bluuebunny/crossref_metadata_2025 huggingface dataset:
A nomogram for predicting the in-hospital mortality after large hemispheric infarction
Authors: Sun Wenzhe , Li Guo , Liu Ziqiang , Miao Jinfeng , Yang Zhaoxia , Zhou Qiao , Liu Run , Zhu Suiqiang , Zhu Zhou
Published: December 2019

Background

Large hemispheric infarction (LHI) is a severe form of stroke with high mortality and disability rates. The purpose of this study was to explore predictive indicators of the in-hospital mortality of LHI patients treated conservatively without decompressive hemicraniectomy.

Method

We performed a retrospective study of 187 consecutive patients with LHI between January 1, 2016 to May 31, 2019. The receiver operating curves were preformed to evaluate predictive performance of demographics factors, biomarkers and radiologic characteristics. Significant prognostic factors were combined to build a nomogram to predict the risk of in-hospital death of individual patients.

Result

One hundred fifty-eight patients with LHI were finally enrolled, 58 of which died. Through multivariate logistic regression analysis, we identified that independent prognostic factors for in-hospital death were age (adjusted odds ratio [aOR] = 1.066; 95% confidence interval [CI], 1.025–1.108; P = 0.001), midline shift (MLS, aOR = 1.330, 95% CI, 1.177–1.503; P <  0.001), and neutrophil-to-lymphocyte ratio (NLR, aOR = 3.319, 95% CI, 1.542–7.144; P = 0.002). NLR may serve as a better predictor than white blood count (WBC) and neutrophil counts. Lastly, we used all of the clinical characteristics to establish a nomogram for predicting the prognosis, area under the curve (AUC) of this nomogram was 0.858 (95% CI, 0.794–0.908).

Conclusion

This study shows that age, MLS, and admission NLR value are independent predictors of in-hospital mortality in patients with LHI. Moreover, nomogram, serve as a precise and convenient tool for the prognosis of LHI patients.
Dose-response relationship of ICS/fast-onset LABA as reliever therapy in asthma
Authors: Beasley Richard , Harper James , Bird Grace , Dunphy Harriette , Semprini Alex , Pavord Ian D. , Papi Alberto , Weatherall Mark
Published: December 2019

Background and objective

The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations.

Methods

A systematic literature review was undertaken to identify randomised controlled trials (RCTs) in which randomised treatments included either i) budesonide/formoterol reliever monotherapy versus budesonide/formoterol fixed dose maintenance with short acting beta agonist (SABA) reliever therapy, or ii) budesonide/formoterol reliever therapy in addition to budesonide/formoterol maintenance versus higher fixed dose maintenance budesonide/formoterol with SABA as reliever therapy. Eligible studies were reviewed to allow determination of the relative potency and efficacy of the comparator regimens to reduce the risk of a severe exacerbation.

Results

The one RCT of budesonide/formoterol reliever monotherapy showed a 4.6-fold (95% CI 2.9 to 7.3) greater potency than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of severe exacerbations. In the one RCT that compared budesonide/formoterol maintenance and reliever therapy with higher fixed dose maintenance budesonide/formoterol plus SABA reliever therapy, there was an additional 26% (95% CI 4 to 42%) reduction in severe exacerbation risk with the addition of budesonide/formoterol reliever therapy to maintenance budesonide/formoterol, despite a 25% lower total budesonide/formoterol dose.

Conclusion

The limited available evidence suggests that budesonide/formoterol reliever therapy has greater potency and efficacy than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of a severe exacerbation. This is an important concept which has the potential to guide clinical practice in asthma, although the small number of studies available highlights the need for further research to better define these pharmacological properties.
The relationship between spinal pain and temporomandibular joint disorders in Korea: a nationwide propensity score-matched study
Authors: Kim Doori , Ko Seong-Gyu , Lee Eun-Kyoung , Jung Boyoung
Published: December 2019

Background

Patients with temporomandibular joint disorder (TMD) often complain of pain in other areas. Several studies have been conducted on spinal pain in TMD patients, but have contained only limited information. Therefore, this study analyzed the relationship between TMD and spinal pain in greater detail by using nationwide data.

Methods

A total of 12,375 TMD patients from the Korean National Health Insurance Review and Assessment database were analyzed. Controls were selected using propensity score-matching. The McNemar test, chi-square test, and paired t-test were used to compare the prevalence and severity of spinal pain between cases and matched controls. Logistic regression and linear regression models were used to analyze factors affecting the prevalence and severity of spinal pain in patients with TMD.

Results

The annual period prevalence of TMD was 1.1%. The prevalence was higher in younger individuals than in individuals of other ages and was higher in women than in men. The medical expenditure for TMD per person was $86. Among TMD patients, 2.5% underwent surgical procedures and 0.3% were hospitalized. The prevalence of spinal pain in patients with TMD was 48%, whereas that in the control group was 34%. Increased severity of TMD was associated with an increased probability of spinal pain. The medical expenditure, mean number of visits, and lengths of treatment for spinal pain were greater for patients with TMD than for controls ($136 vs. $81, 4.8 days vs. 2.7 days, 5.5 days vs. 3.3 days). Higher TMD grade was associated with greater differences in average medical expenditure, number of visits, and lengths of treatment for spinal pain between cases and controls. Additionally, for women, living in a rural area and having an older age and more severe TMD were associated with a greater probability of spinal pain and higher medical expenditure related to spinal pain.

Conclusion

A strong association was observed between the presence of TMD and the presence of spinal pain. The association became stronger as the severity of TMD increased, indicating a positive correlation between the severity of TMD and spinal pain.
Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series
Authors: Shen Yimin , Song Xiaoxiao , Ren Yuezhong
Published: December 2019

Background

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS.

Case presentation

We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed.

Conclusion

High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.
Association of childhood socioeconomic status with edentulism among Chinese in mid-late adulthood
Authors: Zhang Xiaoning , Chen Shuang
Published: December 2019

Background

The aim of this study was to examine the association between childhood socioeconomic status (SES) and edentulism.

Methods

The edentulous status of Chinese in mid-late adulthood was determined using self-reported lost all of teeth from the Health and Retirement Longitudinal Study (CHARLS). Childhood SES was determined based on the following parameters: the education, occupation and working status of the parents; financial situation of the family; relationship with the parents; care, love and affection from the mother; quarrels and fights between parents; primary residence; neighbors’ willingness to help and with close-knit relationships. Adulthood SES was assessed by educational achievements. This study used principal component analysis (PCA) to select variables and binary logistic regression models to determine the association between childhood SES and edentulism.

Results

Data were available from a total of 17,713 respondents, 984 of whom were edentulous (2.9%). The prevalence of edentulism in mid- to late-age Chinese individuals was higher in those with poor childhood SES. In final regression model, edentulism was significantly associated with willingness of neighbors to help with close-knit relationships (OR = 0.89, 95% CI = 0.79–0.99), parents with high school education or above (OR = 1.18, 95% CI = 1.01–1.39) and drinking and smoking habits of the father (OR = 1.10, 95% CI = 0.97–1.24).

Conclusion

Childhood SES was significantly associated with the prevalence of edentulism in mid- to late-age Chinese individuals. In particular, parents with high school education or above, unwillingness of neighbor to help with close-knit relationships, drinking and smoking habits of the father independent of adulthood SES were significantly associated with edentulism. Accordingly, the development of optimal recommendations and more effective intervention strategies requires considering the experiences in early life associated with poor SES contributes to poor oral health.
Palliative home parenteral nutrition in patients with ovarian cancer and malignant bowel obstruction: experiences of women and family caregivers
Authors: Sowerbutts Anne Marie , Lal Simon , Sremanakova Jana , Clamp Andrew R. , Jayson Gordon C. , Teubner Antje , Hardy Lisa , Todd Chris , Raftery Anne-Marie , Sutton Eileen , Morgan Robert D. , Vickers Alexander J. , Burden Sorrel
Published: December 2019

Background

Malnutrition is a problem in advanced cancer, particularly ovarian cancer where malignant bowel obstruction (MBO) is a frequent complication. Parenteral nutrition is the only way these patients can received adequate nutrition and is a principal indication for palliative home parenteral nutrition (HPN). Giving HPN is contentious as it may increase the burden on patients. This study investigates patients’ and family caregivers’ experiences of HPN, alongside nutritional status and survival in patients with ovarian cancer and MBO.

Methods

This mixed methods study collected data on participant characteristics, clinical details and body composition using computed tomography (CT) combined with longitudinal in-depth interviews underpinned by phenomenological principles. The cohort comprised 38 women with ovarian cancer and inoperable MBO admitted (10/2016 to 12/ 2017) to a tertiary referral hospital. Longitudinal interviews (n = 57) were carried out with 20 women considered for HPN and 13 of their family caregivers.

Results

Of the 38 women, 32 received parenteral nutrition (PN) in hospital and 17 were discharged on HPN. Nutritional status was poor with 31 of 33 women who had a CT scan having low muscle mass, although 10 were obese. Median overall survival from admission with MBO for all 38 women was 70 days (range 8–506) and for those 17 on HPN was 156 days (range 46–506).

Women experienced HPN as one facet of their illness, but viewed it as a “lifeline” that allowed them to live outside hospital. Nevertheless, HPN treatment came with losses including erosion of normality through an impact on activities of daily living and dealing with the bureaucracy surrounding the process. Family caregivers coped but were often left in an emotionally vulnerable state.

Conclusions

Women and family caregivers reported that the inconvenience and disruption caused by HPN was worth the extended time they had at home.
Patient safety culture in Peking University Cancer Hospital in China: baseline assessment and comparative analysis for quality improvement
Authors: Zhong Xiyao , Song Yuqin , Dennis Christine , Slovensky Donna J. , Wei Lim Yee , Chen Jie , Ji Jiafu
Published: December 2019

Background

Limited information is available regarding the patient safety culture in Chinese hospitals. This study aims to assess the patient safety culture in Peking University Cancer Hospital and to identify opportunities for improving the organization’s safety culture.

Methods

A cross-sectional study was conducted in April 2018 and 2019, respectively. Data on patient safety culture were collected from clinical and administrative staffs using the Hospital Survey on Patient Safety Culture (HSOPSC).

Results

Twelve composite dimension variables were hierarchically clustered. Three highest positive response dimensions include ‘Organizational Learning and continuous improvement’ (92.9%), ‘Teamwork within units’ (89.7%), and ‘Hospital management support for patient safety’ (83.7%), while 3 lowest positive response dimensions included ‘Frequency of events reported’ (43.9%), ‘Non-punitive response to error’ (51.1%), ‘Communication openness’ (52.2%), and ‘Staffing’ (53.7%). Compared to the average scores of the United States, the scores of the Peking University Cancer Hospital was significantly lower on ‘Communication openness’ and ‘Frequency of events reported’. After targeted continuous improvement based on results in 2018, all 12 dimensions surprisingly increased in the safety culture conducted in 2019.

Conclusion

Inadequate feedback and communications about error and lack of communication openness are key challenges for patient safety in the delivery of care in this hospital. Results of this baseline survey indicate the need for a modified approach and attention to context when designing interventions aimed at improving the safety culture in this organization.
Efficient production of α-acetolactate by whole cell catalytic transformation of fermentation-derived pyruvate
Authors: Dorau Robin , Chen Lin , Liu Jianming , Jensen Peter Ruhdal , Solem Christian
Published: December 2019

Background

Diacetyl provides the buttery aroma in products such as butter and margarine. It can be made via a harsh set of chemical reactions from sugarcane bagasse, however, in dairy products it is normally formed spontaneously from α-acetolactate, a compound generated by selected lactic acid bacteria in the starter culture used. Due to its bacteriostatic properties, it is difficult to achieve high levels of diacetyl by fermentation. Here we present a novel strategy for producing diacetyl based on whole-cell catalysis, which bypasses the toxic effects of diacetyl.

Results

By expressing a robust α-acetolactate synthase (ALS) in a metabolically optimizedLactococcus lactisstrain we obtained a whole-cell biocatalyst that efficiently converted pyruvate into α-acetolactate. After process optimization, we achieved a titer for α-acetolactate of 172 ± 2 mM. Subsequently we used a two-stage production setup, where pyruvate was produced by an engineeredL. lactisstrain and subsequently used as the substrate for the biocatalyst. Using this approach, 122 ± 5 mM and 113 ± 3 mM α-acetolactate could be made from glucose or lactose in dairy waste, respectively. The whole-cell biocatalyst was robust and fully active in crude fermentation broth containing pyruvate.

Conclusions

An efficient approach for converting sugar into α-acetolactate, via pyruvate, was developed and tested successfully. Due to the anaerobic conditions used for the biotransformation, little diacetyl was generated, and this allowed for efficient biotransformation of pyruvate into α-acetolactate, with the highest titers reported to date. The use of a two-step procedure for producing α-acetolactate, where non-toxic pyruvate first is formed, and subsequently converted into α-acetolactate, also simplified the process optimization. We conclude that whole cell catalysis is suitable for converting lactose in dairy waste into α-acetolactate, which favors resource utilization.
Associations between GUCY1A3 genetic polymorphisms and large artery atherosclerotic stroke risk in Chinese Han population: a case-control study
Authors: Li Jian-li , Liu Liu-yu , Jiang Dong-dong , Jiang Yi-ying , Zhou Guo-qiu , Mo Dong-can , Luo Man
Published: December 2019

Background

Previous genome-wide association studies have found two single nucleotide polymorphisms (SNP) rs7692387 and rs1842896 located on or near the GUCY1A3 gene were associated with coronary artery disease (CAD). GUCY1A3 was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of the GUCY1A3 and large artery atherosclerotic (LAA) stroke. This study aimed to investigate the associations between the GUCY1A3 rs7692387, rs1842896 polymorphisms and LAA stroke susceptibility.

Methods

A total of 298 LAA stroke patients and 300 control subjects from a southern Chinese Han population were included. SNaPshot technique was used for genotype analysis. Associations between genotypes and LAA stroke susceptibility were analyzed with logistic regression model.

Results

Our study found that under the recessive model (TT vs. GT + GG), the GUCY1A3 rs1842896 polymorphism was significantly correlated with LAA stroke (OR = 1.48, 95%CI: 1.07–2.04, P = 0.018). After adjustment for its effects on age, gender, cigarette smoking, total cholesterol, low-density lipoprotein cholesterol, HbA1c, hypertension, diabetes mellitus, and CAD, the rs1842896 TT genotype retained association with increased susceptibility to LAA stroke (recessive model: adjusted OR = 1.96, 95%CI: 1.22–3.17, P = 0.006). However, association between rs7692387 polymorphism with LAA stroke was not observed.

Conclusion

Our results indicate that the GUCY1A3 rs1842896 polymorphism is an LAA stroke risk factor in Southern Han Chinese.
Pathophysiological importance of bile cholesterol reabsorption: hepatic NPC1L1-exacerbated steatosis and decreasing VLDL-TG secretion in mice fed a high-fat diet
Authors: Toyoda Yu , Takada Tappei , Yamanashi Yoshihide , Suzuki Hiroshi
Published: December 2019

Background

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, although its pathogenesis remains to be elucidated. A recent study revealed that hepatic Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol re-absorber from bile to the liver expressed on the bile canalicular membrane, is an exacerbation factor of NAFLD. Indeed, transgenic mice with hepatic expression of human NPC1L1 under a liver-specific promoter (L1-Tg mice) developed steatosis with a high-fat diet (HFD) containing cholesterol within a few weeks. However, the mechanism underlying diet-induced hepatic NPC1L1-mediated lipid accumulation is poorly defined.

Methods

To achieve a deeper understanding of steatosis development in L1-Tg mice, the biochemical features of hepatic NPC1L1-mediated steatosis were investigated. Hemizygous L1-Tg mice and wild-type littermate controls fed a HFD or control-fat diet were used. At the indicated time points, the livers were evaluated for cholesterol and triglyceride (TG) contents as well as mRNA levels of hepatic genes involved in the maintenance of lipid homeostasis. The hepatic ability to secrete very low-density lipoprotein (VLDL)-TG was also investigated.

Results

Unlike the livers of wild-type mice that have little expression of hepatic Npc1l1, the livers of L1-Tg mice displayed time-dependent changes that indicated steatosis formation. In steatosis, there were three different stages of development: mild accumulation of hepatic cholesterol and TG (early stage), acceleration of hepatic TG accumulation (middle stage), and further accumulation of hepatic cholesterol (late stage). In the early stage, between WT and L1-Tg mice fed a HFD for 2 weeks, there were no significant differences in the hepatic expression of Pparα, Acox1, Fat/Cd36, Srebf1, and Srebf2; however, the hepatic ability to secrete VLDL-TG decreased in L1-Tg mice (P < 0.05). Furthermore, this decrease was completely prevented by administration of ezetimibe, an NPC1L1-selective inhibitor.

Conclusion

Hepatic NPC1L1 exacerbates diet-induced steatosis, which was accompanied by decreased hepatic ability of VLDL-TG secretion. The obtained results provide a deeper understanding of L1-Tg mice as a promising NAFLD animal model that is able to re-absorb biliary-secreted cholesterol similar to humans. Furthermore, this work supports further studies of the pathophysiological impact of re-absorbed biliary cholesterol on the regulation of hepatic lipid homeostasis.
BAP31 regulates IRAK1-dependent neuroinflammation in microglia
Authors: Liu Xia , Jiao Kun , Jia Cong-cong , Li Guo-xun , Yuan Qing , Xu Ji-kai , Hou Yue , Wang Bing
Published: December 2019

Background

Microglia, the mononuclear immune cells of the central nervous system (CNS), are essential for the maintenance of CNS homeostasis. BAP31, a resident and ubiquitously expressed protein of the endoplasmic reticulum, serves as a sorting factor for its client proteins, mediating the subsequent export, retention, and degradation or survival. Recently, BAP31 has been defined as a regulatory molecule in the CNS, but the function of BAP31 in microglia has yet to be determined. In the present study, we investigated whether BAP31 is involved in the inflammatory response of microglia.

Methods

This study used the BV2 cell line and BAP31 conditional knockdown mice generated via the Cre/LoxP system. A BAP31 knockdown experiment was performed to elucidate the role of BAP31 in the endogenous inflammatory cytokine production by microglial BV2 cells. A mouse model of lipopolysaccharide (LPS)-induced cognitive impairment was established to evaluate the neuroprotective effect of BAP31 against neuroinflammation-induced memory deficits. Behavioral alterations were assessed with the open field test (OFT), Y maze, and Morris water maze. The activation of microglia in the hippocampus of mice was observed by immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and reverse transcription quantitative real-time polymerase chain reaction (RT-PCR) were used to clarify the mechanisms.

Results

BAP31 deficiency upregulates LPS-induced proinflammatory cytokines in BV2 cells and mice by upregulating the protein level of IRAK1, which in turn increases the translocation and transcriptional activity of NF-κB p65 and c-Jun, and moreover, knockdown of IRAK1 or use of an IRAK1 inhibitor reverses these functions. In the cognitive impairment animal model, the BAP31 knockdown mice displayed increased severity in memory deficiency accompanied by an increased expression of proinflammatory factors in the hippocampus.

Conclusions

These findings indicate that BAP31 may modulate inflammatory cytokines and cognitive impairment induced by neuroinflammation through IRAK1, which demonstrates that BAP31 plays an essential role in microglial inflammation and prevention of memory deficits caused by neuroinflammation.
CXCR5-negative natural killer cells ameliorate experimental autoimmune myasthenia gravis by suppressing follicular helper T cells
Authors: Yang Chun-Lin , Zhang Peng , Liu Ru-Tao , Zhang Na , Zhang Min , Li Heng , Du Tong , Li Xiao-Li , Dou Ying-Chun , Duan Rui-Sheng
Published: December 2019

Background

Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated.

Methods

To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation.

Results

In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells.

Conclusions

These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.
Equitable access to mental healthcare integrated in primary care for people with severe mental disorders in rural Ethiopia: a community-based cross-sectional study
Authors: Hailemariam Maji , Fekadu Abebaw , Medhin Girmay , Prince Martin , Hanlon Charlotte
Published: December 2019

Background

Integration of mental healthcare into non-specialist settings is advocated to expand access to care for people with severe mental disorders (SMD) in low-income countries. However, the impact upon equitable access for disenfranchised members of society has not been investigated. The purpose of this study was to (1) estimate contact coverage for SMD of a new service in primary healthcare (PHC) in a rural Ethiopian district, and (2) investigate equity of access for rural residents, women, people with physical impairments and people of low socio-economic status.

Methods

Community key informants were trained to identify and refer people with probable SMD in Sodo district, south-central Ethiopia, using vignettes of typical presentations. Records of those referred to the new PHC-based service were linked to healthcare records to identify people who engaged with care and non-engagers over a 6 month period. Standardised interviews by psychiatric nurses were used to confirm the diagnosis in those attending PHC. Non-engagers were visited in their homes and administered the Psychosis Symptom Questionnaire. Socio-economic status, discrimination, disability, substance use, social support and distance to the nearest health facility were measured.

Results

Contact coverage for the new service was estimated to be 81.3% (300 engaged out of 369 probable cases of SMD identified). Reimbursement for transport and time may have elevated coverage estimates. In the fully adjusted multivariable model, rural residents had 3.81 increased odds (95% CI 1.22, 11.89) of not accessing care, in part due to geographical distance from the health facility (odds ratio 3.37 (1.12, 10.12)) for people living more than 180 min away. There was no association with lower socioeconomic status, female gender or physical impairment. Higher levels of functional impairment were associated with increased odds of engagement. Amongst non-engagers, the most frequently endorsed barriers were thinking the problem would get better by itself and concerns about the cost of treatment.

Conclusion

Integrating mental healthcare into primary care can achieve high levels of coverage in a rural African setting, which is equitable with respect to gender and socio-economic status. Service outreach into the community may be needed to achieve better contact coverage for rural residents.
Kallistatin inhibits tumour progression and platinum resistance in high-grade serous ovarian cancer
Authors: Wu Huan , Li Rongrong , Zhang Zhiwei , Jiang Huiyang , Ma Hanlin , Yuan Cunzhong , Sun Chenggong , Li Yingwei , Kong Beihua
Published: December 2019

Ovarian cancer is the most lethal gynaecologic malignancy. Although there are various subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer deaths. Chemoresistance is the primary reason for the unfavourable prognosis of HGSOC. Kallistatin (KAL), also known as SERPINA4, is part of the serpin family. Kallistatin has been discovered to exert multiple effects on angiogenesis, inflammation and tumour progression. However, the roles and clinical significance of kallistatin in HGSOC remain unclear. Here, we showed that kallistatin was significantly downregulated in HGSOC compared to normal fallopian tube (FT) tissues. Low expression of kallistatin was associated with unfavourable prognosis and platinum resistance in HGSOC. Overexpression of kallistatin significantly inhibited proliferation and metastasis, and enhanced platinum sensitivity and apoptosis in ovarian cancer cells. Collectively, these findings demonstrate that kallistatin serves as a prognostic predictor and provide a potential therapeutic target for HGSOC.
Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species
Authors: Manara Serena , Asnicar Francesco , Beghini Francesco , Bazzani Davide , Cumbo Fabio , Zolfo Moreno , Nigro Eleonora , Karcher Nicolai , Manghi Paolo , Metzger Marisa Isabell , Pasolli Edoardo , Segata Nicola
Published: December 2019

Background

Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.

Results

We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.

Conclusions

The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.
Tools and best practices for retrotransposon analysis using high-throughput sequencing data
Authors: Teissandier Aurélie , Servant Nicolas , Barillot Emmanuel , Bourc’his Deborah
Published: December 2019

Background

Sequencing technologies give access to a precise picture of the molecular mechanisms acting upon genome regulation. One of the biggest technical challenges with sequencing data is to map millions of reads to a reference genome. This problem is exacerbated when dealing with repetitive sequences such as transposable elements that occupy half of the mammalian genome mass. Sequenced reads coming from these regions introduce ambiguities in the mapping step. Therefore, applying dedicated parameters and algorithms has to be taken into consideration when transposable elements regulation is investigated with sequencing datasets.

Results

Here, we used simulated reads on the mouse and human genomes to define the best parameters for aligning transposable element-derived reads on a reference genome. The efficiency of the most commonly used aligners was compared and we further evaluated how transposable element representation should be estimated using available methods. The mappability of the different transposon families in the mouse and the human genomes was calculated giving an overview into their evolution.

Conclusions

Based on simulated data, we provided recommendations on the alignment and the quantification steps to be performed when transposon expression or regulation is studied, and identified the limits in detecting specific young transposon families of the mouse and human genomes. These principles may help the community to adopt standard procedures and raise awareness of the difficulties encountered in the study of transposable elements.
Serotype distribution, antimicrobial susceptibility, antimicrobial resistance genes and virulence genes of Salmonella isolated from a pig slaughterhouse in Yangzhou, China
Authors: Li Quan , Yin Jian , Li Zheng , Li Zewei , Du Yuanzhao , Guo Weiwei , Bellefleur Matthew , Wang Shifeng , Shi Huoying
Published: December 2019

Salmonella is an important food-borne pathogen associated with public health and high economic losses. To investigate the prevalence and the characteristics of Salmonella in a pig slaughterhouse in Yangzhou, a total of 80 Salmonella isolates were isolated from 459 (17.43%) samples in 2016–2017. S. Derby (35/80, 43.75%) was the most prevalent, followed by S. Rissen (16/80, 20.00%) and S. Newlands (11/80, 13.75%). The highest rates of susceptibility were observed to cefoxitin (80/80, 100.0%) and amikacin (80/80, 100.0%), followed by aztreonam (79/80, 98.75%) and nitrofurantoin (79/80, 98.75%). The highest resistance rate was detected for tetracycline (65/80, 81.25%), followed by ampicillin (60/80, 75.00%), bactrim (55/80, 68.75%), and sulfisoxazole (54/80, 67.50%). Overall, 91.25% (73/80) of the isolates were resistant to at least one antibiotic, while 71.25% (57/80) of the isolate strains were multidrug resistant in the antimicrobial susceptibility tested. In addition, 86.36% (19/22) of the 22 antimicrobial resistance genes in the isolates were identified. Our data indicated that the resistance to certain antimicrobials was significantly associated, in part, with antimicrobial resistance genes. Furthermore, 81.25% (65/80) isolates harbored the virulence gene of mogA, of which 2 Salmonella Typhimurium isolates carried the mogA, spvB and spvC virulence genes at the same time. The results showed that swine products in the slaughterhouse were contaminated with multidrug resistant Salmonella commonly, especially some isolates carry the spv virulence genes. The virulence genes might facilitate the dissemination of the resistance genes to consumers along the production chain, suggesting the importance of controlling Salmonella during slaughter for public health.
Effectiveness of remineralising agents in prevention and treatment of orthodontically induced white spot lesions: a protocol for a systematic review incorporating network meta-analysis
Authors: Hu Huimin , Feng Chong , Jiang Zhaowei , Wang Lufei , Shrestha Sonu , Su Xiaoming , Shu Yu , Ge Long , Lai Wenli , Hua Fang , Long Hu
Published: December 2019

Background

White spot lesions (WSLs) are common adverse effects in fixed orthodontic treatment. Remineralising agents are widely used to prevent WSLs formation and are the first-line treatment for existing WSLs. Previous systematic reviews have evaluated the effectiveness of remineralisation agents in the management of WSLs. However, their conclusions were contradictory. The objective of this study will be to compare the effectiveness and safety of current remineralising agents used in the management of WSLs in patients treated with fixed orthodontic appliances in any orthodontic setting.

Methods

Literature searches will be conducted in several electronic databases (from inception onwards): MEDLINE (via Ovid), Scopus, Embase, the Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), among others. Grey literature will be identified through searching clinical trials registries. Randomised controlled trials that compared the effectiveness of different remineralisation agents in the prevention and treatment of WSLs will be included. Two researchers will independently screen all citations, full-text articles, and abstract data. The study risk bias will be appraised using an appropriate tool. The primary outcomes will be WSLs incidence and severity of WSLs. Secondary outcomes will be subjective measures of WSLs and adverse effects. The mean difference (MD) and relative risk (RR) with corresponding 95% confidence intervals (CI) will be chosen as effect measures for continuous and binary outcomes, respectively. If feasible, fixed and random-effects pairwise meta-analyses and frequentist network meta-analyses will be conducted where appropriate.

Discussion

This network meta-analysis will compare the effectiveness of remineralising agents in the prevention and treatment of orthodontically induced WSLs. By integrating the evidence from direct and indirect comparisons and ranking all evaluated interventions, our findings have the potential to help clinicians make more accurate treatment decisions.

Systematic review registration

PROSPERO CRD42019116852, registered on March 15, 2019
Observation of magnetic susceptibility changes within the thalamus: a comparative study between healthy and Parkinson’s disease afflicted cynomolgus monkeys using 7 T MRI
Authors: Kim Sangwoo , Lee Youngjeon , Jeon Chang-Yeop , Jin Yeung Bae , Oh Sukhoon , Lee Chulhyun
Published: December 2019

Background

Although the thalamus is known to modulate basal ganglia function related to motor control activity, the abnormal changes within the thalamus during distinct medical complications have been scarcely investigated. In order to explore the feasibility of assessing iron accumulation in the thalamus as an informative biomarker for Parkinson’s disease (PD), this study was designed to employ quantitative susceptibility mapping using a 7 T magnetic resonance imaging system in cynomolgus monkeys. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-injected cynomolgus monkey and a healthy control (HC) were examined by 7 T magnetic resonance imaging. Positron emission tomography with 18F-N-(3-fluoro propyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane was also employed to identify the relationship between iron deposits and dopamine depletion. All acquired values were averaged within the volume of interest of the nigrostriatal pathway.

Findings

Compared with the HC, the overall elevation of iron deposition within the thalamus in the Parkinson’s disease model (about 53.81% increase) was similar to that in the substantia nigra (54.81%) region. Substantial susceptibility changes were observed in the intralaminar part of the thalamus (about 70.78% increase). Additionally, we observed that in the Parkinson’s disease model, binding potential values obtained from positron emission tomography were considerably decreased in the thalamus (97.51%) and substantia nigra (92.48%).

Conclusions

The increased iron deposition in the thalamus showed negative correlation with dopaminergic activity in PD, supporting the idea that iron accumulation affects glutaminergic inputs and dopaminergic neurons. This investigation indicates that the remarkable susceptibility changes in the thalamus could be an initial major diagnostic biomarker for Parkinson’s disease-related motor symptoms.
Development of mass media resources to improve the ability of parents of primary school children in Uganda to assess the trustworthiness of claims about the effects of treatments: a human-centred design approach
Authors: Semakula Daniel , Nsangi Allen , Oxman Matt , Rosenbaum Sarah Ellen , Oxman Andrew David , Austvoll-Dahlgren Astrid , Glenton Claire , Lewin Simon , Kaseje Margaret , Morelli Angela , Fretheim Atle , Sewankambo Nelson Kaulukusi
Published: December 2019

Background

Claims about what we need to do to improve our health are everywhere. Most interventions simply tell people what to do, and do not empower them to critically assess health information. Our objective was to design mass media resources to enable the public to critically appraise the trustworthiness of claims about the benefits and harms of treatments and make informed health choices.

Methods

Research was conducted between 2013 and 2016 across multiple iterative phases. Participants included researchers, journalists, parents, other members of the public. First, we developed a list of 32 key concepts that people need to understand to be able to assess the trustworthiness of claims about treatment effects. Next, we used a human-centred design approach, to generate ideas for resources for teaching the key concepts, and developed and user-tested prototypes through qualitative interviews. We addressed identified problems and repeated this process until we had a product that was deemed relevant and desirable by our target audience, and feasible to implement.

Results

We generated over 160 ideas, mostly radio-based. After prototyping some of these, we found that a podcast produced collaboratively by health researchers and journalists was the most promising approach. We developed eight episodes of the Informed Health Choices podcast, a song on critical thinking about treatments and a reminder checklist. Early versions of the podcast were reportedly too long, boring and confusing. We shortened the episodes, included one key concept per episode, and changed to story-telling with skits. The final version of the podcast was found to be useful, understandable, credible and desirable.

Conclusion

We found many problems with various prototypes of mass media resources. Using a human-centred design approach, we overcame those problems. We have developed a guide to help others prepare similar podcasts.
Modeling the potential climate change- induced impacts on future genus Rhipicephalus (Acari: Ixodidae) tick distribution in semi-arid areas of Raya Azebo district, Northern Ethiopia
Authors: Hadgu Meseret , Menghistu Habtamu Taddele , Girma Atkilt , Abrha Haftu , Hagos Haftom
Published: December 2019

Background

Climate change is believed to be continuously affecting ticks by influencing their habitat suitability. However, we attempted to model the climate change-induced impacts on future genus Rhipicephalus distribution considering the major environmental factors that would influence the tick. Therefore, 50 tick occuance points were taken to model the potential distribution using maximum entropy (MaxEnt) software and 19 climatic variables, taking into account the ability for future climatic change under representative concentration pathways (RCPs) 4.5 and 8.5, were used.

Results

MaxEnt model performance was tested and found with the AUC value of 0.99 which indicates excellent goodness-of-fit and predictive accuracy. Current models predict increased temperatures, both in the mid and end terms together with possible changes of other climatic factors like precipitation which may lead to higher tick-borne disease risks associated with expansion of the range of the targeted tick distribution. Distribution maps were constructed for the current, 2050, and 2070 for the two greenhouse gas scenarios and the most dramatic scenario; RCP 8.5 produced the highest increase probable distribution range.

Conclusions

The future potential distribution of the genus Rhipicephalus show potential expansion to the new areas due to the future climatic suitability increase. These results indicate that the genus population of the targeted tick could emerge in areas in which they are currently lacking; increased incidence of tick-borne diseases poses further risk which can affect cattle production and productivity, thereby affecting the livelihood of smallholding farmers. Therefore, it is recommended to implement climate change adaptation practices to minimize the impacts.
On the mesh resolution of industrial LES based on the DNS of flow over the T106C turbine
Authors: Alhawwary Mohammad , Wang Z.J.
Published: December 2019

A high-order Navier-Stokes solver based on the flux reconstruction (FR) or the correction procedure via reconstruction (CPR) formulation is employed to perform a direct numerical simulation (DNS) and large eddy simulations (LES) of a well-known benchmark problem – transitional flow over the low-pressure T106C turbine cascade. Hp-refinement studies are carried out to assess the resolution requirement. A 4th order (p3) simulation on the fine mesh is performed with a DNS resolution to establish a "converged" solution, including the mean pressure and skin-friction distributions, and the power spectral density in the wake. Then LES on the coarse and fine meshes with lower order schemes are conducted to assess the mesh and order dependence of the solution. In particular, we study the error in the transition location, the mean skin-friction distribution, and the mean lift and drag coefficients. These h- and p-refinement studies provide a much-needed guideline in h- and p- resolutions to achieve a certain level of accuracy for industrial LES applications.
An ethno-nutritional study on spices used in traditional foods of the Western Regions of Cameroon: the case of nah poh
Authors: Djiazet Stève , Mezajoug Kenfack Laurette Blandine , Linder Michel , Tchiégang Clergé
Published: December 2019

The consumption rate of traditional foods is gradually being reduced with time due to the globalization of the food systems and non-availability of modernized ready-to-use traditional food products. In order to contribute to the sustainability and to promote the consumption of nah poh, the present study was undertaken to gather traditional culinary knowledge related to the consumption of some local spices in nah poh, as to contribute to the development of a ready-to-use spice formulation. It consisted in carrying out a qualitative and quantitative survey. The study revealed that there is a great variability with respect to the different Divisions of the Western Regions of Cameroon, regarding the spice composition of nah poh. All the local spices used for this study are utilized for the preparation of nah poh. Seven spices were found to be essential in most Divisions. Scorodophloeus zenkeri fruits and Xylopia africana were shown to be essential spices for consumers in Mezam Division. The quantities of essential spices for one litre of nah poh varied between 0.61 ± 0.24 g and 4.59 ± 2.06 g.