bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers of lipid metabolism in patients with juvenile idiopathic arthritis: relationship with disease subtype and inflammatory activity
Authors: Rodrigues Wellington Douglas Rocha , Sarni Roseli Oselka Saccardo , Fonseca Fernando Luiz Affonso , Araújo Annelyse , Len Claudio Arnaldo , Terreri Maria Teresa
Published: May 2021

Background

To describe the biomarkers of lipid metabolism in children and adolescents with polyarticular and systemic JIA and to relate them to diseases subtypes, diseases activity markers, and nutritional status.

Methods

A cross-sectional study including 62 JIA patients was performed. The following variables were evaluated: disease activity and medications used, body mass index, height for age (z-score), skin folds (bicipital, tricipital, subscapular and suprailiac), food intake based on three 24-h food recalls, lipid profile (total cholesterol (CT), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and non-HDL (N-HDLc), glycemia and insulin, erythrocyte sedimentation rate (ESR), ultrasensitive C-reactive protein (us-CRP) and apolipoproteins A-I and B (Apo A-I and Apo B).

Results

Dyslipidemia was observed in 83.3% of the patients. Based on classical lipid profile, low HDL-c levels was the most frequently alteration observed. Inadequate levels of LDL-c, Apo B and NHDL-c were significantly more frequent in the systemic JIA subtype when compared to the polyarticular subtype (p = 0.017, 0.001 and 0.042 respectively). Patients on biological therapy had a better adequacy of Apo A-I concentrations. The ESR showed a negative correlation with Apo A-I level (r = − 0.25,p = 0.047).

Conclusion

We concluded that dyslipidemia is common in patients with JIA, especially in systemic subtype. The systemic subtype and an elevated ESR were associated with lower concentrations of Apo A-I, suggesting the participation of the inflammatory process.
Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder
Authors: Schindler Patrick , Grittner Ulrike , Oechtering Johanna , Leppert David , Siebert Nadja , Duchow Ankelien S. , Oertel Frederike C. , Asseyer Susanna , Kuchling Joseph , Zimmermann Hanna G. , Brandt Alexander U. , Benkert Pascal , Reindl Markus , Jarius Sven , Paul Friedemann , Bellmann-Strobl Judith , Kuhle Jens , Ruprecht Klemens
Published: May 2021

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG+) NMOSD.

Methods

sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG+ patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG+ patients over a median observation period of 4.25 years.

Results

In patients with AQP4-IgG+ NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG+ patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG+, but not MOG-IgG+ patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = − 1.28, p = 0.01). While in AQP4-IgG+, but not MOG-IgG+ patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = − 1.75, p = 0.06) in patients with AQP4-IgG+ NMOSD. Patients with AQP4-IgG+ NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP ≤ 90 pg/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3–105.6], p = 0.03). In contrast, baseline sNfL levels above the 75th age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG+ NMOSD.

Conclusion

These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG+ NMOSD in phases of clinical remission.
Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV
Authors: Rolle Charlotte-Paige , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin
Published: May 2021

Background

Dolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA).

Methods

This retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13–11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch.

Results

Of 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12–244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36.

Conclusions

In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.
Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer
Authors: Zhang Li , Wang Yinkui , Li Zhongwu , Lin Dongmei , Liu Yiqiang , Zhou Linxin , Wang Dongliang , Wu Aiwen , Li Ziyu
Published: May 2021

Objectives

Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients.

Methods

The data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS).

Results

Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%).

Conclusions

Using IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.
Stakeholder selected strategies for obesity prevention in childcare: results from a small-scale cluster randomized hybrid type III trial
Authors: Swindle Taren , McBride Nicole M. , Selig James P. , Johnson Susan L. , Whiteside-Mansell Leanne , Martin Janna , Staley Audra , Curran Geoffrey M.
Published: May 2021

Background

Together, We Inspire Smart Eating (WISE) is an intervention for the early care and education setting to support children’s exposure to and intake of fruits and vegetables. WISE emphasizes 4 evidence-based practices (EBPs): (1) use of a mascot; (2) educators’ role modeling; (3) positive feeding practices; and (4) hands-on exposures. The current study reports on a small-scale implementation trial aimed at improving the use of WISE EBPs by teachers.

Methods

A Hybrid Type III Cluster Randomized Design compared a Basic and Enhanced implementation strategy. The Basic Strategy included training and reminders only; the Enhanced strategy was a multi-faceted package of stakeholder-selected strategies including a leadership commitment, an implementation blueprint, a local champion, an environmental reminder of the EBPs, facilitation, and tailored educational resources and incentives. All study sites were Head Starts. Sites were randomized using a balancing technique that considered site characteristics; 4 sites (20 classrooms, 39 educators, 305 children) received Enhanced support; 5 sites (18 classrooms, 36 educators, 316 children) received Basic support. RE-AIM guided the evaluation, and implementation fidelity was the primary outcome. Strategies were assessed using examination of data distributions and unadjusted comparisons (t tests) as well as general linear and mixed effects models controlling for covariates.

Results

For the primary outcome of fidelity, the Enhanced group had significantly higher means for 3 of 4 EBPs. Multivariate models explained a significant portion of variance for both mascot use and hands-on exposure with a significant positive effect observed for treatment condition. The Enhanced group also had higher rates of Appropriateness and Organizational Readiness for Implementing Change (as indicators of implementation and adoption, respectively). There was no significant difference between groups for indicators of Reach, Effectiveness or Maintenance. Formative interviews indicated key targets for iteration and potential mechanisms. Key events were catalogued to provide context for interpretation (e.g., 61% of classrooms with turnover).

Conclusions

Findings were mixed but suggested promise for the Enhanced strategy, especially considering key events of the study. Implementation fidelity improvements occurred mainly in the last 3 months of the school year; additional time may be needed to translate to improvements in child outcomes.

Trial registration

NCT03075085 Registered 20 February 2017.
RETRACTED ARTICLE: Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model: a randomized controlled trial
Authors: Alves J. C. , dos Santos Ana Margarida Moniz Pereira , Jorge Patrícia , Lavrador Catarina Falcão Trigoso Vieira Bran , Carreira L. Miguel
Published: May 2021

Background

Osteoarthritis (OA) is a complex joint disease and chronic pain source, affecting a patient’s quality of life and posing a financial burden. As the dog is considered a nearly ideal species for translation research of human OA and the most used model for research, exploring spontaneous dog OA under the One Health/One Medicine concept can improve both humans and dogs’ health and well-being.

Methods

In a clinical treatment experiment, forty (N=40) joints were selected and randomly assigned to a control group (CG), which received 0.9% NaCl or a treatment (HG), which received Hylan G-F 20. Evaluations were performed on treatment day (T0), 8, 15, 30, 90, and 180 days post-treatment. They consisted of four different Clinical Metrology Instruments (CMI), evaluation of weight distribution, joint range of motion, thigh girth, radiographic and digital thermography imaging, synovial fluid interleukin-1 (IL-1), and C-reactive protein concentrations. Results were compared with repeated measures ANOVA, with a Huynh-Feldt correction, Paired samplesT-test, or Wilcoxon signed-ranks test, withp<0.05.

Results

Patients had a mean age of 6.5±2.4 years and a bodyweight of 26.6±5.2kg, and joints graded as mild (n=28, 70%), moderate (n=6, 15%), and severe OA (n=6, 15%). No differences were found between groups at T0. Symmetry index and deviation showed significant improvements in HG from 30 days (p<0.01) up to 180 days (p=0.01). Several CMI scores, particularly pain scores, improved from 90 to 180 days. Radiographic signs progressed in both groups. In both groups, increasing body weight and age corresponded to worse clinical presentation. IA hyaluronan administration produced increased lameness in six cases, which resolved spontaneously.

Conclusions

This study characterizes the response to treatment with Hylan G-F 20, which can produce significant functional and pain level improvements in patients with OA, even those with factors related to worse response to treatment.
Application and effects of an early childhood education machine on analgesia and sedation in children after cardiothoracic surgery
Authors: Chen Li-Li , Lei Yu-Qing , Liu Jian-Feng , Cao Hua , Yu Xian-Rong , Chen Qiang
Published: May 2021

Objective

To study the effect of an early childhood education machine on sedation and analgesia in children after cardiothoracic surgery.

Methods

A prospective randomized controlled study was conducted in a provincial hospital in China. Fifty-two patients (aged from 1 to 5 years) underwent cardiothoracic surgery (including: ventricular septal defect, patent ductus arteriosus, atrial septal defect, pulmonary stenosis, pulmonary sequestration and congenital cystic adenomatoid lung malformation) were divided into the study group (n = 26) and the control group (n = 26). The patients in the study group underwent intervention with an early childhood education machine (uniform type) in addition to routine standard treatment and nursing, while the patients in the control group only received routine standard treatment and nursing. Richmond agitation sedation score (RASS) and face, legs, activity, cry, consolability (FLACC) score of all of the patients were evaluated, and the negative emotions (self-rating anxiety scale (SAS) score and self-rating depression scale (SDS) score) of the parents of the two groups were compared.

Results

There was no significant difference in the general clinical data between the two groups. The RASS and FLACC scores in the study group were significantly lower than those in the control group, and the SAS and SDS scores of the parents in the study group were significantly lower than those in the control group.

Conclusion

The application of an early childhood education machine for children after cardiothoracic surgery can effectively reduce postoperative agitation, improve sedation and analgesia of the patients, and ease the pessimistic mood of the patients’ parents.
Determination of the protective effects of Hua‐Zhuo‐Jie‐Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing
Authors: Zhou Pingping , Hao Xinyu , Liu Yu , Yang Zeqi , Xu Miaochan , Liu Shaowei , Zhang Shixiong , Yang Tianxiao , Wang Xiaomei , Wang Yangang
Published: May 2021

Background

Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats.

Methods

The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites.

Results

The H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC–MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance ofTuricibacterwas increased, and the relative abundance ofDesulfococcusandEscherichiawere decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites,Escherichiaexhibited a negative correlation with l-Leucine,Turicibacterwas negatively correlated with urea, andDesulfococcusexhibited a positive correlation with trimethylamine, and a negative correlation with choline.

Conclusions

HZJD could protect CAG by regulating intestinal microbiota and its metabolites.
Drivers of carbon flux in drip irrigation maize fields in northwest China
Authors: Guo Hui , Li Sien , Wong Fuk-Ling , Qin Shujing , Wang Yahui , Yang Danni , Lam Hon-Ming
Published: May 2021

Background

Under the escalating threat to sustainable development from the global increase in carbon dioxide concentrations, the variations in carbon flux in the farmland ecosystem and their influencing factors have attracted global attention. Over the past few decades, with the development of eddy covariance technology, the carbon fluxes of farmlands have been determined in many countries. However, studies are very limited for drip irrigation maize the arid regions in northwestern China, which covers a large area where a mixed mode of agriculture and grazing is practiced.

Results

To study the effects of drip irrigation on the net ecosystem productivity (NEE), ecosystem respiration (ER), gross primary production (GPP) and net biome productivity (NBP) in the arid regions of northwestern China, we measured the carbon flux annually from 2014 to 2018 using an eddy covariance system. Our results showed that the maize field carbon flux exhibited single-peak seasonal patterns during the growing seasons. During 2014–2018, the NEE, ER and GPP of the drip-irrigated maize field ranged between − 407 ~ − 729 g C m−2, 485.46 ~ 975.46 g C m−2, and 1068.23 ~ 1705.30 g C m−2. In four of the 5 study years, the ER released back to the atmosphere was just over half of the carbon fixed by photosynthesis. The mean daily NEE, ER and GPP were significantly correlated with the net radiation (Rn), air temperature (Ta), leaf area index (LAI) and soil moisture (SWC). The results of path analysis showed that leaf area index is the main driving force of seasonal variation of carbon flux. When harvested removals were considered, the annual NBP was − 234 g C m−2, and the drip-irrigated maize field was a carbon source.

Conclusions

This study shows the variation and influencing factors of NEE, ER and GPP in the growth period of spring maize under film drip irrigation in arid areas of northwest China. The ecosystem was a carbon sink before maize harvest, but it was converted into a carbon source considering the carbon emissions after harvest. The variation of carbon flux was influenced by both environmental and vegetation factors, and its leaf area index was the main driver that affects the seasonal variation of carbon flux.
Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy
Authors: Gong Ying , Klein Wolterink Roel G. J. , Wang Jianxiang , Bos Gerard M. J. , Germeraad Wilfred T. V.
Published: May 2021

Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
Lower limb biomechanics in individuals with chronic ankle instability during gait: a case‐control study
Authors: Moisan Gabriel , Mainville Camille , Descarreaux Martin , Cantin Vincent
Published: May 2021

Background

Individuals with chronic ankle instability (CAI) exhibit many biomechanical changes to lower limbs during walking. However, only a few studies have investigated the differences in lower limb biomechanics of individuals with CAI compared to healthy controls using a comprehensive approach including kinematic, kinetic and electromyography (EMG) measures. Consequently, the theoretical framework explaining the biomechanical adaptations in individuals with CAI is mostly based on the results of studies including heterogenous methods and participants' specificities (e.g., level of disability). More studies using a comprehensive approach are needed to better understand the biomechanical adaptations associated with CAI. The objective of this case‐control study was to identify the kinematic, kinetic and EMG differences between individuals with CAI and healthy controls during walking.

Methods

Twenty‐eight individuals with CAI and 26 healthy controls were recruited to walk at a self‐selected speed during which lower limb kinematics, kinetics and EMG were analysed. Ankle and knee angles and moments as well as gluteus medius, vastus lateralis, gastrocnemius lateralis, peroneus longus and tibialis anterior muscles activity were compared between the CAI and control groups using one‐dimensional statistical parametric mapping.

Results

The CAI group exhibited greater ankle inversion angles from 14 to 48% of the stance phase (%SP) (p = 0.008), ankle eversion moments from 40 to 78%SP (p < 0.001), knee abduction moments from 3 to 6%SP and peroneus longus muscle activity from 0 to 15%SP (p = 0.003) and 60 to 76%SP (p = 0.003) compared to the control group. No significant between‐group differences in ankle sagittal and transverse angles and moments, knee angles, knee sagittal and transverse moments as well as gluteus medius, vastus lateralis, gastrocnemius lateralis and tibialis anterior muscles activity were found.

Conclusions

During the first half of the stance phase, individuals with CAI could be at more risk of sustaining recurrent LAS mostly due to greater ankle inversion angles. However, the greater ankle eversion moments and peroneus longus muscle activity during the second half of the stance phase were an efficient mechanism to correct this maladaptive gait pattern and allowed to attenuate the faulty ankle movements during the pre‐swing phase.
Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation
Authors: Dai Lan , Wang Chen , Song Keqi , Wang Wenjing , Di Wen
Published: May 2021

Background

Adipocytes, active facilitators of epithelial ovarian cancer (EOC) growth, have been implicated in the link between obesity and EOC. However, the current understanding of the mechanisms underlying adipocyte-induced EOC cell proliferation remains incomplete.

Results

We provide the first evidence showing that sphingosine kinase (SphK) 1 is critical for adipocyte-induced EOC cell proliferation. Adipocytes are capable of activating SphK1, which then leads to extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, adipocyte-induced SphK1 activation is ERK dependent. Furthermore, sphingosine 1-phosphate receptor (S1PR) 1 and S1PR3, key components of the SphK1 signalling pathway, participate in adipocyte-mediated growth-promoting action in EOC cells.

Conclusions

Our study reveals a previously unrecognized role of SphK1 in adipocyte-induced growth-promoting action in EOC, suggesting a new target for EOC therapy.
Zymomonas diversity and potential for biofuel production
Authors: Felczak Magdalena M. , Bowers Robert M. , Woyke Tanja , TerAvest Michaela A.
Published: May 2021

Background

Zymomonas mobilis is an aerotolerant α-proteobacterium, which has been genetically engineered for industrial purposes for decades. However, a comprehensive comparison of existing strains on the genomic level in conjunction with phenotype analysis has yet to be carried out. We here performed whole-genome comparison of 17 strains including nine that were sequenced in this study. We then compared 15 available Zymomonas strains for their natural abilities to perform under conditions relevant to biofuel synthesis. We tested their growth in anaerobic rich media, as well as growth, ethanol production and xylose utilization in lignocellulosic hydrolysate. We additionally compared their tolerance to isobutanol, flocculation characteristics, and ability to uptake foreign DNA by electroporation and conjugation.

Results

Using clustering based on 99% average nucleotide identity (ANI), we classified 12 strains into four clusters based on sequence similarity, while five strains did not cluster with any other strain. Strains belonging to the same 99% ANI cluster showed similar performance while significant variation was observed between the clusters. Overall, conjugation and electroporation efficiencies were poor across all strains, which was consistent with our finding of coding potential for several DNA defense mechanisms, such as CRISPR and restriction–modification systems, across all genomes. We found that strain ATCC31821 (ZM4) had a more diverse plasmid profile than other strains, possibly leading to the unique phenotypes observed for this strain. ZM4 also showed the highest growth of any strain in both laboratory media and lignocellulosic hydrolysate and was among the top 3 strains for isobutanol tolerance and electroporation and conjugation efficiency.

Conclusions

Our findings suggest that strain ZM4 has a unique combination of genetic and phenotypic traits that are beneficial for biofuel production and propose investing future efforts in further engineering of ZM4 for industrial purposes rather than exploring new Zymomonas isolates.
Soluble guanylate cyclase stimulator reduced the gastrointestinal fibrosis in bleomycin-induced mouse model of systemic sclerosis
Authors: Yamamoto Yuzuru , Okano Takaichi , Yamada Hirotaka , Akashi Kengo , Sendo Sho , Ueda Yo , Morinobu Akio , Saegusa Jun
Published: May 2021

Background

Systemic sclerosis (SSc) is a chronic autoimmune-mediated connective tissue disorder. Although the etiology of the disease remains undetermined, SSc is characterized by fibrosis and proliferative vascular lesions of the skin and internal organs. SSc involves the gastrointestinal tract in more than 90 % of patients. Soluble guanylate cyclase (sGC) stimulator is used to treat pulmonary artery hypertension (PAH) and has been shown to inhibit experimental skin fibrosis.

Methods

Female C57BL/6J mice were treated with BLM or normal saline by subcutaneous implantation of osmotic minipump. These mice were sacrificed on day 28 or day 42. Gastrointestinal pathologies were examined by Masson Trichrome staining. The expression of fibrosis-related genes in gastrointestinal tract was analyzed by real-time PCR, and the levels of collagen in the tissue were measured by Sircol collagen assay. To evaluate peristaltic movement, the small intestinal transport (ITR%) was calculated as [dyeing distance × (duodenum − appendix)] − 1 × 100 (%). We treated BLM-treated mice with sGC stimulator or DMSO orally and analyzed them on day 42.

Results

Histological examination revealed that fibrosis from lamina propria to muscularis mucosa in the esophagus was significantly increased in BLM-treated mice, suggesting that BLM induces esophageal hyperproliferative and prefibrotic response in C57BL/6J mice. In addition, the gene expression levels of Col3a1, CCN2, MMP-2, MMP-9, TIMP-1, and TIMP-2 in the esophagus were significantly increased in BLM-treated mice. More severe hyperproliferative and prefibrotic response was observed in the mice sacrificed on day 42 than the mice sacrificed on day 28. The ITR% was found to be significantly lower in BLM-treated mice, suggesting that gastrointestinal peristaltic movement was reduced in BLM-treated mice. Furthermore, we demonstrated that sGC stimulator treatment significantly reduced hyperproliferative and prefibrotic response of esophagus and intestine in BLM-treated mice, by histological examination and Sircol collagen assay.

Conclusions

These findings suggest that BLM induces gastrointestinal hyperproliferative and prefibrotic response in C57BL/6J mice, and treatment with sGC stimulator improves the BLM-induced gastrointestinal lesion.
Intestinal parasites among intellectually disabled individuals in Iran: a systematic review and meta-analysis
Authors: Abbaszadeh Afshar Mohammad Javad , Mohebali Mehdi , Mohtasebi Sina , Teimouri Aref , Sedaghat Bahareh , Saberi Reza
Published: May 2021

Background

Poor self-care skills and personal hygiene resulted from limitations in learning and understanding, put intellectually disabled individuals at greater risk for intestinal parasitic infections (IPIs). Despite several regional reports in Iran, the overall burden on IPIs among intellectually disabled individuals is poorly understood. Hence, the present study aimed to estimate the pooled prevalence of IPIs among intellectually disabled individuals in Iran.

Methods

Using the PRISMA guidelines, we conducted a systematic review and meta-analysis of data retrieved from seven electronic databases (PubMed, Web of Science, Scopus, Embase, and ProQuest for English articles, as well as SID and Magiran for Persian) from their inception up to December 2020. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI) and depicted as a forest plot, while heterogeneity was evaluated using Cochran’s Q-test.

Results

Exactly 1263 of the 3004 intellectually disabled individuals examined by 14 studies across 10 provinces of Iran were positive for IPIs. Overall pooled prevalence estimate was 41% (95% CI 29–53%) with a range of 21% (95% CI 10–32%) to 68% (95% CI 55–80%) across sub-groups. Entamoeba coli (16.2%; 95% CI 10.3–22%), Blastocystis spp. (12.2%; 95% CI 7.2–17.2%), and Giardia duodenalis (11.9%; 95% CI 7.4–16.3%) were the most prevalent protozoan species. In terms of helminthic agents, the most prevalent species were Enterobius vermicularis (11.3%; 95% CI 6.3–16.3%) followed by Strongyloides stercoralis (10.9%; 95% CI 5.0–16.9%) and Hymenolepis nana (2.8%; 95% CI 0.4–5.2%)

Conclusion

IPIs are highly prevalent among intellectually disabled individuals in Iran. Improving the health status and implementing infectious disease prevention strategies in rehabilitation centers, health promotion interventions to improve personal hygiene of intellectually disabled individuals, as well as utilize sensitive diagnostic methods besides routine stool examination techniques, and treatment of infected individuals will help in the control of these infections among intellectually disabled individuals.
Investigating the relationship between BMI across adulthood and late life brain pathologies
Authors: Lane Christopher A. , Barnes Josephine , Nicholas Jennifer M. , Baker John W. , Sudre Carole H. , Cash David M. , Parker Thomas D. , Malone Ian B. , Lu Kirsty , James Sarah-Naomi , Keshavan Ashvini , Buchanan Sarah , Keuss Sarah , Murray-Smith Heidi , Wong Andrew , Gordon Elizabeth , Coath William , Modat Marc , Thomas David , Hardy Rebecca , Richards Marcus , Fox Nick C. , Schott Jonathan M.
Published: May 2021

Background

In view of reported associations between high adiposity, particularly in midlife and late-life dementia risk, we aimed to determine associations between body mass index (BMI), and BMI changes across adulthood and brain structure and pathology at age 69–71 years.

Methods

Four hundred sixty-five dementia-free participants from Insight 46, a sub-study of the British 1946 birth cohort, who had cross-sectional T1/FLAIR volumetric MRI, and florbetapir amyloid-PET imaging at age 69–71 years, were included in analyses. We quantified white matter hyperintensity volume (WMHV) using T1 and FLAIR 3D-MRI; β-amyloid (Aβ) positivity/negativity using a SUVR approach; and whole brain (WBV) and hippocampal volumes (HV) using 3D T1-MRI. We investigated the influence of BMI, and BMI changes at and between 36, 43, 53, 60–64, 69 and 71 years, on late-life WMHV, Aβ-status, WBV and mean HV. Analyses were repeated using overweight and obese status.

Results

At no time-point was BMI, change in BMI or overweight/obese status associated with WMHV or WBV at age 69–71 years. Decreasing BMI in the 1–2 years before imaging was associated with an increased odds of being β-amyloid positive (OR 1.45, 95% confidence interval 1.09, 1.92). There were associations between being overweight and larger mean HV at ages 60–64 (β = 0.073 ml, 95% CI 0.009, 0.137), 69 (β = 0.076 ml, 95% CI 0.012, 0.140) and 71 years (β = 0.101 ml, 95% CI 0.037, 0.165). A similar, albeit weaker, trend was seen with obese status.

Conclusions

Using WMHV, β-amyloid status and brain volumes as indicators of brain health, we do not find evidence to explain reported associations between midlife obesity and late-life dementia risk. Declining BMI in later life may reflect preclinical Alzheimer’s disease.
Thrombosed left ventricular pseudoaneurysm following myocardial infarction: a case report
Authors: Zouari Fatma , Tlili Rami , Azaiez Fares , Zayed Sofien , Ben Romdhane Rim , Ziadi Jalel , Ben Ameur Youssef
Published: May 2021

Background

Pseudoaneurysm of inferior wall of the left ventricle is an uncommon complication of myocardial infarction with high mortality.

Case presentation

We report the case of a 63-year-old Tunisian man, diagnosed with a thrombosed left ventricular pseudoaneurysm and a pericardial effusion after 1 week of angina.

Conclusions

Left ventricular pseudoaneurysm is a serious complication of myocardial infarction that has atypical presentations. Diagnosis is generally established by transthoracic echocardiography but confirmed by magnetic resonance imaging. Urgent surgery is the treatment choice given the risk of embolization and rupture.
Reduction en masse of inguinal hernia after self-reduction: a case report
Authors: Najjari Khosrow , zabihi Mahmoudabadi Hossein , Seyedjavadeyn Seyed Zeynab , Hajebi Reza
Published: May 2021

Background

Reduction en mass (REM) is one of the rare complications of inguinal hernia reduction. Although REM can be detected on the basis of specific computed tomography (CT) scan findings, many radiologists are not familiar with its radiological appearance because of the scarcity of this complication, which may cause a delay in diagnosis.

Case presentation

The patient reported in this article was a 50-year-old Persian man with a history of inguinal hernia, who had been referred with the periumbilical pain that radiated to the right lower quadrant and developed following hernia replacement by the patient himself. REM diagnosis was based on clinical examination and CT scan findings, and surgical treatment was performed by the Lichtenstein repair and mesh implantation.

Conclusions

Although REM usually occurs after reduction with compression in the inguinal hernia, this unique case report highlighted the possibility of REM after self-reduction. Surgeons and radiologists should consider REM in patients with a history of inguinal hernia presenting with intestinal obstruction symptoms, even without any apparent signs of hernia in the physical examination.
Deep learning integration of molecular and interactome data for protein–compound interaction prediction
Authors: Watanabe Narumi , Ohnuki Yuuto , Sakakibara Yasubumi
Published: May 2021

Motivation

Virtual screening, which can computationally predict the presence or absence of protein–compound interactions, has attracted attention as a large-scale, low-cost, and short-term search method for seed compounds. Existing machine learning methods for predicting protein–compound interactions are largely divided into those based on molecular structure data and those based on network data. The former utilize information on proteins and compounds, such as amino acid sequences and chemical structures; the latter rely on interaction network data, such as protein–protein interactions and compound–compound interactions. However, there have been few attempts to combine both types of data in molecular information and interaction networks.

Results

We developed a deep learning-based method that integrates protein features, compound features, and multiple types of interactome data to predict protein–compound interactions. We designed three benchmark datasets with different difficulties and applied them to evaluate the prediction method. The performance evaluations show that our deep learning framework for integrating molecular structure data and interactome data outperforms state-of-the-art machine learning methods for protein–compound interaction prediction tasks. The performance improvement is statistically significant according to the Wilcoxon signed-rank test. This finding reveals that the multi-interactome data captures perspectives other than amino acid sequence homology and chemical structure similarity and that both types of data synergistically improve the prediction accuracy. Furthermore, experiments on the three benchmark datasets show that our method is more robust than existing methods in accurately predicting interactions between proteins and compounds that are unseen in training samples.
Increased dietary availability of selenium in rainbow trout (Oncorhynchus mykiss) improves its plasma antioxidant capacity and resistance to infection with Piscirickettsia salmonis
Authors: Pérez-Valenzuela Javiera , Mejías Madelaine , Ortiz Daniela , Salgado Pablo , Montt Liliana , Chávez-Báez Ignacio , Vera-Tamargo Francisca , Mandakovic Dinka , Wacyk Jurij , Pulgar Rodrigo
Published: May 2021

Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is the most important infectious disease in the Chilean salmon farming industry. An opportunity to control this disease is to use functional micronutrients to modulate host mechanisms of response to the infection. Since P. salmonis may affect the host antioxidant system in salmonids, particularly that dependent on selenium (Se), we hypothesized that fish’s dietary selenium supplementation could improve the response to the bacterial infection. To address this, we defined a non-antibiotic, non-cytotoxic concentration of selenium to evaluate its effect on the response to in vitro infections of SHK-1 cells with P. salmonis. The results indicated that selenium supplementation reduced the cytopathic effect, intracellular bacterial load, and cellular mortality of SHK-1 by increasing the abundance and activity of host glutathione peroxidase. We then prepared diets supplemented with selenium up to 1, 5, and 10 mg/kg to feed juvenile trout for 8 weeks. At the end of this feeding period, we obtained their blood plasma and evaluated its ability to protect SHK-1 cells from infection with P. salmonis in ex vivo assays. These results recapitulated the observed ability of selenium to protect against infection with P. salmonis by increasing the concentration of selenium and the antioxidant capacity in fish’s plasma. To the best of our knowledge, this is the first report of the protective capacity of selenium against P. salmonis infection in salmonids, becoming a potential effective host-directed dietary therapy for SRS and other infectious diseases in animals at a non-antibiotic concentration.
Cerebral organoids and their potential for studies of brain diseases in domestic animals
Authors: Pain Bertrand , Baquerre Camille , Coulpier Muriel
Published: May 2021

The brain is a complex organ and any model for studying it in its normal and pathological aspects becomes a tool of choice for neuroscientists. The mastering and dissemination of protocols allowing brain organoids development have paved the way for a whole range of new studies in the field of brain development, modeling of neurodegenerative or neurodevelopmental diseases, understanding tumors as well as infectious diseases that affect the brain. While studies are so far limited to the use of human cerebral organoids, there is a growing interest in having similar models in other species. This review presents what is currently developed in this field, with a particular focus on the potential of cerebral organoids for studying neuro-infectious diseases in human and domestic animals.
Media forensics on social media platforms: a survey
Authors: Pasquini Cecilia , Amerini Irene , Boato Giulia
Published: May 2021

The dependability of visual information on the web and the authenticity of digital media appearing virally in social media platforms has been raising unprecedented concerns. As a result, in the last years the multimedia forensics research community pursued the ambition to scale the forensic analysis to real-world web-based open systems. This survey aims at describing the work done so far on the analysis of shared data, covering three main aspects: forensics techniques performing source identification and integrity verification on media uploaded on social networks, platform provenance analysis allowing to identify sharing platforms, and multimedia verification algorithms assessing the credibility of media objects in relation to its associated textual information. The achieved results are highlighted together with current open issues and research challenges to be addressed in order to advance the field in the next future.
Group signature with time-bound keys and unforgeability of expiry time for smart cities
Authors: Fang Junli , Feng Tao
Published: May 2021

Internet of Things (IoT) lays the foundation for the various applications in smart cities, yet resource-constrained IoT devices are prone to suffer from devastating cyberattacks and privacy leak threats, thus are inevitability supposed as the weakest link of the systems in smart cities. Mitigating the security risks of data and the computing limitation of edge devices, especially identity authentication and key validity management of group devices are essential for IoT system security. In order to tackle the issues of anonymity, traceability, unforgeability of expiry time as well as efficient membership revocation for life-cycle management of devices in IoT setting, we presented a dynamic time-bound group signature with unforgeability of expiry time. Unforgeability of expiry time disables a revoked signer to create a valid signature by means of associating the signing key with an expiry time. The anonymity and traceability of the proposed scheme contribute to the identity privacy of the entities and supervision for authority agency. Moreover, our proposal is feasible in the resource-constrained setting for efficient computational cost of signing and verification algorithms.
M-ary nonlinear sine chirp spread spectrum for underwater acoustic communication based on virtual time-reversal mirror method
Authors: Liu Songzuo , Zuberi Habib Hussain , Lou Yi , Farooq Muhmmad Bilal , Shaikh Shahabuddin , Raza Waleed
Published: May 2021

Linear chirp spread spectrum technique is widely used in underwater acoustic communication because of their resilience to high multipath and Doppler shift. Linear frequency modulated signal requires a high spreading factor to nearly reach orthogonality between two pairs of signals. On the other hand, nonlinear chirp spread spectrum signals can provide orthogonality at a low spreading factor. As a result, it improves spectral efficiency and is more insensitive to Doppler spread than the linear counterpart. To achieve a higher data rate, we propose two variants (half cycle sine and full cycle sine) of the M-ary nonlinear sine chirp spread spectrum technique based on virtual time-reversal mirror (VTRM). The proposed scheme uses different frequency bands to transmit chirp, and VTRM is used to improve the bit error rate due to high multipath. Its superior Doppler sensitivity makes it suitable for underwater acoustic communication. Furthermore, the proposed method uses a simple, low-power bank of matched filters; thus, it reduces the overall system complexity. Simulations are performed in different underwater acoustic channels to verify the robustness of the proposed scheme.