bluuebunny/crossref_metadata_2025 huggingface dataset:
How the logics of the market, bureaucracy, professionalism and care are reconciled in practice: an empirical ethics approach
Authors: Kruse Florien M. , Ligtenberg Wieke M. R. , Oerlemans Anke J. M. , Groenewoud Stef , Jeurissen Patrick P. T.
Published: November 2020

Background

In the Netherlands, the for-profit sector has gained a substantial share of nursing home care within just a few years. The ethical question that arises from the growth of for-profit care is whether the market logic can be reconciled with the provision of healthcare. This question relates to the debate on the Moral Limits of Markets (MLM) and commodification of care.

Methods

The contribution of this study is twofold. Firstly, we construct a theoretical framework from existing literature; this theoretical framework differentiates four logics: the market, bureaucracy, professionalism, and care. Secondly, we follow an empirical ethics approach; we used three for-profit nursing homes as case studies and conducted qualitative interviews with various stakeholders.

Results

Four main insights emerge from our empirical study. Firstly, there are many aspects of the care relationship (e.g. care environment, personal relationships, management) and every aspect of the relationship should be considered because the four logics are reconciled differently for each aspect. The environment and conditions of for-profit nursing homes are especially commodified. Secondly, for-profit nursing homes pursue a different professional logic from the traditional, non-profit sector – one which is inspired by the logic of care and which contrasts with bureaucratic logic. However, insofar as professionals in for-profit homes are primarily responsive to residents’ wishes, the market logic also prevails. Thirdly, a multilevel approach is necessary to study the MLM in the care sector since the degree of commodification differs by level. Lastly, it is difficult for the market to engineer social cohesion among the residents of nursing homes.

Conclusions

The for-profit nursing home sector does embrace the logic of the market but reconciles it with other logics (i.e. logic of care and logic of professionalism). Importantly, for-profit nursing homes have created an environment in which care professionals can provide person-oriented care, thereby reconciling the logic of the market with the logic of care.
Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank
Authors: Petermann-Rocha Fanny , Hanlon Peter , Gray Stuart R. , Welsh Paul , Gill Jason M. R. , Foster Hamish , Katikireddi S. Vittal , Lyall Donald , Mackay Daniel F. , O’Donnell Catherine A. , Sattar Naveed , Nicholl Barbara I. , Pell Jill P. , Jani Bhautesh D. , Ho Frederick K. , Mair Frances S. , Celis-Morales Carlos
Published: November 2020

Background

Frailty has been associated with worse prognosis following COVID-19 infection. While several studies have reported the association between frailty and COVID-19 mortality or length of hospital stay, there have been no community-based studies on the association between frailty and risk of severe infection. Considering that different definitions have been identified to assess frailty, this study aimed to compare the association between frailty and severe COVID-19 infection in UK Biobank using two frailty classifications: the frailty phenotype and the frailty index.

Methods

A total of 383,845 UK Biobank participants recruited 2006–2010 in England (211,310 [55.1%] women, baseline age 37–73 years) were included. COVID-19 test data were provided by Public Health England (available up to 28 June 2020). An adapted version of the frailty phenotype derived by Fried et al. was used to define frailty phenotype (robust, pre-frail, or frail). A previously validated frailty index was derived from 49 self-reported questionnaire items related to health, disease and disability, and mental wellbeing (robust, mild frailty, and moderate/severe frailty). Both classifications were derived from baseline data (2006–2010). Poisson regression models with robust standard errors were used to analyse the associations between both frailty classifications and severe COVID-19 infection (resulting in hospital admission or death), adjusted for sociodemographic and lifestyle factors.

Results

Of UK Biobank participants included, 802 were admitted to hospital with and/or died from COVID19 (323 deaths and 479 hospitalisations). After analyses were adjusted for sociodemographic and lifestyle factors, a higher risk of COVID-19 was observed for pre-frail (risk ratio (RR) 1.47 [95% CI 1.26; 1.71]) and frail (RR 2.66 [95% CI 2.04; 3.47]) individuals compared to those classified as robust using the frailty phenotype. Similar results were observed when the frailty index was used (RR mildly frail 1.46 [95% CI 1.26; 1.71] and RR moderate/severe frailty 2.43 [95% CI 1.91; 3.10]).

Conclusions

Frailty was associated with a higher risk of severe COVID-19 infection resulting in hospital admission or death, irrespective of how it was measured and independent of sociodemographic and lifestyle factors. Public health strategies need to consider the additional risk that COVID-19 poses in individuals with frailty, including which additional preventive measures might be required.
The intensity of physiological and behavioral responses of horses to predator vocalizations
Authors: Janczarek Iwona , Stachurska Anna , Kędzierski Witold , Wiśniewska Anna , Ryżak Magdalena , Kozioł Agata
Published: November 2020

Background

Predatory attacks on horses can become a problem in some parts of the world, particularly when considering the recovering gray wolf populations. The issue studied was whether horses transformed by humans and placed in stable-pasture environments had retained their natural abilities to respond to predation risk. The objective of the study was to determine the changes in cardiac activity, cortisol concentrations, and behavior of horses in response to the vocalizations of two predators: the gray wolf (Canis lupus), which the horses of the breed studied had coevolved with but not been exposed to recently, and Arabian leopard (Panthera pardus nimr), from which the horses had been mostly isolated. In addition, we hypothesized that a higher proportion of Thoroughbred (TB) horse ancestry in the pedigree would result in higher emotional excitability in response to predator vocalizations. Nineteen horses were divided into groups of 75%, 50% and 25% TB ancestry. The auditory test conducted in a paddock comprised a 10-min prestimulus period, a 5-min stimulus period when one of the predators was heard, and a 10-min poststimulus period without any experimental stimuli.

Results

The increase in heart rate and saliva cortisol concentration in response to predator vocalizations indicated some level of stress in the horses. The lowered beat-to-beat intervals revealed a decrease in parasympathetic nervous system activity. The behavioral responses were less distinct than the physiological changes. The responses were more pronounced with leopard vocalizations than wolf vocalizations.

Conclusions

The horses responded with weak signs of anxiety when exposed to predator vocalizations. A tendency towards a stronger internal reaction to predators in horses with a higher proportion of TB genes suggested that the response intensity was partly innate. The more pronounced response to leopard than wolf may indicate that horses are more frightened of a threatening sound from an unknown predator than one known by their ancestors. The differing response can be also due to differences in the characteristic of the predators’ vocalizations. Our findings suggested that the present-day horses’ abilities to coexist with predators are weak. Hence, humans should protect horses against predation, especially when introducing them into seminatural locations.
Isolation and characterization of low pathogenic H7N7 avian influenza virus from a red-crowned crane in a zoo in South Korea
Authors: Si Young-Jae , Lee Yu-Na , Cheon Sun-Ha , Park Yu-Ri , Baek Yoon-Gi , Kye Soo-Jeong , Lee Myoung-Heon , Lee Youn-Jeong
Published: November 2020

Background

South Korea conducts annual national surveillance programs to detect avian influenza (AI) in domestic poultry, live bird markets, and wild birds. In March 2017, an AIV was isolated from fecal samples in an outdoor aviary flight cage in a zoo in Korea.

Results

Nucleotide sequencing identified the isolate as low pathogenic avian influenza virus (LPAIV) H7N7, and DNA barcoding analysis identified the host species as red-crowned crane. This isolate was designated A/red-crowned crane/Korea/H1026/2017 (H7N7). Genetic analysis and gene constellation analysis revealed that A/red-crowned crane/Korea/H1026/2017 (H7N7) showed high similarity with four H7N7 LPAIVs isolated from wild bird habitats in Seoul and Gyeonggi in early 2017.

Conclusions

Considering the genetic similarity and similar collection dates of the viruses, and the fact that zoo bird cages are vulnerable to AIV, it is likely that fecal contamination from wild birds might have introduced LPAIV H7N7 into the red-crowned crane at the zoo. Therefore, our results emphasize that enhanced biosecurity measures should be employed during the wild bird migration season, and that continued surveillance should be undertaken to prevent potential threats to avian species in zoos and to humans.
Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure
Authors: Rubio Camila Peres , Saril Ahmet , Kocaturk Meriç , Tanaka Ryou , Koch Jorgen , Ceron Jose Joaquin , Yilmaz Zeki
Published: November 2020

Background

Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum.

Results

KC-like was significantly increased in dogs of stage-C (P < 0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KC-like decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01).

Conclusion

Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.
Translocation of intestinal bacteria as a cause of subcutaneous abscesses of the neck and head in American mink (Neovison vison) – a case report
Authors: Wlazło Łukasz , Łopuszyński Wojciech , Nowakowicz-Dębek Bożena , Ossowski Mateusz , Bis-Wencel Hanna
Published: November 2020

Background

The problem of transmission of intestinal microorganisms to tissues occurs when intestinal epithelial cells do not adhere tightly (tight junction), which is caused by improper nutrition, usually associated with poor mucosal status. The impact on maintaining its proper condition in the case of animals also depends on the proper preparation and fragmentation of the ingredients of the feed. Intestinal microbiota disorders are increasingly indicated as one of the causes of many autoimmune, neurodevelopmental and metabolic diseases. However, there are no studies indicating damage to the intestinal barrier of animals resulting in the penetration of microorganisms from the gastrointestinal tract directly into the bloodstream which may result in the development of chronic inflammation.

Case presentation

On a mink (Neovison vison) farm with a foundation stock of 4,000 females, abscesses were observed in the head, followed by progressive deaths. Antibiotic treatment with amoxicillin and clavulanic acid added to the animals’ feed was not successful. Macroscopic and microscopic changes indicated local suppurative inflammation of the skin and subcutaneous tissue with the presence of purulent fistulas. Microbiological analysis showed a significant increase in Escherichia coli in all samples taken from the abscesses. The results indicate the migration of intestinal bacteria through disturbance of the permeability of the intestinal barrier and their transfer to the blood. Symptoms were alleviated in all animals following changes in the feed components and in feed particle size.

Conclusions

It is necessary to take into account the possibility of transmission of intestinal bacteria in the etiology of inflammatory diseases in animals. Conducting more research in this field will improve the understanding of the relationship between intestinal microbes and the health of the body as a whole.
In silico pathway analysis based on chromosomal instability in breast cancer patients
Authors: Kour Akeen , Sambyal Vasudha , Guleria Kamlesh , Singh Neeti Rajan , Uppal Manjit Singh , Manjari Mridu , Sudan Meena
Published: November 2020

Background

Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability.

Methods

Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 h Peripheral lymphocyte culturing and GTG-banding. Reactome database from Cytoscape software version 3.7.1 was used to perform in-silico analysis (functional interaction and gene enrichment).

Results

Frequency of chromosomal aberrations (structural and numerical) was found to be significantly higher in patients as compared to controls. The genes harbored by chromosomal regions showing increased aberration frequency in patients were further analyzed in-silico. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription.

Conclusion

The current study employs the information inferred from chromosomal instability analysis in a non-target tissue for determining the genes and the pathways associated with breast cancer. These results can be further extrapolated by performing either mutation analysis in the genes/pathways deduced or expression analysis which can pinpoint the relevant functional impact of chromosomal instability.
Additional work of breathing from trigger errors in mechanically ventilated children
Authors: Blokpoel Robert G. T. , Koopman Alette A. , van Dijk Jefta , Kneyber Martin C. J.
Published: November 2020

Background

Patient–ventilator asynchrony is associated with increased morbidity and mortality. A direct causative relationship between Patient–ventilator asynchrony and adverse clinical outcome have yet to be demonstrated. It is hypothesized that during trigger errors excessive pleural pressure swings are generated, contributing to increased work-of-breathing and self-inflicted lung injury. The objective of this study was to determine the additional work-of-breathing and pleural pressure swings caused by trigger errors in mechanically ventilated children.

Methods

Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Patients ventilated > 24 h and < 18 years old were studied. Patients underwent a 5-min recording of the ventilator flow–time, pressure–time and oesophageal pressure–time scalar. Pressure–time–product calculations were made as a proxy for work-of-breathing. Oesophageal pressure swings, as a surrogate for pleural pressure swings, during trigger errors were determined.

Results

Nine-hundred-and-fifty-nine trigger errors in 28 patients were identified. The additional work-of-breathing caused by trigger errors showed great variability among patients. The more asynchronous breaths were present the higher the work-of-breathing of these breaths. A higher spontaneous breath rate led to a lower amount of trigger errors. Patient–ventilator asynchrony was not associated with prolonged duration of mechanical ventilation or paediatric intensive care stay.

Conclusions

The additional work-of-breathing caused by trigger errors in ventilated children can take up to 30–40% of the total work-of-breathing. Trigger errors were less common in patients breathing spontaneously and those able to generate higher pressure–time–product and pressure swings.

Trial registration

Not applicable.
Computed tomography patterns predict clinical course of idiopathic pulmonary fibrosis
Authors: Kwon Byoung Soo , Choe Jooae , Do Kyung Hyun , Hwang Hee Sang , Chae Eun Jin , Song Jin Woo
Published: November 2020

Background

A new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF.

Methods

Clinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria.

Results

The median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335–0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group.

Conclusions

Our results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.
Prices of medicines for the management of pain, diabetes and cardiovascular diseases in private pharmacies and the national health insurance in Tanzania
Authors: Kirua Rashid Bakari , Temu Mary Justin , Mori Amani Thomas
Published: November 2020

Background

High price is a major challenge limiting access to essential medicines especially among the poorest families in developing countries. The study aims to compare the prices of medicines used in the management of pain, diabetes, and cardiovascular diseases in private pharmacies and the National Health Insurance Fund (NHIF) in Tanzania. Pharmacy prices were also compared with the prices of medicines surveyed nationally by WHO/HAI in 2012.

Method

This cross-sectional study was conducted in Dar es Salaam, Morogoro, Dodoma, and Kilimanjaro regions from February to April 2015. Data were collected from 33 private pharmacies, NHIF and, the HAI database. The study used the WHO/HAI methodology. The analysis was done using non-parametric Kruskal-Wallis and post-hoc pair-wise comparison Dunn test, while a possible change in prices between our survey and 2012 WHO/HAI national survey data was tested using a Sign test in Stata version 16.1.

Results

Twenty-eight essential medicines, of which 9 are used for management of pain, 7 for diabetes, and 12 for cardiovascular diseases were analyzed. There was a significant difference in the mean pharmacy prices of some medicines between the regions and between the pharmacies and NHIF reference prices. NHIF reference prices were higher than the pharmacy prices for 16 of the 28 medicines. There was a significant increase in the prices of 5 out of the 8 medicines that were also nationally surveyed by the WHO/HAI in 2012.

Conclusion

The study found that medicine prices in private pharmacies vary a lot between the study regions, which raises equity concerns. Also, there was a significant difference between the pharmacy and the NHIF reimbursement prices, which may expose patients to fraudulent co-payments or hinder timely access to prescribed medicines. Therefore, effective price control policies and regulations for medicines are warranted in Tanzania.
Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy
Authors: Zhang Bin , Cheng Ping
Published: November 2020

As a promising therapeutic strategy, oncolytic virotherapy has shown potent anticancer efficacy in numerous pre-clinical and clinical trials. Oncolytic viruses have the capacity for conditional-replication within carcinoma cells leading to cell death via multiple mechanisms, including direct lysis of neoplasms, induction of immunogenic cell death, and elicitation of innate and adaptive immunity. In addition, these viruses can be engineered to express cytokines or chemokines to alter tumor microenvironments. Combination of oncolytic virotherapy with other antitumor therapeutic modalities, such as chemotherapy and radiation therapy as well as cancer immunotherapy can be used to target a wider range of tumors and promote therapeutic efficacy. In this review, we outline the basic biological characteristics of oncolytic viruses and the underlying mechanisms that support their use as promising antitumor drugs. We also describe the enhanced efficacy attributed to virotherapy combined with other drugs for the treatment of cancer.
Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review
Authors: Roeder F. , Meldolesi E. , Gerum S. , Valentini V. , Rödel C.
Published: November 2020

The role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.
Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques
Authors: Natunen Teemu , Martiskainen Henna , Marttinen Mikael , Gabbouj Sami , Koivisto Hennariikka , Kemppainen Susanna , Kaipainen Satu , Takalo Mari , Svobodová Helena , Leppänen Luukas , Kemiläinen Benjam , Ryhänen Simo , Kuulasmaa Teemu , Rahunen Eija , Juutinen Sisko , Mäkinen Petra , Miettinen Pasi , Rauramaa Tuomas , Pihlajamäki Jussi , Haapasalo Annakaisa , Leinonen Ville , Tanila Heikki , Hiltunen Mikko
Published: November 2020

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms underlying these two diseases remain elusive.

Methods

Mice with different AD- and/or tauopathy-linked genetic backgrounds (APPswe/PS1dE9, Tau P301L and APPswe/PS1dE9/Tau P301L) were fed for 6 months with standard diet or typical Western diet (TWD). After behavioral and metabolic assessments of the mice, the effects of TWD on global gene expression as well as dystrophic neurite and microglia pathology were elucidated. Consequently, mechanistic aspects related to autophagy, cell survival, phagocytic uptake as well as Trem2/Dap12 signaling pathway, were assessed in microglia upon modulation of PI3K-Akt signaling. To evaluate whether the mouse model-derived results translate to human patients, the effects of diabetic phenotype on microglial pathology were assessed in cortical biopsies of idiopathic normal pressure hydrocephalus (iNPH) patients encompassing β-amyloid pathology.

Results

TWD led to obesity and diabetic phenotype in all mice regardless of the genetic background. TWD also exacerbated memory and learning impairment in APPswe/PS1dE9 and Tau P301L mice. Gene co-expression network analysis revealed impaired microglial responses to AD-related pathologies in APPswe/PS1dE9 and APPswe/PS1dE9/Tau P301L mice upon TWD, pointing specifically towards aberrant microglial functionality due to altered downstream signaling of Trem2 and PI3K-Akt. Accordingly, fewer microglia, which did not show morphological changes, and increased number of dystrophic neurites around β-amyloid plaques were discovered in the hippocampus of TWD mice. Mechanistic studies in mouse microglia revealed that interference of PI3K-Akt signaling significantly decreased phagocytic uptake and proinflammatory response. Moreover, increased activity of Syk-kinase upon ligand-induced activation of Trem2/Dap12 signaling was detected. Finally, characterization of microglial pathology in cortical biopsies of iNPH patients revealed a significant decrease in the number of microglia per β-amyloid plaque in obese individuals with concomitant T2D as compared to both normal weight and obese individuals without T2D.

Conclusions

Collectively, these results suggest that diabetic phenotype in mice and humans mechanistically associates with abnormally reduced microglial responses to β-amyloid pathology and further suggest that AD and T2D share overlapping pathomechanisms, likely involving altered immune function in the brain.
Measures of depression, generalized anxiety, and posttraumatic stress disorders amongst Yazidi female survivors of ISIS slavery and violence
Authors: Taha Perjan Hashim , Slewa-Younan Shameran
Published: November 2020

Background

In 2014 the Islamic State of Iraq and Syria (ISIS) undertook a systematic and deliberate campaign against minority groups and non-Sunni Muslim communities. Amongst some of the greatest atrocities were those targeted towards Yazidi communities and in particular their women. The mental health outcomes of those women held in captivity requires investigation. This study sought to examine and compare levels of general psychological distress, depression, generalized anxiety, posttraumatic stress disorder (PTSD) and self-reported suicidal thoughts and behaviors amongst Yazidi women held in captivity compared with those without such experiences.

Method

Between January to May 2019, a total 348 Yazidi women located in internal displaced person (IDP) camps were interviewed. Of these 348, 139 females were survivors of ISIS captivity. Measures used included Kessler Psychological Distress Scale (K10), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), and Harvard Trauma Questionnaire part IV (HTQ part IV).

Results

Formerly enslaved Yazidi females showed a significantly higher prevalence of severe mental distress (97.1%; P < 0.001), more severe levels of depression (36.7%; P < 0.001) and general anxiety symptoms (37.4%; P < 0.001), greater rates of PTSD (90.6%; P < 0.001) and higher reported rates of suicidal ideation (38.1%; P < 0.001). Logistic regression analysis undertaken to examine the role of sociodemographic factors as predictors of the assessed mental health conditions. Amongst the formerly enslaved group, no such significance was found, however amongst the non-enslaved group, unemployment was found to statistically determine depression, generalized anxiety and PTSD. Specifically, women from the non-enslaved group who were unemployed were 2.5 times more likely to have depression, 3 times more likely to have generalized anxiety and 3.3 times more likely to have PTSD. Finally, amongst the non-enslaved group, those women with between 5 to 8 siblings were significantly less likely to have depression than those with fewer siblings.

Conclusion

Rates of distress and trauma related symptomology were significantly higher amongst those with history of enslavement. Sociodemographic factors and duration of enslavement do not seem to predict mental disorders among enslaved females.
Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology
Authors: Gao Kai , Song Yan-Ping , Song Anna
Published: November 2020

Background

COVID-19 has caused a global pandemic, and there is no wonder drug for epidemic control at present. However, many clinical practices have shown that traditional Chinese medicine has played an important role in treating the outbreak. Among them, ephedra-bitter almond is a common couplet medicine in anti-COVID-19 prescriptions. This study aims to conduct an exploration of key components and mechanisms of ephedra-bitter almond anti-COVID-19 based on network pharmacology.

Material and methods

We collected and screened potential active components of ephedra-bitter almond based on the TCMSP Database, and we predicted targets of the components. Meanwhile, we collected relevant targets of COVID-19 through the GeneCards and CTD databases. Then, the potential targets of ephedra-bitter almond against COVID-19 were screened out. The key components, targets, biological processes, and pathways of ephedra-bitter almond anti-COVID-19 were predicted by constructing the relationship network of herb-component-target (H-C-T), protein-protein interaction (PPI), and functional enrichment. Finally, the key components and targets were docked by AutoDock Vina to explore their binding mode.

Results

Ephedra-bitter almond played an overall regulatory role in anti-COVID-19 via the patterns of multi-component-target-pathway. In addition, some key components of ephedra-bitter almond, such as β-sitosterol, estrone, and stigmasterol, had high binding activity to 3CL and ACE2 by molecular docking simulation, which provided new molecular structures for new drug development of COVID-19.

Conclusion

Ephedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.
Isolation and characterization of exosomes for cancer research
Authors: Zhu Le , Sun Hao-Ting , Wang Shun , Huang Sheng-Lin , Zheng Yan , Wang Chao-Qun , Hu Bei-Yuan , Qin Wei , Zou Tian-Tian , Fu Yan , Shen Xiao-Tian , Zhu Wen-Wei , Geng Yan , Lu Lu , Jia Hu-liang , Qin Lun-Xiu , Dong Qiong-Zhu
Published: November 2020

Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma
Authors: Xu Yangyang , Liu Zhenchuan , Lv Lixin , Li Ping , Xiu Bing , Qian Wenbin , Liang Aibin
Published: November 2020

Background

CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions.

Methods

Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models.

Results

MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation.

Conclusions

MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.
ATPase-based implementation of enforced ATP wasting in Saccharomyces cerevisiae for improved ethanol production
Authors: Zahoor Ahmed , Messerschmidt Katrin , Boecker Simon , Klamt Steffen
Published: November 2020

Background

Enforced ATP wasting has been recognized as a promising metabolic engineering strategy to enhance the microbial production of metabolites that are coupled to ATP generation. It also appears to be a suitable approach to improve production of ethanol by Saccharomyces cerevisiae. In the present study, we constructed different S. cerevisiae strains with heterologous expression of genes of the ATP-hydrolyzing F1-part of the ATPase enzyme to induce enforced ATP wasting and quantify the resulting effect on biomass and ethanol formation.

Results

In contrast to genomic integration, we found that episomal expression of the αβγ subunits of the F1-ATPase genes of Escherichia coli in S. cerevisiae resulted in significantly increased ATPase activity, while neither genomic integration nor episomal expression of the β subunit from Trichoderma reesei could enhance ATPase activity. When grown in minimal medium under anaerobic growth-coupled conditions, the strains expressing E. coli’s F1-ATPase genes showed significantly improved ethanol yield (increase of 10% compared to the control strain). However, elevated product formation reduces biomass formation and, therefore, volumetric productivity. We demonstrate that this negative effect can be overcome under growth-decoupled (nitrogen-starved) operation with high and constant biomass concentration. Under these conditions, which mimic the second (production) phase of a two-stage fermentation process, the ATPase-expressing strains showed significant improvement in volumetric productivity (up to 111%) compared to the control strain.

Conclusions

Our study shows that expression of genes of the F1-portion of E. coli’s ATPase induces ATPase activity in S. cerevisiae and can be a promising way to improve ethanol production. This ATP-wasting strategy can be easily applied to other metabolites of interest, whose formation is coupled to ATP generation.
Parasites and vector-borne diseases disseminated by rehomed dogs
Authors: Wright Ian , Jongejan Frans , Marcondes Mary , Peregrine Andrew , Baneth Gad , Bourdeau Patrick , Bowman Dwight D. , Breitschwerdt Edward B. , Capelli Gioia , Cardoso Luís , Dantas-Torres Filipe , Day Michael J. , Dobler Gerhard , Ferrer Lluis , Gradoni Luigi , Irwin Peter , Kempf Volkhard A. J. , Kohn Barbara , Krämer Friederike , Lappin Michael , Madder Maxime , Maggi Ricardo G. , Maia Carla , Miró Guadalupe , Naucke Torsten , Oliva Gaetano , Otranto Domenico , Pennisi Maria Grazia , Penzhorn Barend L. , Pfeffer Martin , Roura Xavier , Sainz Angel , Shin SungShik , Solano-Gallego Laia , Straubinger Reinhard K. , Tasker Séverine , Traub Rebecca , Little Susan
Published: November 2020

The Companion Vector-Borne Diseases (CVBD) World Forum is a working group of leading international experts who meet annually to evaluate current scientific findings and future trends concerning the distribution, pathogenesis, clinical presentation, diagnosis and prevention of vector-borne infections of dogs and cats. At the 14th Symposium of the CVBD World Forum in Trieste, Italy (March 25–28, 2019), we identified the need to (i) bring attention to the potential spread of parasites and vectors with relocated dogs, and (ii) provide advice to the veterinary profession regarding the importance of surveillance and treatment for parasites and vector-borne infections when rehoming dogs. This letter shares a consensus statement from the CVBD World Forum as well as a summary of the problem faced, including the role of veterinary professionals in parasite surveillance, causal issues, and the importance of interdisciplinary cooperation in addressing the problem. To limit opportunities for dissemination of parasites and vectors, whenever possible, underlying problems creating the need for dog rehoming should be addressed. However, when it is necessary to rehome dogs, this should ideally take place in the country and national region of origin. When geographically distant relocation occurs, veterinary professionals have a vital role to play in public education, vigilance for detection of exotic vectors and infections, and alerting the medical community to the risk(s) for pathogen spread. With appropriate veterinary intervention, dog welfare needs can be met without inadvertently allowing global spread of parasites and their vectors.
Multispecies reservoir of Spirometra erinaceieuropaei (Cestoda: Diphyllobothridae) in carnivore communities in north-eastern Poland
Authors: Kondzior Eliza , Kowalczyk Rafał , Tokarska Małgorzata , Borowik Tomasz , Zalewski Andrzej , Kołodziej-Sobocińska Marta
Published: November 2020

Background

Spirometra erinaceieuropaei is a diphylobothriid tapeworm with a complex life-cycle including definitive, intermediate and paratenic (transport) hosts. Multiple routes of parasite transmission often make it impossible to determine what type of host a specific infected animal is considered to be. Spargana larvae cause sparganosis, a severe food- and water-borne disease mainly found in Asia. In Poland, Spirometra sp. was reported in large carnivores in Białowieża Primeval Forest for the first time in the 1940s and was recently confirmed as S. erinaceieuropaei in several mammals and snakes using molecular methods.

Methods

In total, 583 carcasses of 9 carnivore species were necropsied between 2013 and 2019 in north-eastern (NE) Poland. The larvae of S. erinaceieuropaei (spargana) were isolated from subcutaneous tissue, counted, and preserved for genetic analyses. We calculated the prevalence and intensity of infection. To assess spatial variation in S. erinaceieuropaei infection probability in NE Poland, we applied a generalized additive model (GAM) with binomial error distribution. To confirm the species affiliation of isolated larvae, we amplified a partial fragment of the 18S rRNA gene (240 bp in length).

Results

Spirometra larvae were found in the subcutaneous tissue of 172 animals of 7 species and confirmed genetically as S. erinaceieuropaei. The overall prevalence in all studied hosts was 29.5% with a mean infection intensity of 14.1 ± 33.8 larvae per individual. Native European badgers and invasive raccoon dogs were characterized by the highest prevalence. An analysis of parasite spread showed a spatially diversified probability of infection with the highest values occurring in the biodiversity hot spot, Białowieża Primeval Forest.

Conclusions

Our study revealed that various mammal species (both native and non-native) can serve as S. erinaceieuropaei reservoirs. The frequency and level of infection may differ between selected hosts and likely depend on host diversity and habitat structure in a given area. Further studies are needed to assess the distribution of the parasite throughout Europe and the environmental and biological factors influencing infection severity in wild mammals.
Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series
Authors: Liang Bo , Yang Si-Yuan , Chen Jia-Min , Liang Ting-Yu , Zhao Hong-Xin , Ding Xing-Huan , Wang Fang , Feng En-Shan
Published: November 2020

Background

Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE.

Methods

A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service.

Results

There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4+ count ranged from 11 to 159 cells/μl (median 92 cells/μl), and serological HIV viral load 0–989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent.

Conclusions

The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Graphical Abstract
Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis
Authors: Wang Wen-Jun , Li Ling-Yu , Cui Jiu-Wei
Published: November 2020

With the rapid development of next-generation sequencing technology, chromosome structural variation has gradually gained increased clinical significance in tumorigenesis. However, the molecular mechanism(s) underlying this structural variation remain poorly understood. A search of the literature shows that a three-dimensional chromatin state plays a vital role in inducing structural variation and in the gene expression profiles in tumorigenesis. Structural variants may result in changes in copy number or deletions of coding sequences, as well as the perturbation of structural chromatin features, especially topological domains, and disruption of interactions between genes and their regulatory elements. This review focuses recent work aiming at elucidating how structural variations develop and misregulate oncogenes and tumor suppressors, to provide general insights into tumor formation mechanisms and to provide potential targets for future anticancer therapies.
Gene expression identifies patients who develop inflammatory arthritis in a clinically suspect arthralgia cohort
Authors: Niemantsverdriet Ellis , van den Akker Erik B. , Boeters Debbie M. , van den Eeden Susan J. F. , Geluk Annemieke , van der Helm-van Mil Annette H. M.
Published: November 2020

Background

Established rheumatoid arthritis (RA) patients display differentially expressed genes coding for cytokine/chemokine-mediated immunity compared to healthy controls. It is unclear, however, if in the pre-arthritis phase of clinically suspect arthralgia (CSA) expression of immune genes differ between patients who do or do not develop clinically evident inflammatory arthritis (IA).

Methods

Two hundred thirty-six consecutive patients presenting with arthralgia clinically suspected for progression to RA were followed until IA development or else for median 24 months (IQR 12–26). Baseline whole blood RNA expression was determined for a previously identified set of 133 genes associated with the innate and adaptive immune system by dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) profiling. Cox proportional hazard models were used.

Results

Twenty percent of CSA patients developed IA. After correction for multiple testing, expression levels of six genes (IFNG, PHEX, IGF-1, IL-7R, CD19, CCR7) at the time of presentation were associated with progression to IA. PHEX and IGF-1 were highly correlated with each other (ρ = 0.97). In multivariable analysis correcting for the different genes, expressions of IL-7R and IGF-1 were independently associated with IA development (p = 0.025,p = 0.046, respectively). Moreover, IL-7R and IGF-1 remained significantly associated even after correction for known predictors (ACPA, CRP, imaging-detected subclinical joint inflammation;p = 0.039,p = 0.005, respectively). These genes are also associated with RA development.

Conclusions

IL-7R and IGF-1 were differentially expressed between CSA patients who did or did not progress to IA, independent from regularly used predictors. These biomarkers may become helpful in prognostication of CSA patients. Furthermore, because both genes are associated with T cell functioning, T cell dysregulation may mediate progression from arthralgia to arthritis.