bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterologous overexpression of bacterial hemoglobin VHb improves erythritol biosynthesis by yeast Yarrowia lipolytica
Authors: Mirończuk Aleksandra M. , Kosiorowska Katarzyna E. , Biegalska Anna , Rakicka-Pustułka Magdalena , Szczepańczyk Mateusz , Dobrowolski Adam 
Published: October 2019

Abstract

Background
Yarrowia lipolytica is an unconventional yeast with a huge industrial potential. Despite many advantages for biotechnological applications, it possesses enormous demand for oxygen, which is a bottleneck in large scale production. In this study a codon optimized bacterial hemoglobin from Vitreoscilla stercoraria (VHb) was overexpressed in Y. lipolytica for efficient growth and erythritol synthesis from glycerol in low-oxygen conditions. Erythritol is a natural sweetener produced by Y. lipolytica under high osmotic pressure and at low pH, and this process requires high oxygen demand.

Results
Under these conditions the VHb overexpressing strain showed mostly yeast-type cells resulting in 83% higher erythritol titer in shake-flask experiments. During a bioreactor study the engineered strain showed higher erythritol productivity (QERY = 0.38 g/l h) and yield (YERY = 0.37 g/g) in comparison to the control strain (QERY = 0.30 g/l h, YERY = 0.29 g/g). Moreover, low stirring during the fermentation process resulted in modest foam formation.

Conclusions
This study showed that overexpression of VHb in Y. lipolytica allows for dynamic growth and efficient production of a value-added product from a low-value substrate.
The historical roots and seminal research on health equity: a referenced publication year spectroscopy (RPYS) analysis
Authors: Yao Qiang , Li Xin , Luo Fei , Yang Lianping , Liu Chaojie , Sun Ju 
Published: October 2019

AbstractBackgroundHealth equity is a multidimensional concept that has been internationally considered as an essential element for health system development. However, our understanding about the root causes of health equity is limited. In this study, we investigated the historical roots and seminal works of research on health equity.MethodsHealth equity-related publications were identified and downloaded from the Web of Science database (n = 67,739, up to 31 October 2018). Their cited references (n = 2,521,782) were analyzed through Reference Publication Year Spectroscopy (RPYS), which detected the historical roots and important works on health equity and quantified their impact in terms of referencing frequency.ResultsA total of 17 pronounced peaks and 31 seminal works were identified. The first publication on health equity appeared in 1966. But the first cited reference can be traced back to 1801. Most seminal works were conducted by researchers from the US (19, 61.3%), the UK (7, 22.6%) and the Netherlands (3, 9.7%). Research on health equity experienced three important historical stages: origins (1800–1965), formative (1966–1991) and development and expansion (1991–2018). The ideology of health equity was endorsed by the international society through the World Health Organization (1946) declaration based on the foundational works of Chadwick (1842), Engels (1945), Durkheim (1897) and Du Bois (1899). The concept of health equity originated from the disciplines of public health, sociology and political economics and has been a major research area of social epidemiology since the early nineteenth century. Studies on health equity evolved from evidence gathering to the identification of cost-effective policies and governmental interventions.ConclusionThe development of research on health equity is shaped by multiple disciplines, which has contributed to the emergence of a new stream of social epidemiology and political epidemiology. Past studies must be interpreted in light of their historical contexts. Further studies are needed to explore the causal pathways between the social determinants of health and health inequalities.
Platinum–gold nanoraspberries as effective photosensitizer in anticancer photothermal therapy
Authors: Depciuch J. , Stec M. , Klebowski B. , Baran J. , Parlinska-Wojtan M. 
Published: October 2019

Abstract

Background
New nanophotosensitizers for photothermal cancer therapy (PTT) are still sought. In this paper we propose fancy shaped, non agglomerated core/shell PtAu NRs nanoraspberries (PtAu NRs) as potential nanophotosensitizers in PTT.

Results
Light microscopy images of two colon cancer cell lines (SW480, SW620) showed, that the laser irradiation combined with PtAu NRs caused visible changes in the cell morphology. Fourier Transform InfraRed (FTIR) and Raman spectroscopies showed chemical changes in the DNA, phospholipids, lipids and protein structures caused by laser irradiation in the presence of PtAu NRs. The MTS assay showed ~ 25% mortality of cancer cells due to the addition of PtAu NRs to the cell culture, while for laser irradiation combined with nanoparticles, the mortality of cancer cells increased to 65% for the 650 nm laser and to 60% for the 808 nm laser. The calculated photothermal conversion efficiency reached 62% and 51% for the 650 nm and 808 nm lasers, respectively.

Conclusions
PtAu NRs could be applied as effective light-absorbers in the PTT anticancer therapy.
Neighborhood walkability and 12-year changes in cardio-metabolic risk: the mediating role of physical activity
Authors: Chandrabose Manoj , Cerin Ester , Mavoa Suzanne , Dunstan David , Carver Alison , Turrell Gavin , Owen Neville , Giles-Corti Billie , Sugiyama Takemi 
Published: October 2019

Abstract

Background
Living in walkable neighborhoods may provide long-term cardio-metabolic health benefits to residents. Little empirical research has examined the behavioral mechanisms in this relationship. In this longitudinal study, we examined the potential mediating role of physical activity (baseline and 12-year change) in the relationships of neighborhood walkability with 12-year changes in cardio-metabolic risk markers.

Methods
The Australian Diabetes, Obesity and Lifestyle study collected data from adults, initially aged 25+ years, in 1999–2000, 2004–05, and 2011–12. We used 12-year follow-up data from 2023 participants who did not change their address during the study period. Outcomes were 12-year changes in waist circumference, weight, systolic and diastolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein cholesterol, and triglycerides. A walkability index was calculated, using dwelling density, intersection density, and destination density, within 1 km street-network buffers around participants’ homes. Spatial data for calculating these measures were sourced around the second follow-up period. Physical activity was assessed by self-reported time spent in moderate-to-vigorous physical activity (including walking). Multilevel models, adjusting for potential confounders, were used to examine the total and indirect relationships. The joint-significance test was used to assess mediation.

Results
There was evidence for relationships of higher walkability with smaller increases in weight (P = 0.020), systolic blood pressure (P < 0.001), and high-density lipoprotein cholesterol (P = 0.002); and, for relationships of higher walkability with higher baseline physical activity (P = 0.020), which, in turn, related to smaller increases in waist circumference (P = 0.006), weight (P = 0.020), and a greater increase in high-density lipoprotein cholesterol (P = 0.005). There was no evidence for a relationship of a higher walkability with a change in physical activity during the study period (P = 0.590).

Conclusions
Our mediation analysis has shown that the protective effects of walkable neighborhoods against obesity risk may be in part attributable to higher baseline physical activity levels. However, there was no evidence of mediation by increases in physical activity during the study period. Further research is needed to understand other behavioral pathways between walkability and cardio-metabolic health, and to investigate any effects of changes in walkability.
Ipsilateral breast metastasis after axillary dissection caused by epithelioid sarcoma: a case report and pathological investigation
Authors: Chen Luyan , Wang Li , Zhang Xiaochen , Yao Minya , Fu Peifen 
Published: October 2019

AbstractBackgroundEpithelioid sarcoma (ES) is a rare malignant soft tissue tumor, commonly occurring in distal extremities, such as fingers, hands and wrists. For oncologists and surgeons, a female patient with enlarged axillary lymph node on one side only is easily diagnosed with an occult breast carcinoma rather than ES. Besides, whole breast metastasis of ES has not been reported yet.Case presentationA 47-year-old Chinese woman came to the outpatient clinic of First Affiliated Hospital of Zhejiang University (FAHZU) with a complaint of an asymptomatic right axillary mass for 3 months. Then she received surgical resection of the right axillary lymph nodes and right supraclavicular lymph nodes. According to the clinical tumor site and routine immunohistochemistry (IHC), suspicion of metastatic epithelial sarcoma and metastatic breast cancer could not be ruled out. Subsequently, with more detailed medical history review and physical examination, a mass on the right forearm was found, which was considered as the primary lesion. Further IHC and Molecular Genetics revealed that all the neoplastic cells exhibited loss of INI1 protein and were negative for ERG gene rearrangement yet positive for epithelial membrane antigen (EMA), cytokeratin (CK) 8, CK19, Vimentin, CD34. The final diagnosis was ES. She received postoperative chemotherapy, without radiotherapy. Unexpectedly, an ipsilateral breast metastasis was developed at ten months after surgery. Regrettably, there was no positive result of the metastatic breast sample, based on a genome sequencing by a 381-cancer-gene panel in a lab. Therefore, she went through another round of chemotherapy and took Apatinib for maintenance treatment. During the last follow-up (26 months after diagnosis), the disease was under control.ConclusionThis rare but interesting case enables breast surgeons and pathologists to accumulate more experience of differential diagnosis of axillary mass for personalized treatment in clinical practice. Meanwhile, ipsilateral breast metastasis of ES we reported in the case urges that clinicians attach greater importance to the tumor metastasis mechanism.
Genotypic characteristics of Chinese patients with BHD syndrome and functional analysis of FLCN variants
Authors: Liu Keqiang , Xu Wenshuai , Tian Xinlun , Xiao Meng , Zhao Xinyue , Zhang Qianli , Qu Tao , Song Jiaxing , Liu Yaping , Xu Kai-Feng , Zhang Xue 
Published: October 2019

Abstract

Background
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease featured by lung cysts, spontaneous pneumothorax, fibrofolliculomas and renal tumors. The causative gene for BHDS is the folliculin (FLCN) gene and more than 200 mutations have been reported in FLCN, mostly truncating mutations. The aim of this study is to better characterize the clinical features and mutation spectrum of Chinese BHDS patients and to systematically evaluate the effects of non-truncating mutations on mRNA splicing pattern.

Methods
We enrolled 47 patients from 39 unrelated families with symptoms highly suggestive of BHDS after informed consent and detailed clinical data were collected. Exon sequencing followed by multiplex ligation-dependent probe amplification testing were applied for mutation screening. The effects of non-truncating mutations, including 15 missense mutations and 6 in-frame deletions, on mRNA splicing were investigated by minigene assays.

Results
A total of 24 FLCN germline variants were found in 39 patients from 31 distinct families. Out of these patients, 100% (36/36) presented with lung cysts and 58.3% (21/36) had experienced spontaneous pneumothorax. Seventeen mutation carriers had skin lesions (47.2%, 17/36) and 9 (30%, 9/30) had kidney lesions including 8 with renal cysts and 1 with renal hamartoma. Among all detected variants 14 (58.3%, 14/24) were novel, including 11 variants classified to be pathogenic and 3 variants of uncertain significance. None of 21 non-truncating mutations changed the mRNA splicing pattern of minigenes.

Conclusions
We found different clinical features of Chinese BHDS patients compared with Caucasians, with more lung cysts and pneumothorax but fewer skin lesions and malignant renal cancer. Chinese patients with BHDS also have a different mutation spectrum from other races. Non-truncating mutations in FLCN did not disrupt mRNA splicing pattern, in turn supporting the hypothesis that these mutations impair folliculin function by disrupting the stability of the FLCN gene product.
Correction to: FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein E stimulates the malignant progression of ovarian cancer
Authors: Lai Huiling , Zhao Xuejiao , Qin Yu , Ding Yi , Chen Ruqi , Li Guannan , Labrie Marilyne , Ding Zhiyong , Zhou Jianfeng , Hu Junbo , Ma Ding , Fang Yong , Gao Qinglei 
Published: October 2019

In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE−/− + PBS group (upper) was a photograph coming from ApoE−/− + BAPN pre-treatment group (lower). The corrected figure appears below. We apologize for any confusion this may have caused.
Age at onset of training in children with hearing and speech disorders and the analysis of related factors in Turkey
Authors: Sahli Ayse Sanem 
Published: October 2019

AbstractBackgroundEarly diagnosis and intervention play a vital role in hearing and speech disorders and the effect of intervention varies according to the age at onset of training of children with such disorders. Aim of this study is to investigate the age at onset of training in children admitted to our center with complaints of hearing and speech disorder, and the related factors.MethodsIn the first phase of the study, data of 473 children admitted to our center between January 2015 and October 2018 with complaints of hearing and speech disorders and no additional disability were retrospectively analyzed. Then, their chronological age, gender, cause of admission, age at onset of training and the effect of factors that may have an impact on the age at onset of training were analyzed statistically. Study data were obtained from patient records.ResultsOf 473 children (350 males and 123 females) admitted to our training center with the complaints of hearing and speech disorders, 252 (53.3%) were presented with speech sound disorders, 90 (19.0%) with stuttering, 87 (18.4%) with delayed speech, 32 (6.8%) with hearing loss and 12 (2.5%) with other causes. Although there was a statistically significant difference between the age at onset of training and the factors; such as cause of admission, parental education level, employment status of the mother, occupation of the father, and socioeconomic status of the family(p < 0.05),no statistically significant difference was found between the age at onset of training and gender(p > 0.05).ConclusionsThe study revealed that children with hearing loss have the chance of early diagnosis thanks to neonatal hearing screening programs and that they commence their training until the age of 2, which is considered to be a critical period for language and speech development. However, it is an undeniable fact that we have not yet reached the ideal age for the commencement of training (6th month). Similarly, the age of diagnosis and initiation of training is delayed in children with speech disorders due to families’ delayed referral to the training centers.
The TREATT Trial (TRial to EvaluAte Tranexamic acid therapy in Thrombocytopenia): safety and efficacy of tranexamic acid in patients with haematological malignancies with severe thrombocytopenia: study protocol for a double-blind randomised controlled trial
Authors:   on behalf of the TREATT Trial Collaboration (provisional), Estcourt Lise J. , McQuilten Zoe , Powter Gillian , Dyer Claire , Curnow Eleanor , Wood Erica M. , Stanworth Simon J. 
Published: October 2019

Abstract

Background
Patients with haematological malignancies often develop thrombocytopenia as a consequence of either their disease or its treatment. Platelet transfusions are commonly given to raise a low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). Recent studies have shown that many patients continue to experience bleeding despite the use of prophylactic platelet transfusions. Tranexamic acid is an anti-fibrinolytic, which reduces the breakdown of clots formed in response to bleeding. Anti-fibrinolytics have been shown to prevent bleeding, decrease blood loss and use of red cell transfusions in elective and emergency surgery, and are used widely in these settings. The aim of this trial is to test whether giving tranexamic acid to patients receiving treatment for haematological malignancies reduces the risk of bleeding or death and the need for platelet transfusions.

Methods
This is a multinational randomised, double-blind, placebo-controlled, parallel, superiority trial. Patients will be randomly assigned to receive tranexamic acid (given intravenously or orally) or a matching placebo in a 1:1 ratio, stratified by site. Patients with haematological malignancies receiving intensive chemotherapy or stem cell transplantation (or both) who are at least 18 years of age and expected to become severely thrombocytopenic for at least 5 days will be eligible for this trial. The primary outcome of the trial is the proportion of patients who died or had bleeding of World Health Organization grade 2 or above during the first 30 days of the trial. We will measure the rates of bleeding daily by using a short, structured assessment of bleeding, and we will record the number of transfusions given to patients. We will assess the risk of arterial and venous thrombosis for 120 days from the start of trial treatment.

Discussion
This trial will assess the safety and efficacy of using prophylactic tranexamic acid during a period of intensive chemotherapy and associated thrombocytopenia in people with haematological disorders.

Trial registration
This study was prospectively registered on Current Controlled Trials on 25 March 2015 (ISRCTN73545489) and is also registered on ClinicalTrials.gov (NCT03136445).
Invariant natural killer T cells are functionally impaired in patients with systemic sclerosis
Authors: Pecher Ann-Christin , Kettemann Felix , Asteriti Elisa , Schmid Hannes , Duerr-Stoerzer Silke , Keppeler Hildegard , Henes Joerg Christoph , Klein Reinhild , Hinterleitner Clemens , Secker Kathy-Ann , Schneidawind Corina , Kanz Lothar , Schneidawind Dominik 
Published: October 2019

Abstract

Background
Systemic sclerosis (SSc) is a potentially fatal autoimmune disease that leads to extensive fibrosis of the skin and internal organs. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes being able to orchestrate dysregulated immune responses. The purpose of this study was to evaluate numbers and function of iNKT cells in patients with SSc and to analyze their correlation with disease parameters.

Methods
Human iNKT cells from 88 patients with SSc and 33 healthy controls were analyzed by flow cytometry. Their proliferative capacity and cytokine production were investigated following activation with CD1d ligand α-galactosylceramide (α-GalCer).

Results
We observed an absolute and relative decrease of iNKT cells in patients with SSc compared with healthy controls. Interestingly, the subtype of SSc, disease severity, or treatment with immunosuppressive drugs did not affect iNKT cell numbers. However, T helper (Th) cell immune polarization was biased towards a Th17 immunophenotype in SSc patients. Moreover, iNKT cells from patients with SSc showed a significantly decreased expansion capacity upon stimulation with α-GalCer.

Conclusion
iNKT cells are deficient and functionally impaired in patients with SSc. Therefore, adoptive transfer strategies using culture-expanded iNKT cells could be a novel approach to treat SSc patients.
Evaluation of the immunogenicity and efficacy of BCG and MTBVAC vaccines using a natural transmission model of tuberculosis
Authors: Roy Alvaro , Tomé Irene , Romero Beatriz , Lorente-Leal Víctor , Infantes-Lorenzo José A. , Domínguez Mercedes , Martín Carlos , Aguiló Nacho , Puentes Eugenia , Rodríguez Esteban , de Juan Lucía , Risalde María A. , Gortázar Christian , Domínguez Lucas , Bezos Javier 
Published: October 2019

Abstract
Effective vaccines against tuberculosis (TB) are needed in order to prevent TB transmission in human and animal populations. Evaluation of TB vaccines may be facilitated by using reliable animal models that mimic host pathophysiology and natural transmission of the disease as closely as possible. In this study, we evaluated the immunogenicity and efficacy of two attenuated vaccines, BCG and MTBVAC, after each was given to 17 goats (2 months old) and then exposed for 9 months to goats infected with M. caprae. In general, MTBVAC-vaccinated goats showed higher interferon-gamma release than BCG vaccinated goats in response to bovine protein purified derivative and ESAT-6/CFP-10 antigens and the response was significantly higher than that observed in the control group until challenge. All animals showed lesions consistent with TB at the end of the study. Goats that received either vaccine showed significantly lower scores for pulmonary lymph nodes and total lesions than unvaccinated controls. Both MTBVAC and BCG vaccines proved to be immunogenic and effective in reducing severity of TB pathology caused by M. caprae. Our model system of natural TB transmission may be useful for evaluating and optimizing vaccines.