bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in the uptake, attendance, and outcomes in a clinical trial of a total diet replacement weight loss programme
Authors: Astbury Nerys M. , Tudor Kate , Aveyard Paul , Jebb Susan A. 
Published: April 2020

Abstract
Background
Trials have shown total diet replacement (TDR) programmes are safe and effective for weight loss in primary care. However, it is not clear whether participant characteristics affect uptake, attendance, or effectiveness of the programme.

Methods
We used data from 272 trial participants who were invited to participate in a clinical weight loss trial via a letter from their GP. We used a Cochran-Mantel-Haenszel analysis to assess whether accepting an invitation to participate in the trial differed by gender, age, BMI, social deprivation, and the presence of a diagnosis of type 2 diabetes or hypertension. We used mixed generalised linear modelling to examine whether participants’ age, gender, or social deprivation based on area of residence were associated with weight change at 12 months.

Results
Men were less likely to enrol than women (RR 0.59 [95% CI 0.47, 0.74]), and people from the middle and highest BMI tertile were more likely to enrol than those from the lowest tertile (RR 2.88 [95% CI 1.97, 4.22] and RR 4.38 [95% CI 3.05, 6.07], respectively). Patients from practices located in most deprived and intermediate deprived tertiles were more likely to enrol compared with those in the least deprived tertile (RR 1.84 [95% CI 1.81, 2.59] and RR 1.68 [95% CI 1.18, 2.85], respectively). There was no evidence that age or a pre-existing diagnosis of type 2 diabetes (RR 1.10 [95% CI 0.81, 1.50]) or hypertension (RR 0.81 [95% CI 0.62, 1.04]) affected enrolment. In the TDR group, 13% of participants were low engagers, 8% engaged with the weight loss phase only, and 79% engaged in both weight loss and weight maintenance phases of the programme. Those who engaged in the entire programme lost most weight. Subgroup analyses suggested that older participants and those with a higher baseline BMI lost more weight at 1 year than their comparators.

Conclusion
Despite some heterogeneity in the uptake and outcomes of the programme, if the results of this trial are replicated in routine practice, there is no evidence that TDR weight loss programmes would increase inequity.

Trial registration
The DROPLET trial was prospectively registered on ISRCTN registry (ISRCTN75092026).
Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies
Authors: Mora-Pereira Mariano , Abarca Eva M. , Duran Sue , Ravis William , McMullen Richard J. , Fischer Britta M. , Lee Yann-Huei Phillip , Wooldridge Anne A. 
Published: April 2020

Abstract
Background
Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes.

Results
Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment.

Conclusions
Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.
Different expression levels of interleukin-35 in asthma phenotypes
Authors: Li Wei , Gao Ruihan , Xin Tong , Gao Peng 
Published: April 2020

Abstract
Background
Interleukin (IL)-35 is a newly discovered inhibitory cytokine which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It plays a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. Our study focuses on the sputum IL-35 level in patients and investigates different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes.

Objective
We aimed to determine the sputum IL-35 levels in asthmatic patients with clinical remission phenotypes and control subjects and to investigate possible correlations among lung function, age, sex, fractional exhaled nitric oxide (FeNO), and smoking history in these phenotypes.

Methods
Sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction. Induced sputum was assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines were measured by ELISA and Cytometric Bead Array, respectively.

Results
Sputum IL-35 (median (q1, q3)) levels showed no significant difference between asthma patients (4.89 ng/mL (2.97, 22.75)) and healthy controls (6.01 ng/mL (4.09, 30.47)). However, the sputum IL-35 level was significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL (2.80, 11.00)) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL (20.59, 65.06), p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL (3.10, 24.60), p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL (2.58, 52.45), p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors.

Conclusions
Sputum IL-35 is likely involved in different pathophysiological mechanisms of NA and EA and exerts different effects in asthma phenotypes.
Gut microbial dysbiosis in individuals with Sjögren’s syndrome
Authors: Mendez Roberto , Watane Arjun , Farhangi Monika , Cavuoto Kara M. , Leith Tom , Budree Shrish , Galor Anat , Banerjee Santanu 
Published: April 2020

Abstract
Background
Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined.

Results
Results showed that Firmicutes was the dominant phylum in the gut, comprising 40–60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p = 0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs.

Conclusions
In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.
LNK promotes the growth and metastasis of triple negative breast cancer via activating JAK/STAT3 and ERK1/2 pathway
Authors: Lv Jianxin , Yu Wei , Zhang Yanan , Cao Xinhua , Han Lifei , Hu Haolin , Wang Chenfei 
Published: April 2020

Abstract
Background
LNK adaptor protein is a crucial regulator of normal hematopoiesis, which down-regulates activated tyrosine kinases at the cell surface resulting in an antitumor effect. To date, little studies have examined activities of LNK in solid tumors except ovarian cancer.

Methods
Clinical tissue chips were obtained from 16 clinical patients after surgery. Western blotting assay and quantitative real time PCR was performed to measure the expression of LNK. We investigate the in vivo and vitro effect of LNK in Triple Negative Breast Cancer by using cell proliferation、migration assays and an in vivo murine xenograft model. Western blotting assay was performed to investigate the mechanism of LNK in triple negative breast cancer.

Results
We found that the levels of LNK expression were elevated in high grade triple-negative breast cancer through Clinical tissue chips. Remarkably, overexpression of LNK can promote breast cancer cell proliferation and migration in vivo and vitro, while silencing of LNK show the opposite phenomenon. We also found that LNK can promote breast cancer cell to proliferate and migrate via activating JAK/STAT3 and ERK1/2 pathway.

Conclusions
Our results suggest that the adaptor protein LNK acts as a positive signal transduction modulator in TNBC.
Novel monoclonal antibodies against thymidine kinase 1 and their potential use for the immunotargeting of lung, breast and colon cancer cells
Authors: Velazquez Edwin J. , Brindley Taylor D. , Shrestha Gajendra , Bitter Eliza E. , Cress Jordan D. , Townsend Michelle H. , Berges Bradford K. , Robison Richard A. , Weber K. Scott , O’Neill Kim L. 
Published: April 2020

Abstract
Background
Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells.

Methods
We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments.

Results
Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73–66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments.

Conclusions
The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.
Dietary intake of Aboriginal Australian children aged 6–36 months in a remote community: a cross-sectional study
Authors: Tonkin Emma , Kennedy Dani , Hanieh Sarah , Biggs Beverley-Ann , Kearns Therese , Gondarra Veronica , Dhurrkay Roslyn , Brimblecombe Julie 
Published: April 2020

Abstract
Background
Scarce literature comprehensively captures the transition to solid foods for children in remote Aboriginal Australian communities, a population expected to be especially vulnerable to nutritional inadequacy for largely socio-economic reasons. This study describes the dietary intake of children aged 6–36 months in a remote Aboriginal community during the years of solids introduction and establishment. Specifically, we aimed to explore milk feeding practices, major sources of nutrition and traditional food consumption, dietary patterns and nutrient and food group intakes, and compare these to national and international recommendations.

Methods
This dietary assessment was conducted as part of an observational, cross-sectional Child Health and Nutrition study. Three 24-h dietary recalls were completed with the parent/care-giver of each participant over 2–4 weeks, capturing a pay-week, non-pay-week and weekend day from October 2017–February 2018. Additional information collected included sociodemographic data, food security status, usual cooking practices, and attendance at playgroup.

Results
Diet histories for 40 children were included in the analysis (~ 40% of the population). Breast feeding rates were high (85%), with mothers exclusively feeding on demand. Very few participants met recommended intakes for wholegrains (n = 4, 10%), vegetables (n = 7, 18%), dairy (n = 5, 18%) and fruit (n = 13, 33%), while more children met the guidelines for meat (n = 19, 48%) and discretionary food intake (n = 28, 70%). Traditional foods were always nutritionally dense and consumed frequently (n = 22, 55% of children). Statistically significant pay-cycle differences in intakes of all macro-, and numerous micro-nutrients were observed.

Conclusions
Many positive early feeding practices are currently enacted in remote Aboriginal communities including responsive and long duration breastfeeding, and nutrient-dense traditional food consumption from earliest solids introduction. However, the non-pay-week/pay-week cycle is impacting the quality and quantity of children’s diets at a time of rapid growth and development.
HDL functions and their interaction in patients with ST elevation myocardial infarction: a case control study
Authors: Thakkar Himani , Vincent Vinnyfred , Roy Ambuj , Singh Sandeep , Ramakrishnan Lakshmy , Kalaivani Mani , Singh Archna 
Published: April 2020

Abstract
Background
Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with acute coronary syndrome (ACS) and healthy controls.

Methods
We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. PON1 activities toward paraoxon and phenyl acetate were assessed by spectrophotometric methods.

Results
We recruited 150 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio = 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio = 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio = 0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1, p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa.

Conclusion
ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.
Homotypic cell membrane-cloaked biomimetic nanocarrier for the accurate photothermal-chemotherapy treatment of recurrent hepatocellular carcinoma
Authors: Sun Yingxue , Zhai Wenhui , Liu Xiaojun , Song Xiangyi , Gao Xiaonan , Xu Kehua , Tang Bo 
Published: April 2020

AbstractBackgroundTumor recurrence in patients after surgery severely reduces the survival rate of surgical patients. Targeting and killing recurrent tumor cells and tissues is extremely important for the cancer treatment.ResultsHerein, we designed a nano-biomimetic photothermal-controlled drug-loading platformHepM-TSLwith good targeting ability and immunocompatibility for the treatment of recurrent hepatocellular carcinoma.HepM-TSLcan accurately target the recurrent tumor area with the aid of the cloaked homotypic cell membrane and release the chemotherapy drugs in a controlled manner. In vivo results have confirmed thatHepM-TSLloaded with drugs and photosensitizer achieves the synergistic treatment of recurrent hepatocellular carcinoma with good therapeutic effect and slight side effects.ConclusionAccordingly,HepM-TSLprovides a sound photothermal-chemotherapy synergistic strategy for the treatment of other recurrent cancers besides of recurrent hepatocellular carcinoma.
Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review
Authors:   on behalf of the ISACA guideline working group, D’Alò Gian Loreto , De Crescenzo Franco , Minozzi Silvia , Morgano Gian Paolo , Mitrova Zuzana , Scattoni Maria Luisa , Amato Laura , Davoli Marina , Schünemann Holger J. 
Published: April 2020

AbstractIntroductionSome recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs.MethodsWe performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility.ResultsWe found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro.The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence).The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect.ConclusionsWe found the administration of PUFAs in children and adolescents with ASD to be potentially equitable, acceptable and feasible. These results are limited by the limited number and quality of retrieved documents, and need to be viewed in light of efficacy and safety data to formulate clinical recommendations.