracranial pressure (ICP) monitoring is important in managing neurosurgical, neurological, and ophthalmological patients with open-angle glaucoma. Non-invasive two-depth transcranial Doppler (TCD) technique is used in a novel method for ICP snapshot measurement that has been previously investigated prospectively, and the results showed clinically acceptable accuracy and precision. The aim of this study was to investigate possibility of using the ophthalmic artery (OA) as a pressure sensor for continuous ICP monitoring. First, numerical modeling was done to investigate the possibility, and then a pilot clinical study was conducted to compare two-depth TCD-based non-invasive ICP monitoring data with readings from an invasive Codman ICP microsensor from patients with severe traumatic brain injury. The numerical modeling showed that the systematic error of non-invasive ICP monitoring was < 1.0 mmHg after eliminating the intraorbital and blood pressure gradient. In a clinical study, a total of 1928 paired data points were collected, and the extreme data points of measured differences between invasive and non-invasive ICP were − 3.94 and 4.68 mmHg (95% CI − 2.55 to 2.72). The total mean and SD were 0.086 ± 1.34 mmHg, and the correlation coefficient was 0.94. The results show that the OA can be used as a linear natural pressure sensor and that it could potentially be possible to monitor the ICP for up to 1 h without recalibration.
Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes
Authors: Zhao Lijun , Liu Fang , Li Lin , Zhang Junlin , Wang Tingli , Zhang Rui , Zhang Wei , Yang Xiaoyan , Zeng Xiaoxi , Wang Yiting , Wu Yucheng , Yang Hao , Wang Shisheng , Zhong Yi , Xu Huan , Wang Shanshan , Guo Ruikun , Ren Honghong , Yang Lichuan , Su Baihai , Zhang Jie , Tong Nanwei , Zhou Xin J. , Cooper Mark E.
Published: February 2021

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.
Identification of an N-acetylneuraminic acid-presenting bacteria isolated from a human microbiome
Authors: Han Zhen , Thuy-Boun Peter S. , Pfeiffer Wayne , Vartabedian Vincent F. , Torkamani Ali , Teijaro John R. , Wolan Dennis W.
Published: February 2021

N-Acetylneuraminic acid is the most abundant sialic acid (SA) in humans and is expressed as the terminal sugar on intestinal mucus glycans. Several pathogenic bacteria harvest and display host SA on their own surfaces to evade Siglec-mediated host immunity. While previous studies have identified bacterial enzymes associated with SA catabolism, no reported methods permit the selective labeling, tracking, and quantitation of SA-presenting microbes within complex multi-microbial systems. We combined metabolic labeling, click chemistry, 16S rRNA gene, and whole-genome sequencing to track and identify SA-presenting microbes from a cultured human fecal microbiome. We isolated a new strain of Escherichia coli that incorporates SA onto its own surface and encodes for the nanT, neuA, and neuS genes necessary for harvesting and presenting SA. Our method is applicable to the identification of SA-presenting bacteria from human, animal, and environmental microbiomes, as well as providing an entry point for the investigation of surface-expressed SA-associated structures.
Guapiaçu virus, a new insect-specific flavivirus isolated from two species of Aedes mosquitoes from Brazil
Authors: de Oliveira Ribeiro Geovani , da Costa Antonio Charlys , Gill Danielle Elise , Ribeiro Edcelha Soares D’Athaide , Rego Marlisson Octavio da S. , Monteiro Fred Julio Costa , Villanova Fabiola , Nogueira Juliana Silva , Maeda Adriana Yurika , de Souza Renato Pereira , Tahmasebi Roozbeh , Morais Vanessa S. , Pandey Ramendra Pati , Raj V. Samuel , Scandar Sirle Abdo Salloum , da Silva Vasami Fernanda Gisele , D’Agostino Leandro Guaraglia , Maiorka Paulo César , Deng Xutao , Nogueira Maurício Lacerda , Sabino Ester Cerdeira , Delwart Eric , Leal Élcio , Cunha Mariana Sequetin
Published: February 2021

Classical insect-flaviviruses (cISFVs) and dual host-related insect-specific flavivirus (dISFV) are within the major group of insect-specific flavivirus. Remarkably dISFV are evolutionarily related to some of the pathogenic flavivirus, such as Zika and dengue viruses. The Evolutionary relatedness of dISFV to flavivirus allowed us to investigate the evolutionary principle of host adaptation. Additionally, dISFV can be used for the development of flavivirus vaccines and to explore underlying principles of mammalian pathogenicity. Here we describe the genetic characterization of a novel putative dISFV, termed Guapiaçu virus (GUAPV). Distinct strains of GUAPV were isolated from pools of Aedes terrens and Aedes scapularis mosquitoes. Additionally, we also detected viral GUAPV RNA in a plasma sample of an individual febrile from the Amazon region (North of Brazil). Although GUAPV did not replicate in tested mammalian cells, 3′UTR secondary structures duplication and codon usage index were similar to pathogenic flavivirus.
The impact of a single surfing paddling cycle on fatigue and energy cost
Authors: Borgonovo-Santos Márcio , Zacca Rodrigo , Fernandes Ricardo J. , Vilas-Boas João Paulo
Published: February 2021

Surfing is one additional sport proposed by the Tokyo 2020 Organizing Committee. Surprisingly, substantial efforts to understand surfing energetics are recent, and the impact of a single surfing paddling cycle on fatigue and energy cost is still not clear. Since surfing paddling technique is highly specific, experiments in real practice conditions are necessary to provide deeper insights. Through a biophysical approach, biomechanical and energetics responses of surfing paddling were quantified and compared from 16 competitive male surfers (23.5 ± 10.0 years old, 65.3 ± 11.4 kg and 1.72 ± 0.01 m) during two sets (PRE and POST) of 10 s all-out tethered paddling plus 20 m sprint paddling, interposed by 6 min of endurance paddling. Faster surfers presented lower energy cost during sprint PRE (r2 = 0.30, p = 0.03) and endurance (r2 = 0.35, p = 0.02) relative surfing paddling velocities. Although the energy cost was higher for a lower velocity at maximal paddling velocity POST, the energy cost of surfing paddling increased with absolute velocity according to a power function (R2 = 0.83). Our results suggest that fatigue seems to occur even following a single surfing paddling cycle. Developing a powerful and endurable metabolic base while reducing energy cost during surfing paddling should be seen as key factors in surfing training programs.
A target enrichment high throughput sequencing system for characterization of BLV whole genome sequence, integration sites, clonality and host SNP
Authors: Ohnuki Nagaki , Kobayashi Tomoko , Matsuo Misaki , Nishikaku Kohei , Kusama Kazuya , Torii Yasushi , Inagaki Yasuko , Hori Masatoshi , Imakawa Kazuhiko , Satou Yorifumi
Published: February 2021

Bovine leukemia virus (BLV) is an oncogenic retrovirus which induces malignant lymphoma termed enzootic bovine leukosis (EBL) after a long incubation period. Insertion sites of the BLV proviral genome as well as the associations between disease progression and polymorphisms of the virus and host genome are not fully understood. To characterize the biological coherence between virus and host, we developed a DNA-capture-seq approach, in which DNA probes were used to efficiently enrich target sequence reads from the next-generation sequencing (NGS) library. In addition, enriched reads can also be analyzed for detection of proviral integration sites and clonal expansion of infected cells since the reads include chimeric reads of the host and proviral genomes. To validate this DNA-capture-seq approach, a persistently BLV-infected fetal lamb kidney cell line (FLK-BLV), four EBL tumor samples and four non-EBL blood samples were analyzed to identify BLV integration sites. The results showed efficient enrichment of target sequence reads and oligoclonal integrations of the BLV proviral genome in the FLK-BLV cell line. Moreover, three out of four EBL tumor samples displayed multiple integration sites of the BLV proviral genome, while one sample displayed a single integration site. In this study, we found the evidence for the first time that the integrated provirus defective at the 5′ end was present in the persistent lymphocytosis cattle. The efficient and sensitive identification of BLV variability, integration sites and clonal expansion described in this study provide support for use of this innovative tool for understanding the detailed mechanisms of BLV infection during the course of disease progression.
Dimensional stability of short fibre reinforced flowable dental composites
Authors: Raju Raju , Rajan Ginu , Farrar Paul , Prusty B. Gangadhara
Published: February 2021

Fibre-reinforced dental composites are proven to have superior mechanical properties in comparison with micro/nano/hybrid filled composites. However, the addition of small quantities of short glass fibres could affect the dimensional stability of the restoration both during initial stages as well as through the life of the restoration. This in-vitro study aims at evaluating the physical properties of short S-Glass reinforced flowable dental composites. Two S-Glass short fibre-particulate reinforced (5 wt% of aspect ratios 50 and 70) and one particulate only reinforced flowable dental composites were prepared with UDMA-TEGDMA based dental monomer systems. Samples were photopolymersied for 60 s and stored in distilled water at 37 °C for 24 h before testing. Depth of cure (through-thickness microhardness), volumetric shrinkage (Archimedes technique), polymerisation stress (cantilever based tensometer), curing exotherm (thermocouple), water sorption and solubility (ISO 4049) and thermal expansion coefficient (dilatometer) were determined. The test results were statistically analysed using one-way ANOVA (p < 0.05). Depth of cure increased by 41%, volumetric shrinkage increased by 8.3%, shrinkage stress increased by 37.6%, exotherm increased by 20.2%, and thermal expansion reduced by 6.4% while water sorption and solubility had a negligible effect with the inclusion of short glass fibres. The study demonstrates that within the same organic resin system and quantity, a small replacement of fillers with short fibres could significantly affect the dimensional stability of the composite system. In conjunction with mechanical properties, this study could help clinicians to gain confidence in fibre reinforced dental composite restorative system.
Sea stars generate downforce to stay attached to surfaces
Authors: Hermes Mark , Luhar Mitul
Published: February 2021

Intertidal sea stars often function in environments with extreme hydrodynamic loads that can compromise their ability to remain attached to surfaces. While behavioral responses such as burrowing into sand or sheltering in rock crevices can help minimize hydrodynamic loads, previous work shows that sea stars also alter body shape in response to flow conditions. This morphological plasticity suggests that sea star body shape may play an important hydrodynamic role. In this study, we measured the fluid forces acting on surface-mounted sea star and spherical dome models in water channel tests. All sea star models created downforce, i.e., the fluid pushed the body towards the surface. In contrast, the spherical dome generated lift. We also used Particle Image Velocimetry (PIV) to measure the midplane flow field around the models. Control volume analyses based on the PIV data show that downforce arises because the sea star bodies serve as ramps that divert fluid away from the surface. These observations are further rationalized using force predictions and flow visualizations from numerical simulations. The discovery of downforce generation could explain why sea stars are shaped as they are: the pentaradial geometry aids attachment to surfaces in the presence of high hydrodynamic loads.
Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
Authors: Letscher Hélène , Agbogan Viviane A. , Korniotis Sarantis , Gastineau Pauline , Tejerina Emmanuel , Gras Christophe , Mégret Jérôme , Moe Alison , Drobyski William R. , Zavala Flora
Published: February 2021

Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+CD11b+dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.
Study of nitrate levels in fruits and vegetables to assess the potential health risks in Bangladesh
Authors: Uddin Rayhan , Thakur Mostak Uddin , Uddin Mohammad Zia , Islam G. M. Rabiul
Published: February 2021

Nitrate is a chemical compound naturally present in fruits and vegetables. This study aims at assessing the nitrate levels and health risks arising from high consumption of fruits and vegetables in Bangladesh. Sixteen species of fruits and vegetables were examined for nitrates using High-Performance Liquid Chromatography with Photo Diode Array (PDA) detector. Ward’s hierarchical cluster analysis was carried out to identify the cluster of tested fruits and vegetables for the nitrate contents. A point estimate of the daily intake was applied to find the health risks that arise due to elevated levels of nitrate in fruits and vegetables. The results show that root and tuber vegetables accumulate significantly higher levels of nitrate in comparison to fruits and fruit vegetables (P < 0.05). In cluster analysis, the nitrate accumulation of fruits and vegetables show four clear clusters contributing to 29.54%, 7.17%, 4.42%, and 58.57% of the total nitrate content in the entire sample. The risk assessment of the Estimated Daily Intake (EDI) and Health Risk Index (HRI) of almost all the tested samples was in the acceptable range, except for radish, thereby indicating the acceptance of risk due to nitrate intake in Bangladesh. As nitrate may have had risk factor for health, during cultivation and storing the product should be properly monitored.
Negative correlations can play a positive role in disordered quantum walks
Authors: Pires Marcelo A. , Duarte Queirós Sílvio M.
Published: February 2021

We investigate the emerging properties of quantum walks with temporal disorder engineered from a binary Markov chain with tailored correlation, C, and disorder strength, r. We show that when the disorder is weak—$$r \ll 1$$

r
≪
1

—the introduction of negative correlation leads to a counter-intuitive higher production of spin-lattice entanglement entropy, $$S_e$$

S
e

, than the setting with positive correlation, that is $$S_e(-|C|)>S_e(|C|)$$

S
e

(
-
|
C
|
)

>

S
e

(
|
C
|
)

. These results show that negatively correlated disorder plays a more important role in quantum entanglement than it has been assumed in the literature.
The concerted emergence of well-known spatial and temporal ecological patterns in an evolutionary food web model in space
Authors: Hamm Michaela , Drossel Barbara
Published: February 2021

Ecological systems show a variety of characteristic patterns of biodiversity in space and time. It is a challenge for theory to find models that can reproduce and explain the observed patterns. Since the advent of island biogeography these models revolve around speciation, dispersal, and extinction, but they usually neglect trophic structure. Here, we propose and study a spatially extended evolutionary food web model that allows us to study large spatial systems with several trophic layers. Our computer simulations show that the model gives rise simultaneously to several biodiversity patterns in space and time, from species abundance distributions to the waxing and waning of geographic ranges. We find that trophic position in the network plays a crucial role when it comes to the time evolution of range sizes, because the trophic context restricts the occurrence and survival of species especially on higher trophic levels.
Radiation dose evaluation of pediatric patients in CT brain examination: multi-center study
Authors: Eddy Fotso Kamdem , Ngano Samba Odette , Jervé Fotue Alain , Serge Abogo
Published: February 2021

There is currently no Pediatric Regulatory Diagnostic Reference Level (DRL) in Cameroon to standardize protocols in hospitals. France, a European country, has DRL allowing them to optimize their examination protocol. For the sake of radiation protection, we have proposed to evaluate the dose and acquisition parameters delivered to our pediatric patients to optimize the protocols used. We also compared the 75th percentile values of dose parameters by acquisition between the three hospitals to Diagnostic Reference Level (DRL) of France. In this retrospective and evaluative multicenter study, a total of 320 patients who had at least one cranial CT scan were enrolled from three medical centers. The CT acquisition parameters including tube potential (kV), tube current (mA), slice Thickness (T), spiral or sequential scanning techniques, volume CT dose index (CTDIvol), and dose length product (DLP) were analyzed. CTDIvol values in our centers were found up to 17.42%, 46.01%, 21.56% respectively for children aged 1–4 higher than values of France's DRL. For those aged 5–9, we obtained 44.58%, 43.15%, 42.21% respectively. In addition, for children aged 10–14 there are also up to 47.73%, 44.11%, 46.39% respectively higher than values of France's DRL. It is similary for DLP values. The study showed a significant dosimetric overshoot compared to the France’s DRL and prompted us to make corrections to the protocols used and to a more rigorous monitoring of the principles of radiation protection and optimization rules in pediatric computed tomography in our hospitals. Our results have led us to make changes to our protocols which are the subject of a new dosimetric evaluation. The development of DRL for improving the pediatric CT scan in our country is necessary to optimize our protocols. Our results have led us to make changes to our protocols which are the subject of a new dosimetric evaluation. It would be necessary to set up a quality control structure in Cameroon and their applications in current practice.
The impact of daily caffeine intake on nighttime sleep in young adult men
Authors: Weibel Janine , Lin Yu-Shiuan , Landolt Hans-Peter , Kistler Joshua , Rehm Sophia , Rentsch Katharina M. , Slawik Helen , Borgwardt Stefan , Cajochen Christian , Reichert Carolin F.
Published: February 2021

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12–16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
Identification of superspreading environment under COVID-19 through human mobility data
Authors: Loo Becky P. Y. , Tsoi Ka Ho , Wong Paulina P. Y. , Lai Poh Chin
Published: February 2021

COVID-19 reaffirms the vital role of superspreaders in a pandemic. We propose to broaden the research on superspreaders through integrating human mobility data and geographical factors to identify superspreading environment. Six types of popular public facilities were selected: bars, shopping centres, karaoke/cinemas, mega shopping malls, public libraries, and sports centres. A historical dataset on mobility was used to calculate the generalized activity space and space–time prism of individuals during a pre-pandemic period. Analysis of geographic interconnections of public facilities yielded locations by different classes of potential spatial risk. These risk surfaces were weighed and integrated into a “risk map of superspreading environment” (SE-risk map) at the city level. Overall, the proposed method can estimate empirical hot spots of superspreading environment with statistical accuracy. The SE-risk map of Hong Kong can pre-identify areas that overlap with the actual disease clusters of bar-related transmission. Our study presents first-of-its-kind research that combines data on facility location and human mobility to identify superspreading environment. The resultant SE-risk map steers the investigation away from pure human focus to include geographic environment, thereby enabling more differentiated non-pharmaceutical interventions and exit strategies to target some places more than others when complete city lockdown is not practicable.