bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trajectory and mortality of preserved ratio impaired spirometry: the Rotterdam Study
Authors: Wijnant Sara Renata Alex , De Roos Emmely , Kavousi Maryam , Stricker Bruno Hugo , Terzikhan Natalie , Lahousse Lies , Brusselle Guy G. 
Published: October 2019

Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7, FEV1  ≥80%), PRISm (FEV1/FVC ≥0.7, FEV1 <80%) and chronic obstructive pulmonary disease (COPD) (FEV1/FVC <0.7) at two study visits. Hazard ratios with 95% confidence intervals for mortality (until December 30, 2018) were adjusted for age, sex, body mass index, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9 years; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of the re-examined PRISm subjects, 15.7% transitioned to normal spirometry and 49.4% to COPD. Median lung function decline was highest in subjects with incident PRISm (FEV1−92.8 mL·year−1, interquartile range (IQR) −131.9– −65.8 mL·year−1; FVC −93.3 mL·year−1, IQR −159.8– −49.1 mL·year−1), but similar in persistent PRISm (FEV1−30.2 mL·year−1, IQR −67.9– −7.5 mL·year−1; FVC −20.1 mL·year−1, IQR −47.7–21.7 mL·year−1) and persistent controls (FEV1−39.6 mL·year−1, IQR −64.3–−12.7 mL·year−1; FVC −20.0 mL·year−1, IQR −55.4–18.8 mL·year−1). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2–4 had increased all-cause mortality (PRISm: HR 1.6, 95% CI 1.2–2.0; COPD GOLD 2–4: HR 1.7, 95% CI 1.4–2.1) and cardiovascular mortality (PRISm: HR 2.8, 95% CI 1.5–5.1; COPD 2–4: HR 2.1, 95% CI 1.2–3.6). Mortality within <1 year was highest in PRISm, with patients often having cardiovascular comorbidities (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.
Direct and indirect costs of COPD progression and its comorbidities in a structured disease management program: results from the LQ-DMP study
Authors: Kirsch Florian , Schramm Anja , Schwarzkopf Larissa , Lutter Johanna I. , Szentes Boglárka , Huber Manuel , Leidl Reiner 
Published: October 2019

Abstract

Background
Evidence on the economic impact of chronic obstructive pulmonary disease (COPD) for third-party payers and society based on large real world datasets are still scarce. Therefore, the aim of this study was to estimate the economic impact of COPD severity and its comorbidities, stratified by GOLD grade, on direct and indirect costs for an unselected population enrolled in the structured German Disease Management Program (DMP) for COPD.

Methods
All individuals enrolled in the DMP COPD were included in the analysis. Patients were only excluded if they were not insured or not enrolled in the DMP COPD the complete year before the last DMP documentation (at physician visit), had a missing forced expiratory volume in 1 s (FEV1) measurement or other missing values in covariates. The final dataset included 39,307 patients in GOLD grade 1 to 4. We used multiple generalized linear models to analyze the association of COPD severity with direct and indirect costs, while adjusting for sex, age, income, smoking status, body mass index, and comorbidities.

Results
More severe COPD was significantly associated with higher healthcare utilization, work absence, and premature retirement. Adjusted annual costs for GOLD grade 1 to 4 amounted to €3809 [€3691–€3935], €4284 [€4176–€4394], €5548 [€5328–€5774], and €8309 [€7583-9065] for direct costs, and €11,784 [€11,257–€12,318], €12,985 [€12,531-13,443], €15,805 [€15,034–€16,584], and €19,402 [€17,853–€21,017] for indirect costs. Comorbidities had significant additional effects on direct and indirect costs with factors ranging from 1.19 (arthritis) to 1.51 (myocardial infarction) in direct and from 1.16 (myocardial infarction) to 1.27 (cancer) in indirect costs.

Conclusion
The findings indicate that more severe GOLD grades in an unselected COPD population enrolled in a structured DMP are associated with tremendous additional direct and indirect costs, with comorbidities significantly increase costs. In direct cost category hospitalization and in indirect cost category premature retirement were the main cost driver. From a societal perspective prevention and interventions focusing on disease control, and slowing down disease progression and strengthening the ability to work would be beneficial in order to realize cost savings in COPD.
Efficient expression vectors and host strain for the production of recombinant proteins by Yarrowia lipolytica in process conditions
Authors: Park Young-Kyoung , Vandermies Marie , Soudier Paul , Telek Samuel , Thomas Stéphane , Nicaud Jean-Marc , Fickers Patrick 
Published: October 2019

Abstract

Background
The oleaginous yeast Yarrowia lipolytica is increasingly used as an alternative cell factory for the production of recombinant proteins. Recently, regulated promoters from genes EYK1 and EYD1, encoding an erythrulose kinase and an erythritol dehydrogenase, respectively, have been identified and characterized in this yeast. Hybrid promoters up-regulated by polyols such as erythritol and erythrulose have been developed based on tandem copies of upstream activating sequences from EYK1 (UAS1EYK1) and XPR2 (encoding extracellular protease, UAS1XPR2) promoters.

Results
The strength of native (pEYD1) and engineered promoters (pEYK1-3AB and pHU8EYK) was compared using the extracellular lipase CalB from Candida antarctica as a model protein and a novel dedicated host strain. This latter is engineered in polyol metabolism and allows targeted chromosomal integration. In process conditions, engineered promoters pEYK1-3AB and pHU8EYK yielded 2.8 and 2.5-fold higher protein productivity, respectively, as compared to the reference pTEF promoter. We also demonstrated the possibility of multicopy integration in the newly developed host strain. In batch bioreactor, the CalB multi-copy strain RIY406 led to a 1.6 fold increased lipase productivity (45,125 U mL−1) within 24 h as compared to the mono-copy strain.

Conclusions
The expression system described herein appears promising for recombinant extracellular protein production in Y. lipolytica.
Tracking longitudinal genetic changes of circulating tumor DNA (ctDNA) in advanced Lung adenocarcinoma treated with chemotherapy
Authors: Han Xiaohong , Han Ying , Tan Qiaoyun , Huang Yu , Yang Jianliang , Yang Sheng , He Xiaohui , Zhou Shengyu , Song Yan , Pi Jinping , Zuo Lijie , Yao Jiarui , Wu Di , Zhang Zhishang , Shi Yuankai 
Published: October 2019

Abstract

Introduction
Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response.

Materials and Methods
We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations.

Results
We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy.

Conclusions
Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.
DNA methylation is maintained with high fidelity in the honey bee germline and exhibits global non-functional fluctuations during somatic development
Authors: Harris Keith D. , Lloyd James P. B. , Domb Katherine , Zilberman Daniel , Zemach Assaf 
Published: October 2019

Abstract

Background
DNA methylation of active genes, also known as gene body methylation, is found in many animal and plant genomes. Despite this, the transcriptional and developmental role of such methylation remains poorly understood. Here, we explore the dynamic range of DNA methylation in honey bee, a model organism for gene body methylation.

Results
Our data show that CG methylation in gene bodies globally fluctuates during honey bee development. However, these changes cause no gene expression alterations. Intriguingly, despite the global alterations, tissue-specific CG methylation patterns of complete genes or exons are rare, implying robust maintenance of genic methylation during development. Additionally, we show that CG methylation maintenance fluctuates in somatic cells, while reaching maximum fidelity in sperm cells. Finally, unlike universally present CG methylation, we discovered non-CG methylation specifically in bee heads that resembles such methylation in mammalian brain tissue.

Conclusions
Based on these results, we propose that gene body CG methylation can oscillate during development if it is kept to a level adequate to preserve function. Additionally, our data suggest that heightened non-CG methylation is a conserved regulator of animal nervous systems.
Mulching as water-saving technique in dryland agriculture: review article
Authors: Kader Mohammad Abdul , Singha Ashutus , Begum Mili Amena , Jewel Arif , Khan Ferdous Hossain , Khan Nazrul Islam 
Published: October 2019

Abstract
Agricultural water resources have been limited over the years due to global warming and irregular rainfall in the arid and semi-arid regions. To mitigate the water stress in agriculture, mulching has a crucial impact as a water-saving technique in rain-fed crop cultivation. It is important mainly for preserving soil moisture, relegating soil temperature, and limiting soil evaporation, which affects the crop yield. Mulching has many strategic effects on soil ecosystem, crop growth, and climate. Mulch insulates the soil, helping to provide a buffer from cold and hot temperatures that have a crucial activity in creating beautiful and protected landscapes. This study has accumulated a series of information about both organic and plastic mulch materials and its applicability on crop cultivation. Moreover, future research potentials of mulching with modeling were discussed to quantify water loss in agriculture.
Dementia 4. Lewy body dementia: diagnosis, treatment and medical management
Authors: Nazarko Linda 
Published: October 2019

In the UK, an estimated 954 000 people have dementia. Lewy body dementia (LBD) can be difficult to diagnose and estimates of its prevalence in the UK range from 38 000–100 000 ( Prince et al , 2014:14, 16; Table 4, 2019 estimates; NHS, 2019 ). This article, the fourth in a series, explains about the pathophysiology and clinical features of LBD, how it is diagnosed, treated and managed
Bowel cancer screening programme
Authors: Peate Ian 
Published: October 2019

This article, third in the series concerning screening programmes, considers the bowel cancer screening programme. In the UK, all four countries offer a bowel cancer screening programme to women and men. The overall aim of this screening programme is to check for bowel cancer— or any abnormalities that could lead to bowel cancer. The healthcare assistant and assistant practitioner (HCA and AP) may be required to assist the patient with regards to some aspects of bowel screening. This article provides an overview of the lower gastrointestinal tract and a brief description of signs and symptoms of bowel cancer. There are age differences in Northern Ireland, Wales and England compared to Scotland. The article describes the fundamental principles underpinning bowel cancer screening programmes.
Measuring sensory and pain thresholds by Semmes-Weinstein monofilaments in patients with leg ulcers: a pilot study
Authors: Jansen Mark MPM , van de Ven Aukje ALM , van der Valk Pieter GM , Wilder-Smith Oliver HG 
Published: October 2019

Objective: Pain is a common and disabling symptom in patients with leg ulcers. Clinical quantification of pain mostly depends on subjective pain reports, which do not reveal underlying mechanisms. The aim of this pilot study is to identify mechanisms underlying the pain in patients with leg ulcers by documenting alterations in pain processing using quantitative sensory testing. Methods: In nine ulcer patients the mechanical sensory thresholds and the mechanical pain thresholds were determined by Semmes-Weinstein monofilaments (SWM) at three different sites: on the contralateral (unaffected) leg, on the skin of the affected leg 10cm from the ulcer margin, and on the affected leg, close (1–2cm) to the ulcer margin. Besides the mechanical sensory thresholds and mechanical pain thresholds, pain at the site of the ulcer, using an 11-point numeric rating scale (NRS), was documented. Results: Mechanical sensory thresholds were increased in all subjects. Almost half (44%) of patients consistently showed allodynia at the unaffected site. The lowering of mechanical pain thresholds correlated with higher scores on the NRS. Conclusion: All patients showed diminished touch and/or protective sensation, which might have contributed to ulcer development via (partial) loss of protective function. The allodynia at the unaffected site suggests the presence of central sensitisation of pain processing.
Free skin micrografts with cyanoacrylate as outpatient treatment for venous leg ulcers
Authors: Sánchez Ferrán Plá , Rial Rodrigo , Artero Iñaki Cernuda , Álvarez Pilar Ruíz , Ducajú Guillermo Moñux , López Isaac Martínez , Fernández Maday Cabrero , Cabeza Oscar Uclés , Hernando Francisco Javier Serrano 
Published: October 2019

Objective: The present study describes an ambulatory, free skin micrograft technique with cyanoacrylate as a coadjuvant venous leg ulcer (VLU) healing strategy and its outcomes after one month. Methods: This prospective study involved Comprehensive Classification System for Chronic Venous Disorders (CEAP) stage C6 patients with good granulation tissue and negative culture results, consecutively recruited in January 2017 in the Hospital Clinico San Carlos. A skin micrograft was harvested from the anterior surface of the patient's thigh with a 0.4cm punch (0.12cm2). The graft was adhered to the ulcer bed with cyanoacrylate. Anti-adherent dressing and double-layer bandaging was applied, with weekly replacements. Measurements were obtained of the surface of the VLU and graft progression (in cm2) using a photographic grid. Results: A total of 12 VLUs in 12 patients were included, with a mean treated surface of 20.32±13.9cm2. A total of 18 grafts were placed and all were found to be viable after one week. Average graft growth was not noticeable after one week but was found to be 0.25±0.08cm2 after week two, 0.41±0.98cm2 after week three, and 0.70±0.15cm2 after week four (p<0.001). There were no complications in the donor zone. Conclusion: The findings of this study show that free skin micrografting with cyanoacrylate as outpatient treatment for VLUs was simple, rapid and without complication in this study, and may contribute to its wider application in clinical use.
Komposisi Spesies dan Struktur Komunitas Moluska Bentik Teluk Jakarta
Authors: Cappenberg Hendrik 
Published: October 2019

<strong>The Composition of Species and Structure of Benthic Mollusc of Jakarta Bay.</strong> The development and increasing of population in mainland may have negative impact on water and sediment quality in the Jakarta Bay as habitat of benthic molluscs. The study was conducted in June and September 2003. The aim of this study was to observe the species composition and diversity of benthic mollusc community in the Jakarta Bay. Samples were collected from 30 stations at 1 – 12 m depth using Smith McIntyre Grab with opening area was 0.05 m². A sieve with 0.5 mm in mesh size used for collecting benthic molluscs as well as for determining the profil of benthic substrates. Results of this study showed that the substrate in the study sites was characterized by muddy, muddy sand and sandy mud sediment. A total of 24 mollusc species were identified, which belong to 18 genera. Abundance of benthic molluscs ranged from 0.3 to 15779.7 individu/m<sup>2</sup> in June and from 0.3 to 820.3 individu/m<sup>2</sup> in September. Tellinidae was the highest species composition, and <em>Alveinus sp</em>. (Kelliellidae) was distributed widely in June and September. Most of the molluscs found in this study area were common species in Indonesia waters. The value of diversity index (H’) ranged from 0.03 to 0.95 and evenness index (J’) ranged from 0.05 to 0.69 in June and in September diversity index (H’) ranged from 0.01 to 1.08 and evenness index (J’) ranged from 0.01 to 1.00. These indexes showed that the diversity of benthic mollusc in Jakarta Bay were relatively low.
Pengukuran Total Petroleum Hidrokarbon (TPH) Melalui Pendekatan Kadar Minyak-Lemak dalam Sedimen di Perairan Delta Cimanuk, Jawa Barat
Authors: Wulandari Ita , Yogaswara Deny , Khozanah Khozanah , Edward Edward , Rositasari Ricky , Falahudin Dede 
Published: October 2019

<strong>Determination of Total Petroleum Hidrokarbon (TPH) through the Concentration of Oil and Grease (OG) in the Surface Sediment of Cimanuk Delta Waters, West Java</strong>. The Estuary of Delta Cimanuk is located in the coastal water of Indramayu, West Java. The pollution in the Cimanuk Delta was originated from households and industrial waste on coastal dan upland areas. Coupled with the traffic activities of fishing vessels at the fish landing (PPI) and fishing port (PP) bases around the waters, oil and grease contamination would be a threat as pollution in Indramayu coastal area. The major source of OG component on coastal waters was animal and vegetal fat and total petroleum hydrocarbon (TPH). The objectives of the study are to estimate the concentration and spatial distribution of TPH in the sediments of the Cimanuk watershed based on OG levels, and identifying the distribution of TPH-contaminated areas. Fourier Transform Infrared Spectroscopy (FTIR) instrument was applied to determine OG compounds in the sediment samples. The results showed that OG concentrations in sediments were varied between &lt;1 to 138.104 mg kg-1 dry weight (dw), while TPH was estimated at 0.24 – 36.60 mg kg-1 dw. The highest concentrations of OG was observed on St-10 in the northeast coast. Compared to the threshold value of sediments quality guidelines according to ANZECC (OG: 280-550 mg kg-1 dw), the TPH levels in eighteen observation stations were within normal range. The increased pollutant intake in Cimanuk watershed will threat the estuary as well as its biodiversity.
Postnatal outcomes of babies diagnosed with hydronephrosis in utero in a tertiary care centre in India over half a decade
Authors: Cherian Anne George , Jacob Tarun John K. , Sebastian Tunny , Vijayaselvi Reeta , David Liji Sarah , Kumar Manish , Beck Manisha Madhai 
Published: October 2019

Abstract

Background
Prenatal hydronephrosis is defined as the dilatation of the fetal renal pelvis and/or calyces and is the commonest anomaly detected in utero

Methods
This was a retrospective study to look at how well 148 antenatally detected cases of fetal hydronephrosis correlated with postnatal evaluation.

Results
Antenatal hydronephrosis was detected with a prevalence of 0.33%. The mean gestational age at diagnosis was 25.48 [standard deviation (SD) 6.36]. One hundred and sixteen (78.3%) fetuses had serial ultrasound scans during pregnancy to look for the progression of the condition. At the time of diagnosis, 30.1% of the fetuses were diagnosed to have mild hydronephrosis, 43.9% to have moderate hydronephrosis and 25.8% to have severe hydronephrosis. Follow-up ultrasounds during the prenatal period, 65% showed progression of the renal pelvis dilatation, 25.8% showed stable disease and 9.1% showed resolution on their subsequent scan. Almost half (46%) were found to have transient/physiological hydronephrosis. Thirty-one (20.9%) of the babies required an operation. An anteroposterior renal pelvis diameter (APD) of the fetal renal pelvis ≥17.5 mm can predict the need for surgery with a sensitivity of 70% and a specificity of 76.6%.

Conclusion
Counselling and decisions must be based on a series of ultrasound scans rather than a single evaluation. We use a cut-off of 17.5 mm as an indicator of possible postnatal surgical intervention.
Maternal Graves’ disease and fetal tetralogy of Fallot: a case series
Authors: Surendran Sushitha , Johnson Jason N. 
Published: October 2019

Abstract

Background
Congenital heart defects have been reported with the use of antithyroid medication with ventricular septal defects (VSD) being the most common. As per the current practice guidelines maternal Graves’ disease (GD) is not an indication for fetal echocardiogram.

Case presentation
We described three neonates with tetralogy of Fallot (TOF) born to mothers with GD. Only one of the mothers was on antithyroid medication. Two of these neonates were diagnosed postnatally when they failed the pulse oximeter congenital cardiac screening and diagnosis was established by postnatal echocardiogram. Two of the mothers had radioactive iodine ablation and were on levothyroxine during pregnancy. The dose of levothyroxine was increased during pregnancy. There was no other complication during pregnancy. The third mother had hyperthyroidism and developed a thyroid storm during pregnancy requiring inpatient admission and treatment with propylthiouracil (PTU), metoprolol and methimazole. All babies had normal thyroid function test postnatally and eventually had successful repair of TOF defect.

Conclusion
We report the largest known case series of children with TOF born to mothers with GD. Apart from the isolated reports of fetal TOF in mothers with GD, there is no clear association between fetal TOF and maternal GD and antithyroid medication. Based on the review of the literature and our case series, there may be an increased incidence of congenital heart defects in maternal GD irrespective of antithyroid medication use. This case series may add to the current knowledge base and support routine fetal echocardiogram screening for all mothers with GD.