bluuebunny/crossref_metadata_2025 huggingface dataset:
Maresin 1 protects the liver against ischemia/reperfusion injury via the ALXR/Akt signaling pathway
Authors: Tang Da , Fu Guang , Li Wenbo , Sun Ping , Loughran Patricia A. , Deng Meihong , Scott Melanie J. , Billiar Timothy R.
Published: February 2021

Background

Hepatic ischemia/reperfusion (I/R) injury can be a major complication following liver surgery contributing to post-operative liver dysfunction. Maresin 1 (MaR1), a pro-resolving lipid mediator, has been shown to suppress I/R injury. However, the mechanisms that account for the protective effects of MaR1 in I/R injury remain unknown.

Methods

WT (C57BL/6J) mice were subjected to partial hepatic warm ischemia for 60mins followed by reperfusion. Mice were treated with MaR1 (5-20 ng/mouse), Boc2 (Lipoxin A4 receptor antagonist), LY294002 (Akt inhibitor) or corresponding controls just prior to liver I/R or at the beginning of reperfusion. Blood and liver samples were collected at 6 h post-reperfusion. Serum aminotransferase, histopathologic changes, inflammatory cytokines, and oxidative stress were analyzed to evaluate liver injury. Signaling pathways were also investigated in vitro using primary mouse hepatocyte (HC) cultures to identify underlying mechanisms for MaR1 in liver I/R injury.

Results

MaR1 treatment significantly reduced ALT and AST levels, diminished necrotic areas, suppressed inflammatory responses, attenuated oxidative stress and decreased hepatocyte apoptosis in liver after I/R. Akt signaling was significantly increased in the MaR1-treated liver I/R group compared with controls. The protective effect of MaR1 was abrogated by pretreatment with Boc2, which together with MaR1-induced Akt activation. MaR1-mediated liver protection was reversed by inhibition of Akt.

Conclusions

MaR1 protects the liver against hepatic I/R injury via an ALXR/Akt signaling pathway. MaR1 may represent a novel therapeutic agent to mitigate the detrimental effects of I/R-induced liver injury.
Effects of multimodal agility-like exercise training compared to inactive controls and alternative training on physical performance in older adults: a systematic review and meta-analysis
Authors: Morat Mareike , Morat Tobias , Zijlstra Wiebren , Donath Lars
Published: February 2021

Background

Multimodal exercise training (MT) as a time-efficient training modality promotes a wide range of physical dimensions. Incorporating agility-like training aspects (coordination, changes of direction and velocity) into MT may further enhance physical outcomes highly relevant for activities of daily living. This meta-analysis investigated the effects of multimodal agility-like exercise training (MAT) on physical and cognitive performance compared to inactive (IC) and active controls (AC) in older adults.

Methods

Literature search was conducted in four health-related databases (PubMed, SCOPUS, SPORTDiscus and Web of Science). Randomized controlled trials with pre-post testing applying MAT (including aspects of training with at least two different traditional domains: strength, balance, endurance) and an agility-like component in community-dwelling older adults were screened for eligibility. Standardized mean differences (SMD) adjusting for small sample sizes (hedges’ g) were used to extract main outcomes (strength, gait, balance, mobility, endurance, cognition). Statistical analysis was conducted using a random effects inverse-variance model.

Results

Twenty trials with 1632 older adults were included. All effects were significantly in favour of MAT compared to IC: Strength, mobility and endurance revealed large overall effects (SMD: 0.88, 0.84, 1.82). Balance showed moderate effects (SMD: 0.6). Small overall effects were observed for gait (SMD: 0.41). Few data were available to compare MAT vs. AC with negligible or small effects in favour of MAT. Funnel plots did not reveal clear funnel shapes, indicating a potential risk of bias.

Conclusions

MAT may serve as a time-efficient training modality to induce positive effects in different physical domains. Compared to isolated training, MAT allows equal effect sizes at lower overall training volumes. More studies are needed to investigate the potential value of MAT with systematic training and load control, especially compared to other exercise-based interventions.
A randomized controlled trial into the cognitive effects of a computer-tailored physical activity intervention in older adults with chronic disease(s)
Authors: Volders Esmee , de Groot Renate H. M. , Coumans Juul M. J. , Bolman Catherine A. W. , Lechner Lilian
Published: February 2021

Background

Cognitive functioning (CF) is important for wellbeing and an independent life. However, older adults with chronic diseases are at a higher risk of poorer CF levels. Although, research suggests that physical activity (PA) could play an essential role in maintaining good CF, older adults with chronic diseases have low levels of PA. PA interventions to prevent cognitive decline for this specific group exist. Yet, until now these interventions focused on a single specific chronic disease. Active Plus is a proven effective computer-tailored PA stimulating intervention focused on increasing PA in daily life for the older adult population suffering from a broad range of chronic diseases. This study tests the cognitive effects of Active Plus in older adults with chronic diseases.

Methods

In this RCT older adults with at least one chronic disease (≥65 years) were allocated to the intervention group (N = 260, mean age = 74.2) or waiting list control group (N = 325, mean age = 74.5). In total, intervention group participants received three times computer-tailored PA stimulating advice within four months (i.e., at baseline, after two months, and after three to four months). The online and print delivered advice were tailored to the specific needs and wishes of the participant and focused on incorporating PA in daily life. Baseline and follow-up measurements of the CF verbal memory (Verbal Learning Test), shifting (Trailmaking Test), inhibition (Stop-signal Task) and processing speed (Letter Digit Substitution Test) were assessed after six and 12 months. Intervention effects were analyzed with multilevel linear mixed-effects models adjusted for the clustered design and confounding variables.

Results

The dropout rate was 19.1% after 6 months and 25.1% after 12 months. Although both conditions improved on all verbal memory outcomes after 6 months, and all CF outcomes except inhibition after 12 months, no intervention effects were found, not even in subgroups (p > .05).

Conclusions

To our knowledge this is the first study to test the cognitive effects of a computer-tailored PA stimulating intervention in older adults suffering from a broad range of chronic diseases. The effects of the Active Plus intervention were not strong enough to improve CF or prevent cognitive decline. A blended approach, in which this computer-tailored intervention is combined with a face-to-face PA intervention and / or cognitive training, might be a good suggestion to increase the effects of Active Plus on PA and CF in older adults with chronic diseases.

Trial registration

Netherlands Trial Register NL6005; Date of Registration 03-21-2017; https://www.trialregister.nl/trial/6005
OsPRR37 Alternatively Promotes Heading Date Through Suppressing the Expression of Ghd7 in the Japonica Variety Zhonghua 11 under Natural Long-Day Conditions
Authors: Hu Yong , Zhou Xin , Zhang Bo , Li Shuangle , Fan Xiaowei , Zhao Hu , Zhang Jia , Liu Haiyang , He Qin , Li Qiuping , Ayaad Mohammed , You Aiqing , Xing Yongzhong
Published: February 2021

Heading date is an important agronomic trait of rice (Oryza sativa L.) and is regulated by numerous genes, some of which exhibit functional divergence in a genetic background-dependent manner. Here, we identified a late heading date 7 (lhd7) mutant that flowered later than wild-type Zhonghua 11 (ZH11) under natural long-day (NLD) conditions. Map-based cloning facilitated by the MutMap strategy revealed that LHD7 was on the same locus as OsPRR37 but exhibited a novel function as a promoter of heading date. A single-nucleotide mutation of G-to-A in the coding region caused a substitution of aspartic acid for glycine at site 159 within the pseudo-receiver (PR) domain of OsPRR37. Transcriptional analysis revealed that OsPRR37 suppressed Ghd7 expression in both ZH11 background under NLD conditions and the Zhenshan 97 background under natural short-day conditions. Consistently, the expression of Ehd1, Hd3a and RFT1 was enhanced by OsPRR37 in the ZH11 background. Genetic analysis indicated that the promotion of heading date and reduction in grain yield by OsPRR37 were partially dependent on Ghd7. Further investigation showed that the alternative function of OsPRR37 required an intact Ghd7-related regulatory pathway involving not only its upstream regulators OsGI and PhyB but also its interacting partner Hd1. Our study revealed the distinct role of OsPRR37 in the ZH11 background, which provides a more comprehensive understanding of OsPRR37 function and enriches the theoretical bases for improvement of rice heading date in the future.
Strategies to Manage Rice Sheath Blight: Lessons from Interactions between Rice and Rhizoctonia solani
Authors: Li Dayong , Li Shuai , Wei Songhong , Sun Wenxian
Published: February 2021

Rhizoctonia solani is an important phytopathogenic fungus with a wide host range and worldwide distribution. The anastomosis group AG1 IA of R. solani has been identified as the predominant causal agent of rice sheath blight, one of the most devastating diseases of crop plants. As a necrotrophic pathogen, R. solani exhibits many characteristics different from biotrophic and hemi-biotrophic pathogens during co-evolutionary interaction with host plants. Various types of secondary metabolites, carbohydrate-active enzymes, secreted proteins and effectors have been revealed to be essential pathogenicity factors in R. solani. Meanwhile, reactive oxygen species, phytohormone signaling, transcription factors and many other defense-associated genes have been identified to contribute to sheath blight resistance in rice. Here, we summarize the recent advances in studies on molecular interactions between rice and R. solani. Based on knowledge of rice-R. solani interactions and sheath blight resistance QTLs, multiple effective strategies have been developed to generate rice cultivars with enhanced sheath blight resistance.
Study of risk factors for urinary colonization in patients with the double J catheter
Authors: Saouli Amine , Karmouni Tarik , El Khader Khalid , Koutani Abdellatif , Andaloussi Ahmed Iben Attya
Published: February 2021

Background

The aim of this study is to evaluate the prevalence of urinary colonization in patients with the JJ stent and to define the predictive factors associated with this colonization.

Methods

This is a monocentric prospective study (between January 2013 and April 2017), conducted in the department of Urology B of Ibn Sina Hospital in Rabat. One hundred and forty-five double ureteral stents carried by 120 patients, 25 of which had bilateral double ureteral stent, were examined. The bacteriological profile of the urine of our patients was followed by the completion of an initial urine examination and another at the time of the removal of the JJ. The comparison of the means was made by the Student's test and the Mann–Whitney test for continuous variables and by the KHI-2 test and Fisher's test for qualitative variables. The threshold of significance is set at 0.05.

Results

The rate of colonization of JJ stent was 35.8% (43 out of 120). The urinary colonization rate was 31.7% (38 out of 120). Average time of indwelling of JJ stent was 90 days.

On double ureteral stent culture, we identified Escherichia Coli as the most predominant colonizing pathogen (47.3% of probes) followed by Enterococcus faecalis and Klebsiella pneumoniae (18.4% and 15.8%, respectively). 11.5% of colonized patients developed infectious complications (5 out of 43) and have been treated successfully except a patient who died from septic shock.

In univariate analysis, diabetes mellitus (p = 0.007, OR = 4.1, CI = 1.46–11.48), urgent establishment of JJ (p = 0.03, OR = 4.61; IC = 1.08–19.6) and time of indwelling of the JJ (p = 0.05, OR = 1.89, CI = 0.95–3.77) were the predictive factors for urinary colonization in patients with JJ. In multivariate analysis, these three factors were statistically associated with this risk: diabetes mellitus (p = 0.005, OR = 0.23, CI = 0.08–0.64), the urgent establishment of JJ (p = 0.05, OR = 0.26, CI = 0, 06–1.04) and time of indwelling of the JJ more than 30 days (p = 0.007, OR = 4.29, CI = 1.49–12.37).

Conclusion

The prevalence of urinary colonization in patients with the double J stent was 31.7%. Diabetes mellitus, time of indwelling of the JJ more than 30 days and urgent JJ ​​ establishment are associated with a higher risk of these urinary colonizations.

Strict monitoring is therefore recommended in patients with these risk factors. These results should be confirmed by multicenter and randomized studies to analyze the development of urinary tract infections in colonized patients.
The saga of the peer review process: author’s perspective
Authors: Agrawal Mayank , Suhani Suhani
Published: February 2021

Peer review system is the cornerstone of scientific publishing. The indented process is not as tedious as it has become, mainly due to the time delay, unavailability of expert reviewers, and the callous attitude of some. While there have been articles explaining the whole process and expressing the editor’s viewpoints on the peer review system, we wish to present the author’s perspective on this system.
Sparse data embedding and prediction by tropical matrix factorization
Authors: Omanović Amra , Kazan Hilal , Oblak Polona , Curk Tomaž
Published: February 2021

Background

Matrix factorization methods are linear models, with limited capability to model complex relations. In our work, we use tropical semiring to introduce non-linearity into matrix factorization models. We propose a method calledSparse Tropical Matrix Factorization() for the estimation of missing (unknown) values in sparse data.

Results

We evaluate the efficiency of the method on both synthetic data and biological data in the form of gene expression measurements downloaded from The Cancer Genome Atlas (TCGA) database. Tests on unique synthetic data showed that approximation achieves a higher correlation than non-negative matrix factorization (), which is unable to recover patterns effectively. On real data, outperforms on six out of nine gene expression datasets. While assumes normal distribution and tends toward the mean value, can better fit to extreme values and distributions.

Conclusion

is the first work that uses tropical semiring on sparse data. We show that in certain cases semirings are useful because they consider the structure, which is different and simpler to understand than it is with standard linear algebra.
A base measure of precision for protein stability predictors: structural sensitivity
Authors: Caldararu Octav , Blundell Tom L. , Kepp Kasper P.
Published: February 2021

Background

Prediction of the change in fold stability (ΔΔG) of a protein upon mutation is of major importance to protein engineering and screening of disease-causing variants. Many prediction methods can use 3D structural information to predict ΔΔG. While the performance of these methods has been extensively studied, a new problem has arisen due to the abundance of crystal structures: How precise are these methods in terms of structure input used, which structure should be used, and how much does it matter? Thus, there is a need to quantify the structural sensitivity of protein stability prediction methods.

Results

We computed the structural sensitivity of six widely-used prediction methods by use of saturated computational mutagenesis on a diverse set of 87 structures of 25 proteins. Our results show that structural sensitivity varies massively and surprisingly falls into two very distinct groups, with methods that take detailed account of the local environment showing a sensitivity of ~ 0.6 to 0.8 kcal/mol, whereas machine-learning methods display much lower sensitivity (~ 0.1 kcal/mol). We also observe that the precision correlates with the accuracy for mutation-type-balanced data sets but not generally reported accuracy of the methods, indicating the importance of mutation-type balance in both contexts.

Conclusions

The structural sensitivity of stability prediction methods varies greatly and is caused mainly by the models and less by the actual protein structural differences. As a new recommended standard, we therefore suggest that ΔΔG values are evaluated on three protein structures when available and the associated standard deviation reported, to emphasize not just the accuracy but also the precision of the method in a specific study. Our observation that machine-learning methods deemphasize structure may indicate that folded wild-type structures alone, without the folded mutant and unfolded structures, only add modest value for assessing protein stability effects, and that side-chain-sensitive methods overstate the significance of the folded wild-type structure.
Identification and elimination of genomic regions irrelevant for magnetosome biosynthesis by large-scale deletion in Magnetospirillum gryphiswaldense
Authors: Zwiener Theresa , Mickoleit Frank , Dziuba Marina , Rückert Christian , Busche Tobias , Kalinowski Jörn , Faivre Damien , Uebe René , Schüler Dirk
Published: February 2021

Background

Magnetosome formation in the alphaproteobacterium Magnetospirillum gryphiswaldense is controlled by more than 30 known mam and mms genes clustered within a large genomic region, the ‘magnetosome island’ (MAI), which also harbors numerous mobile genetic elements, repeats, and genetic junk. Because of the inherent genetic instability of the MAI caused by neighboring gene content, the elimination of these regions and their substitution by a compact, minimal magnetosome expression cassette would be important for future analysis and engineering. In addition, the role of the MAI boundaries and adjacent regions are still unclear, and recent studies indicated that further auxiliary determinants for magnetosome biosynthesis are encoded outside the MAI. However, techniques for large-scale genome editing of magnetic bacteria are still limited, and the full complement of genes controlling magnetosome formation has remained uncertain.

Results

Here we demonstrate that an allelic replacement method based on homologous recombination can be applied for large-scale genome editing in M. gryphiswaldense. By analysis of 24 deletion mutants covering about 167 kb of non-redundant genome content, we identified genes and regions inside and outside the MAI irrelevant for magnetosome biosynthesis. A contiguous stretch of ~ 100 kb, including the scattered mam and mms6 operons, could be functionally substituted by a compact and contiguous ~ 38 kb cassette comprising all essential biosynthetic gene clusters, but devoid of interspersing irrelevant or problematic gene content.

Conclusions

Our results further delineate the genetic complement for magnetosome biosynthesis and will be useful for future large-scale genome editing and genetic engineering of magnetosome biosynthesis.
The relationship between seasonality, latitude and tuberculosis notifications in Pakistan
Authors: Butt Mohsin F. , Younis Sidra , Wu Zhenqiang , Hadi Syed H. , Latif Abdullah , Martineau Adrian R.
Published: February 2021

Background

Pakistan ranks amongst the top 20 highest burden tuberculosis (TB) countries in the world. Approximately 369,548 cases of TB (all forms) were notified in 2018, with an estimated incidence of 265 per 100,000 people per year. In other settings, TB has been shown to demonstrate seasonal variation, with higher incidence in the spring/summer months and lower incidence in the autumn/winter; the amplitude of seasonal variation has also been reported to be higher with increasing distance from the equator.

Methods

Notifications of newly-diagnosed pulmonary and extrapulmonary TB cases were obtained for 139 districts in Pakistan from 2011 to 2017. Data were provided by the Pakistan National TB Control Programme, Islamabad, Pakistan. Statistical analyses were performed to determine whether there was seasonal variation in TB notifications in Pakistan; whether the amplitude of seasonal variation in TB notifications varied according to latitude; whether the amplitude of seasonal variation of TB in Pakistan differed between extrapulmonary TB vs. pulmonary TB. To assess the quarterly seasonality of TB, we used the X-13-ARIMA-SEATS seasonal adjustment programme from the United States Census Bureau. The mean difference and corresponding 95% confidence intervals of seasonal amplitudes between different latitudes and clinical phenotype of TB were estimated using linear regression.

Results

TB notifications were highest in quarter 2, and lowest in quarter 4. The mean amplitude of seasonal variation was 25.5% (95% CI 25.0 to 25.9%). The mean seasonal amplitude of TB notifications from latitude 24.5°N- < 26.5°N was 29.5% (95% CI 29.3 to 29.7%) whilst the mean seasonal amplitude of TB notifications from latitude 34.5°N - < 36.5°N was 21.7% (95% CI 19.6 to 23.9%). The mean seasonal amplitude of TB notifications across Pakistan between latitudes 24.5°N to 36.5°N reached statistically significant difference (p < 0.001). The amplitude of seasonal variation was greater for extrapulmonary TB (mean seasonal amplitude: 32.6, 95% CI 21.4 to 21.8%) vs. smear positive pulmonary TB mean seasonal amplitude: 21.6, 95% CI 32.1 to 33.1%),p < 0.001.

Conclusion

TB notifications in Pakistan exhibit seasonal variation with a peak in quarter 2 (April–June) and trough in quarter 4 (October–December). The amplitude of seasonality decreases with increasing latitude, and is more pronounced for extrapulmonary than for pulmonary TB.
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa
Authors: Obasa Adetayo Emmanuel , Ambikan Anoop T. , Gupta Soham , Neogi Ujjwal , Jacobs Graeme Brendon
Published: February 2021

Background

HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients on the South African national second-line cART regimen receiving bPIs.

Methods

During 2017 and 2018, 67 patient samples were sequenced using high-throughput sequencing (HTS), of which 56 samples were included in the final analysis because the patient’s treatment regimen was available at the time of sampling. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.

Results

Statistically significantly higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p = 0.042) and integrase inhibitor RAM (4%; 2/56; p = 0.002). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase.

Conclusions

HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in < 20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.
Monitoring HIV testing and pre-exposure prophylaxis information seeking by combining digital and traditional data
Authors: Johnson Derek C. , Nobles Alicia L. , Caputi Theodore L. , Liu Michael , Leas Eric C. , Strathdee Steffanie A. , Smith Davey M. , Ayers John W.
Published: February 2021

Background

Public health is increasingly turning to non-traditional digital data to inform HIV prevention and control strategies. We demonstrate a parsimonious method using both traditional survey and internet search histories to provide new insights into HIV testing and pre-exposure prophylaxis (PrEP) information seeking that can be easily extended to other settings.

Method

We modeled how US internet search volumes from 2019 for HIV testing and PrEP compared against expected search volumes for HIV testing and PrEP using state HIV prevalence and socioeconomic characteristics as predictors. States with search volumes outside the upper and lower bound confidence interval were labeled as either over or under performing. State performance was evaluated by (a) Centers for Disease Control and Prevention designation as a hotspot for new HIV diagnoses (b) expanding Medicaid coverage.

Results

Ten states over-performed in models assessing information seeking for HIV testing, while eleven states under-performed. Thirteen states over-performed in models assessing internet searches for PrEP information, while thirteen states under-performed. States that expanded Medicaid coverage were more likely to over perform in PrEP models than states that did not expand Medicaid coverage. While states that were hotspots for new HIV diagnoses were more likely to over perform on HIV testing searches.

Conclusion

Our study derived a method of measuring HIV and PrEP information seeking that is comparable across states. Several states exhibited information seeking for PrEP and HIV testing that deviated from model assessments. Statewide search volume for PrEP information was affected by a state’s decision to expand Medicaid coverage. Our research provides health officials with an innovative way to monitor statewide interest in PrEP and HIV testing using a metric for information-seeking that is comparable across states.
Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
Authors: Santana Bárbara Brasil , Queiroz Maria Alice Freitas , Cerveira Rodrigo Arcoverde , Rodrigues Claudia Mendonça , da Silva Graça Amoras Ednelza , da Costa Carlos Araújo , de Sousa Maisa Silva , Ishak Ricardo , Goulart Luiz Ricardo , Vallinoto Antonio Carlos Rosário
Published: February 2021

Background

Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients.

Methods

This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results

ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000).

Conclusions

Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.
Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
Authors: Yu Libo , Shi Qingtao , Jin Yan , Liu Zhixin , Li Jiaxin , Sun Wenzhou
Published: February 2021

Background

Activation of autophagy flux contributed to resistance of breast cancer (BC) cells to current chemotherapeutic drugs, which seriously limited their therapeutic efficacy and facilitated BC recurrence in clinic. However, the detailed mechanisms are still not fully understood. In the present study, we identified that inactivation of AMPK-ULK1 signaling cascade mediated protective autophagy sensitized BC cells to doxorubicin in vitro.

Methods

Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to evaluate cell proliferation abilities. Trypan blue staining assay was used to examine cell viability, and Annexin V-FITC/PI double staining method was conducted to determine cell apoptosis. The autophagosomes in BC cells were observed and photographed by electronic microscope (EM). Western Blot analysis was employed to examine genes expressions at protein levels.

Results

The parental doxorubicin-sensitive BC (DS-BC) cells were exposed to increasing concentrations of doxorubicin to establish doxorubicin-resistant BC (DR-BC) cells, and the DR-BC cells were much more resistant to high-dose doxorubicin treatment compared to the DS-BC cells. Interestingly, high-dose doxorubicin specifically increased LC3B-II/I ratio, promoted autophagosomes formation and decreased p62 expression levels to facilitate autophagy in DR-BC cells, instead of DS-BC cells, and the autophagy inhibitor 3-methyladenine (3-MA) enhanced the cytotoxic effects of high-dose doxorubicin on DR-BC cells. In addition, we proved that high-dose doxorubicin triggered protective autophagy in DR-BC cells by activating AMPK-ULK1 pathway. Functionally, high-dose doxorubicin increased the expression levels of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) to activate AMPK-ULK1 pathway in DR-BC cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) blocked autophagy to promote cell death and slow down cell growth in DR-BC cells treated with high-dose doxorubicin.

Conclusions

Collectively, our in vitro data indicated that blockage of AMPK-ULK1 signaling cascade mediated protective autophagy might be a promising strategy to increase doxorubicin sensitivity for BC treatment.
Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies
Authors: Ying Zhitao , He Ting , Wang Xiaopei , Zheng Wen , Lin Ningjing , Tu Meifeng , Xie Yan , Ping Lingyan , Zhang Chen , Liu Weiping , Deng Lijuan , Wu Meng , Feng Feier , Leng Xin , Du Tingting , Qi Feifei , Hu Xuelian , Ding Yanping , Lu Xin-an , Song Yuqin , Zhu Jun
Published: February 2021

Background

The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.

Methods

NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry.

Results

CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7–21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.

Conclusions

CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects.

Trial registration

The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421.
Outcomes of bicanalicular nasal stent inserted by sheath-guided dacryoendoscope in patients with lacrimal passage obstruction: a retrospective observational study
Authors: Kamao Tomoyuki , Zheng Xiaodong , Shiraishi Atsushi
Published: February 2021

Background

The dacryoendoscope is the only instrument that can observe the luminal side of the lacrimal passage with minimal invasiveness. It was developed to treat lacrimal passage obstructions by inserting a bicanalicular nasal stent with sheath-guided bicanalicular intubation (SG-BCI). The purpose of this study was to determine the outcomes of SG-BCI to treat lacrimal passage obstructions. In addition, to determine the effects of SG-BCI treatment on the quality of life.

Methods

This was a retrospective observational study of 128 patients (mean age 70.9 ± 11.0 years, range 28–93 years) diagnosed with a unilateral lacrimal passage obstruction. There were 73 patients with a nasolacrimal duct obstruction, 37 with a lacrimal canaliculus obstruction, 7 with a lacrimal punctum obstruction, and 11 with common lacrimal canaliculus and nasolacrimal duct obstructions. They were all treated with SG-BCI. The postoperative subjective outcomes were assessed by the answers to the Glasgow Benefit Inventory (GBI) questionnaire and to an ocular specific questionnaire on 6 symptoms including tearing, ocular discharges, swelling, pain, irritation, and blurred vision. The objective assessments were the surgical success rates and the patency at 6 months after the bicanalicular nasal stent was removed. The patients were divided into those with a pre-saccal obstruction, Group 1, and with a post-saccal obstruction, Group 2. The subjective and objective outcomes were compared between the two groups.

Results

One hundred twenty-four sides (96.9%) had a successful probing and intubation of the lacrimal passage obstruction by SG-BCI. Of the 124 sides, 110 sides (88.7%) retained the patency after the stent was removed for at least 6 months. The GBI total, general subscale, social support, and physical health scores were + 37.1 ± 29.0, + 41.5 ± 30.0, + 28.0 ± 39.4, and + 24.1 ± 37.7, respectively, postoperatively. All of the 6 ocular specific symptom scores improved significantly postoperatively. The postoperative score of tearing improved in Group 1 (P < 0.0001), while the postoperative scores of all symptoms improved significantly in Group 2.

Conclusions

The relatively high surgical success rates and positive GBI scores, and improved ocular symptom scores indicate that SG-BCI is a good minimally invasive method to treat lacrimal passage obstructions.
Clinical signs associated with earlier diagnosis of children with autism Spectrum disorder
Authors: Sicherman Nachum , Charite Jimmy , Eyal Gil , Janecka Magdalena , Loewenstein George , Law Kiely , Lipkin Paul H. , Marvin Alison R. , Buxbaum Joseph D.
Published: February 2021

Background

The objective of this study is to gain new insights into the relationship between clinical signs and age at diagnosis.

Method

We utilize a new, large, online survey of 1743 parents of children diagnosed with ASD, and use multiple statistical approaches. These include regression analysis, factor analysis, and machine learning (regression tree).

Results

We find that clinical signs that most strongly predict early diagnosis are not necessarily specific to autism, but rather those that initiate the process that eventually leads to an ASD diagnosis. Given the high correlations between symptoms, only a few signs are found to be important in predicting early diagnosis. For several clinical signs we find that their presence and intensity are positively correlated with delayed diagnosis (e.g., tantrums and aggression). Even though our data are drawn from parents’ retrospective accounts, we provide evidence that parental recall bias and/or hindsight bias did not play a significant role in shaping our results.

Conclusion

In the subset of children without early deficits in communication, diagnosis is delayed, and this might be improved if more attention will be given to clinical signs that are not necessarily considered as ASD symptoms. Our findings also suggest that careful attention should be paid to children showing excessive tantrums or aggression, as these behaviors may interfere with an early ASD diagnoses.
“When you have a high life, and you like sex, you will be afraid”: a qualitative evaluation of adolescents’ decision to test for HIV in Zambia and Kenya using the health belief model
Authors: Katirayi Leila , Akuno Job , Kulukulu Bright , Masaba Rose
Published: February 2021

Background

HIV testing among adolescents is significantly lower than among adults and many adolescents living with HIV do not know their status. Adolescent perceptions of HIV testing are poorly understood and may negatively affect testing uptake. Using a qualitative design, this study sought to explore perceptions about HIV testing and treatment among adolescents living with HIV and adolescents of unknown HIV status in Lusaka, Zambia and Kenya.

Methods

Study participants were adolescents aged 15–19 years old. The adolescents living with HIV were recruited from HIV support groups at health facilities. Adolescents of unknown HIV status were recruited from existing adolescent groups within the community. In both Zambia and Kenya, four focus group discussions (FGDs) were conducted with adolescents living with HIV and four FGDs were conducted with adolescents whose HIV status was unknown, for a total of 16 FDGs. FGDs consisted of 6–12 participants, a moderator, and a note-taker. FGDs were audio-recorded, transcribed, and translated into transcripts. Transcripts were coded in the qualitative analysis software program MAXQDA v. 12. Data reduction and summary tables were generated to help identify themes across the two study population groups. Data were interpreted within the health belief model.

Results

Adolescents discussed the challenges of facing a positive HIV test result, including fear of a positive result and need to change their lifestyle, fear of social isolation, and perception of the lost opportunity to achieve future dreams. Most adolescents of unknown status were not as aware of the benefits of learning their HIV status, nor were they aware of the ability to live a long and healthy life on ART. HIV-positive adolescents reported that the messages targeted towards adolescents focus on the need to remain HIV-negative, as opposed to the benefits of knowing one’s status. Adolescents described age and requirements for parental permission as a significant limitation in their ability to access HIV testing.

Conclusions

Adolescents require more information about the benefits of testing early and the ability to live a long and healthy life on ART. Educating adolescents that HIV testing is a normative behavior among their peers could strengthen HIV testing among adolescents.
Anthropometric measures of obesity and associated cardiovascular disease risk in the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study
Authors:   on behalf of the ECHORN Writing Group, Hassan Saria , Oladele Carol , Galusha Deron , Adams Oswald Peter , Maharaj Rohan G. , Nazario Cruz M. , Nunez Maxine , Nunez-Smith Marcella
Published: February 2021

Background

Accurately defining obesity using anthropometric measures that best capture obesity-related risk is important for identifying high risk groups for intervention. The purpose of this study is to compare the association of different anthropometric measures of obesity with 10-year cardiovascular disease (CVD) risk in adults in the Eastern Caribbean.

Methods

Data from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study (ECS) were analyzed. The ECS is comprised of adults aged 40 and older residing in the US Virgin Islands, Puerto Rico, Barbados, and Trinidad. 10-year CVD risk was calculated using the American Heart Association (ACC/AHA) ASCVD Risk Algorithm and categorized in the following high-risk groups: > 7.5, > 10, and > 20%. Logistic regression was used to examine associations between four anthropometric measures of obesity (BMI, waist circumference, waist-to-hip ratio, waist-to height ratio) and 10-year CVD risk.

Results

Mean age (SD) of participants (n = 1617) was 56.6 years (±10.2), 64% were women, 74% were overweight/obese, and 24% had an ASCVD risk score above 10%. Elevated body mass index (BMI, > 30 kg/m2) and waist circumference were not associated with CVD risk. Elevated waist-to-hip ratio (WHR, > 0.9 men, > 0.85 women) and elevated waist-to-height ratio (> 0.5) were associated with all three categories of CVD risk. Area under the receiver curve was highest for WHR for each category of CVD risk. Elevated WHR demonstrated odds of 2.39, 2.58, and 3.32 (p < 0.0001) for CVD risk of > 7.5, > 10 and > 20% respectively.

Conclusion

Findings suggest that WHR is a better indicator than BMI of obesity-related CVD risk and should be used to target adults in the Caribbean, and of Caribbean-descent, for interventions.
Adverse childhood experiences and depression among women in rural Pakistan
Authors: LeMasters Katherine , Bates Lisa M. , Chung Esther O. , Gallis John A. , Hagaman Ashley , Scherer Elissa , Sikander Siham , Staley Brooke S. , Zalla Lauren C. , Zivich Paul N. , Maselko Joanna
Published: February 2021

Background

Adverse Childhood Experiences (ACEs) are a common pathway to adult depression. This pathway is particularly important during the perinatal period when women are at an elevated risk for depression. However, this relationship has not been explored in South Asia. This study estimates the association between ACEs and women’s (N = 889) depression at 36 months postpartum in rural Pakistan.

Method

Data come from the Bachpan Cohort study. To capture ACEs, an adapted version of the ACE-International Questionnaire was used. Women’s depression was measured using both major depressive episodes (MDE) and depressive symptom severity. To assess the relationship between ACEs and depression, log-Poisson models were used for MDE and linear regression models for symptom severity.

Results

The majority (58%) of women experienced at least one ACE domain, most commonly home violence (38.3%), followed by neglect (20.1%). Women experiencing four or more ACEs had the most pronounced elevation of symptom severity (β = 3.90; 95% CL = 2.13, 5.67) and MDE (PR = 2.43; 95% CL = 1.37, 4.32). Symptom severity (β = 2.88; 95% CL = 1.46, 4.31), and MDE (PR = 2.01; 95% CL = 1.27, 3.18) were greater for those experiencing community violence or family distress (β = 2.04; 95%; CL = 0.83, 3.25) (PR = 1.77; 95% CL = 1.12, 2.79).

Conclusions

Findings suggest that ACEs are substantively distinct and have unique relationships to depression. They signal a need to address women’s ACEs as part of perinatal mental health interventions and highlight women’s lifelong experiences as important factors to understanding current mental health.

Trial registration

NCT02111915. Registered 11 April 2014. NCT02658994. Registered 22 January 2016. Both trials were prospectively registered.
Associations between supermarket availability and body size in Australia: a cross-sectional observational study comparing state and territory capital cities
Authors: Carroll Suzanne J. , Turrell Gavin , Dale Michael J. , Daniel Mark
Published: February 2021

Background

Residential environment features such as availability of supermarkets may shape dietary behaviour and thus overweight and obesity. This relationship may not be consistent between cities. This Australian national-level study examined: 1) the relationship between supermarket availability and body size; and 2) whether this relationship varied by capital city.

Methods

This study used 2017–18 Australian National Health Survey data including individual-level socio-demographic information (age, sex, country of birth, education, occupation, household income), and measured body size (height and weight to derive body mass index [BMI], and waist circumference [WC]). Objectively-expressed measures of residential environments included: counts of supermarkets (major chain outlets), counts of amenities (representing walkable destinations including essential services, recreation, and entertainment), and area of public open space - each expressed within road-network buffers at 1000 m and 1500 m; population density (1km2grid cells); and neighbourhood disadvantage (Index of Relative Socioeconomic Disadvantage) expressed within Statistical Area Level 1 units. Data for adult respondents ≥18 years residing in each of Australia’s state and territory capital cities (n = 9649) were used in multilevel models to estimate associations between supermarket availability and body size sequentially accounting for individual and other environment measures. An interaction term estimated city-specific differences in associations between supermarket availability and body size. Models were consequently repeated stratified by city.

Results

Body size (BMI and WC) and supermarket availability varied between cities. Initial inverse associations between supermarket availability and body size (BMI and WC) were attenuated to null with inclusion of all covariates, except for BMI in the 1000 m buffer model (beta = − 0.148, 95%CI -0.27, − 0.01,p = 0.025). In stratified analyses, the strengths of associations varied between cities, remaining statistically significant only for some cities (BMI: Melbourne, Brisbane Hobart; WC: Brisbane, Hobart) in fully adjusted models. Different patterns of attenuation of associations with inclusion of covariates were evident for different cities.

Conclusions

For Australian capital cities, greater availability of supermarkets is associated with healthful body size. Marked between-city variations in body size, supermarket availability, and relationships between supermarket availability and body size do not, however, support universal, “one-size-fits-all” solutions to change built environments to support healthful body size.