bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
Authors: Cancino-Marentes Martha E. , Hernández-Flores Georgina , Ortiz-Lazareno Pablo Cesar , Villaseñor-García María Martha , Orozco-Alonso Eduardo , Sierra-Díaz Erick , Solís-Martínez Raúl Antonio , Cruz-Gálvez Claudia Carolina , Bravo-Cuellar Alejandro
Published: March 2021

Background

Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) comprises the first line of treatment. However, the response is poor due to chemoresistance and toxicity. On the other hand, Pentoxifylline (PTX) is an unspecific inhibitor of phosphodiesterases; experimental, and clinically it has been described as sensitizing tumor cells to chemotherapy, increasing apoptosis and decreasing senescence. We study whether the PTX sensitizes prostate cancer cells to DTX for greater effectiveness.

Methods

PC3 human prostate cancer cells were treated in vitro at different doses and times with PTX, DTX, or their combination. Viability was determined by the WST-1 assay by spectrophotometry, cell cycle progression, apoptosis, generic caspase activation and senescence by flow cytometry, DNA fragmentation and caspases-3, -8, and -9 activity by ELISA.

Results

We found that PTX in PC3 human prostate cancer cells induces significant apoptosis per se and increases that generated by DTX, while at the same time it reduces the senescence caused by the chemotherapy and increases caspases-3,-8, and -9 activity in PTX + DTX-treated cells. Both treatments blocked the PC3 cell in the G1 phase.

Conclusions

Our results show that PTX sensitizes prostate tumor cells to apoptosis induced by DTX. Taken together, the results support the concept of chemotherapy with rational molecular bases.
The impact of early phase price agreements on prices of orphan drugs
Authors: Nuijten Mark , Van Wilder Philippe
Published: March 2021

Background

Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors.

Methods

We used a Pricing Model, which determines the minimum (break-even) price of an innovative drug from an investor’s perspective. This model is based on economic valuation theory, which uses the expected free cash flows and the required cost of capital. We selected two orphan drugs with a positive clinical assessment and an ICER higsher than the Dutch maximum threshold of €80,000 per QALY gained to use as examples in the model: Spinraza for spinal muscular atrophy and Orkambi for cystic fibrosis.

RESULTS: The results show that early pricing agreements before phase III trials can substantially lower the drug price resulting from a lower cost of capital. The minimum price for orphan drugs can be reduced by 27.4%, when cost of capital decreases from 12 to 9%. An additional adjustment of other critical parameters due to early pricing agreements (lower probabilities of phase III failure and lower research and development (R&D) costs) can further reduce the minimal price by 62.8%.

Conclusion

This study shows that earlier timing of price negotiations resulting in an agreement on drug price can substantially lower the minimal price of orphan drugs for the investor.
Correction to: Providing dental insurance can positively impact oral health outcomes in Ontario
Authors: Zivkovic Nevena , Aldossri Musfer , Gomaa Noha , Farmer Julie W. , Singhal Sonica , Quiñonez Carlos , Ravaghi Vahid
Published: March 2021

An amendment to this paper has been published and can be accessed via the original article.
An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients
Authors: Zhu Gongmin , Xia Hongwei , Tang Qiulin , Bi Feng
Published: March 2021

Background

Tumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients.

Methods

Gene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments.

Results

An EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion.

Conclusion

The EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.
Performance of a sensitive haemozoin‐based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon
Authors: de Melo Gisely Cardoso , Netto Rebeca Linhares Abreu , Mwangi Victor Irungu , Salazar Yanka Evellyn Alves Rodrigues , de Souza Sampaio Vanderson , Monteiro Wuelton Marcelo , de Almeida e Val Fernando Fonseca , Rocheleau Anne , Thota Priyaleela , Lacerda Marcus Vinícius Guimarães
Published: March 2021

Background

Vivax malaria diagnosis remains a challenge in malaria elimination, with current point of care rapid diagnostic tests (RDT) missing many clinically significant infections because of usually lower peripheral parasitaemia. Haemozoin-detecting assays have been suggested as an alternative to immunoassay platforms but to date have not reached successful field deployment. Haemozoin is a paramagnetic crystal by-product of haemoglobin digestion by malaria parasites and is present in the food vacuole of malaria parasite-infected erythrocytes. This study aimed to compare the diagnostic capability of a new haemozoin-detecting platform, the Gazelle™ device with optical microscopy, RDT and PCR in a vivax malaria-endemic region.

Methods

A comparative, double-blind study evaluating symptomatic malaria patients seeking medical care was conducted at an infectious diseases reference hospital in the western Brazilian Amazon. Optical microscopy, PCR, RDT, and Gazelle™ were used to analyse blood samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa values were calculated.

Results

Out of 300 patients, 24 test results were excluded from the final analysis due to protocol violation (6) and inconclusive and/or irretrievable results (18). Gazelle™ sensitivity was 96.1 % (91.3–98.3) and 72.1 % (65.0–78.3) when compared to optical microscopy and PCR, respectively whereas it was 83.9 % and 62.8 % for RDTs. The platform presented specificity of 100 % (97.4–100), and 99.0 % (94.8–99.9) when compared to optical microscopy, and PCR, respectively, which  was the same for RDTs. Its correct classification rate was 98.2 % when compared to optical microscopy and 82.3 % for PCR; the test’s accuracy when compared to optical microscopy was 98.1 % (96.4–99.7), when compared to RDT was 95.2 % (93.0–97.5), and when compared to PCR was 85.6 % (82.1–89.1). Kappa (95 % CI) values for Gazelle™ were 96.4 (93.2–99.5), 88.2 (82.6–93.8) and 65.3 (57.0–73.6) for optical microscopy, RDT and PCR, respectively.

Conclusions

The Gazelle™ device was shown to have faster, easier, good sensitivity, specificity, and accuracy when compared to microscopy and was superior to RDT, demonstrating to be an alternative for vivax malaria screening particularly in areas where malaria is concomitant with other febrile infections (including dengue fever, zika, chikungunya, Chagas, yellow fever, babesiosis).
“My first 48 hours out”: drug users’ perspectives on challenges and strategies upon release from prison
Authors: Jamin Daniela , Vanderplasschen Wouter , Sys Orphée , Jauffret-Roustide Marie , Michel Laurent , Trouiller Philippe , Neisa Andreia , Homen Mariana , Mendes Vânia , Stöver Heino
Published: March 2021

Background

Prisoners report much higher prevalence rates of drug use and more harmful consumption patterns than the general population. People who use drugs have above-average experiences with the criminal justice system in general, and the prison system and subsequent release situations in particular. Release from prison is associated with increased mortality rates among drug users due to the risk of overdose. The EU-funded project ‘My first 48 hours out’ aimed to address the gaps in continuity of care for long-term drug users in prison and upon release, with a special focus on drug user’s perspectives on needs and challenges upon release.

Methods

A multi-country (Belgium, France, Germany and Portugal) qualitative study was set up to explore drug users’ perceptions of drug use and risk behaviour upon prison release, experiences of incarceration and release, and strategies to avoid risks when being released. In total, 104 prisoners and recently released persons with a history of drug use participated in semi-structured interviews and focus groups discussions on these topics.

Results

Respondents pointed out that there are numerous challenges for people who use drugs when released from prison. Lack of stable housing and employment support were frequently mentioned, as well as complex administrative procedures regarding access to services, health insurance and welfare benefits. Besides structural challenges, individual issues may challenge social reintegration like ‘old habits’, mental health problems and disrupted social networks. As a result, (ex-)prisoners adopt individual strategies to cope with the risks and challenges at release.

Conclusion

Measures to prepare prisoners for release often do not focus on the individual and specific challenges of persons who use drugs. Psychosocial and medical support need to be improved and adjusted to drug users’ needs inside and outside prison. To improve the quality and continuity of care around release, the perspectives and coping strategies of people who use drugs should be used to better address their needs and barriers to treatment.
A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
Authors: Liu Renjie , Wang Guifu , Zhang Chi , Bai Dousheng
Published: March 2021

Background

Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated.

Methods

To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model.

Results

Compared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram.

Conclusion

Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.
Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries
Authors: Rowley Seth , Garcia-Gonzalez Pat , Radich Jerald P. , Novakowski Ann Kim , Usherenko Irina , Babigumira Joseph B.
Published: March 2021

Purpose

To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs).

Methods

We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid’s GeneXpert® IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives.

Results

The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges.

Conclusion

Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.
The ‘Eat Well @ IGA’ healthy supermarket randomised controlled trial: process evaluation
Authors: Blake Miranda R. , Sacks Gary , Zorbas Christina , Marshall Josephine , Orellana Liliana , Brown Amy K. , Moodie Marj , Ni Mhurchu Cliona , Ananthapavan Jaithri , Etilé Fabrice , Cameron Adrian J.
Published: March 2021

Background

Successful implementation and long-term maintenance of healthy supermarkets initiatives are crucial to achieving potential population health benefits. Understanding barriers and enablers of implementation of real-world trials will enhance wide-scale implementation. This process evaluation of a healthy supermarket intervention sought to describe (i) customer, retailer and stakeholder perspectives on the intervention; (ii) intervention implementation; and (iii) implementation barriers and enablers.

Methods

Eat Well @ IGAwas a 12-month randomised controlled trial conducted in 11 Independent Grocers of Australia (IGA) chain supermarkets in regional Victoria, Australia (5 intervention and 6 wait-listed control stores). Intervention components included trolley and basket signage, local area and in-store promotion, and shelf tags highlighting the healthiest packaged foods. A sequential mixed-methods process evaluation was undertaken. Customer exit surveys investigated demographics, and intervention recall and perceptions. Logistic mixed-models estimated associations between customer responses and demographics, with store as random effect. Supermarket staff surveys investigated staff demographics, interactions with customers, and intervention component feedback. Semi-structured stakeholder interviews with local government, retail and academic partners explored intervention perceptions, and factors which enabled or inhibited implementation, maintenance and scalability. Interviews were inductively coded to identify key themes.

Results

Of 500 customers surveyed, 33%[95%CI:23,44] recalled theEat Well @ IGAbrand and 97%[95%CI:93,99] agreed that IGA should continue its efforts to encourage healthy eating. The 82 staff surveyed demonstrated very favourable intervention perceptions. Themes from 19 interviews included that business models favour sales of unhealthy foods, and that stakeholder collaboration was crucial to intervention design and implementation. Staff surveys and interviews highlighted the need to minimise staff time for project maintenance and to regularly refresh intervention materials to increase and maintain salience among customers.

Conclusions

This process evaluation found that interventions to promote healthy diets in supermarkets can be perceived as beneficial by retailers, customers, and government partners provided that barriers including staff time and intervention salience are addressed. Collaborative partnerships in intervention design and implementation, including retailers, governments, and academics, show potential for encouraging long-term sustainability of interventions.

Trial registration

ISRCTN,ISRCTN37395231Registered 4 May 2017.
Predictive value of C-reactive protein to albumin ratio as a biomarker for initial and repeated intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients: a prospective cohort study
Authors: Liu Xiaoliang , Wang Lin , Zhou Kaiyu , Shao Shuran , Hua Yimin , Wu Mei , Liu Lei , Wang Chuan
Published: March 2021

Background

Intravenous immunoglobulin (IVIG) resistance prediction is one pivotal topic of interests in Kawasaki disease (KD). This study aimed to prospectively investigated the value of C-reactive protein-to-albumin (CAR) in predicting both initial and repeated IVIG resistance in patients with KD, and to test the hypothesis that CAR was more valuable or accurate than either C-reactive protein (CRP) or albumin (ALB) alone in IVIG resistance prediction.

Method

A prospective cohort study involving 550 patients with KD was conducted. The clinical and laboratory data were compared between IVIG-response group and IVIG-resistance group. Multivariate logistic regression analysis was performed to identify the independent risk factors of initial/repeated IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of CAR, CRP and ALB in predicting both initial and repeated IVIG resistance.

Results

CAR was significantly higher in IVIG non-responders and was identified as independent risk factor for both initial and repeated IVIG resistance in KD. The best cut-off value of CAR for initial and repeated IVIG resistance prediction was 2.07 and 3.34, with a corresponding sensitivity of 0.610 and 0.548, a specificity of 0.552 and 0.813, respectively. The value of CAR was not better than either CRP or ALB alone for both initial and repeated IVIG resistance prediction.

Conclusion

A higher CAR was an independent risk factor for both initial and repeated IVIG resistance. However, similar with that of CRP or ALB, the predictive value of CAR was not good enough for both initial and repeated IVIG resistance prediction in KD.
Sustained remission after haploidentical bone marrow transplantation in a child with refractory systemic juvenile idiopathic arthritis
Authors: Morelle Guillaume , Castelle Martin , Pinto Graziella , Breton Sylvain , Bendavid Matthieu , Boussard Charlotte , Mouy Richard , Bader-Meunier Brigitte , Semeraro Michaela , Faye Albert , Cavazzana Marina , Neven Bénédicte , Blanche Stéphane , Quartier Pierre , Moshous Despina
Published: March 2021

Background

Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high.

Case report

A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs.

Conclusion

Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.
Factors associated with age-disparate sexual partnerships among males and females in South Africa: a multinomial analysis of the 2012 national population-based household survey data
Authors: Mabaso Musawenkosi , Mlangeni Lungelo , Makola Lehlogonolo , Oladimeji Olanrewaju , Naidoo Inbarani , Naidoo Yogandra , Chibi Buyisile , Zuma Khangelani , Simbayi Leickness
Published: March 2021

Background

In South Africa, age-disparate to sexual relationships where the age difference between partners is 5 years or greater is an important contributor to the spread of HIV. However, little is known about the predictors of age-disparate sexual relationships. This study investigates factors associated with age-disparate sexual relationships among males and females in South Africa.

Methods

This analysis used the 2012 nationally representative population-based household survey conducted using multi-stage stratified cluster sampling design. Multivariate multinomial stepwise logistic regression models were used to determine factors associated with age-disparate sexual relationships.

Results

Of 15,717 participants, who responded to the question on age-disparate sexual relationships, 62% males versus 58.5% females had partners within 5 years older or younger, 34.7% of males versus 2.7% of females had partners at least 5 years younger and 3.3% of males versus 38.8% of females had partners at least 5 years older. Among both males and females predictors of age-disparate sexual relationships were education, employment, socioeconomic status, locality type, age at sexual debut, condom use at last sexual act and HIV status while race was also an additional predictor for among females. Including unprotected sex and risk of HIV infection among adolescent girls and young women with sexual partners 5 years older their age.

Conclusions

This study suggest that there is a need for reprioritizing the combination of behavioural and structural interventions to address risky sexual behaviours, unprotected sex, poverty, limited education and gender inequitable norms related to age-disparate sexual relationships and HIV.
The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice
Authors: Sugimoto Hisako , Horii Takuro , Hirota Jun-Na , Sano Yoshitake , Shinoda Yo , Konno Ayumu , Hirai Hirokazu , Ishizaki Yasuki , Hirase Hajime , Hatada Izuho , Furuichi Teiichi , Sadakata Tetsushi
Published: March 2021

The HapMap Project is a major international research effort to construct a resource to facilitate the discovery of relationships between human genetic variations and health and disease. The Ser19Stop single nucleotide polymorphism (SNP) of human phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL) gene was detected in HapMap project and registered in the dbSNP. PHYHIPL gene expression is altered in global ischemia and glioblastoma multiforme. However, the function of PHYHIPL is unknown. We generated PHYHIPL Ser19Stop knock-in mice and found that PHYHIPL impacts the morphology of cerebellar Purkinje cells (PCs), the innervation of climbing fibers to PCs, the inhibitory inputs to PCs from molecular layer interneurons, and motor learning ability. Thus, the Ser19Stop SNP of the PHYHIPL gene may be associated with cerebellum-related diseases.
Frequency of asymptomatic carriers of SARS-CoV-2 among children and adults after school reopening
Authors: Milani Gregorio P. , Marchisio Paola , Rocchi Alessia , Bertolozzi Giuseppe , Furlan Ludovico , La Vecchia Adriano , Agostoni Carlo , Costantino Giorgio
Published: March 2021

Background

Children often develop an asymptomatic form of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but it is debated if children are at higher risk than adults to be asymptomatic carriers of SARS-CoV-2, especially during the school reopening. The main aim of this study was to investigate the frequency of SARS-CoV-2 asymptomatic carriers in children and adults during the reopening of the schools in Milan, Italy.

Methods

We conducted a cross-sectional study at the pediatric and adult Emergency Department (ED) of the Ca' Granda Ospedale Maggiore Policlinico (Milan) between October 1 and 31, 2020, i.e. 3 weeks after the reopening of schools. Patients admitted to the ED short stay observation and without any sign or symptom consistent with a SARS-CoV-2 were eligible. These patients underwent a nasopharyngeal swab specimen for the detection of SARS-CoV-2. The odds ratio and its 95% confidence interval (CI) was calculated to assess the risk of asymptomatically carrying the SARS-CoV-2 infection in children and adults.

Results

A total of 69 (27 females, median age 8.7 years) children and 251 (107 females, median age 71 years) adults were enrolled. Pediatric and adult subjects tested positive for SARS-CoV-2 with a similar frequency (1/69 [1.4%] vs 4/251 [1.6%]). Children had an odds ratio to be a carrier of 0.91 (CI 0.02– 9.38) compared to adults.

Conclusions

The frequency of asymptomatic SARS-CoV-2 carriers was similar among children and adults. Considering the emerging diffusion of new SARS-CoV-2 variants, the asymptomatic spread of SARS-CoV-2 infection among children and adults should be monitored.
Dietary and lifestyle inflammatory scores are associated with increased risk of metabolic syndrome in Iranian adults
Authors: Farhadnejad Hossein , Parastouei Karim , Rostami Hosein , Mirmiran Parvin , Azizi Fereidoun
Published: March 2021

Background

In the current study, we aimed to investigate the association of dietary inflammation scores (DIS) and lifestyle inflammation scores (LIS) with the risk of metabolic syndrome (MetS) in a prospective population-based study.

Methods

A total of 1625 participants without MetS were recruited from among participants of the Tehran Lipid and Glucose Study(2006–2008) and followed a mean of 6.1 years. Dietary data of subjects were collected using a food frequency questionnaire at baseline to determine LIS and DIS. Multivariable logistic regression models, were used to calculate the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across tertiles of DIS and LIS.

Results

Mean ± SD age of individuals (45.8 % men) was 37.5 ± 13.4 years. Median (25–75 interquartile range) DIS and LIS for all participants was 0.80 (− 2.94, 3.64) and 0.48 (− 0.18, − 0.89), respectively. During the study follow-up, 291 (17.9 %) new cases of MetS were identified. Based on the age and sex-adjusted model, a positive association was found between LIS (OR = 7.56; 95% CI 5.10–11.22, P for trend < 0.001) and risk of MetS, however, the association of DIS and risk of MetS development was not statistically significant (OR = 1.30;95% CI 0.93–1.80, P for trend = 0.127). In the multivariable model, after adjustment for confounding variables, including age, sex, body mass index, physical activity, smoking, and energy intake, the risk of MetS is increased across tertiles of DIS (OR = 1.59; 95% CI 1.09–2.33, P for trend = 0.015) and LIS(OR = 8.38; 95% CI 5.51–12.7, P for trend < 0.001).

Conclusions

The findings of the current study showed that greater adherence to LIS and DIS, determined to indicate the inflammatory potential of diet and lifestyle, are associated with increased the risk of MetS.
Reprogrammed mesenchymal stem cells derived from iPSCs promote bone repair in steroid-associated osteonecrosis of the femoral head
Authors: Zhou Meiling , Xi Jiaoya , Cheng Yaofeng , Sun Denglong , Shu Peng , Chi Shuiqing , Tian Shuo , Ye Shunan
Published: March 2021

Background

Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations.

Methods

In the present study, the bone marrow samples of patients with ONFH (n = 16) and patients with the fracture of the femoral neck (n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups (n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation.

Results

The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head.

Conclusion

Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.
Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway
Authors: Xu Haoying , Yang Yanlei , Fan Linyuan , Deng Luchan , Fan Junfen , Li Di , Li Hongling , Zhao Robert Chunhua
Published: March 2021

Background

Obesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and differentiation. The objective of the present study was to identify and investigate the function and regulatory mechanism of lncRNAs on adipogenic differentiation of hADSCs.

Methods

We used lncRNA arrays to identify the prominent differentially expressed lncRNAs before and after hADSC adipogenic differentiation and verified their biological function through antisense oligonucleotide knockdown or lentivirus overexpression. The adipogenic differentiation of hADSCs was assessed by oil red O staining as well as the mRNA and protein levels of adipogenic marker genes through qRT-PCR and western blot. Bioinformatic tool LncPro and immunofluorescence was performed to uncover the interaction between lnc13728 and ZBED3. WNT/β-catenin signaling pathway was evaluated by western blot and immunofluorescence.

Results

The lncRNA arrays showed that lnc13728 expression was significantly upregulated after hADSC adipogenic differentiation and was correlated positively with the expression of the adipogenesis-related genes in human adipose tissue. Lnc13728 knockdown in hADSCs suppressed the expression of the adipogenesis-related genes at both mRNA and protein level and weakened lipid droplet production. Accordingly, lnc13728 overexpression enhanced hADSC adipogenic differentiation. Beyond that, lnc13728 co-localized with ZBED3 in the cytoplasm and regulated its expression positively. DownregulatingZBED3had a negative effect on adipogenic differentiation, while the expression of WNT/β-catenin signaling pathway-related proteins was upregulated.

Conclusions

Lnc13728 promotes hADSC adipogenic differentiation possibly by positively regulating the expression of ZBED3 which plays a role in inhibiting the WNT/β-catenin pathway.
Concentrated exosomes from menstrual blood-derived stromal cells improves ovarian activity in a rat model of premature ovarian insufficiency
Authors: Zhang Siwen , Huang Boxian , Su Peng , Chang Qiyuan , Li Pingping , Song Aixin , Zhao Xinyang , Yuan Zhengwei , Tan Jichun
Published: March 2021

Background

Premature ovarian insufficiency (POI) is one of the major causes of infertility. We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) effectively improved ovarian function in a murine model of POI. Recent studies indicated that mesenchymal stem cell-derived exosomes were important components in tissue repair. In this study, we investigated the therapeutic effects of MenSCs-derived exosomes (MenSCs-Exos) in a rat model of POI and its mechanism in restoring ovulation.

Methods

Ovaries of 4.5-day-old Sprague Dawley rats (SD rats) were cultured in vitro to evaluate the effects of MenSCs-Exos exposure on early follicle development. Furthermore, POI in rats was induced by intraperitoneal administration of 4-vinylcyclohexene diepoxide (VCD). Forty-eight POI rats were randomly assigned to four groups, each receiving a different treatment: PBS, MenSCs, MenSCs-Exos, and Exo-free culture supernatant of MenSCs. Estrous cyclicity, ovarian morphology, follicle dynamics, serum hormones, pregnancy outcomes, and molecular changes were investigated.

Results

Exposure to MenSCs-Exos promoted the proliferation of granulosa cells in primordial and primary follicles in vitro and increased the expression of early follicle markers Deleted In Azoospermia Like (DAZL) and Forkhead Box L2 (FOXL2) while inhibiting follicle apoptosis. In vivo, MenSCs-Exos transplantation effectively promoted follicle development in the rat model of POI and restored the estrous cyclicity and serum sex hormone levels, followed by improving the live birth outcome. In addition, transplantation of MenSCs-Exos regulated the composition of the ovarian extracellular matrix and accelerated the recruitment of dormant follicles in the ovarian cortex and increased proliferation of granulosa cells in these follicles.

Conclusion

MenSCs-Exos markedly promoted follicle development in vitro and in vivo and restored fertility in POI rats, suggesting a restorative effect on ovarian functions. The therapeutic effect of MenSCs-Exos transplantation was sustainable, consistent with that of MenSCs transplantation. Our results suggested that MenSCs-Exos transplantation may be a promising cell-free bioresource in the treatment of POI.
Validating Star-Oddi heart rate and acceleration data storage tags for use in Atlantic salmon (Salmo salar)
Authors: Zrini Zoe Amanda , Gamperl A. Kurt
Published: March 2021

Background

Data storage tags (DSTs) record and store information about animals and their environment, and can provide important data relevant to fish culture, ecology and conservation. A DST has recently been developed that records heart rate (fH), electrocardiograms (ECGs), tri-axial acceleration and temperature. However, at the time of this study, no research using these tags had been performed on fish or determined the quality of the data collected. Thus, our research asked: do these DSTs provide reliable and meaningful data? To examine this question, Atlantic salmon (1.4 ± 0.7 kg) were implanted with DSTs, then swam at increasing speeds in a swim tunnel after 1 week of recovery. Further, in two separate experiments, salmon (2.4 ± 0.1 kg) were implanted with DSTs and held in a large tank with conspecifics for 1 week at 11 °C or 6 weeks at 8–12 °C.

Results

External acceleration (EA) and variation in EA (VAR) increased exponentially with swimming speed and tail beat frequency. The quality index (QI) assigned to ECG recordings (where QI0 means very good quality, and QI1, QI2 and QI3 are of reduced quality) did not change significantly with increasing swimming speed (QI0 ~ 60–80%). However, we found that the accuracy of the tag algorithm in estimating fH from ECGs was reduced when QI>0. Diurnal patterns of fH and EA were evident from the time the salmon were placed in the tank. Heart rate appeared to stabilize by ~ 4 days post-surgery in the first experiment, but extended holding showed that fH declined for 2–3 weeks. During extended holding, the tag had difficulty recording low fH values < 30 bpm, and for this reason, in addition to the fact that the algorithm can miscalculate fH, it is highly recommended that ECGs be saved when possible for quality control and so that fH values with QI>0 can be manually calculated.

Conclusions

With these DSTs, parameters of acceleration can be used to monitor the activity of free-swimming salmon. Further, changes in fH and heart rate variability (HRV) due to diurnal rhythms, and in response to temperature, activity and stressors, can be recorded.
Very preterm infants engage in an intervention to train their control of attention: results from the feasibility study of the Attention Control Training (ACT) randomised trial
Authors: Perra Oliver , Wass Sam , McNulty Alison , Sweet David , Papageorgiou Kostas A. , Johnston Matthew , Bilello Delfina , Patterson Aaron , Alderdice Fiona
Published: March 2021

Background

Very premature birth (gestational age between 28 and 31 + 6 weeks) is associated with increased risk of cognitive delay and attention deficit disorder, which have been linked to anomalies in the development of executive functions (EFs) and their precursors. In particular, very preterm (VP) infants display anomalies in controlling attention and gathering task-relevant information. Early interventions that support attention control may be pivotal in providing a secure base for VP children’s later attainments. The Attention Control Training (ACT) is a cognitive training intervention that targets infants’ abilities to select visual information according to varying task demands but had not been tested in VP infants. We conducted a feasibility study to test the processes we intend to use in a trial delivering the ACT to VP infants.

Methods and design

We tested recruitment and retention of VP infants and their families in a randomised trial, as well as acceptability and completion of baseline and outcome measures. To evaluate these aims, we used descriptive quantitative statistics and qualitative methods to analyse feedback from infants’ caregivers. We also investigated the quality of eye-tracking data collected and indicators of infants’ engagement in the training, using descriptive statistics.

Results

Twelve VP infants were recruited, and 10 (83%) completed the study. Participants’ parents had high education attainment. The rate of completion of baseline and outcome measures was optimal. VP infants demonstrated engagement in the training, completing on average 84 min of training over three visits, and displaying improved performance during this training. Eye-tracking data quality was moderate, but this did not interfere with infants’ engagement in the training.

Discussion

The results suggest the ACT can be delivered to VP infants. However, challenges remain in recruitment of numerous and diverse samples. We discuss strategies to overcome these challenges informed by results of this study.

Trial registration

Registered Registration ID: NCT03896490. Retrospectively registered at Clinical Trials Protocol Registration and Results System (clinicaltrials.gov).
The effect of expertise, target usefulness and image structure on visual search
Authors: Robson Samuel G. , Tangen Jason M. , Searston Rachel A.
Published: March 2021

Experts outperform novices on many cognitive and perceptual tasks. Extensive training has tuned experts to the most relevant information in their specific domain, allowing them to make decisions quickly and accurately. We compared a group of fingerprint examiners to a group of novices on their ability to search for information in fingerprints across two experiments—one where participants searched for target features within a single fingerprint and another where they searched for points of difference between two fingerprints. In both experiments, we also varied how useful the target feature was and whether participants searched for these targets in a typical fingerprint or one that had been scrambled. Experts more efficiently located targets when searching for them in intact but not scrambled fingerprints. In Experiment 1, we also found that experts more efficiently located target features classified as more useful compared to novices, but this expert-novice difference was not present when the target feature was classified as less useful. The usefulness of the target may therefore have influenced the search strategies that participants used, and the visual search advantages that experts display appear to depend on their vast experience with visual regularity in fingerprints. These results align with a domain-specific account of expertise and suggest that perceptual training ought to involve learning to attend to task-critical features.
Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients
Authors: Ermis Ummehan , Rust Marcus Immanuel , Bungenberg Julia , Costa Ana , Dreher Michael , Balfanz Paul , Marx Gernot , Wiesmann Martin , Reetz Kathrin , Tauber Simone C. , Schulz Jörg B.
Published: March 2021

Background

The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany.

Methods

Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS).

Results

Major clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR.

Conclusions

In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.