bluuebunny/crossref_metadata_2025 huggingface dataset:
Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?
Authors:   for the ICONA Foundation Study Group, Shanyinde Milensu , Girardi Enrico , Puoti Massimo , De Luca Andrea , Sighinolfi Laura , Caterina Uberti Foppa , Caramello Pietro , Lampe Fiona C. , D’Arminio Monforte Antonella , Cozzi-Lepri Alessandro
Published: October 2019

Background

Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy.

Methods

We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD.

Results

Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03–2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94–1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population.

Conclusions

Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals.
Soybean plants expressing the Bacillus thuringiensis cry8-like gene show resistance to Holotrichia parallela
Authors: Qin Di , Liu Xiao-Yi , Miceli Cristina , Zhang Qi , Wang Pi-wu
Published: October 2019

Background

Cry8-like from Bacillus thuringiensis (Bt) encodes an insecticidal crystal (Cry) protein. Holotrichia parallela (Coleoptera: Scarabaeoidae), commonly known as the dark black chafer, is a troublesome pest of soybean (Glycine max). To test whether cry8-like can confer resistance against H. parallela to soybean, we introduced cry8-like from the Bt strain HBF-18 into soybean cultivar Jinong 28.

Results

Quantitative reverse transcription-PCR analysis demonstrated that cry8-like was expressed most highly in soybean leaves. In addition, Southern blot assays revealed that one copy of the integrated fragment was present in the transformed plants. Eight independent cry8-like transgenic lines were subsequently fed on by H. parallela. Under H. parallela feeding stress, the survival rates of the non-transgenic plants were 92% lower than those of the transgenic plants. The mortality rate of H. parallela increased when the larvae fed on the roots of T1 transgenic soybean plants. Moreover, the surviving larvae were deformed, and their growth was inhibited.

Conclusions

Collectively, our data suggest that transgenic soybean plants expressing the cry8-like gene are more resistant to H. parallela than non-transgenic plants and that transgenic expression of the cry8-like gene may represent a promising strategy for engineering pest tolerance. The events generated in this study could thus be utilized in soybean breeding programs.
Elevated serum levels of aminotransferases in relation to unhealthy foods intake: Tehran lipid and glucose study
Authors: Mirmiran Parvin , Gaeini Zahra , Bahadoran Zahra , Azizi Fereidoun
Published: October 2019

Background

Abnormal levels of liver enzymes, particularly aminotransferases, are prognostic features of non-alcoholic fatty liver disease (NAFLD). Considering the important role of dietary intakes in development of NAFLD, we aimed to determine possible association of unhealthy foods (fast foods, soft drinks, sweet and salty snacks) consumption with elevated levels of aminotransferases.

Methods

This cross-sectional study was conducted within the framework of sixth phase of the Tehran Lipid and Glucose Study (2014–2017), on 187 adult men and 249 adult women (19–70 y). Usual intakes of unhealthy foods (kcal/week) were measured using a validated semi-quantitative 147-items food frequency questionnaire. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured. Multivariable logistic regression models were used to estimate the odds of elevated aminotransferases in each tertile of energy-dense unhealthy foods.

Results

Mean age of participants was 44.44 ± 15.09 years, 43% of participants were men. Higher consumption of fast foods (> 11.39% kcal/week) was associated with elevated ALT to AST ratio (OR: 3.27; 95% CI: 1.90–5.63) and elevated ALT (OR: 2.74; 95% CI: 1.57–4.76). Also, each 1 SD increased energy intakes from fast foods was related to increased chance of having elevated ALT and ALT to AST ratio by 35% (OR: 1.35; 95% CI: 1.08–1.68, OR: 1.35; 95% CI: 1.10–1.66, respectively). There was no significant association between consumption of soft drinks, sweet or salty snacks and elevated aminotransferases.

Conclusions

Higher intakes of energy from fast foods seems to be associated with an elevated serum levels of ALT and ALT to AST ratio, as indicators of development of NAFLD.
Trajectories of Rehabilitation across Complex Environments (TRaCE): design and baseline characteristics for a prospective cohort study on spinal cord injury and acquired brain injury
Authors: Legg Melissa , Foster Michele , Parekh Sanjoti , Nielsen Mandy , Jones Rachel , Kendall Elizabeth , Fleming Jennifer , Geraghty Timothy
Published: October 2019

Purpose

Trajectories of Rehabilitation across Complex Environments (TRaCE), a consented prospective cohort study, addresses a critical need to better understand access to the healthcare system after acute treatment and specialist inpatient rehabilitation for acquired disability. It is expected that this study will produce new knowledge on access to healthcare through the linkage of administrative, survey, and spatial datasets on the one cohort. This paper outlines the study design and baseline characteristics of the cohort.

Methods

The TRaCE cohort is comprised of 165 inpatients who are currently being followed up for 12 months after discharge from specialist rehabilitation for acquired brain injury (ABI) and spinal cord injury (SCI). This project combines a data linkage framework on health service use with a prospective survey on psychosocial wellbeing, geographical information systems to examine spatial accessibility to services, and qualitative interviews with a sub-cohort on experiences of service access.

Conclusion

Ultimately, TRaCE will have strong translational impact on strategies for more targeted interventions to improve the healthcare system and support individuals with acquired disabilities in the long-term.
Trends in socioeconomic inequalities in stunting prevalence in Latin America and the Caribbean countries: differences between quintiles and deciles
Authors: Flores-Quispe Maria del Pilar , Restrepo-Méndez María Clara , Maia Maria Fátima S. , Ferreira Leonardo Z. , Wehrmeister Fernando C.
Published: October 2019

Background

With the adoption of the Sustainable Development Goals (SDGs), there is a renewed commitment of tackling the varied challenges of undernutrition, particularly stunting (SDG 2.2). Health equity is also a priority in the SDG agenda and there is an urgent need for disaggregated analyses to identify disadvantaged subgroups. We compared time trends in socioeconomic inequalities obtained through stratification by wealth quintiles and deciles for stunting prevalence.

Methods

We used 37 representative Demographic and Health Surveys and Multiple Indicator Cluster surveys from nine Latin American and Caribbean (LAC) countries conducted between 1996 and 2016. Stunting in children under-5 years was assessed according to the 2006 WHO Child Growth Standards and stratified by wealth quintiles and deciles. Within-country socioeconomic inequalities were measured through concentration index (CIX) and slope index of inequality (SII). We used variance-weighted least squares regression to estimate annual changes.

Results

Eight out of nine countries showed a statistical evidence of reduction in stunting prevalence over time. Differences between extreme deciles were larger than between quintiles in most of countries and at every point in time. However, when using summary measures of inequality, there were no differences in the estimates of SII with the use of deciles and quintiles. In absolute terms, there was a reduction in socioeconomic inequalities in Peru, Honduras, Dominican Republic, Belize, Suriname and Colombia. In relative terms, there was an increase in socioeconomic inequalities in Peru, Bolivia, Haiti, Honduras and Guatemala.

Conclusions

LAC countries have made substantial progress in terms of reducing stunting,. Nevertheless, renewed actions are needed to improve equity. Particularly in those countries were absolute and relative inequalities did not change over time such Bolivia and Guatemala. Finer breakdowns in wealth distribution are expected to elucidate more differences between subgroups; however, this approach is relevant to cast light on those subgroups that are still lagging behind within populations and inform equity-oriented health programs and practices.
Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules
Authors: Villar-Alvarez E. , Cambón A. , Pardo A. , Arellano L. , Marcos A. V. , Pelaz B. , del Pino P. , Bouzas Mosquera A. , Mosquera V. X. , Almodlej A. , Prieto G. , Barbosa S. , Taboada P.
Published: October 2019

Background

Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity.

Results

We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism.

Conclusions

This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.
Mapping function from FACT-B to EQ-5D-5 L using multiple modelling approaches: data from breast cancer patients in China
Authors: Yang Qing , Yu Xue Xin , Zhang Wei , Li Hui
Published: October 2019

Background

The Functional Assessment of Cancer Therapy-Breast (FACT-B) is the most commonly used scale for assessing quality of life in patients with breast cancer. The lack of preference-based measures limits the cost-utility of breast cancer in China. The goal of this study was to explore whether a mapping function can be established from the FACT-B to the EQ-5D-5 L when the EQ-5D health-utility index is not available.

Methods

A cross-sectional survey of adults with breast cancer was conducted in China. All patients included in the study completed the EQ-5D-5 L and the disease-specific FACT-B questionnaire, and demographic and clinical data were also collected. The Chinese tariff value was used to calculate the EQ-5D-5 L utility scores. Five models were evaluated using three different modelling approaches: the ordinary least squares (OLS) model, the Tobit model and the two-part model (TPM). Total scores, domain scores, squared terms and interaction terms were introduced into models. The goodness of fit, signs of the estimated coefficients, and normality of prediction errors of the model were also assessed. The normality of the prediction error is determined by calculating the root mean squared error (RMSE), the mean absolute deviation (MAD), and the mean absolute error (MAE). Akaike information criteria (AIC) and Bayes information criteria (BIC) were also used to assess models and predictive performances. The OLS model was followed by simple linear equating to avoid regression to the mean.

Results

The performance of the models was improved after the introduction of the squared terms and the interaction terms. The OLS model, including the squared terms and the interaction terms, performed best for mapping the EQ-5D-5 L. The explanatory power of the OLS model was 70.0%. The AIC and BIC of this model were the smallest (AIC = -705.106, BIC = -643.601). The RMSE, MAD and MAE of the OLS model, Tobit model and TPM were similar. The MAE values of the 5-fold cross-validation of the multiple models in this study were 0.07155~0.08509; meanwhile, the MAE of the TPM was the smallest, followed by that of the OLS model. The OLS regression proved to be the most accurate for the mean, and linearly equated scores were much closer to observed scores.

Conclusions

This study establishes a mapping algorithm based on the Chinese population to estimate the EQ-5D-5 L index of the FACT-B and confirms that OLS models have higher explanatory power and that TPMs have lower prediction error. Given the accuracy of the mean prediction and the simplicity of the model, we recommend using the OLS model. The algorithm can be used to calculate EQ-5D scores when EQ-5D data are not directly collected in a study.
Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life
Authors: Paghera S. , Quiros-Roldan E. , Sottini A. , Properzi M. , Castelli F. , Imberti L.
Published: October 2019

Background

While immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection.

Methods

We compared thymic and bone marrow output, telomere length (measured by Real-Time PCR) and T-cell receptor repertoire (determined by spectratyping) of 21 perinatally HIV-infected subjects (with a median of 27 years of infection) with those of 19 age-matched non-perinatally HIV-infected patients and 40 healthy controls. All patients received a combined antiretroviral therapy.

Results

While thymic and bone marrow output were not different among the analyzed groups, telomere length in peripheral blood cells and T-cell receptor diversity were significantly lower in HIV-perinatally and non-perinatally infected individuals compared to healthy controls.

Conclusions

In HIV-infected subjects, a normal thymic output together with a reduced telomere length and a restricted T-cell receptor repertoire could be explained by the shift of newly produced cells into memory subsets. This phenomenon may allow to control viral infection and maintain peripheral homeostasis.
Short-term results of bilateral internal mammary arterial grafting for patients aged 60–75 years – a retrospective study
Authors: Guo Yilong , Wang Xiaoqi , He Shuwu , Shu Yue , Wang Tianguang , Chen Zelun
Published: October 2019

Background

Bilateral internal mammary artery (BIMA) grafting has a good long-term survival rate and graft patency rate, but it is only recommended in young patients due to its high technical requirements and high incidence of sternal complications. Previous studies indicated that BIMA grafting has a significant benefit in patients aged 50–59 years, but this benefit does not extend to patients aged > 60 years. Thus, this study was designed to analyse the immediate artery graft function, short-term (3 months) results, and experience in preventing sternal complications for BIMA grafting in elderly patients (60–75 years old).

Methods

Clinical records and echocardiographic and coronary artery computed tomography angiography data of 155 patients who underwent BIMA grafting for coronary artery disease between 2015 and 2017 in our hospital were analysed retrospectively to summarise the operative experience and short-term (3 months) results. Patients were divided into two groups: Group A (n = 95), aged < 60 years and Group B (n = 60), aged 60–75 years. The operation time, aortic clamp time, and cardiopulmonary bypass time of these two groups were compared to analyse the operation difficulty and the flow and pulsatility index were compared to analyse the immediate artery graft function. The left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) of these two groups were compared to analyse heart function.

Results

There were no significant differences in the operation time, aortic clamp time, and cardiopulmonary bypass time as well as the flow and pulsatility index between these two groups (P > 0.05). There was no significant difference in the incidence of sternal wound complications, graft occlusion, and other common complications 3 months post-BIMA grafting between these two groups (P > 0.05). Furthermore, there was no significant difference in LVEDD and LVEF between the groups 3 months post-operation (P > 0.05).

Conclusions

BIMA grafting was safe and effective for older patients (60–75 years). Similar to younger patients (< 60 years), BIMA grafting in elderly patients (60–75 years) can also achieve a satisfactory short-term (3 months) result. Thus, advanced age (60–75 years) should not be a contraindication for BIMA grafting.
Dynamic observation and analysis of metabolic response to moxibustion stimulation on ethanol-induced gastric mucosal lesions (GML) rats
Authors: Zhang Yuan , Huang Miao-sen , Liu Cai-chun , Lian Lin-yu , Shen Jia-cheng , He Qi-da , Wang Ying-jie , Zhang Long-bin , Liu Mi , Yang Zong-bao
Published: October 2019

Background

Gastric mucosal lesion (GML) is the initiating pathological process in many refractory gastric diseases. And moxibustion is an increasingly popular alternative therapy that prevents and treats diseases. However, there are few published reports about developing pathology of GML and therapeutic mechanism of moxibustion treatment on GML. In this study, we investigated pathology of GML and therapeutic mechanism of moxibustion treatment on GML.

Methods

The male Sprague-Dawley (SD) rats were induced by intragastric administration of 75% ethanol after fasting for 24 h and treated by moxibustion at Zusanli (ST36) and Liangmen (ST21) for 1 day, 4 days or 7 days. Then we applied1H NMR-based metabolomics to dynamic analysis of metabolic profiles in biological samples (stomach, cerebral cortex and medulla). And the conventional histopathological examinations as well as metabolic pathways assays were also performed.

Results

Moxibustion intervention showed a beneficial effect on GML by modulating comprehensive metabolic alterations caused by GML, including energy metabolism, membrane metabolism, cellular active and neurotransmitters function.

Conclusions

Moxibustion can effectively treat gastric mucosal damage and effectively regulate the concentration of some related differential metabolites to maintain the stability of the metabolic pathway.
APRIL and BAFF: novel biomarkers for central nervous system lymphoma
Authors: Mulazzani Matthias , Huber Marion , Borchard Sabine , Langer Sigrid , Angele Barbara , Schuh Elisabeth , Meinl Edgar , Dreyling Martin , Birnbaum Tobias , Straube Andreas , Koedel Uwe , von Baumgarten Louisa
Published: October 2019

Background

Early diagnosis of CNS lymphoma (CNSL) is essential for successful therapy of this rapidly progressing brain tumor. However, in patients presenting with focal brain lesions, fast and reliable diagnosis of PCNSL remains a challenge. A proliferation-inducing ligand (APRIL) and B cell activating factor (BAFF) are important factors in the pathophysiology, diagnosis, and prognosis of systemic B cell malignancies. However, their utility as biomarkers for the diagnosis of CNSL and their effects on CNSL cells remain unclear.

Methods

In this prospective study, we analyzed the levels of APRIL and BAFF in the cerebrospinal fluid (CSF) of 116 patients with suspected focal brain lesions, including 53 CNSL patients. Additionally, we serially measured their levels during chemotherapy and relapse. Furthermore, we analyzed the effect of APRIL and BAFF on two B cell lymphoma cell lines using proliferation, viability, and chemotaxis assays.

Results

CSF levels of APRIL and BAFF reliably differentiated CNSL from other focal brain lesions (including primary and metastatic brain tumors, autoimmune-inflammatory lesions, and neuroinfectious lesions) with a specificity of 93.7% (APRIL, BAFF) and a sensitivity of 62.3% (APRIL) and 47.1% (BAFF). Serial CSF analysis of CNSL patients during chemotherapy and relapse demonstrates a close correlation of APRIL CSF levels and the course of this disease. In vitro, APRIL and BAFF showed anti-apoptotic effects during MTX treatment and mediated chemotaxis of malignant B cells.

Conclusion

This study extends the spectrum of valuable diagnostic biomarkers in CNSL. In patients with focal brain lesions, measurement of APRIL in CSF could help accelerating the diagnosis of CNSL. Moreover, our results highlight an important role of APRIL and BAFF in the pathophysiology of CNSL.
What are the most important unanswered research questions in trial retention? A James Lind Alliance Priority Setting Partnership: the PRioRiTy II (Prioritising Retention in Randomised Trials) study
Authors: Brunsdon Dan , Biesty Linda , Brocklehurst Peter , Brueton Valerie , Devane Declan , Elliott Jim , Galvin Sandra , Gamble Carrol , Gardner Heidi , Healy Patricia , Hood Kerenza , Jordan Joan , Lanz Doris , Maeso Beccy , Roberts Amanda , Skene Imogen , Soulsby Irene , Stewart Derek , Torgerson David , Treweek Shaun , Whiting Caroline , Wren Sharon , Worrall Andrew , Gillies Katie
Published: October 2019

Background

One of the top three research priorities for the UK clinical trial community is to address the gap in evidence-based approaches to improving participant retention in randomised trials. Despite this, there is little evidence supporting methods to improve retention. This paper reports the PRioRiTy II project, a Priority Setting Partnership (PSP) that identified and prioritised unanswered questions and uncertainties around trial retention in collaboration with key stakeholders.

Methods

This PSP was conducted in collaboration with the James Lind Alliance, a non-profit making initiative, to support key stakeholders (researchers, patients, and the public) in jointly identifying and agreeing on priority research questions.

There were three stages. (1) First an initial online survey was conducted consisting of six open-ended questions about retention in randomised trials. Responses were coded into thematic groups to create a longlist of questions. The longlist of questions was checked against existing evidence to ensure that they had not been answered by existing research. (2) An interim stage involved a further online survey where stakeholders were asked to select questions of key importance from the longlist. (3) A face-to-face consensus meeting was held, where key stakeholder representatives agreed on an ordered list of 21 unanswered research questions for methods of improving retention in randomised trials.

Results

A total of 456 respondents yielded 2431 answers to six open-ended questions, from which 372 questions specifically about retention were identified. Further analysis included thematically grouping all data items within answers and merging questions in consultation with the Steering Group. This produced 27 questions for further rating during the interim survey. The top 21 questions from the interim online survey were brought to a face-to-face consensus meeting in which key stakeholder representatives prioritised the order. The ‘Top 10’ of these are reported in this paper. The number one ranked question was ’What motivates a participant’s decision to complete a clinical trial?’ The entire list will be available at www.priorityresearch.ie.

Conclusion

The Top 10 list can inform the direction of future research on trial methods and be used by funders to guide projects aiming to address and improve retention in randomised trials.
Use of fusion transcription factors to reprogram cellulase transcription and enable efficient cellulase production in Trichoderma reesei
Authors: Wang Fangzhong , Zhang Ruiqin , Han Lijuan , Guo Wei , Du Zhiqiang , Niu Kangle , Liu Yucui , Jia Chunjiang , Fang Xu
Published: October 2019

Background

Trichoderma reesei is widely used for cellulase production and accepted as an example for cellulase research. Cre1-mediated carbon catabolite repression (CCR) can significantly inhibit the transcription of cellulase genes during cellulase fermentation in T. reesei. Early efforts have been undertaken to modify Cre1 for the release of CCR; however, this approach leads to arrested hyphal growth and decreased biomass accumulation, which negatively affects cellulase production.

Results

In this study, novel fusion transcription factors (fTFs) were designed to release or attenuate CCR inhibition in cellulase transcription, while Cre1 was left intact to maintain normal hyphal growth. Four designed fTFs were introduced into the T. reesei genome, which generated several transformants, named Kuace3, Kuclr2, Kuace2, and Kuxyr1. No obvious differences in growth were observed between the parent and transformant strains. However, the transcription levels of cel7a, a major cellulase gene, were significantly elevated in all the transformants, particularly in Kuace2 and Kuxyr1, when grown on lactose as a carbon source. This suggested that CCR inhibition was released or attenuated in the transformant strains. The growth of Kuace2 and Kuxyr1 was approximately equivalent to that of the parent strain in fed-batch fermentation process. However, we observed a 3.2- and 2.1-fold increase in the pNPCase titers of the Kuace2 and Kuxyr1 strains, respectively, compared with that of the parent strain. Moreover, we observed a 6.1- and 3.9-fold increase in the pNPCase titers of the Kuace2 and Kuxyr1 strains, respectively, compared with that of Δcre1 strain.

Conclusions

A new strategy based on fTFs was successfully established in T. reesei to improve cellulase titers without impairing fungal growth. This study will be valuable for lignocellulosic biorefining and for guiding the development of engineering strategies for producing other important biochemical compounds in fungal species.
Detection of Brucellae in peripheral blood mononuclear cells for monitoring therapeutic efficacy of brucellosis infection
Authors: Yang Heng , Zhang Guoxia , Luo Peifang , He Zuoping , Hu Feihuan , Li Linhai , Allain Jean-Pierre , Li Chengyao , Wang Wenjing
Published: October 2019

Background

Brucellosis is one of the most severe widespread zoonoses caused by the Gram-negative bacterium Brucella species. The diagnosis and clinical assessment of human brucellosis are very important for the management of patients, while there is a lack of effective methods to detect Brucellae. Classical culture of Brucella species is time consuming and often fails. A simple and sensitive assay is needed for diagnosis of Brucella infection and monitoring of treatment in man.

Methods

Blood samples and peripheral blood mononuclear cells (PBMCs) were collected from 154 patients hospitalized for brucellosis. Brucella antibodies were detected by Rose Bengal Plate Test (RBPT), Standard Tube Agglutination Test (SAT) and enzyme-linked immunosorbent assay (ELISA). Intracellular Brucellae were detected by blood culture and immunofluorescence staining (IFS).

Results

Among 154 brucellosis patients, 59.7% (92/154) were antibody reactive by RBPT, 81.8% (126/154) by SAT and 95.5% (147/154) by ELISA, respectively. Only 3.2% (5/154) of patient blood samples resulted in positive Brucella culture, while 68.8% (106/154) carried IFS detectable Brucella antigens in PBMCs. Gender (P = 0.01) but not age (P > 0.05) was a significant risk factor. The frequency of intracellular Brucella antigens was similar between patients receiving different treatment regimens (P > 0.05). However, a significant decrease of intracellular Brucellae was observed only in patients with acute brucellosis after the third course of treatment (P < 0.05), suggesting that current regimens to treat chronic brucellosis were not effective.

Conclusions

IFS appears a sensitive assay for detection of Brucella antigens in PBMCs and could be used for diagnosis and therapeutic monitoring of brucellosis in clinical practice.
Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy
Authors: Rehorst Wiebke A. , Thelen Maximilian P. , Nolte Hendrik , Türk Clara , Cirak Sebahattin , Peterson Jonathan M. , Wong G. William , Wirth Brunhilde , Krüger Marcus , Winter Dominic , Kye Min Jeong
Published: October 2019

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, which causes dysfunction/loss of lower motor neurons and muscle weakness as well as atrophy. While SMA is primarily considered as a motor neuron disease, recent data suggests that survival motor neuron (SMN) deficiency in muscle causes intrinsic defects. We systematically profiled secreted proteins from control and SMN deficient muscle cells with two combined metabolic labeling methods and mass spectrometry. From the screening, we found lower levels of C1q/TNF-related protein 3 (CTRP3) in the SMA muscle secretome and confirmed that CTRP3 levels are indeed reduced in muscle tissues and serum of an SMA mouse model. We identified that CTRP3 regulates neuronal protein synthesis including SMN via mTOR pathway. Furthermore, CTRP3 enhances axonal outgrowth and protein synthesis rate, which are well-known impaired processes in SMA motor neurons. Our data revealed a new molecular mechanism by which muscles regulate the physiology of motor neurons via secreted molecules. Dysregulation of this mechanism contributes to the pathophysiology of SMA.
A tool for estimating antiretroviral medication coverage for HIV-infected women during pregnancy (PMTCT-ACT)
Authors: Larson Bruce A. , Halim Nafisa , Tsikhutsu Isaac , Bii Margaret , Coakley Peter , Rockers Peter C.
Published: October 2019

Background

In the typical prevention of mother to child transmission (PMTCT) of HIV cascade of care discussion or analysis, the period of analysis begins at the first visit for antenatal care (ANC) for that pregnancy. This starting point is problematic for two reasons: (1) a large number of HIV-infected women are already on life-long antiretroviral therapy (ART) when presenting for ANC; and (2) women present to ANC at different gestational ages. The PMTCT ART Coverage Tool (PMTCT-ACT), which estimates the proportion of days covered (PDC) with ART, was developed to address each of these problems.

Methods

PDC is a preferred method to measure adherence to chronic medications, such as ART. For evaluating the PMTCT cascade of care, as indicated by PDC with ART over various time periods, a “starting point” based on a specific day before delivery must be defined that applies to all women (treatment experienced or naïve at the first ANC visit at any gestational age). Using the example of 168 days prior to delivery (24 weeks), PMTCT-ACT measures PDC with ART during that period. PMTCT-ACT is provided as a STATA do-file. Using an example dataset for two women (ID1 is treatment experienced; ID2 is treatment naïve), the details of each major portion of the tool (Parts 1–5) are presented. PMTCT-ACT along with the intermediate datasets created during the analysis are provided as supplemental files.

Conclusions

Evaluating the PMTCT cascade of care requires a standard definition of the follow-up period during pregnancy that applies to all HIV-infected pregnant women and a standard measure of adherence. PMTCT-ACT is a new tool that fits this purpose. PMTCT-ACT can also be easily adjusted to evaluate other ante- and post-natal periods (e.g., final 4 weeks, final 8 weeks, complete pregnancy period, initial 24 weeks postpartum, time periods consistent with infant HIV testing guidelines).
Traditional knowledge system in palung salt-making in Bali Island
Authors: Rochwulaningsih Yety , Sulistiyono Singgih Tri , Utama Mahendra Pudji , Masruroh Noor Naelil , Rukayah Siti , Efendy Makhfud , Gozan Misri
Published: October 2019

This study presents the case of an original and traditional knowledge system of palung, which is used in salt-making in the coastal communities of Bali. The study emphasizes the practicalities of the system and its epistemology using anthropological and sociological methods. It is known that the traditional knowledge system of palung salt production has been preserved through the generations as a form of local wisdom. This traditional knowledge system emphasizes the use of local natural resources in accordance with the coastal ecosystems of Bali, where the cultivation of extracted soil (tanah sari), sand, bamboo, and coconut trees is carried out manually. This study has evidenced that the palung process successfully produces salt of excellent taste and quality. Based on laboratory tests conducted on palung salt samples, the results show that it does not contain any heavy metals and that it has good nutritional content. Because of its use of available natural resources, this traditional knowledge system is sustainable and environmentally friendly.
The effect of addition of cyclin-dependent kinase 4 & 6 (CDK 4/6) inhibitor to endocrine therapy in the cardiovascular toxicity in advanced breast cancer patients: A systematic review and meta-analysis.
Authors: Bebero Katrina Gaelic Moncano , Marayag Eric John Arca , Regala Eugenio Vistan
Published: October 2019

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Background: The addition of CDK 4/6 inhibitor to endocrine therapy has shown promising advantage over endocrine therapy alone. Cardiac toxicity impacts quality of life and poses potential confounder to mortality. This study aims to review an analyze the cardiovascular toxicities reported among clinical trials of addition of CDK 4/6 inhibitors to endocrine therapy. Methods: Literature search was conducted through PubMed, Cochrane, ASCO, and ESMO databases. Included were articles with Phase II/III randomized clinical trials in metastatic breast cancer with assessable cardiovascular toxicity report. PRISMA Assessment Tool was used to validate the articles. Review Manager Version 5.3 was used for analyses. Risk ratio with corresponding 95% confidence interval were the main outcome measures. Results: Initial screening generated 543 articles, 38 of which were deemed relevant from which 4 articles were eligible for meta-analysis. A total of 2079 patients were analyzed. Risk ratio for all cardiovascular toxicity was 1.39 (95% CI:0.91,2.10, p=0.010). Identified all-grade cardiovascular toxicities with corresponding risk ratios were hypertension 1.14(95% CI: 0.86, 1.50, p=0.22), QT prolongation 2.30(95%CI:1.31,4.01, p=0.79), deep vein thrombosis 2.5 (95% CI: 0.12,51.59, p=0.55), pulmonary embolism 3.5(95% CI: 0.18, 67.38, p=0.41), atrial fibrillation 2.5 (95% CI: 0.12, 51.79, p=0.55). Hypertension and QT prolongation were observed in both palbociclib and ribociclib studies while deep vein thrombosis, pulmonary embolism, and atrial fibrillation were only seen in ribociclib. Conclusions: Addition of CDK 4/6 inhibitor to endocrine therapy increases the risk for cardiovascular toxicity by 39% compared to endocrine therapy alone. Hypertension and QT prolongation were the common cardiovascular adverse events with increase in risk by 14% and 130%, respectively.
MAIA (Medical Artificial Intelligence Assistant) as interface for a new cancer healthcare integrative platform.
Authors: Pino Luis Eduardo , Large Eduardo , Mejía Jorge , Triana Ivan Camilo
Published: October 2019

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Background: Cancer healthcare systems are an example of inequity and waste in low and middle income countries. Access to high quality cancer pathways focused in early diagnosis, molecular biology, proper staging and evidence based treatments are scarce and the patient`s care experience is dramatic and difficult in a majority of cases. There are no integrative healthcare models based on new technologies that improve outcomes and make more comfortable and expeditious all the patient and physician´s journey in cancer. Methods: Our team developed and trained a talkbot called MAIA (Medical Artificial Intelligence Assistant) using an algorithmic translation of medical language focused in the state or art for non small cell lung cancer. Our clinical team developed decision trees in diagnosis, staging, medical and surgical treatment and molecular biology that were incorporated in a virtual platform and then integrated onto a narrow artificial intelligence bot brain using neural networks with the proposal of generate clinical support to the physician and create a standard text using the verbal information captured in the oncological consultation and integrated images (reports) through a image edition software and then create a unique medical record without using computers by the physician. MAIA also can create medical treatment choices in first line of treatment and create alerts and alarms through an own app (MAIA Hip). Results: Our proof of concept was released in video at this link https://drive.google.com/file/d/12YtiOkhfEmIsL2bFp9T3QyfHHWxBvvKU/view?ts=5ceec096 Due to our decision trees size we can´t upload them, but are available for presentation. Conclusions: A talkbot trained as a narrow artificial intelligence interface for an integrative cancer healthcare platform (HIP) is possible through the clinical and engineer integration of languages using a neural network method and other software tools. MAIA is for now a patient and physician experience improvement, but the real impact will be in the data standarization and acquisition for advanced analytics. The final scope of MAIA HIP will be a blockchain for cancer in low and middle income countries.
Effect of Dosage of 17ß-Estradiol on Uterine Growth in Turner Syndrome—A Randomized Controlled Clinical Pilot Trial
Authors: Cleemann Line , Holm Kirsten , Fallentin Eva , Møller Nini , Kristensen Bent , Skouby Sven O , Leth-Esbensen Per , Jeppesen Eva M , Jensen Andreas K , Gravholt Claus H
Published: October 2019

Context

Most Turner syndrome (TS) girls need exogenous estrogen treatment to induce puberty and normal uterine growth. After puberty, the optimal estrogen treatment protocol has not been determined.

Objective

To compare 2 doses of oral 17ß-estradiol on uterine size.

Design

A double-blind, 5-year randomized controlled clinical trial.

Setting

Ambulatory care.

Participants

Twenty young TS women (19.2 ± 2.5 years, range 16.0–24.9) participated. Sixteen patients completed the study. No patients withdrew due to adverse effects.

Intervention

The lower dose (LD) group took 2 mg 17ß-estradiol/d orally and placebo. The higher dose (HD) group took 4 mg 17ß-estradiol/d orally.

Main Outcome Measure(s)

Uterine volume evaluated by transabdominal ultrasound yearly.

Results

Uterine size increased significantly more in the HD group compared with the LD group (P = 0.038), with a gain in uterine volume within the first 3 years of treatment of 19.6 mL (95% confidence interval [CI] = 4.0-19.0) in the HD group compared with 11.5 mL (95% CI = 11.2-27.9) in the LD group. The difference in 3-year gain was 8.1 mL (95% CI = 0.7-15.9). At the last visit, there were no significant differences in uterine volume between the groups.

Conclusion

HD oral 17ß-estradiol induces a steeper increase in uterine volume within the first years of treatment compared with the LD. However, the uterine growth potential seems to be the same in most young TS women making the duration of treatment equally significant as estrogen dose, although a few TS women did not experience sufficient uterine growth on 2 mg of estradiol.

ClinicalTrials.gov

NCT00134745

Abbreviations: BMI, body mass index; BSA, body surface area; DHEAS, dihydroepiandrosteronesulfate; HD, higher dose; HRT, hormone replacement therapy; LD, lower dose; TS, Turner syndrome; US, ultrasound
Maternal Exposure to Environmental Disruptors and Sexually Dimorphic Changes in Maternal and Neonatal Oxidative Stress
Authors: Puttabyatappa Muraly , Banker Margaret , Zeng Lixia , Goodrich Jaclyn M , Domino Steven E , Dolinoy Dana C , Meeker John D , Pennathur Subramaniam , Song Peter X K , Padmanabhan Vasantha
Published: October 2019

Context

Early pregnancy exposure to endocrine disrupting chemicals (EDCs) may contribute to poor birth outcomes through oxidative stress (OS)-mediated disruption of the maternal and fetal milieu. Most studies have investigated the effect of single EDC exposures on OS.

Objective

Assess the association of uniquely weighted mixtures of early pregnancy exposures with the maternal and neonatal OS markers.

Design

Prospective analysis of mother–infant dyads

Setting

University hospital.

Participants

56 mother–infant dyads.

Main Outcome Measures

The association of OS markers (nitrotyrosine, dityrosine, chlorotyrosine) in maternal first trimester and term, and cord blood plasma with maternal first trimester exposure levels of each of 41 toxicants (trace elements, metals, phenols, and phthalates) from 56 subjects was analyzed using Spearman correlations and linear regression. The association of OS markers with inflammatory cytokines and birth outcomes were analyzed by Spearman correlation and linear regression analysis, respectively. Weighted mixtures of early pregnancy exposures were created by principal component analysis and offspring sex-dependent and independent associations with oxidative stress markers were assessed.

Results

(1) An inverse relationship between levels of maternal/cord OS markers and individual EDCs was evident. In contrast, when assessed as EDC mixtures, both direct and inverse associations were evident in a sex-specific manner; (2) the maternal term OS marker, nitrotyrosine, was inversely associated with gestational age, and (3) both direct and inverse associations were evident between the 3 OS markers and individual cytokines.

Conclusions

Provides proof of concept that effects of exposures on OS varies when assessed as EDC mixtures versus individually.
Noninvasive Evaluation of GPR119 Agonist Effects on β-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT
Authors: Murakami Takaaki , Fujimoto Hiroyuki , Fujita Naotaka , Hamamatsu Keita , Matsumoto Koji , Inagaki Nobuya
Published: October 2019

Longitudinal observation of pancreatic β-cell mass (BCM) remains challenging because noninvasive techniques for determining BCM in vivo have not been established. Such observations would be useful for the monitoring of type 2 diabetes mellitus, a progressive disease involving loss of pancreatic BCM and function. An indium 111 (111In)–labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4) targeting the glucagon-like peptide-1 receptor has been developed recently as a promising probe for quantifying the BCM noninvasively. In the present study, we used the 111In-exendin-4 single-photon emission CT/CT (SPECT/CT) technique to investigate the efficacy of DS-8500a, a novel G protein–coupled receptor-119 agonist currently under investigation for type 2 diabetes mellitus treatment in prediabetic db/db mice under dietary restriction. During the 8-week study, the treatment of mice with DS-8500a delayed and attenuated the progression of glucose intolerance compared with mice under dietary restriction alone. 111In-exendin-4 SPECT/CT of db/db mice revealed continuously decreasing radioactive isotope (RI) intensity in the pancreas during the 8-week intervention. DS-8500a attenuated this decrease and preserved pancreatic RI accumulation compared with dietary restriction alone at the end of the observation period. This result was corroborated not only by ex vivo pancreatic analysis using the [Lys12(111In-BnDTPA-Ahx)]exendin-4 probe but also by conventional histological BCM analysis. These results indicate that DS-8500a attenuates the progression of BCM loss beyond that of dietary restriction alone in prediabetic db/db mice. These results have shown that 111In-exendin-4 SPECT/CT will be useful for noninvasive longitudinal investigation of BCM in vivo.
An intrinsically disordered proteins community for ELIXIR
Authors: Davey Norman E. , Babu M. Madan , Blackledge Martin , Bridge Alan , Capella-Gutierrez Salvador , Dosztanyi Zsuzsanna , Drysdale Rachel , Edwards Richard J. , Elofsson Arne , Felli Isabella C. , Gibson Toby J. , Gutmanas Aleksandras , Hancock John M. , Harrow Jen , Higgins Desmond , Jeffries Cy M. , Le Mercier Philippe , Mészáros Balint , Necci Marco , Notredame Cedric , Orchard Sandra , Ouzounis Christos A. , Pancsa Rita , Papaleo Elena , Pierattelli Roberta , Piovesan Damiano , Promponas Vasilis J. , Ruch Patrick , Rustici Gabriella , Romero Pedro , Sarntivijai Sirarat , Saunders Gary , Schuler Benjamin , Sharan Malvika , Shields Denis C. , Sussman Joel L. , Tedds Jonathan A. , Tompa Peter , Turewicz Michael , Vondrasek Jiri , Vranken Wim F. , Wallace Bonnie Ann , Wichapong Kanin , Tosatto Silvio C. E.
Published: October 2019

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled “An intrinsically disordered protein user community proposal for ELIXIR” held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders.