bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED ARTICLE: Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production
Authors: Liu Ya-nan , Guan Yan , Shen Jian , Jia Yong-liang , Zhou Jian-cang , Sun Yun , Jiang Jun-xia , Shen Hui-juan , Shu Qiang , Xie Qiang-min , Xie Yicheng
Published: June 2020

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.
Dynamics of anti-malarial antibodies in non-immune patients during and after a first and unique Plasmodium falciparum malaria episode
Authors: Bisoffi Zeno , Bertoldi Marco , Silva Ronaldo , Bertoli Giulia , Ursini Tamara , Marocco Stefania , Piubelli Chiara , Pomari Elena , Buonfrate Dora , Gobbi Federico
Published: June 2020

Background

Malaria is a major travel medicine issue. Retrospective confirmation of a malaria episode diagnosed in an endemic area can have relevant implications in transfusional medicine in Europe, where blood donors are excluded from donation on the basis of positive malaria serology. However, there is scarce evidence on the dynamics of anti-malarial antibodies after a first malaria episode in non-immune individuals. The first aim of this study was to describe the dynamics of anti-malarial antibodies in a first malaria episode in non-immune travellers. Secondary objectives were to assess the sensitivity of serology for a retrospective diagnosis in non-immune travellers diagnosed while abroad and to discuss the implications in transfusional medicine.

Methods

Retrospective analysis of the results of an indirect fluorescence antibody test (IFAT) for malaria available for patients with a first malaria episode by Plasmodium falciparum and admitted at the IRCCS Sacro Cuore Don Calabria hospital in a 14-year period. The antibody titres were collected at baseline and during further follow up visits. Epidemiological, demographic and laboratory test results (including full blood count and malaria parasite density) were anonymously recorded in a study specific electronic Case Report Form created with OpenClinica software. Statistical analysis was performed with SAS software version 9.4.

Results

Thirty-six patients were included. Among them, all but two were Europeans (one African and one American). Median length of fever before diagnosis was 2 days (IQR 1–3). Thirty-five patients had seroconversion between day 1 and day 4 from admission, and the titre showed a sharply rising titre, often to a very high level in a few days. Only a single patient remained negative in the first 5 days from admission, after which he was no more tested. Six patients were followed up for at least 2 months, and they all showed a decline in IFAT titre, tending to seroreversion (confirmed in one patient with the longest follow up, almost 4 years).

Conclusions

Serology demonstrated reliable for retrospective diagnosis in non-immune travellers. The decline in the anti-malarial titre might be included in the screening algorithms of blood donors, but further studies are needed.
Health equity and COVID-19: global perspectives
Authors: Shadmi Efrat , Chen Yingyao , Dourado Inês , Faran-Perach Inbal , Furler John , Hangoma Peter , Hanvoravongchai Piya , Obando Claudia , Petrosyan Varduhi , Rao Krishna D. , Ruano Ana Lorena , Shi Leiyu , de Souza Luis Eugenio , Spitzer-Shohat Sivan , Sturgiss Elizabeth , Suphanchaimat Rapeepong , Uribe Manuela Villar , Willems Sara
Published: June 2020

The COVID-19 is disproportionally affecting the poor, minorities and a broad range of vulnerable populations, due to its inequitable spread in areas of dense population and limited mitigation capacity due to high prevalence of chronic conditions or poor access to high quality public health and medical care. Moreover, the collateral effects of the pandemic due to the global economic downturn, and social isolation and movement restriction measures, are unequally affecting those in the lowest power strata of societies. To address the challenges to health equity and describe some of the approaches taken by governments and local organizations, we have compiled 13 country case studies from various regions around the world: China, Brazil, Thailand, Sub Saharan Africa, Nicaragua, Armenia, India, Guatemala, United States of America (USA), Israel, Australia, Colombia, and Belgium. This compilation is by no-means representative or all inclusive, and we encourage researchers to continue advancing global knowledge on COVID-19 health equity related issues, through rigorous research and generation of a strong evidence base of new empirical studies in this field.
A structural equation model to assess the pathways of body adiposity and inflammation status on dysmetabolic biomarkers via red cell distribution width and mean corpuscular volume: a cross-sectional study in overweight and obese subjects
Authors: Rondanelli Mariangela , Perna Simone , Alalwan Tariq A. , Cazzola Roberta , Gasparri Clara , Infantino Vittoria , Perdoni Federica , Iannello Giancarlo , Pepe Daniele , Guido Davide
Published: June 2020

Background

A study has been performed in overweight and obese subjects to assess the effects of adiposity and inflammation indicators on dysmetabolic biomarkers via red cell distribution width (RDW) and mean corpuscular volume (MCV), taking into account pro-antioxidant balance.

Methods

Data from 166 overweight subjects were analyzed by a path analysis model using structural equation modelling (SEM) to evaluate the direct and indirect pathway effects of adiposity, measured by body mass index (BMI) and waist circumference (WC), and inflammation status, measured by pro-antioxidant balance [reactive oxygen species (ROS)], lag-time and slope and C-reactive protein (CRP) values on dysmetabolic biomarkers, via RDW and MCV.

Results

BMI was strongly linked to CRP and ROS levels. Moreover, there was a significant negative decrease of MCV (1.546 femtoliters) linked to BMI indirectly via high CRP levels. Furthermore, WC affected RDW, indicating a possible mediatory role for RDW in relation to the relationship between WC and homeostatic model assessment (HOMA), insulin and high density lipoprotein (HDL), respectively. This was evident by the elevated HOMA and insulin levels and the decreased levels of HDL. Finally, ROS-related markers did not affect directly RDW and MCV.

Conclusion

The reported outcomes suggest that RDW might play a mediatory role in the relationship between WC and the dysmetabolic outcomes in overweight and obese individuals. CRP seems to modulate the linkage between BMI and MCV. This study provides the backbone structure for future scenarios and lays the foundation for further research on the role of RDW and MCV as suitable biomarkers for the assessment of cardiovascular disease (HDL-cholesterol), inflammatory bowels and insulin resistance.
How gender-specific are predictors of post-MI HRQoL? A longitudinal study
Authors: Wlodarczyk Dorota , Zietalewicz Urszula
Published: June 2020

Purpose

Extant research shows that health-related quality of life (HRQoL) differs between female and male survivors of myocardial infarction (MI), but the reasons for this are not fully understood. We aimed to examine the predictors of HRQoL in female and male survivors during the first year after MI.

Methods

At timepoints 1 and 2, the sample comprised 222 MI survivors (59 women and 163 men; mean age 53.84 years, range 24–65) referred for in-patient cardiac rehabilitation. This number dropped to 140 participants (42 women and 98 men) at the third timepoint, approximately one year after the MI. We examined the gender differences in various predictors of physical and mental HRQoL: demographic factors (e.g., age, education, marital status), disease-related factors (pre- and post-MI), personality and coping with stress.

Results

Initially, both physical and mental HRQoL were lower in women than men, but the differences disappeared at timepoint 3. Stepwise regressions performed separately for men and women revealed that the factors shaping HRQoL were different in both genders; they also changed over time. Substantially fewer factors predicted physical HRQoL in women than in men. Trait anxiety seems to play a similarly negative role in both genders.

Conclusions

The psychosocial resources that influence HRQoL were different for women and men. There were also differences concerning predictors of HRQoL dimensions. Further studies with a different or broader range of predictors are needed, especially among women.
Health, subjective financial situation and well-being: a longitudinal observational study
Authors: Downward Paul , Rasciute Simona , Kumar Harish
Published: June 2020

Background

An individual’s financial situation is a key contributor to their overall well-being. Existing research has examined the direct economic consequences of changes in health upon out-of-pocket healthcare expenditure, participation in the labour force and potential earnings. There is also research exploring an individual’s concern about their subjective financial situation regardless of the level of their income or work status on their health. In contrast, this paper conducts a causal analysis of the effects of general and mental health on an individual’s subjective evaluation of their financial situation controlling for their work status and income. This is of importance because current health policy in the United Kingdom (UK) stresses the role of health as an asset which can mediate the wider flourishing of individuals. Moreover, subjective financial situation comprises a key component of well-being now being measured and sought in social welfare policy.

Methods

Fixed effects instrumental variable panel data regression analysis is applied to 25 years of longitudinal data, from 1991, drawn from the harmonised British Household Panel Survey (BHPS) and Understanding Society Survey (USS).

Results

Improved general health and reduced mental illness both improve the subjective financial situation of males and females. However, these affects diminish across older cohorts of males and females.

Conclusions

Investing in and improving general and mental health can improve the subjective financial situation and hence well-being of individuals. The targeting of health also needs to take account of an individuals’ life-stage.
GelPOINT single-port laparoscopy-assisted transanal minimum invasive surgery for low rectal cancer: a preliminary report on the use of the GOD VISION wireless smart glass-shaped monitor
Authors: Matsuhashi Nobuhisa , Iwata Yoshinori , Kawajiri Mana , Takahashi Takao , Kiyama Shigeru , Kiriyama Shunya , Uehara Machi , Imai Takeharu , Imai Hisashi , Tanaka Yoshihiro , Okumura Naoki , Yoshida Kazuhiro
Published: June 2020

Background

The GOD VISION wireless smart glass-shaped monitor (INBYTE) was used in the treatment of an elderly patient with mixed breathing disorder undergoing transanal minimally invasive surgery (TAMIS) for low rectal cancer under lumbar anesthesia.

Method

After wearing the GOD VISION wireless smart glass-shaped monitor, we attached it to the Gel POINT Path® (Applied Medical). The tumor was surgically removed from all layers of the rectum using an ENDOPATH Electrosurgery PROBE PLUS II System® (a spatula-type electric scalpel) and the site was closed after sufficient washing.

Results

The total operation time was 93 min, and the estimated blood loss was 6 mL. The patient was discharged without complications on postoperative day 14. No local recurrence or distant metastasis in the 7 months after the operation. The patient remained in a good condition with the preservation of the anal function.

Conclusions

It is necessary to accumulate cases and to perform long-term follow-up. In addition, the anal side operators are able to operate without discomfort. In the present case, the GOD VISION wireless smart glass-shaped monitor allowed the TAMIS operation to be performed more comfortably.
Cooking skills related to potential benefits for dietary behaviors and weight status among older Japanese men and women: a cross-sectional study from the JAGES
Authors: Tani Yukako , Fujiwara Takeo , Kondo Katsunori
Published: June 2020

Background

Poor cooking skills have been linked to unhealthy diets. However, limited research has examined associations of cooking skills with older adults’ health outcomes. We examined whether cooking skills were associated with dietary behaviors and body weight among older people in Japan.

Methods

We used cross-sectional data from the 2016 Japan Gerontological Evaluation Study, a self-report, population-based questionnaire study of men (n = 9143) and women (n = 10,595) aged ≥65 years. The cooking skills scale, which comprises seven items with good reliability, was modified for use in Japan. We calculated adjusted relative risk ratios of unhealthy dietary behaviors (low frequency of home cooking, vegetable/fruit intake; high frequency of eating outside the home) using logistic or Poisson regression, and relative risk ratios of obesity and underweight using multinomial logistic regression.

Results

Women had higher levels of cooking skills, compared with men. Women with a moderate to low level of cooking skills were 3.35 (95% confidence interval [CI]: 2.87–3.92) times more likely to have a lower frequency of home cooking and 1.61 (95% CI: 1.36–1.91) times more likely to have a lower frequency of vegetable/fruit intake, compared with women with a high level of cooking skills. Men with a low level of cooking skills were 2.56 (95% CI: 2.36–2.77) times more likely to have a lower frequency of home cooking and 1.43 (95% CI: 1.06–1.92) times more likely to be underweight, compared with men with a high level of cooking skills. Among men in charge of meals, those with a low level of cooking skills were 7.85 (95% CI: 6.04–10.21) times more likely to have a lower frequency of home cooking, 2.28 (95% CI: 1.36–3.82) times more likely to have a higher frequency of eating outside the home, and 2.79 (95% CI: 1.45–5.36) times more likely to be underweight, compared with men with a high level of cooking skills. Cooking skills were unassociated with obesity.

Conclusions

A low level of cooking skills was associated with unhealthy dietary behaviors and underweight, especially among men in charge of meals. Research on improving cooking skills among older adults is needed.
Prevalence characteristics of cervical human papillomavirus (HPV) infection in the Zhoupu District, Shanghai City, China
Authors: Li Huaping , Li Peiqun , Huang Luyi , Sun Liping , Ren He , Li Ping
Published: June 2020

Background

Human papillomavirus (HPV) infection is the leading cause of genital diseases. It can cause a series of cervical lesions. The distribution of HPV genotypes indicates that the increased prevalence of high-risk HPV (HR-HPV) is positively correlated with the severity of cervical lesions. In addition, persistent HR-HPV infection is associated with the risk of cervical cancer. Considering the latest approval of homemade HPV vaccine in China and the prevalence of HPV distribution, this is of great significance for guiding HPV vaccination work.

Objective

Our study’s purpose was to examine trends of cervical HPV infection rate in each 5-year age group from 2011 to 2019.

Methods

Retrospective analysis of human papillomavirus prevalence rate of 59,541 women from 2011 to 2019 in the District Zhoupu of Shanghai City in China. HPV genotype testing is performed using a commercial kit designed to detect 15 high-risk HPV genotypes and 6 low-risk HPV genotypes. Trends were examined for each 5-year age group.

Results

In the District Zhoupu of Shanghai City in China, the prevalence rate of cervical HPV increased significantly among women aged 15–34 years. The most prevalent HR-HPV genotypes were 52, 16, 58, 53, 39, and 51.

Conclusion

Cervical HPV prevalence rate is very high in younger women in suburb Shanghai. Due to significant differences in infection rates between specific age groups and HPV subtypes, timely intervention is required for these vulnerable populations.
Altered brain fluid management in a rat model of arterial hypertension
Authors: Naessens Daphne M. P. , Coolen Bram F. , de Vos Judith , VanBavel Ed , Strijkers Gustav J. , Bakker Erik N. T. P.
Published: June 2020

Background

Proper neuronal function is directly dependent on the composition, turnover, and amount of interstitial fluid that bathes the cells. Most of the interstitial fluid is likely to be derived from ion and water transport across the brain capillary endothelium, a process that may be altered in hypertension due to vascular pathologies as endothelial dysfunction and arterial remodelling. In the current study, we investigated the effects of hypertension on the brain for differences in the water homeostasis.

Methods

Magnetic resonance imaging (MRI) was performed on a 7T small animal MRI system on male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) of 10 months of age. The MRI protocol consisted of T2-weighted scans followed by quantitative apparent diffusion coefficient (ADC) mapping to measure volumes of different anatomical structures and water diffusion respectively. After MRI, we assessed the spatial distribution of aquaporin 4 expression around blood vessels.

Results

MRI analysis revealed a significant reduction in overall brain volume and remarkably higher cerebroventricular volume in SHR compared to WKY. Whole brain ADC, as well as ADC values of a number of specific anatomical structures, were significantly lower in hypertensive animals. Additionally, SHR exhibited higher brain parenchymal water content. Immunohistochemical analysis showed a profound expression of aquaporin 4 around blood vessels in both groups, with a significantly larger area of influence around arterioles. Evaluation of specific brain regions revealed a decrease in aquaporin 4 expression around capillaries in the corpus callosum of SHR.

Conclusion

These results indicate a shift in the brain water homeostasis of adult hypertensive rats.
“I need to take care of myself”: a qualitative study on coping strategies, support and health promotion for social workers serving refugees and homeless individuals
Authors: Mette Janika , Wirth Tanja , Nienhaus Albert , Harth Volker , Mache Stefanie
Published: June 2020

Background

Social workers provide support for various groups of clients, such as refugees and homeless people. Refugees and homeless individuals represent particularly vulnerable groups in precarious living conditions. Therefore, social workers serving these clients are likely to be confronted with extensive job demands. The aim of this study was to investigate the coping strategies of social workers serving refugees and homeless individuals and to explore their support sources and health promotion offers at work as well as their respective needs.

Methods

26 semi-structured qualitative interviews were carried out with social workers in Berlin and Hamburg and analysed according to Mayring’s qualitative content analysis.

Results

The respondents reported various coping strategies to deal with their job demands which involved both problem-oriented (e.g. time management, setting boundaries, seeking support in conflict situations) and emotion-focused approaches (e.g. self-care, distance from work, leisure activities). In addition, they emphasised various sources of workplace (social) support, e.g. provided by team members, supervisors, and other institutions. However, unmet needs for support were also formulated by the workers, e.g. in terms of individual supervision and regular exchange. Furthermore, several employees did not know about any health promotion offers at their workplace and expressed a desire for structural and behavioural health promotion measures.

Conclusions

In view of the diverse needs of the workers, the results can provide a basis to design needs-based health promotion interventions for staff in social work.
The governance of traditional medicine and herbal remedies in the selected local markets of Western Kenya
Authors: Chebii Willy Kibet , Muthee John Kaunga , Kiemo Karatu
Published: June 2020

Background

A lot of emphasis is often placed on modern governance systems and little or no attention is given to traditional governance practices which remain largely undocumented. The study aimed at finding out important traditional and modern governance practices that regulate traditional medicine sector in Western Kenya.

Materials and methods

The study was carried out in selected market centres of Western Kenya where the identified traditional medicine practitioners (TMPs) sell their traditional medicine. All consenting TMPs and professional experts were interviewed with the aid of a semi-structured questionnaire. Purposive sampling design with elements of snowball techniques was employed in tracing competent traditional medicine (TM) experts and relevant professional experts. The data collected was processed in Microsoft Excel and descriptive statistics performed. Pearson’s chi-square statistics was carried out to determine the significance of the traditional and modern governance data sets using the STATA software.

Results

Modern governance practices were not significantly different in all the market centres surveyed (p = 0.080). Equally, the traditional governance practices were also not significantly different in all the selected market centres (p = 1.000).

Conclusions

Traditional governance practices play an important role in the governance of traditional medicine and are shaped by the socio-cultural beliefs of the local communities. Modern governance practices, on the other hand, are widely perceived as top downregulation of the traditional medicine growing industry.
Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study
Authors: Luyt Charles-Edouard , Hékimian Guillaume , Bonnet Isabelle , Bréchot Nicolas , Schmidt Matthieu , Robert Jérôme , Combes Alain , Aubry Alexandra
Published: June 2020

Background

The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR–based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4–5 h. We performed this study to evaluate the concordance between the multiplex PCR–based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP.

Methods

All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared.

Results

Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa.

Conclusions

Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa.
Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology
Authors: Blohmer Martin , Zhu Li , Atkinson Jennifer M. , Beriwal Sushil , Rodríguez-López Joshua L. , Rosenzweig Margaret , Brufsky Adam M. , Tseng George , Lucas Peter C. , Lee Adrian V. , Oesterreich Steffi , Jankowitz Rachel C.
Published: June 2020

Background

Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival.

Methods

We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the “OM cohort,” to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.

Results

Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28–77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%,p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months,p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM.

Conclusions

OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.
A daf-7-related TGF-β ligand (Hc-tgh-2) shows important regulations on the development of Haemonchus contortus
Authors: He Li , Liu Hui , Zhang Bi-Ying , Li Fang-Fang , Di Wen-Da , Wang Chun-Qun , Zhou Cai-Xian , Liu Lu , Li Ting-Ting , Zhang Ting , Fang Rui , Hu Min
Published: June 2020

Background

In most multicellular organisms, the transforming growth factor-β (TGF-β) signalling pathway is involved in regulating the growth and stem cell differentiation. Previous studies have demonstrated the importance of three key molecules in this pathway in the parasitic nematode Haemonchus contortus, including one TGF-β type I receptor (Hc-tgfbr1), one TGF-β type II receptor (Hc-tgfbr2), and one co-Smad (Hc-daf-3), which regulated the developmental transition from the free-living to the parasitic stages of this parasite. However, almost nothing is known about the function of the TGF-β ligand (Hc-tgh-2) of H. contortus.

Methods

Here, the temporal transcription profiles of Hc-tgh-2 at eight different developmental stages and spatial expression patterns of Hc-TGH-2 in adult female and male worms of H. contortus have been examined by real-time PCR and immunohistochemistry, respectively. In addition, RNA interference (RNAi) by soaking was employed to assess the importance of Hc-tgh-2 in the development from exsheathed third-stage larvae (xL3s) to fourth-stage larvae (L4s) in H. contortus.

Results

Hc-tgh-2 was continuously transcribed in all eight developmental stages of H. contortus studied with the highest level in the infective third-stage larvae (iL3) and Hc-TGH-2 was located in the muscle of the body wall, intestine, ovary of adult females and testes of adult males. Silencing Hc-tgh-2 by the specific double-stranded RNA (dsRNA), decreased the transcript level of Hc-tgh-2 and resulted in fewer xL3s developing to L4s in vitro.

Conclusions

These results suggested that the TGF-β ligand, Hc-TGH-2, could play important roles in the developmental transition from the free-living (L3s) to the parasitic stage (L4s). Furthermore, it may also take part in the processes such as digestion, absorption, host immune response and reproductive development in H. contortus adults.
The relationship between cancer and medication exposure in patients with systemic lupus erythematosus: a nested case-control study
Authors: Guo Jinyan , Ren Zhigang , Li Jianhao , Li Tianfang , Liu Shengyun , Yu Zujiang
Published: June 2020

Background

Systemic lupus erythematosus (SLE) is associated with increased risk of cancer and the mechanism remains unclear. Here, we examined the level of auto-antibodies and disease activity index scores in SLE patients with cancers and analyzed whether medications for SLE management might contribute to the higher cancer risk in SLE patients.

Methods

In this retrospective study, we carried out a nested case-control study in a large cohort of SLE patients. We screened 5858 SLE patients to identify the newly diagnosed and yet to be treated cancers. The following clinical features were evaluated: auto-antibodies levels, SLE disease activity index scores, and previous medication used for SLE management. Systemic glucocorticoid, cyclophosphamide, hydroxychloroquine (HCQ), methotrexate, and azathioprine were considered the main medication indices.

Results

Our analyses identified 51 SLE patients who also had cancer and 204 matched control patients who had SLE but not cancer. Of the 51 SLE patients, thyroid cancer (14/51, 27.45%), cervical cancer (10/51, 19.61%), and lung cancer (7/51, 13.73%) were the most common types. Our analyses did not reveal any significant differences in the levels of auto-antibodies in SLE patients with cancers relative to the control group. Further, we observed that disease activity was significantly lower in SLE patients with cancers relative to the matched control SLE group. There was no statistically significant association between the cancer risk and the use of systemic glucocorticoid, cyclophosphamide, methotrexate, or azathioprine. Importantly, the administration of HCQ was significantly lower in SLE patients suffering cancers relative to the cancer-free matched control group.

Conclusions

Our analyses indicate that SLE patients with cancers might have a lower disease activity at the time of cancer diagnosis. HCQ was negatively associated with cancer risk in SLE patients. These findings highlight a potential and novel prevention strategy for SLE.
Prognostic and predictive value of PD-L2 DNA methylation and mRNA expression in melanoma
Authors: Hoffmann Friederike , Zarbl Romina , Niebel Dennis , Sirokay Judith , Fröhlich Anne , Posch Christian , Holderried Tobias A. W. , Brossart Peter , Saavedra Gonzalo , Kuster Pia , Strieth Sebastian , Gielen Gerrit H. , Ring Sandra S. , Dietrich Jörn , Pietsch Torsten , Flatz Lukas , Kristiansen Glen , Landsberg Jennifer , Dietrich Dimo
Published: June 2020

Background

PD-L1 (programmed cell death 1 ligand 1) expression in melanoma has been associated with a better response to anti-PD-1 (programmed cell death 1) therapy. However, patients with PD-L1-negative melanomas can respond to anti-PD-1 blockade, suggesting that the other PD-1 ligand, PD-L2 (programmed cell death 1 ligand 2), might also be relevant for efficacy of PD-1 inhibition. We investigated PD-L2 expression and methylation as a prognostic and predictive biomarker in melanoma.

Methods

DNA methylation at five CpG loci and gene expression of PD-L2 were evaluated with regard to survival in 470 melanomas from The Cancer Genome Atlas. PD-L2 promoter methylation in correlation with PD-L2 mRNA and protein expression was analyzed in human melanoma cell lines. Prognostic and predictive value of PD-L2 methylation was validated using quantitative methylation-specific PCR in a multicenter cohort of 129 melanoma patients receiving anti-PD-1 therapy. mRNA sequencing data of 121 melanoma patients receiving anti-PD-1 therapy provided by Liu et al. were analyzed for PD-L2 mRNA expression.

Results

We found significant correlations between PD-L2 methylation and mRNA expression levels in melanoma tissues and cell lines. Interferon-γ inducible PD-L2 protein expression correlated with PD-L2 promoter methylation in melanoma cells. PD-L2 DNA promoter hypomethylation and high mRNA expression were found to be strong predictors of prolonged overall survival. In pre-treatment melanoma samples from patients receiving anti-PD-1 therapy, low PD-L2 DNA methylation and high PD-L2 mRNA expression predicted longer progression-free survival.

Conclusion

PD-L2 expression seems to be regulated via DNA promoter methylation. PD-L2 DNA methylation and mRNA expression may predict progression-free survival in melanoma patients receiving anti-PD-1 immunotherapy. Assessment of PD-L2 should be included in further clinical trials with anti-PD-1 antibodies.
Giant primary angiosarcoma of an adolescent girl’s breast diagnosed postmortem: a case report
Authors: Darré Tchin , Brun Luc Valère Codjo , Seidou Falilath , Djiwa Toukilnan , Ballé Marie Claire , Napo-Koura Gado
Published: June 2020

Background

Angiosarcoma is an endothelial malignant tumor; angiosarcoma located in the breast is extremely rare, less than 0.01%. We report a case of a giant angiosarcoma diagnosed postmortem in a 16-year-old girl in a resource-constrained country.

Case presentation

A 16-year-old black African girl was admitted for altered consciousness and a left breast tumor. She was admitted in a state of apparent death. Her death was confirmed on clinical examination. A postmortem biopsy of the mammary tumor showed standard histology of a proliferation of fusiform or rounded tumor cells in places, which were not very cohesive with marked anisokaryosis and numerous foci of tumor necrosis. Immunohistochemistry showed a positivity of CD31 and factor VIII markers with a proliferation index (Ki-67) estimated at 30%.

Conclusion

Primary angiosarcoma of the breast is exceptional in adolescents and has a poor prognosis, especially in countries with limited resources.
Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials
Authors: Li Zhonghao , Dong Xiaoke , Tian Min , Liu Chongchong , Wang Kaiyue , Li Lili , Liu Zunjing , Liu Jinmin
Published: June 2020

Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) − 1.63, 95% confidence intervals (CI) − 2.73 to − 0.53,I2 =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24,I2 = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65,I2 = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.
Directly induced human Schwann cell precursors as a valuable source of Schwann cells
Authors: Kim Han-Seop , Kim Jae Yun , Song Cho Lok , Jeong Ji Eun , Cho Yee Sook
Published: June 2020

Background

Schwann cells (SCs) are primarily responsible for regeneration and repair of the peripheral nervous system (PNS). Renewable and lineage-restricted SC precursors (SCPs) are considered highly desirable and promising cell sources for the production of SCs and for studies of SC lineage development, but SCPs are extremely limited. Here, we present a novel direct conversion strategy for the generation of human SCPs, capable of differentiating into functional SCs.

Methods

Easily accessible human skin fibroblast cells were directly induced into integration-free SCPs using episomal vectors (Oct3/4, Klf4, Sox2, L-Myc, Lin28 and p53 shRNA) under SCP lineage-specific chemically defined medium conditions. Induced SCPs (iSCPs) were further examined for their ability to differentiate into SCs. The identification and functionality of iSCPs and iSCP-differentiated SCs (iSCs) were confirmed according to morphology, lineage-specific markers, neurotropic factor secretion, and/or standard functional assays.

Results

Highly pure, Sox 10-positive of iSCPs (more than 95% purity) were generated from human skin fibroblasts within 3 weeks. Established iSCPs could be propagated in vitro while maintaining their SCP identity. Within 1 week, iSCPs could efficiently differentiate into SCs (more than 95% purity). The iSCs were capable of secreting various neurotrophic factors such as GDNF, NGF, BDNF, and NT-3. The in vitro myelinogenic potential of iSCs was assessed by myelinating cocultures using mouse dorsal root ganglion (DRG) neurons or human induced pluripotent stem cell (iPSC)-derived sensory neurons (HSNs). Furthermore, iSC transplantation promoted sciatic nerve repair and improved behavioral recovery in a mouse model of sciatic nerve crush injury in vivo.

Conclusions

We report a robust method for the generation of human iSCPs/iSCs that might serve as a promising cellular source for various regenerative biomedical research and applications, such as cell therapy and drug discovery, especially for the treatment of PNS injury and disorders.
Inhibition of Notch pathway enhances the anti-tumor effect of docetaxel in prostate cancer stem-like cells
Authors: Wang Lei , Zi Hao , Luo Yi , Liu Tongzu , Zheng Hang , Xie Conghua , Wang Xinghuan , Huang Xing
Published: June 2020

Background

Prostate cancer stem-like cells (PCSCs) likely participate in tumor progression and recurrence and demonstrate resistance to chemotherapy. The Notch pathway plays a role in the maintenance of the stemness in PCSCs. This study aimed to investigate the efficacy of Notch signaling inhibition as an adjuvant to docetaxel (DOX) in PCSCs.

Methods

PCSCs derived from the PC-3 cell line were examined for Notch-1 expression. The effect of Notch inhibition on response to DOX was evaluated in PCSCs in vitro and in murine models using a γ-secretase inhibitor (GSI), PF-03084014. Impacts on cell proliferation, apoptosis, cell cycle, and sphere formation were evaluated.

Results

PC-3 PCSCs expressed elevated Notch-1 mRNA compared with PC-3 parental cells. The combination of GSI with DOX promoted DOX-induced cell growth inhibition, apoptosis, cell cycle arrest, and sphere formation in PCSCs. In nude mice bearing PC-3 PCSC-derived tumors, the combination of GSI and DOX reduced the tumor growth, which was associated with the decreased Notch-1 expression in tumor tissues.

Conclusions

These results reveal that inhibition of the Notch pathway enhances the anti-tumor effect of DOX in PC-3 PCSCs, and suggest that Notch inhibition may have clinical benefits in targeting PCSCs.
Ensemble patch transformation: a flexible framework for decomposition and filtering of signal
Authors: Kim Donghoh , Choi Guebin , Oh Hee-Seok
Published: June 2020

This paper considers the problem of signal decomposition and filtering by extending its scope to various signals that cannot be effectively dealt with existing methods. For the core of our methodology, we introduce a new approach, termed “ensemble patch transformation” that provides a framework for decomposition and filtering of signals; thus, as a result, it enhances identification of local characteristics embedded in a signal that is crucial for signal decomposition and designs flexible filters that allow various data analyses. In literature, there are some data-adaptive decomposition methods such as empirical mode decomposition (EMD) by Huang (Proc. R. Soc. London A 454:903–995, 1998). Along the same line of EMD, we propose a new decomposition algorithm that extracts essential components from a signal. Some theoretical properties of the proposed algorithm are investigated. To evaluate the proposed method, we analyze several synthetic examples and real signals.
User scheduling for multicast transmission in high throughput satellite systems
Authors: Zhang Shuo , Jia Min , Wei Yuming , Guo Qing
Published: June 2020

Adopting full frequency reuse in high throughput satellite (HTS) systems is expected to cope with huge communication demands and large user populations. Moreover, a kind of multicast transmission, which embeds the data of several users in each frame, can be employed to increase the efficiency of HTS systems. Multicast precoding is usually utilized in such systems to mitigate the co-frequency interference between beams and improve the efficiency of transmission. In this context, considering that the number of users may exceed the number of available communication resources in the system, we investigate user scheduling for the multicast transmission in HTS systems with full frequency reuse and multicast precoding. We perform user scheduling according to the user channel state information and decouple the scheduling problem into two phases: intra-beam and inter-beam scheduling. Intra-beam scheduling determines the users involved in the transmission of each frame with the purpose of reducing the influence of the multicast fashion. For intra-beam scheduling, we put forth a fixed-size user grouping algorithm. In contrast to previous studies, this algorithm takes the interference among beams into consideration during the scheduling. In inter-beam scheduling, user groups belonging to different beams are scheduled to improve the performance of the multiplexed transmission. An inter-beam scheduling algorithm is proposed to improve the fairness among users. The simulation results verify the superiority of the proposed algorithms in terms of fairness and spectral efficiency.
RETRACTED ARTICLE: Research on English teaching system based on artificial intelligence and WBIETS wireless network system
Authors: Tan Minghua
Published: June 2020

The English teaching network system is a distant teaching based on the Web. This teaching method can stimulate students’ interests so that students can acquire knowledge voluntarily, and automatic test paper generation is one of the most important modules in the English teaching network system. This article first briefly introduces the architecture of the wireless sensor network and then gives a wireless sensor network teaching experiment system based on a genetic algorithm. The multiple sensor nodes in the system can form a variety of different topologies, the collected data can be sent to the user terminal through the GSM network, and the user can also control the remote sensor node through the GSM network. This paper first describes the automatic test problems, a constrained multi-objective problem, then the design of the genetic algorithm to improve the test paper and puts forward questions based on an encoding method and based on the difficulty and test points of F fitness function for dynamic adjustment of the parameters in the iterative process. Finally, it is verified by experiments that the test paper made by this method satisfies users’ requests for questions, contents, and scores, and at the same time, it also improves the running efficiency of a random optimization algorithm by 7–17 times.