bluuebunny/crossref_metadata_2025 huggingface dataset:
Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma
Authors: Meng Fei , Zhang Luojin , Zhang Mingjun , Ye Kaiqin , Guo Wei , Liu Yu , Yang Wulin , Zhai Zhimin , Wang Hongzhi , Xiao Jun , Dai Haiming
Published: June 2021

Background

BCL2L13belongs to theBCL2super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown thatBCL2L13has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly.

Methods

Multiple web-based portals were employed to analyze the effect ofBCL2L13in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs ofBCL2L13co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation ofBCL2L13protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function ofBCL2L13in ccRCC cell line 786-0.

Results

BCL2L13expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulatedBCL2L13is independent of patients’ gender or tumor grade. Furthermore,BCL2L13only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates withSLC25A4. As a downstream effector ofBCL2L13in its pro-apoptotic pathway,SLC25A4is found as one of the hub genes that involved in the physiological function ofBCL2L13in kidney cancer tissues.

Conclusions

Down-regulation ofBCL2L13renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, soBCL2L13can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.
Characterization of the substrate binding site of an iron detoxifying membrane transporter from Plasmodium falciparum
Authors: Sharma Pragya , Tóth Veronika , Hyland Edel M. , Law Christopher J.
Published: June 2021

Background

Plasmodiumspecies are entirely dependent upon their host as a source of essential iron. Although it is an indispensable micronutrient, oxidation of excess ferrous iron to the ferric state in the cell cytoplasm can produce reactive oxygen species that are cytotoxic. The malaria parasite must therefore carefully regulate the processes involved in iron acquisition and storage. A 273 amino acid membrane transporter that is a member of the vacuolar iron transporter (VIT) family and an orthologue of the yeast Ca2+-sensitive cross complementer (CCC1) protein plays a major role in cytosolic iron detoxification ofPlasmodiumspecies and functions in transport of ferrous iron ions into the endoplasmic reticulum for storage. While this transporter, termed PfVIT, is not critical for viability of the parasite evidence from studies of mice infected with VIT-deficientPlasmodiumsuggests it could still provide an efficient target for chemoprophylactic treatment of malaria. Individual amino acid residues that constitute the Fe2+binding site of the protein were identified to better understand the structural basis of substrate recognition and binding by PfVIT.

Methods

Using the crystal structure of a recently published plant VIT as a template, a high-quality homology model of PfVIT was constructed to identify the amino acid composition of the transporter’s substrate binding site and to act as a guide for subsequent mutagenesis studies. To test the effect of mutation of the substrate binding-site residues on PfVIT function a yeast complementation assay assessed the ability of overexpressed, recombinant wild type and mutant PfVIT to rescue an iron-sensitive deletion strain (ccc1∆) ofSaccharomyces cerevisiaeyeast from the toxic effects of a high concentration of extracellular iron.

Results

The combined in silico and mutagenesis approach identified a methionine residue located within the cytoplasmic metal binding domain of the transporter as essential for PfVIT function and provided insight into the structural basis for the Fe2+-selectivity of the protein.

Conclusion

The structural model of the metal binding site of PfVIT opens the door for rational design of therapeutics to interfere with iron homeostasis within the malaria parasite.
Nanoparticles prepared from pterostilbene reduce blood glucose and improve diabetes complications
Authors: Zhao Xi , Shi Anhua , Ma Qiong , Yan Xueyan , Bian Ligong , Zhang Pengyue , Wu Junzi
Published: June 2021

Background

Diabetes complications are the leading cause of mortality in diabetic patients. The common complications are decline in antioxidant capacity and the onset of micro-inflammation syndrome. At present, glucose-responsive nanoparticles are widely used, as they can release insulin-loaded ultrafine particles intelligently and effectively reduce blood sugar. However, the toxicology of this method has not been fully elucidated. The plant extracts of pterostilbene (PTE) have a wide range of biological applications, such as antioxidation and inflammatory response improvement. Therefore, we have proposed new ideas for the cross application of plant extracts and biomaterials, especially as part of a hypoglycaemic nano-drug delivery system.

Results

Based on the PTE, we successfully synthesised poly(3-acrylamidophenyl boric acid-b-pterostilbene) (p[AAPBA-b-PTE]) nanoparticles (NPs). The NPs were round in shape and ranged between 150 and 250 nm in size. The NPs possessed good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin-loaded NPs was approximately 56%, and the drug loading (LC) capacity was approximately 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to changes in the glucose concentration, thus achieving an effective, sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under normal physiological conditions, NPs were completely degraded within 40 days. Fourteen days after mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, or kidney. Moreover, NPs effectively reduced blood glucose, improved antioxidant capacity and reversed micro-inflammation in mice.

Conclusions

p(AAPBA-b-PTE) NPs were successfully prepared using PTE as raw material and effectively reduced blood glucose, improved antioxidant capacity and reduced the inflammatory response. This novel preparation can enable new combinations of plant extracts and biomaterials to adiministered through NPs or other dosage forms in order to regulate and treat diseases.

Graphic abstract
Is expected substance type associated with timing of drug checking service utilization?: A cross-sectional study
Authors: Beaulieu Tara , Wood Evan , Tobias Samuel , Lysyshyn Mark , Patel Priya , Matthews Jennifer , Ti Lianping
Published: June 2021

Background

Drug checking is a harm reduction intervention aiming to reduce substance use-related risks by improving drug user knowledge of the composition of unregulated drugs. With increasing fears of fentanyl adulteration in unregulated drugs, this study sought to examine whether the expected type of drug checked (stimulant vs. opioid) was associated with timing of drug checking service utilization (pre-consumption vs. post-consumption).

Methods

Data were derived from drug checking sites in British Columbia between October 31, 2017 and December 31, 2019. Pearson’s Chi-square test was used to examine the relationship between expected sample type (stimulant vs. opioid) and timing of service utilization. Odds ratios (OR) were calculated to assess the strength of this relationship. The Mantel–Haenszel (MH) test was used to adjust for service location.

Results

A total of 3561 unique stimulant and opioid samples were eligible for inclusion, including 691 (19.40%) stimulant samples; and 2222 (62.40%) samples that were tested pre-consumption. Results indicated a positive association between testing stimulant samples and testing pre-consumption (OR = 1.45; 95% CI 1.21–1.73). Regions outside of the epicenter of the province’s drug scene showed a stronger association with testing pre-consumption (ORMH = 2.33; 95% CI 1.51–3.56) than inside the epicenter (ORMH = 1.33; 95% CI 1.09–1.63).

Conclusion

Stimulant samples were more likely to be checked pre-consumption as compared with opioid samples, and stimulant samples were more likely to be tested pre-consumption in regions outside the epicenter of the province’s drug scene. This pattern may reflect a concern for fentanyl-adulterated stimulant drugs.
Regulation of exosome secretion by cellular retinoic acid binding protein 1 contributes to systemic anti-inflammation
Authors: Lin Yi-Wei , Nhieu Jennifer , Wei Chin-Wen , Lin Yu-Lung , Kagechika Hiroyuki , Wei Li-Na
Published: June 2021

Background

Intercellular communications are important for maintaining normal physiological processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular vesicles. Among various vesicles, exosomes can be detected in a wide variety of biological systems, but the regulation and biological implication of exosome secretion/uptake remains largely unclear.

Methods

Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clinical relevance was accessed by mining multiple clinical datasets.

Results

This study uncovers Crabp1 as a negative regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the negative control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clinical relevance of this pathway is supported by patients’ data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway.

Conclusions

This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation.
Nomogram for short-term outcome assessment in AChR subtype generalized myasthenia gravis
Authors: Zhao Rui , Wang Ying , Huan Xiao , Zhong Huahua , Zhou Zhirui , Xi Jianying , Da Yuwei , Lei Lin , Chang Ting , Ruan Zhe , Luo Lijun , Li Shengnan , Yang Huan , Li Yi , Luo Sushan , Zhao Chongbo
Published: June 2021

Background

An accurate prediction for prognosis can help in guiding the therapeutic options and optimizing the trial design for generalized myasthenia gravis (gMG). We aimed to develop and validate a predictive nomogram to assess the short-term outcome in patients with the anti-acetylcholine receptor (AChR) subtype gMG.

Methods

We retrospectively reviewed 165 patients with AChR subtype gMG who were immunotherapy naïve at the first visit from five tertiary centers in China. The short-term clinical outcome is defined as the achievement of minimal symptom expression (MSE) at 12 months. Of them, 120 gMG patients from Huashan Hospital were enrolled to form a derivation cohort (n = 96) and a temporal validation cohort (n = 24) for the nomogram. Then, this nomogram was externally validated using 45 immunotherapy naïve AChR subtype gMG from the other four hospitals. Multivariate logistic regression was used to screen independent factors and construct the nomogram.

Results

MSE was achieved in 70 (72.9%), 20 (83.3%), and 33 (73.3%) patients in the training, temporal validation, and external validation cohort, respectively. The duration ≤ 12 months (p = 0.021), ocular score ≤ 2 (p = 0.006), QMG score > 13 (p = 0.008), and gross motor score ≤ 9 (p = 0.006) were statistically associated with MSE in AChR subtype gMG. The nomogram has good performance in predicting MSE as the concordance indexes are 0.81 (95% CI, 0.72–0.90) in the development cohort, 0.944 (95% CI, 0.83–1.00) in the temporal validation cohort, and 0.773 (95% CI, 0.63–0.92) in the external validation cohort.

Conclusion

The nomogram achieved an optimal prediction of MSE in AChR subtype gMG patients using the baseline clinical characters.
A cross-sectional cohort study of the activity and turnover of neutrophil granulocytes in juvenile idiopathic arthritis
Authors: Backlund Malin , Venge Per , Berntson Lillemor
Published: June 2021

Background

The inflammatory process in juvenile idiopathic arthritis (JIA) involves both the innate and the adaptive immune system. The turnover and activity of neutrophil granulocytes may be reflected by proteins secreted from primary or secondary granules and from the cytoplasm of sequestered cells. Our primary aim was to compare the levels of the secondary neutrophil granule protein human neutrophil lipocalin (HNL), in JIA patients and controls, and to explore a possible priming of neutrophils through parallel analyses in plasma and serum. A secondary aim was to relate the levels of HNL to two other well-studied leukocyte proteins, S100A8/A9 and myeloperoxidase (MPO), as well as to clinical aspects of JIA.

Methods

The concentrations of the three biomarkers in serum, two of them also in plasma, were measured using enzyme-linked immunosorbent assay in 37 children with JIA without medical treatment, in high disease activity based on juvenile arthritis disease activity score 27 (JADAS27), 32 children on medical treatment, mainly in lower disease activity, and 16 healthy children. We assessed for differences between two groups using the Mann-Whitney U test, and used the Kruskal-Wallis test for multiple group comparisons. Spearman rank correlation, linear and multiple regression analyses were used for evaluation of associations between biomarker concentrations and clinical scores.

Results

The concentrations of HNL and MPO in serum were significantly increased in children with JIA (p < 0.001, p = 0.002) compared with healthy children, but we found no difference in the plasma levels of HNL and MPO between children with JIA and controls. The serum concentrations of MPO and HNL were unaffected by medical treatment, but S100A8/A9 was reduced by medical treatment and correlated with JADAS27 in both univariate (r = 0.58, p < 0.001) and multivariate (r = 0.59, p < 0.001) analyses.

Conclusions

Neutrophil granulocytes in children with JIA are primed to release primary and secondary granule proteins, without relation to medical treatment, whereas signs of increased turnover and sequestration of neutrophil granulocytes are reduced by treatment. Levels of neutrophil-originating proteins in serum most likely reflect underlying disease activities of JIA.
Assessment of transition readiness in adolescents in Thailand with rheumatic diseases: a cross-sectional study
Authors: Kittivisuit Sirinthip , Lerkvaleekul Butsabong , Soponkanaporn Sirisucha , Ngamjanyaporn Pintip , Vilaiyuk Soamarat
Published: June 2021

Background

Most childhood-onset rheumatic diseases are chronic health conditions, which need long-term care throughout adulthood. A well-organized transition care is challenging and patient assessment of transition skills is needed for transfer preparation to an adult care setting. The Transition Readiness Assessment Questionnaire (TRAQ) is used to assess transition skills in chronically ill patients. Currently, limited transition skill assessment data exist in pediatric patients with rheumatic diseases, especially in Asian countries. This study aimed to determine the transition readiness skills in patients with rheumatic diseases and ascertain predictive factors contributing to high transition readiness skills.

Methods

This is a cross-sectional study. All patients with rheumatic diseases aged 15–20 years were recruited. The TRAQ was cross-culturally adapted into the Thai language with good internal consistency and reliability. Patients completed the Thai TRAQ at the recent clinic visit and took the retest at a 2-week interval. Demographic data, baseline characteristics, clinical manifestations, and disease status were collected. Descriptive and logistic regression analyses were performed.

Results

A total of 111 patients with a mean age of 17.4 ± 1.8 years were included. Median (IQR) disease duration was 6.4 (3.2–9.0) years. The most common rheumatic disease was juvenile idiopathic arthritis (48.6%), followed by systemic lupus erythematosus (35.1%). The mean TRAQ score was 3.85 ± 0.69. Independent visits (OR 4.35, 95% CI 1.23–15.37) was a predictor of a high TRAQ score. Furthermore, dependent visits (OR 7.84, 95% CI 2.41–25.50) was a predictor of low TRAQ score in the “appointment keeping” domain, whereas inactive disease (OR 4.54, 95% CI 1.25–16.55) was a predictor of a low TRAQ score in “tracking health issues” domain. Lack of knowledge and skills on health insurance coverage, financial management, appointment arrangement, and coping with their illness were issues causing lower TRAQ score.

Conclusions

Patients, who had independent visits, had a higher chance to obtain higher TRAQ scores, whereas patients, who had an inactive disease or dependent visits, had less transition readiness skills. Physicians and parents should prepare to transfer patients to adult care settings, mainly encouraging independent living skills.
HIVIntact: a python-based tool for HIV-1 genome intactness inference
Authors: Wright Imogen A. , Bale Michael J. , Shao Wei , Hu Wei-Shau , Coffin John M. , Van Zyl Gert U. , Kearney Mary F.
Published: June 2021

The characterisation of the HIV-1 reservoir, which consists of replication-competent integrated proviruses that persist on antiretroviral therapy (ART), is made difficult by the rarity of intact proviruses relative to those that are defective. While the only conclusive test for the replication-competence of HIV-1 proviruses is carried out in cell culture, genetic characterization of genomes by near full-length (NFL) PCR and sequencing can be used to determine whether particular proviruses have insertions, deletions, or substitutions that render them defective. Proviruses that are not excluded by having such defects can be classified as genetically intact and, possibly, replication competent. Identifying and quantifying proviruses that are potentially replication-competent is important for the development of strategies towards a functional cure. However, to date, there are no programs that can be incorporated into deep-sequencing pipelines for the automated characterization and annotation of HIV genomes. Existing programs that perform this work require manual intervention, cannot be widely installed, and do not have easily adjustable settings. Here, we present HIVIntact, a python-based software tool that characterises genomic defects in NFL HIV-1 sequences, allowing putative intact genomes to be identified in-silico. Unlike other applications that assess the genetic intactness of HIV genomes, this tool can be incorporated into existing sequence-analysis pipelines and applied to large next-generation sequencing datasets.
Influence of perceived stress on prenatal depression in Surinamese women enrolled in the CCREOH study
Authors: Gokoel Anisma R. , Abdoel Wahid Firoz , Zijlmans Wilco C. W. R. , Shankar Arti , Hindori-Mohangoo Ashna D. , Covert Hannah H. , MacDonald-Ottevanger Meerte-Sigrid , Lichtveld Maureen Y. , Harville Emily W.
Published: June 2021

Background

Prenatal depression may have adverse health effects on mothers and their offspring. Perceived stress is an important risk factor for depression during pregnancy. Studies have shown that both perceived stress and depression may negatively influence birth outcomes. While 20% of pregnancies in Suriname, a middle-income Caribbean country located in northern South America, results in adverse birth outcomes, data on prenatal depression and its risk factors are lacking. This study aimed to assess the influence of perceived stress on depression during pregnancy in Surinamese women.

Methods

Survey data were used from 1143 pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health-MeKiTamara prospective cohort study that addresses the impact of chemical and non-chemical environmental exposures in mother/child dyads in Suriname. The Edinburgh Depression Scale and Cohen Perceived Stress Scale were used to screen for probable depression (cut-off ≥ 12) and high stress (cut-off ≥ 20), respectively. The association between perceived stress and depression was examined using bivariate and multiple logistic regression analyses, adjusted for social support (including resilience) and maternal demographics.

Results

The prevalence of high perceived stress during the first two trimesters and the third trimester were 27.2% and 24.7% respectively. 22.4% of the participants had probable depression during first or second trimester and 17.6% during the third trimester. Women experiencing high stress levels during the first two trimesters had 1.92 increased odds (95% CI 1.18–3.11, p = 0.008) of having probable depression during the third trimester of pregnancy than those with low stress levels. Pregnant women with low individual resilience during early pregnancy (52.1%) had 1.65 (95% CI 1.03–2.63, p = 0.038) increased odds of having probable depression during later stages of pregnancy compared to those with high individual resilience. Low educational level (p = 0.004) and age of the mother (20–34 years) (p = 0.023) were significantly associated with probable depression during the third trimester.

Conclusions

Early detection and management of stress and depression during pregnancy are important. Health education programs, targeting the reduction of stress during pregnancy, may help to reduce depression and its potential adverse health effects on the mother and child.
Male–female concordance in reported involvement of women in contraceptive decision-making and its association with modern contraceptive use among couples in rural Maharashtra, India
Authors: Dixit Anvita , Johns Nicole E. , Ghule Mohan , Battala Madhusudana , Begum Shahina , Yore Jennifer , Saggurti Niranjan , Silverman Jay G. , Reed Elizabeth , Benmarhnia Tarik , Averbach Sarah , Raj Anita
Published: June 2021

Objective

Women’s involvement in contraceptive decision-making increases contraceptive use and reduces unmet need, but study of this has been limited to women’s self-reports. Less research is available examining couple concordance and women’s involvement in contraceptive decision-making as reported by both men and women.

Study design

We carried out a cross-sectional study using data from rural India (N = 961 young married couples). Using multivariable regression we examined the association between concordance or discordance in spousal reports of wife’s involvement in contraceptive decision-making and modern contraceptive use, adjusting for demographics, intimate partner violence, and contraceptive use discussion.

Results

More than one third (38.3%) of women reported current modern contraceptive use. Report of women’s involvement in contraceptive decision-making showed 70.3% of couples agreed that women were involved, jointly or alone (categorized as Concordant 1), 4.2% agreed women were not involved (categorized at Concordant 2), 13.2% had women report involvement but men report women were uninvolved (categorized as Discordant 1), and 12.2% had women report uninvolvement but men report that women were involved (categorized as Discordant 2). Discordant 2 couples had lower odds of modern contraceptive use relative to Concordant 1 couples (adjusted RR = 0.61, 95% CI 0.45–0.83). No other significant differences between Concordant 1 couples and other categories were observed.

Conclusion

One in four couples indicated discordance on women’s involvement in contraceptive decision making, with Discordant 2 category having lower odds of contraceptive use. Couples’ concordance in women’s involvement in contraceptive decision-making offers a target for family planning research and interventions to better meet their needs.

Trial registration ClinicalTrial.gov, NCT03514914. https://clinicaltrials.gov/ct2/show/NCT03514914
Sequential motor learning transfers from real to virtual environment
Authors: Takeo Yuhi , Hara Masayuki , Shirakawa Yuna , Ikeda Takashi , Sugata Hisato
Published: June 2021

Background

Skill acquisition of motor learning between virtual environments (VEs) and real environments (REs) may be related. Although studies have previously examined the transfer of motor learning in VEs and REs through the same tasks, only a small number of studies have focused on studying the transfer of motor learning in VEs and REs by using different tasks. Thus, detailed effects of the transfer of motor skills between VEs and REs remain controversial. Here, we investigated the transfer of sequential motor learning between VEs and REs conditions.

Methods

Twenty-seven healthy volunteers performed two types of sequential motor learning tasks; a visually cued button-press task in RE (RE task) and a virtual reaching task in VE (VE task). Participants were randomly assigned to two groups in the task order; the first group was RE task followed by VE task and the second group was VE task followed by RE task. Subsequently, the response time in RE task and VE task was compared between the two groups respectively.

Results

The results showed that the sequential reaching task in VEs was facilitated after the sequential finger task in REs.

Conclusions

These findings suggested that the sequential reaching task in VEs can be facilitated by a motor learning task comprising the same sequential finger task in REs, even when a different task is applied.
Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging
Authors: Yu Xinfeng , Yin Xinzhen , Hong Hui , Wang Shuyue , Jiaerken Yeerfan , Zhang Fan , Pasternak Ofer , Zhang Ruiting , Yang Linglin , Lou Min , Zhang Minming , Huang Peiyu
Published: June 2021

Background

White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs.

Methods

Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds.

Results

We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds.

Conclusions

Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.
Evaluating implementation of International Health Regulations core capacities: using the Electronic States Parties Self-Assessment Annual Reporting Tool (e-SPAR) to monitor progress with Joint External Evaluation indicators
Authors: Razavi Ahmed , Collins Samuel , Wilson Anne , Okereke Ebere
Published: June 2021

Background

The International Health Regulations (IHR) are a legally binding instrument designed to improve Global Health Security by limiting the cross boarder spread of health risks. All 196 signatories to the IHR (2005) are required to report progress towards IHR core capacity implementation through an annual multi-sectoral self-assessment process known as the State Parties Self-Assessment Annual Reporting (SPAR). This mandatory process sits alongside the voluntary, external, peer-reviewed Joint External Evaluations (JEE) as two core components of the IHR monitoring and evaluation framework. JEEs are intended to occur once every 4–5 years following a voluntary request from the member state. This means that interim monitoring of IHR core capacity compliance, can be challenging and additional data sources are required. The outputs of the SPAR process represent one such source. Although the JEE and SPAR tools are intended to be complimentary, there has been no publicly available mapping of JEE indicators to SPAR indicators in order to inform progress on IHR compliance.

Results

This paper mapped JEE indicators to SPAR indicators and found a high level of correlation suggesting the SPAR process offers a method for countries and technical assistance programmes to monitor progress on IHR compliance and identify gaps in between JEE visits. However, coverage was not complete, and several gaps were identified most notably in antimicrobial resistance (AMR) and vaccinations.

Conclusion

Enhancing alignment between JEE and SPAR could offer a more consistent and complete way of assessing compliance with IHR.
Protocol development for somatic embryogenesis, SSR markers and genetic modification of Stipagrostis pennata (Trin.) De Winter
Authors: Asadi-Aghbolaghi Masoumeh , Dedicova Beata , Ranade Sonali Sachi , Le Kim-Cuong , Sharifzadeh Farzad , Omidi Mansoor , Egertsdotter Ulrika
Published: June 2021

Background

Stipagrostis pennata (Trin.) De Winter is an important species for fixing sand in shifting and semi-fixed sandy lands, for grazing, and potentially as a source of lignocellulose fibres for pulp and paper industry. The seeds have low viability, which limits uses for revegetation. Somatic embryogenesis offers an alternative method for obtaining large numbers of plants from limited seed sources.

Results

A protocol for plant regeneration from somatic embryos of S. pennata was developed. Somatic embryogenesis was induced on Murashige & Skoog (MS) medium supplemented with 3 mg·L–1 2,4-D subsequently shoots were induced on MS medium and supplemented with 5 mg·L–1 zeatin riboside. The highest shoots induction was obtained when embryogenic callus derived from mature embryos (96%) in combination with MS filter-sterilized medium was used from Khuzestan location. The genetic stability of regenerated plants was analysed using ten simple sequence repeats (SSR) markers from S. pennata which showed no somaclonal variation in regenerated plants from somatic embryos of S. pennata. The regenerated plants of S. pennata showed genetic stability without any somaclonal variation for the four pairs of primers that gave the expected amplicon sizes. This data seems very reliable as three of the PCR products belonged to the coding region of the genome.

Furthermore, stable expression of GUS was obtained after Agrobacterium-mediated transformation using a super binary vector carried by a bacterial strain LBA4404.

Conclusion

To our knowledge, the current work is the first attempt to develop an in vitro protocol for somatic embryogenesis including the SSR marker analyses of regenerated plants, and Agrobacterium-mediated transformation of S. pennata that can be used for its large-scale production for commercial purposes.
Semi-supervised few-shot learning approach for plant diseases recognition
Authors: Li Yang , Chao Xuewei
Published: June 2021

Background

Learning from a few samples to automatically recognize the plant leaf diseases is an attractive and promising study to protect the agricultural yield and quality. The existing few-shot classification studies in agriculture are mainly based on supervised learning schemes, ignoring unlabeled data's helpful information.

Methods

In this paper, we proposed a semi-supervised few-shot learning approach to solve the plant leaf diseases recognition. Specifically, the public PlantVillage dataset is used and split into the source domain and target domain. Extensive comparison experiments considering the domain split and few-shot parameters (N-way, k-shot) were carried out to validate the correctness and generalization of proposed semi-supervised few-shot methods. In terms of selecting pseudo-labeled samples in the semi-supervised process, we adopted the confidence interval to determine the number of unlabeled samples for pseudo-labelling adaptively.

Results

The average improvement by the single semi-supervised method is 2.8%, and that by the iterative semi-supervised method is 4.6%.

Conclusions

The proposed methods can outperform other related works with fewer labeled training data.
A low-cost automated growth chamber system for continuous measurements of gas exchange at canopy scale in dynamic conditions
Authors: Salvatori Nicole , Giorgio Alberti , Muller Onno , Rascher Uwe , Peressotti Alessandro
Published: June 2021

Background

Obtaining instantaneous gas exchanges data is fundamental to gain information on photosynthesis. Leaf level data are reliable, but their scaling up to canopy scale is difficult as they are acquired in standard and/or controlled conditions, while natural environments are extremely dynamic. Responses to dynamic environmental conditions need to be considered, as measurements at steady state and their related models may overestimate total carbon (C) plant uptake.

Results

In this paper, we describe an automatic, low-cost measuring system composed of 12 open chambers (60 × 60 × 150 cm; around 400 euros per chamber) able to measure instantaneous CO2 and H2O gas exchanges, as well as environmental parameters, at canopy level. We tested the system’s performance by simulating different CO2 uptake and respiration levels using a tube filled with soda lime or pure CO2, respectively, and quantified its response time and measurement accuracy. We have been also able to evaluate the delayed response due to the dimension of the chambers, proposing a method to correct the data by taking into account the response time ($${t}_{0}$$

t
0

) and the residence time (τ). Finally, we tested the system by growing a commercial soybean variety in fluctuating and non-fluctuating light, showing the system to be fast enough to capture fast dynamic conditions. At the end of the experiment, we compared cumulative fluxes with total plant dry biomass.

Conclusions

The system slightly over-estimated (+ 7.6%) the total C uptake, even though not significantly, confirming its ability in measuring the overall CO2 fluxes at canopy scale. Furthermore, the system resulted to be accurate and stable, allowing to estimate the response time and to determine steady state fluxes from unsteady state measured values. Thanks to the flexibility in the software and to the dimensions of the chambers, even if only tested in dynamic light conditions, the system is thought to be used for several applications and with different plant canopies by mimicking different environmental conditions.
The association of workplace health education with smoking-related behaviour and unequal gains by job position in China: ABWMC programme findings
Authors: Lin Haoxiang , Chen Meijun , Zheng Yunting , Yun Qingping , Chang Chun
Published: June 2021

Background

Although the Chinese government has introduced a series of regulations to promote tobacco-related health education in workplaces, their implementation has been far from satisfactory. The aim of the present study was to explore the association of company-level tobacco-related health education and employee smoking behaviour.

Methods

Data from the 2018 Asia Best Workplace Mainland China programme were used to address these aims. This was a cross-sectional study that included 14,195 employees from 79 companies in mainland China. Spearman correlation tests were used to examine unadjusted correlations between the study variables, and binary logistic regression was used for multivariable analysis. The dependent variables included smoking-related variables or health information-seeking behaviour. The explanatory variable was the company-level tobacco-related health education.

Results

Tobacco-related health education was associated with better smoking harm awareness (OR = 2.23; 95% CI = 1.94–2.56), lower second-hand smoke exposure (OR = 0.73; 95% CI = 0.66–0.81), better perception of the workplace environment (OR = 2.04; 95% CI = 1.84–2.26) and positive health information-seeking behaviour (OR = 2.07; 95% CI = 1.86–2.30). Job position interacted with health education, suggesting that the positive association of health education was lower for general employees than employees who held an administrative position.

Conclusions

Tobacco-related health education is not only associated with lower SHS exposure but also related to more positive environmental perceptions and health attitudes, and these effects are significant for higher-ranking employees. Policy makers should recognize and reduce these potential health disparities.
Nuclear lamin A in rotator cuff tear margin tenocytes: an antiapoptotic and cell mechanostat factor
Authors: Gumina Stefano , Peruzzi Barbara , Leopizzi Martina , Porta Natale , Di Maio Valeria , Rocca Carlo Della , Candela Vittorio
Published: June 2021

Background

The network of intermediate filament proteins underlying the inner nuclear membrane forms the nuclear lamin. A- and B-type lamins are the major components of the nuclear lamina. Lamins function in many nuclear activities. The role of lamin A and transcription factors (NF-kB) as anti-apoptotic is well documented. Recently, lamin A has also been considered as a mechanosensor protein that is able to maintain nuclear integrity from mechanical insults.

We aimed to verify how lamin A expression varies in healthy cuff cells and in those with different-sized tears where various mechanical stresses are present.

Methods

Forty-three patients with rotator cuff tear (RCT) [23M–20F, mean age (SD): 63.5 (6.1)] were enrolled. Tissue samples excised from the most medial point of tear margins were analyzed for lamin A expression by immunohistochemistry. Controls were represented by samples obtained by normal supraspinatus tendons excised from patients submitted to reverse shoulder prosthesis implant [8M–7F, mean age (SD): 67.9 (7.1)]. The intensity of staining was graded, and an H-score was assigned. Statistical analysis was performed.

Results

Our study revealed a moderate intensity of lamin A in the healthy cuff tendons, a higher expression of this protein in the small tears, and a significant decrease of lamin A with increasing tear size (p < 0.0001).

Conclusions

Our study emphasizes the importance of early repair of small RCTs since nuclear stability is maintained, and the cellular function is protected by lamin A overexpression. High re-tear of massive cuff repair could be due to cellular apoptosis and nuclear modifications induced by lamin A lack.

Level of evidence

III
Prevalence of and factors associated with depression in the hill tribe population aged 40 years and older in northern Thailand
Authors: Singkhorn Onnalin , Apidechkul Tawatchai , Pitchalard Khanittha , Moonpanane Katemanee , Hamtanon Pawadee , Sunsern Rachanee , Leaungsomnapa Yosapon , Thepsaw Jintana
Published: June 2021

Background

Depression is globally recognized as a major mental health problem in all age categories, particularly among those living in poor economic conditions and with low levels of education, including the hill tribe people in northern Thailand.

Methods

This cross-sectional study aimed to estimate the prevalence of depression and determine the factors associated with depression in the hill tribe population aged 40 and over in northern Thailand. Hill tribe people who lived in the selected villages and met the inclusion criteria were invited to participate in the study. A validated questionnaire and the Patient Health Questionnaire-9 (PHQ-9) were used for data collection. An interview was conducted in a private and confidential room in the selected villages between January and April 2019. Logistic regression was used to determine the factors associated with depression at a significance level of α = 0.05.

Results

A total of 601 participants were recruited into the study. More than half (64.23%) were women, 46.76% were Akha, 61.90% were aged 40–59 years, and 76.37% were married. Half of the participants were Christian (57.07%) and had no monthly income (51.25%), and 85% were illiterate. The overall prevalence of depression was 39.10%: 75.74% had mild depression, 17.88% had moderate depression, and 6.38% had severe depression. In the multivariate model, three variables were found to be associated with depression: being female, having a history of substance abuse, and experiencing stress six months prior. Compared to men, women were 2.09 times (95% CI 1.30–3.35) more likely to have depression. Those who had a history of substance abuse were more likely to have depression than those who did not have a history of substance abuse (AOR = 1.97; 95% CI 1.25–3.10). Those who had a history of stress in the prior 6 months were more likely to have depression than those who did not (AOR = 6.43; 95% CI 4.20–9.85).

Conclusion

Public health screening programs to identify depression in the hill tribe population are urgently needed, particularly for women, those who have abused psychoactive substances, and those who have experienced stress.
A positive feedback loop between Periostin and TGFβ1 induces and maintains the stemness of hepatocellular carcinoma cells via AP-2α activation
Authors: Chen Gang , Wang Yi , Zhao Xin , Xie Xiao-zai , Zhao Jun-gang , Deng Tuo , Chen Zi-yan , Chen Han-bin , Tong Yi-fan , Yang Zhen , Ding Xi-wei , Guo Peng-yi , Yu Hai-tao , Wu Li-jun , Zhang Si-na , Zhu Qian-dong , Li Jun-jian , Shan Yun-feng , Yu Fu-xiang , Yu Zheng-ping , Xia Jing-lin
Published: June 2021

Background

Liver cancer stem cells (LCSCs) play key roles in the metastasis, recurrence, and chemotherapeutic resistance of hepatocellular carcinoma (HCC). Our previous research showed that the POSTN gene is closely related to the malignant progression and poor prognosis of HCC. This study aimed to elucidate the role of POSTN in generating LCSCs and maintaining their stemness as well as the underlying mechanisms.

Methods

Human HCC tissues and matched adjacent normal tissues were obtained from 110 patients. Immunohistochemistry, western blotting (WB), and RT-PCR were performed to detect the expression of POSTN and stemness factors. The roles of transforming growth factor (TGF)-β1 and AP-2α in the POSTN-induced stemness transformation of HCC cells were explored in vitro and in vivo using LCSCs obtained by CD133+ cell sorting.

Results

The high expression of POSTN was correlated with the expression of various stemness factors, particularly CD133, in our HCC patient cohort and in TCGA and ICGC datasets. Knockdown of POSTN expression decreased the abilities of HCC cell lines to form tumours in xenograft mouse models. Knockdown of POSTN expression also suppressed cell viability and clone formation, invasion, and sphere formation abilities in vitro. Knockdown of AP-2α attenuated the generation of CD133+ LCSCs and their malignant behaviours, indicating that AP-2α was a critical factor that mediated the POSTN-induced stemness transformation and maintenance of HCC cells. The role of AP-2α was verified by using a specific αvβ3 antagonist, cilengitide, in vitro and in vivo. Activation of POSTN could release TGFβ1 from the extracellular matrix and initiated POSTN/TGFβ1 positive feedback signalling. Furthermore, we found that the combined use of cilengitide and lenvatinib suppressed the growth of HCC cells with high POSTN expression more effectively than the use of lenvatinib alone in the patient-derived xenograft (PDX) mouse model.

Conclusions

The POSTN/TGFβ1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.
Ambulance deceleration causes increased intra cranial pressure in supine position: a prospective observational proof of principle study
Authors: Maissan Iscander M. , Vlottes Boris , Hoeks Sanne , Bosch Jan , Stolker Robert Jan , den Hartog Dennis
Published: June 2021

Background

Ambulance drivers in the Netherlands are trained to drive as fluent as possible when transporting a head injured patient to the hospital. Acceleration and deceleration have the potential to create pressure changes in the head that may worsen outcome. Although the idea of fluid shift during braking causing intra cranial pressure (ICP) to rise is widely accepted, it lacks any scientific evidence. In this study we evaluated the effects of driving and deceleration during ambulance transportation on the intra cranial pressure in supine position and 30° upright position.

Methods

Participants were placed on the ambulance gurney in supine position. During driving and braking the optical nerve sheath diameter (ONSD) was measured with ultrasound. Because cerebro spinal fluid percolates in the optical nerve sheath when ICP rises, the diameter of this sheath will distend if ICP rises during braking of the ambulance. The same measurements were taken with the headrest in 30° upright position.

Results

Mean ONSD in 20 subjects in supine position increased from 4.80 (IQR 4.80–5.00) mm during normal transportation to 6.00 (IQR 5.75–6.40) mm (p < 0.001) during braking. ONSD’s increased in all subjects in supine position.

After raising the headrest of the gurney 30° mean ONSD increased from 4.80 (IQR 4.67–5.02) mm during normal transportation to 4.90 (IQR 4.80–5.02) mm (p = 0.022) during braking. In 15 subjects (75%) there was no change in ONSD at all.

Conclusions

ONSD and thereby ICP increases during deceleration of a transporting vehicle in participants in supine position. Raising the headrest of the gurney to 30 degrees reduces the effect of breaking on ICP.