bluuebunny/crossref_metadata_2025 huggingface dataset:
Online monitoring for floating raft structure displacement based on optimal placement of measuring points
Authors: Cheng Guanghui , Zhang Zhenhai , Shi Liang , Qiu Yuanran
Published: August 2021

The structure displacement of the raft of vibration isolation for ships is an important factor that affects shafting alignment accuracy and the safety of the equipment on the raft. In order to realize real-time monitoring of the raft structure displacement, which is the uncertain loadings and complex in shape, a measuring point placement strategy and an online monitoring method based on the displacement parameters to identify the displacement of the raft are proposed. FEM-based simulations for a prototyped raft have been conducted to obtain the displacement contour map. According to the displacement contour map based on displacement gradient and index evaluation, the measuring points have been combined and optimized. Displacement reconstruction principle based on a surface spline interpolation function method has been elaborated and derived. Structure displacement at any point can be obtained by a few measuring points. Finally, a case study of a certain type of floating raft is analyzed by the simulation analysis, and experimental research. The simulation and experimental results verify the validity of the measuring point placement strategy and the average of relative error with a value of less than 4% under different uncertain loadings. This method can effectively solve the problem of online monitoring of floating raft structure displacement under different changing loadings.
Predictive value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for primary patency of percutaneous transluminal angioplasty in hemodialysis arteriovenous fistula stenosis
Authors: Zhu Feng , Yao Yao , Ci Hongbo , Shawuti Alimujiang
Published: August 2021

Objective

The aim of this study is to investigate the potential association of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula (AVF) stenosis.

Methods

This study conducted a retrospective review of patients with end-stage renal disease referred for hemodialysis AVF stenosis in one center. The study consisted of 114 patients with significant (significant stenosis was defined as a reduction in the caliber of the fistula vein of > 50% with respect to the non-aneurysmal venous segment). AVF stenosis patients were treated with PTA, with conventional balloon angioplasty. The NLR and PLR were calculated from the pre-interventional blood samples. The patients were classified into two groups: group A, primary patency < 12 months ( n = 35) and group B, and primary patency ≥ 12 months ( n = 79). Comparisons between the groups were performed using the Mann–Whitney U test. Kaplan–Meier analysis was performed to compare the factors, NLR and PLR, for association with primary patency AVFs. A receiver-operating characteristic curve analysis was performed to identify the sensitivity and specificity of the NLR and PLR cut-off values in the prediction of primary patency time.

Results

There was no difference in gender; age; side of AVF; AVF type; comorbid diseases such as diabetes mellitus and hypertension; or blood parameters such as white cell count, erythrocytes, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils, basophils, C-reactive protein, NLR, or PLR between the two groups ( p > 0.05). There was also no significant difference in the patency rate between the NLR < 4.13 and NLR ≥ 4.13 groups at 12 months (NLR cut-off point = 4.13, p = 0.273). There were statistically significant differences between the primary patency rates of the PLR < 187.86 and PLR ≥ 187.86 groups at 12 months (PLR cut-off point = 187.86, p = 0.023). The cut-off value for PLR for the determination of primary patency was 187.86, with a sensitivity of 57.0% and specificity of 34.4%.

Conclusion

An increased level of PLR may be a risk factor for the development of early AVF restenosis after successful PTA. However, more studies are needed to validate this finding.
A case of delayed-onset multiple oculogyric crisis and torticollis episodes after low dose intramuscular haloperidol in a non-neuroleptic drug overdose setting
Authors: Khoe Howard Cai Hao , Wong Vivian Shi Yin
Published: August 2021

This report documents a rare case of delayed-onset multiple acute dystonias after treatment with low dose intramuscular (IM) haloperidol lactate injection in a setting of non-neuroleptic drug overdose. The drug–drug interactions between haloperidol and high levels of paracetamol and naproxen are deliberated upon. A 25-year-old Asian female was admitted after an intentional overdose of medications (paracetamol, naproxen and pregabalin). She received 5 mg of IM haloperidol injection for agitation. 21 hours later she experienced mild intermittent ocular deviation in an upward and outward direction and generalised stiffness, which were self-resolving. An hour later, she required another 2.5 mg of IM haloperidol injection for further agitation. In the 35 hours following her first IM haloperidol (13 hours after the second IM haloperidol), she developed a total of three episodes of oculogyric crisis (OGC) with torticollis. Each episode was treated promptly with IM diphenhydramine 25 mg, and there was remission of symptoms within 15 minutes of treatment. An objective causality assessment revealed a definite relationship between the episodes of acute dystonia with IM haloperidol therapy. Where oral alternatives and IM atypical antipsychotics/benzodiazepines are unavailable, rapid tranquillisation with a high-potency typical antipsychotic is a possibility. However, consideration should be made to combine haloperidol with an anticholinergic agent as prophylaxis against acute dystonia, especially in the setting of drug overdose, even if it is that of a non-neuroleptic drug (in this case, paracetamol and naproxen).
Pulmonary embolism after discharge for COVID-19: A report of two cases
Authors: Deutch Mikkel Rodin , Holmberg Mathias J , Gissel Tina , Hollingdal Malene
Published: August 2021

Previous studies have found critically ill patients with COVID-19 to have an increased risk of thromboembolic complications. In this case report of two patients admitted with symptomatic COVID-19, both patients developed pulmonary embolism within a few days after hospital discharge. Both patients received thromboprophylaxis and had an increasing fibrin D-dimer during their hospital stay. Continued thromboprophylaxis after hospital discharge may be indicated for patients with COVID-19, especially for patients at high risk of thrombosis with elevated levels of fibrin D-dimer.
Anxiety and depression symptoms in older adults during coronavirus disease 2019 pandemic: A community-based cross-sectional study
Authors: Jemal Kemal , Geleta Tinsae Abeya , Deriba Berhanu Senbeta , Awol Mukemil
Published: August 2021

Objectives:

The coronavirus disease 2019 pandemic has caused high morbidity and mortality in older adults over the world. Because the coronavirus disease 2019 pandemic greatly affects older adults who have a preexisting health condition, they are generally susceptible to a high incidence of severe symptoms of anxiety and depression. Therefore, we aimed to assess the prevalence of anxiety and depression symptoms in older adults during the coronavirus disease 2019 pandemic.

Methods:

Community-based cross-sectional study was completed in August 2020. Standardized and pretested General Anxiety Disorder–7 and Geriatric Depression Scale were used to screen the symptoms of anxiety and depression, respectively. Data were entered into EpiData (version 4.3.2) and transferred to SPSS (version 24) for further analysis. Bivariate and multivariate logistic regression analyses were carried out to determine the significantly associated variables with a 95% confidence interval at p < 0.05.

Results:

Of the total older adults interviewed, 68.7% had developed symptoms of anxiety and 59.9% had symptoms of depression during the coronavirus disease 2019 pandemic. Female participants, having a chronic disease and poor knowledge of the coronavirus disease 2019 pandemic, were significantly associated with anxiety symptoms. Age category of 81 to 90 and above 90, lack of social support, and having a chronic disease were significantly associated with symptoms of depression.

Conclusion:

The symptoms of anxiety and depression among older adults in the North Shoa Zone during coronavirus disease 2019 were higher than before the coronavirus disease 2019 happened. The results were evidence points for developing a psychological intervention to tackle the older adults’ mental health needs in the community during and after the coronavirus disease 2019 pandemic.
Area- and Individual-Level Correlates of Self-Rated Health: Implications for Geographic Health Disparities
Authors: Moss Jennifer L. , Roy Siddhartha , Clebak Karl T. , Radico Julie , Sell Jarrett , Scartozzi Christina , Zhou Shuai , Chi Guangqing , Oser Tamara
Published: August 2021

Background

Self-rated health (SRH) is a common measure of overall health. However, little is known about multilevel correlates of physical and mental SRH.

Methods

Patients attending primary care clinics completed a survey before their appointment, which we linked to community data from American Community Survey and other sources (n = 455). We conducted multilevel logistic regression to assess correlates of excellent/very good versus good/fair/poor physical and mental SRH.

Results

43.9% of participants had excellent/very good physical SRH, and 55.2% had excellent/very good mental SRH. Physical SRH was associated with age (odds ratio[OR] = 0.82 per 10 years; 95% confidence interval[CI] = 0.72-0.93) and community correlates, including retail establishment density (OR = 0.94, 95% CI = 0.90-0.99) and percent of students eligible for free/reduced lunch (OR = 1.60, 95% CI = 1.08-2.38) (all P < .05). Mental SRH was not associated with any characteristics.

Conclusions

Practitioners in public health, social work, and medicine could use zip codes to intervene in patients and communities to improve physical SRH.
The Mediating Role of Employee Commitment in the Relationship Between Corporate Social Responsibility and Firm Performance in Serbia
Authors: Marić Slobodan , Berber Nemanja , Slavić Agneš , Aleksić Marko
Published: August 2021

This study aims to increase the knowledge on relations between corporate social responsibility (CSR), employee commitment, and firm performance in Serbia. The theoretical part of the article analyzes the relations between CSR and firm performances, as well as CSR and employee commitment, based on available world-wide research results. The empirical part of the article presents the research results for large companies in Serbia, regarding the relations between CSR and firm performance, CSR and employee commitment, and the mediating role of employee commitment on the relationship between CSR and firm performances. The sample consists of 53 large companies, each with more than 250 employees. The database was compiled between October 2019 and March 2020 using self-developed questionnaires. PLS-SEM analysis was implemented to uncover the relationship that exists between the variables. The authors determined that there was no direct effect of CSR on firm performances, but positive, statistically significant effects on employee commitment. Although the direct effect is missing, employee commitment has a positive mediation effect on CSR-firm performance link. The concluding part of the article outlines the theoretical and practical implications, acknowledges research limitations, and offers future research directions.
Tendon-Derived Progenitor Cells With Multilineage Potential Are Present Within Human Patellar Tendon
Authors: Leonardi Erika A. , Xiao Michelle , Murray Iain R. , Robinson William H. , Abrams Geoffrey D.
Published: August 2021

Background:

Progenitor cells serve as a promising source of regenerative potential in a variety of tissue types yet remain underutilized in tendinopathy. Tendon-derived progenitor cells (TDPCs) have previously been isolated from hamstring tendon but only as part of a concomitant medical procedure. Determining the presence of TDPCs in patellar tendon may facilitate clinical utilization of these cells because of the relative accessibility of this location for tissue harvest.

Purpose:

To characterize TDPCs in human patellar tendon samples.

Study Design:

Descriptive laboratory study.

Methods:

Human patellar tendon samples were obtained during elective knee surgery. TDPCs were isolated and seeded at an optimal low cell density and subcultured to confluence for up to 2 passages. Flow cytometry was used to analyze for the expression of CD90+, CD105+, CD44+, and CD31–, CD34–, and CD45– markers. The multilineage differentiation potential of TDPCs was tested in vitro via adipogenic, osteogenic, and chondrogenic culture with subsequent cytochemical staining for Oil Red O, Alizarin Red, and Alcian Blue, respectively. Enzyme-linked immunosorbent assay was used to quantify the amount of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 secreted into cell culture supernatant for further confirmation of lineage differentiation. Results were analyzed statistically using the 2-tailed Student t test.

Results:

TDPCs demonstrated near-uniform expression of CD90, CD105, and CD44 with minimal expression of CD34, CD31, and CD45. Adipogenic, osteogenic, and chondrogenic differentiation of TDPCs was confirmed using qualitative analysis. The expression of adiponectin, alkaline phosphatase, and SRY-box transcription factor 9 were significantly increased in differentiated cells versus undifferentiated TDPCs ( P < .05).

Conclusion:

TDPCs can be successfully isolated from human patellar tendon samples, and they exhibit characteristics of multipotent progenitor cells.

Clinical Relevance:

These data demonstrate the promise of patellar tendon tissue as a source of progenitor cells for use in biologic therapies for the treatment of tendinopathy.
Tendencies of the Absorptive Capacity and Its Correlation with Innovation and the Incubated Companies’ Performance
Authors: Miranda Ana Lucia Brenner Barreto , Nodari Cristine Hermann , Severo Eliana Andrea , Engelman Raquel
Published: August 2021

This study aims at mapping the scientific production of absorptive capacity (ACAP) and identifying how these studies analyse the correlation of ACAP with company innovation and with organisational performance. For such, a bibliometric study was carried out, and it used criteria that selected the main articles that have been published on absorptive capacity in two research bases—ISI Web of Science and Scopus—within a temporal cut from the past 5 years (2014–2018). With the help of the HistCiteTM and VOSviewer software, it was possible to select the articles that addressed the correlation of absorptive capacity with company innovation and organisational performance in the incubated companies’ context. By analysing these articles’ findings, it can be concluded that the absorptive capacity is an antecedent of innovation in companies and has a positive correlation with organisational performance. The studies’ tendencies show that the factors which help with the external knowledge intake are social networks, bonds with agents and partner proximity. However, the incubated companies need the incubators’ support to help with these factors, since they are novice companies and do not keep in touch with important partners. They also need to know how to explore and transform external knowledge into internal benefits.
What Governance Lesson Does Mekong Bear for Ganges–Brahmaputra–Meghna (GBM) Basin?
Authors: Ghosh Nilanjan , Modak Sayanangshu
Published: August 2021

This article talks of the various governance lessons that the Mekong basin bears for the Ganges–Brahmaputra–Meghna (GBM) basin. It highlights the existing hydropolitical and ecological problems associated with the GBM basin, the reasons for which are attributed to the reductionist colonial engineering paradigm also delineated in this article as ‘arithmetic hydrology’. The transboundary interactions in the GBM to resolve the problems have largely relied on an issue-based, piecemeal, fragmented approach that has further complicated the problems. It is in this context, the article brings in how a cooperative mechanism in the institutional form of the Mekong River Commission (MRC) has been attempting to promote a participative and integrated approach to river basin governance. The article, therefore, talks of some of the replicable practices and learnings that may help in takeaways for the GBM riparians and stakeholders from the Mekong system.

JEL Codes: F02, N50, Q01, Q22, Q24, Q25, Q28
Frond architecture of the rootless duckweed Wolffia globosa
Authors: Yang Jingjing , Zhao Xuyao , Li Gaojie , Hu Shiqi , Hou Hongwei
Published: August 2021

Background

The plant body in duckweed species has undergone reduction and simplification from the ancient Spirodela species towards more derived Wolffia species. Among the five duckweed genera, Wolffia members are rootless and represent the smallest and most reduced species. A better understanding of Wolffia frond architecture is necessary to fully explore duckweed evolution.

Results

We conducted a comprehensive study of the morphology and anatomy of Wolffia globosa, the only Wolffia species in China. We first used X-ray microtomography imaging to reveal the three-dimensional and internal structure of the W. globosa frond. This showed that new fronds rapidly budded from the hollow reproductive pocket of the mother fronds and that several generations at various developmental stages could coexist in a single W. globosa frond. Using light microscopy, we observed that the meristem area of the W. globosa frond was located at the base of the reproductive pocket and composed of undifferentiated cells that continued to produce new buds. A single epidermal layer surrounded the W. globosa frond, and the mesophyll cells varied from small and dense palisade-like parenchyma cells to large, vacuolated cells from the ventral to the dorsal part. Furthermore, W. globosa fronds contained all the same organelles as other angiosperms; the most prominent organelles were chloroplasts with abundant starch grains.

Conclusions

Our study revealed that the reproductive strategy of W. globosa plants enables the rapid accumulation of biomass and the wide distribution of this species in various habitats. The reduced body plan and size of Wolffia are consistent with our observation that relatively few cell types are present in these plants. We also propose that W. globosa plants are not only suitable for the study of structural reduction in higher plants, but also an ideal system to explore fundamental developmental processes of higher plants that cannot be addressed using other model plants.
Pyopneumothorax from coinfection by Trichomonas tenax and Geotrichum capitatum in a child from China: a case report
Authors: Wu Yuhui , Ye Yuanzhen , Yang Yanlan , Yang Weiguo , Lin Jiayin , Cao Ke
Published: August 2021

Background

Trichomonas tenax may appear in the oral cavity of humans due to poor dentition or oral hygiene. Pyopneumothorax is a serious complication of lower respiratory tract infections that very rarely can be caused by a trichomonad species in predisposed individuals. We report a rare case of pleurisy due to T. tenax with coinfection by a fungus.

Case presentation

We describe a 16-year-old patient with cerebral palsy who presented with severe pyopneumothorax. T. tenax was identified by microscopic examination of the pleural effusion and next-generation sequencing. We also identified Geotrichum capitatum in the pleural effusion and bronchoalveolar lavage fluid cultures. Treatment with voriconazole and metronidazole successfully eliminated these pathogens and relieved the clinical symptoms. A literature review indicated this is the first reported case of pleurisy due to T. tenax with coinfection by a fungus.

Conclusion

The rarity of pyopneumothorax caused by T. tenax coinfection with a fungus should not be overlooked in the clinic. These patients should be and treated in a timely manner.
Stroke risk factors, subtypes and outcome in elderly Thai patients
Authors: Samuthpongtorn Chatpol , Jereerat Tul , Suwanwela Nijasri C.
Published: August 2021

Background

Nowadays, the number of elderly has steadily increased annually.

Elderly patients with ischemic stroke often have worse outcomes than younger patients. However, there has not been a study of ischemic stroke in the elderly in Thailand. A better knowledge of the risk factors, subtypes, and outcomes of strokes in the elderly may have significant practical implications for the aged society in the future. The objective of the study was to assess the risk factor, stroke subtypes, and outcome of stroke in the elderly compared to the younger patients.

Method

All patients presented with acute ischemic stroke and transient ischemic attack (TIA) aged over 45 years who were admitted in the Stroke unit between November 1st, 2016 and December 31st, 2017 were retrospectively studied.

Result

Five hundred forty-two patients were included. The average age was 68.78 ± 12.03, 44.8% of them were male. 186 (34.3%) patients were 75 or older. Cardioembolism was found to be the most common cause of ischemic stroke in 156 patients (28.8%) and was associated with poor outcome. Patients who were 75 or older had significantly worse outcomes in all categories including NIHSS at discharge, modified Rankin scale, length of stay and the number of deaths compared to the younger group. Atrial fibrillation was the risk factors associated with older age with OR 3.861 (p value< 0.001). Aged 75 years or older, atrial fibrillation, more NIHSS score on admission and history of the previous stroke were the risk factors associated with a patient’s death.

Conclusion

The elderly who are 75 years or older accounts for more than one-third of ischemic stroke in our study. Stroke in the elderly correlates with higher mortality and poorer outcome. Cardioembolism related to atrial fibrillation is the major cause of stroke in this population.
Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment
Authors: Zhou Hao , Zheng Miaosen , Shi Muqi , Wang Jinjie , Huang Zhanghao , Zhang Haijian , Zhou Youlang , Shi Jiahai
Published: August 2021

Background

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky.

Methods

The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model.

Result

Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094).

Conclusion

Our study provides a robust signature for predicting patients’ prognosis, which might be helpful for therapeutic strategies discovery of LUAD.
Individualized diagnosis of major depressive disorder via multivariate pattern analysis of thalamic sMRI features
Authors: Li Hanxiaoran , Song Sutao , Wang Donglin , Tan Zhonglin , Lian Zhenzhen , Wang Yan , Zhou Xin , Pan Chenyuan
Published: August 2021

Background

Magnetic resonance imaging (MRI) studies have found thalamic abnormalities in major depressive disorder (MDD). Although there are significant differences in the structure and function of the thalamus between MDD patients and healthy controls (HCs) at the group level, it is not clear whether the structural and functional features of the thalamus are suitable for use as diagnostic prediction aids at the individual level. Here, we were to test the predictive value of gray matter density (GMD), gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) in the thalamus using multivariate pattern analysis (MVPA).

Methods

Seventy-four MDD patients and 44 HC subjects were recruited. The Gaussian process classifier (GPC) was trained to separate MDD patients from HCs, Gaussian process regression (GPR) was trained to predict depression scores, and Multiple Kernel Learning (MKL) was applied to explore the contribution of each subregion of the thalamus.

Results

The primary findings were as follows: [1] The balanced accuracy of the GPC trained with thalamic GMD was 96.59% (P < 0.001). The accuracy of the GPC trained with thalamic GMV was 93.18% (P < 0.001). The correlation between Hamilton Depression Scale (HAMD) score targets and predictions in the GPR trained with GMD was 0.90 (P < 0.001, r2 = 0.82), and in the GPR trained with GMV, the correlation between HAMD score targets and predictions was 0.89 (P < 0.001, r2 = 0.79). [2] The models trained with ALFF and fALFF in the thalamus failed to discriminate MDD patients from HC participants. [3] The MKL model showed that the left lateral prefrontal thalamus, the right caudal temporal thalamus, and the right sensory thalamus contribute more to the diagnostic classification.

Conclusions

The results suggested that GMD and GMV, but not functional indicators of the thalamus, have good potential for the individualized diagnosis of MDD. Furthermore, the thalamus shows the heterogeneity in the structural features of thalamic subregions for predicting MDD. To our knowledge, this is the first study to focus on the thalamus for the prediction of MDD using machine learning methods at the individual level.
On-site testing and case management to improve hepatitis C care in drug users: a prospective, longitudinal, multicenter study in the DAA era
Authors: Busschots Dana , Bielen Rob , Koc Özgür M. , Heyens Leen , Dercon Eefje , Verrando Rita , Janssens Filip , Van den Bergh Luc , Van Lint Peter , Bruckers Liesbeth , Nevens Frederik , Robaeys Geert
Published: August 2021

Background

Screening and treatment of hepatitis C virus (HCV) infection in people who use drugs (PWUD) remains insufficient. Reducing the burden of HCV infection in PWUD requires interventions focusing on the different steps of the HCV care cascade.

Methods

We performed a prospective, multicenter study, evaluating the impact of an HCV care model on the HCV care cascade among PWUD attending an addiction care center in Belgium between 2015 and 2018. Interventions within the care model consisted of pre-test counseling, on-site HCV screening and case management services. A multiple logistic regression model was performed to identify the independent factors influencing the outcomes.

Results

During the study period, 441 PWUD were registered at the addiction care center, 90% (395/441) were contacted, 88% (349/395) were screened for HCV infection. PWUD were more likely to be screened if they had ever injected drugs (p < .001; AOR 6.411 95% CI 3.464–11.864). In 45% (157/349), the HCV antibody (Ab) test was positive, and in 27% (94/349) HCV RNA was positive. Within the Belgian reimbursement criteria (fibrosis stage ≥ F2), 44% (41/94) were treated. Specialist evaluation at the hospital was lower for PWUD receiving decentralized opioid agonist therapy (p = .005; AOR 0.430 95% CI 0.005–0.380), PWUD with unstable housing in the past 6 months before inclusion (p = .015; AOR 0.035 95% CI 0.002–0.517) or if they were recently incarcerated (p = .001; AOR 0.010 95% CI 0.001–0.164).

Conclusions

This HCV care model demonstrated high screening, linkage to care, and treatment initiation among PWUD in Belgium. Using the cascade of care to guide interventions is easy and necessary to monitor results. This population needs guidance, not only for screening and treatment initiation but also for the long-term follow-up since one in six had cirrhosis and could develop hepatocellular carcinoma. Further interventions are necessary to increase linkage to care and treatment initiation. Universal access to direct-acting antiviral therapy from 2019 will contribute to achieving HCV elimination in the PWUD population.

Trial registration

Clinical trial registration details: www.clinicaltrials.gov (NCT03106194).
Metformin as a new option in the medical management of breast fibroadenoma; a randomized clinical trial
Authors: Alipour Sadaf , Abedi Mahboubeh , Saberi Azin , Maleki-Hajiagha Arezoo , Faiz Firoozeh , Shahsavari Saeed , Eslami Bita
Published: August 2021

Background

Fibroadenoma (FA) is the most common benign solid breast mass in women, with no definite method of management. Because fibroadenoma is dependent on female sex hormones and comprises hypertrophic changes at cellular levels, we investigated the effects of metformin (MF), a safe hypoglycemic agent with anti-estrogenic and anti-proliferative properties, in the management of fibroadenoma.

Methods

In this randomized clinical trial study, eligible women with fibroadenomas were assigned randomly to the metformin (1000 mg daily for six months) or the placebo group. Breast physical and ultrasound exam was performed before and after the intervention, and the changes in the size of fibroadenomas were compared in the two groups.

Results

Overall, 83 patients in the treatment, and 92 in the placebo group completed the study. A statistically significant difference in changing size between the two groups was observed only in the smallest mass. In the largest FAs, the rate of size reduction was higher in the treatment group (60.2 % vs. 43.5 %); while a higher rate of enlargement was observed in the placebo group (38 % vs. 20.5 %). In the smallest FAs, the rate of the masses that got smaller or remained stable was about 90 % in the treatment group and 50 % in the placebo group. We categorized size changes of FAs into < 20 % enlargement and ≥ 20 % enlargement. The odds ratio (OR) for an elargemnt less than 20% was 1.48 (95 % CI = 1.10–1.99) in the treatment group in comparison with the placebo group; the odds for an enlargement less than 20% was higher in women with multiples fibroadenomas (OR = 4.67, 95 % CI: 1.34–16.28). In our study, no serious adverse effect was recorded, and the medicine was well-tolerated by all users.

Conclusions

This is the first study that evaluates the effect of MF on the management of fibroadenoma, and the results suggest a favorable effect. Larger studies using higher doses of MF and including a separate design for patients with single or multiple FAs are suggested in order to confirm this effect.

Trial registration

This trial (IRCT20100706004329N7) was retrospectively registered on 2018-10-07.
Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study
Authors: Na Ding , Tao Guo , Shu-Ying Liu , Qin-Yi Wang , Xiao-Li Qu , Yong-Fang Li , Yang-Na Ou , Zhi-Feng Sheng , Yan-Yi Yang
Published: August 2021

Background

The occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT.

Methods

This was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group.

Results

Among the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged.

Conclusion

Biochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis.
Pitx controls amphioxus asymmetric morphogenesis by promoting left-side development and repressing right-side formation
Authors: Xing Chaofan , Pan Rongrong , Hu Guangwei , Liu Xian , Wang Yiquan , Li Guang
Published: August 2021

Background

Left-right (LR) asymmetry is an essential feature of bilateral animals. Studies in vertebrates show that LR asymmetry formation comprises three major steps: symmetry breaking, asymmetric gene expression, and LR morphogenesis. Although much progress has been made in the first two events, mechanisms underlying asymmetric morphogenesis remain largely unknown due to the complex developmental processes deployed by vertebrate organs.

Results

We here addressed this question by studying Pitx gene function in the basal chordate amphioxus whose asymmetric organogenesis, unlike that in vertebrates, occurs essentially in situ and does not rely on cell migration. Pitx null mutation in amphioxus causes loss of all left-sided organs and incomplete ectopic formation of all right-sided organs on the left side, whereas Pitx partial loss-of-function leads to milder phenotypes with only some LR organs lost or ectopically formed. At the N1 to N3 stages, Pitx expression is gradually expanded from the dorsal anterior domain to surrounding regions. This leads to activation of genes like Lhx3 and/or Prop1 and Pit, which are essential for left-side organs, and downregulation of genes like Hex and/or Nkx2.1 and FoxE4, which are required for right-side organs to form ectopically on the left side. In Pitx mutants, the left-side expressed genes are not activated, while the right-side genes fail to decrease expression on the left side. In contrast, in embryos overexpressing Pitx genes, the left-side genes are induced ectopically on the right side, and the right-side genes are inhibited. Several Pitx binding sites are identified in the upstream sequences of the left-side and right-side genes which are essential for activation of the former and repression of the latter by Pitx.

Conclusions

Our results demonstrate that (1) Pitx is a major (although not the only) determinant of asymmetric morphogenesis in amphioxus, (2) the development of different LR organs have distinct requirements for Pitx activity, and (3) Pitx controls amphioxus LR morphogenesis probably through inducing left-side organs and inhibiting right-side organs directly. These findings show much more dependence of LR organogenesis on Pitx in amphioxus than in vertebrates. They also provide insight into the molecular developmental mechanism of some vertebrate LR organs like the lungs and atria, since they show a right-isomerism phenotype in Pitx2 knockout mice like right-sided organs in Pitx mutant amphioxus. Our results also explain why some organs like the adenohypophysis are asymmetrically located in amphioxus but symmetrically positioned in vertebrates.
Long non-coding RNA NEAT1 facilitates the growth, migration, and invasion of ovarian cancer cells via the let-7 g/MEST/ATGL axis
Authors: Yin Lili , Wang Yu
Published: August 2021

Background/Aim

Growing evidence indicates a significant role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) in ovarian cancer, a frequently occurring malignant tumor in women; however, the possible effects of an interplay of NEAT1 with microRNA (miRNA or miR) let-7 g in ovarian cancer are not known. The current study aimed to investigate the role of the NEAT1/let-7 g axis in the growth, migration, and invasion of ovarian cancer cells and explore underlying mechanisms.

Methods

NEAT1 expression levels were examined in clinical tissue samples and cell lines. The relationships between NEAT1, let-7 g, and MEST were then analyzed. Gain- or loss-of-function approaches were used to manipulate NEAT1 and let-7 g. The effects of NEAT1 on cell proliferation, migration, invasion, and apoptosis were evaluated. Mouse xenograft models of ovarian cancer cells were established to verify the function of NEAT1 in vivo.

Results

NEAT1 expression was elevated while let-7 g was decreased in ovarian cancer clinical tissue samples and cell lines. A negative correlation existed between NEAT1 and let-7 g, whereby NEAT1 competitively bound to let-7 g and consequently down-regulate let-7 g expression. By this mechanism, the growth, migration, and invasion of ovarian cancer cells were stimulated. In addition, let-7 g targeted mesoderm specific transcript (MEST) and inhibited its expression, leading to promotion of adipose triglyceride lipase (ATGL) expression and inhibition of ovarian cancer cell growth, migration, and invasion. However, the effect of let-7 g was abolished by overexpression of MEST. Furthermore, silencing of NEAT1 decreased the xenograft tumor growth by decreasing MEST while up-regulating let-7 g and ATGL.

Conclusions

Cumulatively, the findings demonstrated that NEAT1 could promote malignant phenotypes of ovarian cancer cells by regulating the let-7 g/MEST/ATGL signaling axis. Therefore, NEAT1 can be regarded as an important molecular target and biomarker for ovarian cancer.
MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway
Authors: Xu Qian , Zhang Qianqian , Dong Mengli , Yu Yuan
Published: August 2021

Background

Previous studies had shown that microRNA-638 (miR-638) exhibited different effects in malignant tumors. Moreover, the function of miR-638 has not been reported in breast cancer. Hence, we designed this research to explore the function of miR-638 in breast cancer.

Methods

Firstly, miR-638 expressions were measured in breast cancer tissues via RT-qPCR. Protein expressions were detected through immunocytochemical (IHC) assay and western blot analysis. Then, Cell Counting Kit-8 (CCK-8) assay and Transwell assay were conducted to observe proliferation and motility of the cells. Dual luciferase assay was performed to confirm the binding site between miR-638 and Homeobox protein Hox-A9 (HOXA9).

Results

Reduced expression of miR-638 was detected in breast cancer. And low miR-638 expression was related to poor prognosis in patients with breast cancer. Functionally, the viability, migration, and invasion of the breast cancer cells were suppressed by miR-638 overexpression. Furthermore, miR-638 can directly bind to HOXA9, and increased expression of HOXA9 was also detected in breast cancer. In particular, HOXA9 upregulation can impair anti-tumor effect of miR-638 in breast cancer, and miR-638 can hinder the Wnt/β-cadherin pathway and epithelial-mesenchymal transition (EMT) in breast cancer.

Conclusion

miR-638 inhibits breast cancer progression through binding to HOXA9.
Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus
Authors: Nair Soumyalekshmi , Guanzon Dominic , Jayabalan Nanthini , Lai Andrew , Scholz-Romero Katherin , Kalita de Croft Priyakshi , Ormazabal Valeska , Palma Carlos , Diaz Emilio , McCarthy Elizabeth A. , Shub Alexis , Miranda Jezid , Gratacós Eduard , Crispi Fátima , Duncombe Gregory , Lappas Martha , McIntyre H. David , Rice Gregory , Salomon Carlos
Published: August 2021

Background

Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9–15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile.

Methods

Discovery: A retrospective, case–control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM.

Results

A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated withJAK-STATsignaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake.

Conclusions

During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.
Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people
Authors: Parry Helen , Bruton Rachel , Stephens Christine , Brown Kevin , Amirthalingam Gayatri , Otter Ashley , Hallis Bassam , Zuo Jianmin , Moss Paul
Published: August 2021

Background

Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’.

Objectives

We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot.

Results

Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022).

Conclusion

Dual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.