bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exhaled volatile organic compounds as markers for medication use in asthma
Authors: Brinkman Paul , Ahmed Waqar M. , Gómez Cristina , Knobel Hugo H. , Weda Hans , Vink Teunis J. , Nijsen Tamara M. , Wheelock Craig E. , Dahlen Sven-Erik , Montuschi Paolo , Knowles Richard G. , Vijverberg Susanne J. , Maitland-van der Zee Anke H. , Sterk Peter J. , Fowler Stephen J. 
Published: September 2019

IntroductionAsthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry).MethodsSamples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation.ResultsData were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01).ConclusionWe have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring.
Impact of transition to a subterranean lifestyle on morphological disparity and integration in talpid moles (Mammalia, Talpidae)
Authors: Sansalone Gabriele , Colangelo Paolo , Loy Anna , Raia Pasquale , Wroe Stephen , Piras Paolo 
Published: September 2019

AbstractBackgroundUnderstanding the mechanisms promoting or constraining morphological diversification within clades is a central topic in evolutionary biology. Ecological transitions are of particular interest because of their influence upon the selective forces and factors involved in phenotypic evolution. Here we focused on the humerus and mandibles of talpid moles to test whether the transition to the subterranean lifestyle impacted morphological disparity and phenotypic traits covariation between these two structures.ResultsOur results indicate non-subterranean species occupy a significantly larger portion of the talpid moles morphospace. However, there is no difference between subterranean and non-subterranean moles in terms of the strength and direction of phenotypic integration.ConclusionsOur study shows that the transition to a subterranean lifestyle significantly reduced morphological variability in talpid moles. However, this reduced disparity was not accompanied by changes in the pattern of traits covariation between the humerus and the mandible, suggesting the presence of strong phylogenetic conservatism within this pattern.
Missense mutations in a transmembrane domain of the Komagataeibacter xylinus BcsA lead to changes in cellulose synthesis
Authors: Salgado Luis , Blank Silvia , Esfahani Reza Alipour Moghadam , Strap Janice L. , Bonetta Dario 
Published: September 2019

Abstract

Background
Cellulose is synthesized by an array of bacterial species. Komagataeibacter xylinus is the best characterized as it produces copious amounts of the polymer extracellularly. Despite many advances in the past decade, the mechanisms underlying cellulose biosynthesis are not completely understood. Elucidation of these mechanisms is essential for efficient cellulose production in industrial applications.

Results
In an effort to gain a better understanding of cellulose biosynthesis and its regulation, cellulose crystallization was investigated in K. xylinus mutants resistant to an inhibitor of cellulose I formation, pellicin. Through the use of forward genetics and site-directed mutagenesis, A449T and A449V mutations in the K. xylinus BcsA protein were found to be important for conferring high levels of pellicin resistance. Phenotypic analysis of the bcsAA449T and bcsAA449V cultures revealed that the mutations affect cellulose synthesis rates and that cellulose crystallinity is affected in wet pellicles but not dry ones.

Conclusions
A449 is located in a predicted transmembrane domain of the BcsA protein suggesting that the structure of the transmembrane domain influences cellulose crystallization either by affecting the translocation of the nascent glucan chain or by allosterically altering protein-protein interactions.
A global picture of family medicine: the view from a WONCA Storybooth
Authors: Cubaka Vincent K. , Dyck Clayton , Dawe Russell , Alghalyini Baraa , Whalen-Browne Molly , Cejas Gabriel , Gibson Christine 
Published: September 2019

AbstractBackgroundFamily Medicine is a novel discipline in many countries, where the motivation for training and value added to communities is not well-described. Our purpose was to understand the reason behind the choice of Family Medicine as a profession, the impact of Family Medicine on communities, and Family Medicine’s characterizing qualities, as perceived by family doctors around the world.MethodsOne-question video interviews were conducted using an appreciative inquiry approach, with volunteer participants at the 2016 World Organization of Family Doctors conference in Rio de Janeiro. Qualitative data analysis applied the thematic, framework method.Results135 family doctors from 55 countries participated in this study. Three overarching themes emerged: 1) key attributes of Family Medicine, 2) core Family Medicine values and 3) shared traits of family doctors. Family Medicine attributes and values were the key expressed motivators to join Family Medicine as a profession and were also among expressed factors that contributed to the impact of Family Medicine globally. Major sub-themes included the principles of comprehensive care, holistic care, continuity of care, patient centeredness, and the patient-provider relationship. Participants emphasized the importance of universal care, human rights, social justice and health equity.ConclusionFamily doctors around the world shared stories about their profession, presenting a heterogeneous picture of global Family Medicine unified by its attributes and values. These stories may inspire and serve as positive examples for Family Medicine programs, prospective students, advocates and other stakeholders.
Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report
Authors: Li Mingming , Chen Wei , Sun Xiaomeng , Wang Zhipeng , Zou Xun , Wei Hua , Wang Zhan , Chen Wansheng 
Published: September 2019

Abstract

Background
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC.

Case presentation
In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months.

Conclusions
This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.
Glioma malignancy is linked to interdependent and inverse AMOG and L1 adhesion molecule expression
Authors: Jiang Qiong , Xie Qing , Hu Chengliang , Yang Zhai , Huang Peizhi , Shen Huifan , Schachner Melitta , Zhao Weijiang 
Published: September 2019

AbstractBackgroundGliomas account for the majority of primary human brain tumors and remain a challenging neoplasm for cure due to limited therapeutic options. Cell adhesion molecules play pivotal roles in the growth and progression of glial tumors. Roles of the adhesion molecules on glia (AMOG) and L1CAM (L1) in glioma cells have been shown to correlate with tumorigenesis: Increased expression of L1 and decreased expression of AMOG correlate with degree of malignancy.MethodsWe evaluated the interdependence in expression of these molecules by investigating the role of AMOG in vitro via modulation of L1 expression and analyzing apoptosis and cell senescence of glioma cells.ResultsImmunohistochemical staining of normal human cortical and glioma tissue microarrays demonstrated that AMOG expression was lower in human gliomas compared to normal tissue and is inversely correlated with the degree of malignancy. Moreover, reduction of AMOG expression in human glioblastoma cells elevated L1 expression, which is accompanied by decreased cell apoptosis as well as senescence.ConclusionAMOG and L1 interdependently regulate their expression levels not only in U-87 MG cells but also in U251 and SHG44 human glioma cell lines. The capacity of AMOG to reduce L1 expression suggests that methods for increasing AMOG expression may provide a therapeutic choice for the management of glial tumors with high expression of L1.
Alcohol consumption pattern in western Nepal: findings from the COBIN baseline survey
Authors: Adhikari Tara Ballav , Rijal Anupa , Kallestrup Per , Neupane Dinesh 
Published: September 2019

Abstract

Background
Harmful use of alcohol is a global public health problem. Differences in alcohol consumption patterns may add valuable information to the design of public health interventions to prevent excessive use of alcohol, which is yet missing in Nepal. Hence, the purpose of the study is to determine the prevalence, patterns of alcohol consumption and socio-economic correlates of lifetime alcohol consumption and binge drinking in the semi-urban area of Pokhara Municipality.

Methods
The cross-sectional data used in this study were collected as part of the COBIN study to understand alcohol consumption patterns and frequency and to determine correlates of lifetime alcohol consumption and binge drinking in the semi-urban area of Pokhara Municipality, Nepal.

Results
Out of 2815 study participants, 35.6% had ever used alcohol in their lifetime (Male 67.2% and Female 18.9%). Among 571 respondents who drank alcohol within the past 30 days, 77.1% male, and 46.9% female reported binge drinking behaviour. On average, males consumed 8.8 ± 0.3 standard alcohol drinks on one occasion, while females consumed only 4.4 ± 0.3 alcoholic drinks. Male (OR = 16; 95% CI: 12.1–21.1), older adults (OR = 1.5; 95% CI: 1.2–1.7) and people belonging to disadvantaged ethnic group (OR = 6.1; 95% CI: 4.9–6.3) had higher odds of lifetime alcohol consumption than their respective counterparts. Whereas, male (OR = 7.9; 95% CI: 4.3–14.6), having higher educational status and agriculture as the occupation had higher odds of binge drinking.

Conclusion
Alcohol consumption frequency was significantly higher among males than females in Western Nepal. Although national program and policies should recommend reducing alcohol consumption in general, targeted interventions are needed for males aged 45–65 years of age and certain ethnic groups (Dalit and Janajati).
Assessment of status of solid waste management in Asella town, Ethiopia
Authors: Lema Gorfnesh , Mesfun Million Getachew , Eshete Amade , Abdeta Gizachew 
Published: September 2019

Abstract

Background
Improper solid waste management (SWM) is a major public health and environmental concern in the urban areas of many developing countries such as Asella Town. The aim of this study was to assess the status of SWM in Asella town.

Methods
A community-based cross-sectional study design was used to assess the status of improper SWM and associated factors in Asella town. From the total of eight kebeles (smallest administrative unit in Ethiopia) four kebeles were randomly selected using lottery method. The sample size was 413 households. The households were proportionally allocated to each randomly selected kebeles. The data was collected by pretested questionnaire in the local language. Data was entered using statistical software Epi Info version seven and transferred to SPSS version 21. Descriptive data analysis was done to summarize the socioeconomic status of the respondents. Chi-square was used to show the association between the status of solid waste management and different variables. Binary logistic regression was used to determine the potential factors for improper SWM.

Result
332 (82.8%), had improper solid waste management practice. Lack of adequate knowledge about solid waste management and not having access to door to door solid waste collection could have contributed to the reported improper solid waste practice. Participants who didn’t have access to door to door solid waste collection service were about three times more likely to practice improper solid waste management when compared to those who had access (AOR = 2.873, 95 CI (1.565,5.273) P = 0.001).

Conclusion
The study finding showed that, the majority of the residents practiced improper solid waste management. Lack of adequate knowledge about solid waste management and not having access to door to door solid waste collection could have contributed to the reported improper solid waste practice. Therefore, there is a need to enhance the awareness of the community about proper SWM and to improve the door to door solid waste collection service by the town municipality.
Enhancing healthy ecosystems in northern Ghana through eco-friendly farm-based practices: insights from irrigation scheme-types
Authors: Agula Caesar , Mabe Franklin Nantui , Akudugu Mamudu Abunga , Dittoh Saa , Ayambila Sylvester Nsobire , Bawah Ayaga 
Published: September 2019

AbstractBackgroundFarming practices vary from farmer to farmer and from place to place depending on a number of factors including the agroclimatic condition, infrastructure (e.g. irrigation facilities) and management mechanisms (private versus state management). These together affect the functioning and sustainability of the ecosystems. For the sustainability of ecosystems, farmers need to employ ecosystem-based farm practices. This paper examines the ecosystem-based farm management practices (EBFMPs) in private and state-managed irrigation schemes. It also analyses the drivers of farmers’ willingness to pay for EBFMPs sustainability. The study employed mixed methods design, using both qualitative and quantitative techniques of data collection through key informant interviews, focus group discussions and semi-structured questionnaires administered to 300 households. The various EBFMPs adopted by farmers were examined and descriptively presented. The Chi-square automatic interaction detector (CHAID) and multiple linear regression were used to assess the predictors of farmers’ willingness to pay for EBFMPs to enhance the health of agroecosystems. Compost application, conservative tilling, conservation of vegetation, mulching, crop rotation, intercropping with legumes, efficient drainage systems and bunding were the EBFMPs captured in this paper.ResultsFarmers in privately-managed irrigation schemes (PIS) more often apply EBFMPs compared with those in state-managed irrigation schemes (SIS). The paper also found that farmers’ willingness to pay to sustain EBFMPs for healthy ecosystems is significantly determined by the type of irrigation scheme they cultivate in (that is, PIS or SIS), their level of education, marital status and perception of soil fertility.ConclusionsPolicy makers, implementers, and other stakeholders need to consider the capacity building of irrigation farmers, especially those in SIS in northern Ghana by educating them on agricultural production and ecosystem nexus to enhance the level of usage and willingness to pay for EBFMPs sustainability.
Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension
Authors: White R. James , Vonk-Noordegraaf Anton , Rosenkranz Stephan , Oudiz Ronald J. , McLaughlin Vallerie V. , Hoeper Marius M. , Grünig Ekkehard , Ghofrani Hossein-Ardeschir , Chakinala Murali M. , Barberà Joan A. , Blair Christiana , Langley Jonathan , Frost Adaani E. 
Published: September 2019

Abstract

Background
Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants.

Methods
AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, ambrisentan 10 mg plus placebo, or tadalafil 40 mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline.

Results
This analysis included 500 participants in the previously defined primary analysis set (n = 155 FC II, n = 345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups.

Conclusions
Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe.
Funded by Gilead Sciences, Inc. and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.
Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles
Authors: Dabrowska Sylwia , Andrzejewska Anna , Lukomska Barbara , Janowski Miroslaw 
Published: September 2019

Abstract
Ischemic stroke is the third cause of death in the developed countries and the main reason of severe disability. Brain ischemia leads to the production of damage-associated molecular patterns (DAMPs) by neurons and glial cells which results in astrocyte and microglia activation, pro-inflammatory cytokines and chemokines production, blood-brain barrier (BBB) disruption, infiltration of leukocytes from the peripheral blood into the infarcted area, and further exacerbation of tissue damage. However, some immune cells such as microglia or monocytes are capable to change their phenotype to anti-inflammatory, produce anti-inflammatory cytokines, and protect injured nervous tissue. In this situation, therapies, which will modulate the immune response after brain ischemia, such as transplantation of mesenchymal stem cells (MSCs) are catching interest. Many experimental studies of ischemic stroke revealed that MSCs are able to modulate immune response and act neuroprotective, through stimulation of neurogenesis, oligodendrogenesis, astrogenesis, and angiogenesis. MSCs may also have an ability to replace injured cells, but the release of paracrine factors directly into the environment or via extracellular vesicles (EVs) seems to play the most pronounced role. EVs are membrane structures containing proteins, lipids, and nucleic acids, and they express similar properties as the cells from which they are derived. However, EVs have lower immunogenicity, do not express the risk of vessel blockage, and have the capacity to cross the blood-brain barrier. Experimental studies of ischemic stroke showed that EVs have immunomodulatory and neuroprotective properties; therefore, they can stimulate neurogenesis and angiogenesis. Up to now, 20 clinical trials with MSC transplantation into patients after stroke were performed, from which two concerned on only hemorrhagic stroke and 13 studied only on ischemic stroke. There is no clinical trial with EV injection into patients after brain ischemia so far, but the case with miR-124-enriched EVs administration is planned and probably there will be more clinical studies with EV transplantation in the near future.