bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD11c regulates hematopoietic stem and progenitor cells under stress
Authors: Hou Lifei , Voit Richard A. , Sankaran Vijay G. , Springer Timothy A. , Yuki Koichi 
Published: December 2020

Abstractβ2 integrins are well-known leukocyte adhesion molecules consisting of 4 members: CD11a-d. Their known biological functions range widely from leukocyte recruitment, phagocytosis, to immunological synapse formation, but the studies have been primarily focused on CD11a and CD11b. CD11c is 1 of the 4 members and is extremely homologous to CD11b. It has been well known as a dendritic cell marker, but the characterization of its function has been limited. We found that CD11c was expressed on the short-term hematopoietic stem cells and multipotent progenitor cells. The lack of CD11c did not affect the number of hematopoietic stem and progenitor cells (HSPCs) in healthy CD11c knockout mice. Different from other β2 integrin members, however, CD11c deficiency was associated with increased apoptosis and significant loss of HSPCs in sepsis and bone marrow transplantation. Although integrins are generally known for their overlapping and redundant roles, we showed that CD11c had a distinct role of regulating the expansion of HSPCs under stress. This study shows that CD11c, a well-known dendritic cell marker, is expressed on HSPCs and serves as their functional regulator. CD11c deficiency leads to the loss of HSPCs via apoptosis in sepsis and bone marrow transplantation.
Cost-effectiveness analysis of a single-inhaler triple therapy for COPD in the UK
Authors: Fenwick Elisabeth , Martin Alan , Schroeder Melanie , Mealing Stuart J. , Solanke Oyinkansola , Risebrough Nancy , Ismaila Afisi S. 
Published: December 2020

UK management costs for COPD, estimated at £1.9 billion/year, are rising. In the FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) study, single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (100/62.5/25 µg) improved clinical outcomesversusbudesonide/formoterol (400/12 µg) in patients with symptomatic COPD at risk of exacerbations. We assessed the cost-effectiveness of fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol for treating COPD from a UK National Health Service perspective.A model was developed combining a trial-based and Markov component and populated with baseline and treatment effect data from FULFIL, together with UK healthcare resource costs and disease-related utilities. Costs per life year and per quality-adjusted life year gained (costing year 2017) for fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol were calculated for a lifetime horizon. Results were explored using deterministic sensitivity, scenario and probabilistic analyses.Fluticasone furoate/umeclidinium/vilanterol was associated with gains in life years (0.533) and quality-adjusted life years (0.506)versusbudesonide/formoterol, but at slightly increased total costs (£26 416versus£25 860). This translated to incremental cost-effectiveness ratios of £1042/life year and £1098/quality-adjusted life year for fluticasone furoate/umeclidinium/vilanterolversusbudesonide/formoterol. In scenario analyses, incremental cost-effectiveness ratios ranged from dominant to £1547/quality-adjusted life year gained.Fluticasone furoate/umeclidinium/vilanterol provides a cost-effective treatment optionversusbudesonide/formoterol for patients with symptomatic COPD in the UK.
Cardiac biomarkers and long-term outcomes of exacerbations of COPD: a long-term follow-up of two cohorts
Authors: Shafuddin Eskandarain , Fairweather Sarah M. , Chang Catherina L. , Tuffery Christine , Hancox Robert J. 
Published: December 2020

BackgroundCOPD patients often have cardiac comorbidities. Cardiac involvement at the time of a COPD exacerbation is associated with a high short-term mortality, but whether this influences long-term outcomes is unknown. We explored whether biomarkers of cardiac dysfunction at the time of a COPD exacerbation predict long-term outcomes.MethodsTwo prospective cohorts of patients admitted to Waikato Hospital for exacerbations of COPD were recruited during 2006–2007 and 2012–2013. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured on admission and were used to indicate cardiac stretch and myocardial injury, respectively. 5-year survival after discharge and subsequent admissions for cardiac disease and COPD exacerbations were analysed using Kaplan–Meier and Cox proportional hazards tests.ResultsThe overall 5-year mortality was 61%. Patients with high NT-proBNP on admission had higher mortality than those with normal cardiac biomarkers (adjusted hazard ratio (aHR) 1.76, 95% CI 1.18–2.62). High NT-proBNP was also associated with a higher risk of future cardiac admissions (aHR 1.75, 95% CI 1.2–2.55). Troponin T levels were not associated with long-term survival (aHR 0.86, 95% CI 0.40–1.83) or future cardiac admissions (aHR 0.74, 95% CI 0.34–1.57). Neither biomarker predicted future COPD exacerbations.ConclusionThe long-term prognosis following a hospitalisation for an exacerbation of COPD is poor with less than half of patients surviving for 5 years. Elevated NT-proBNP at the time of a COPD exacerbation is associated with higher long-term mortality and a greater likelihood of future cardiac admissions, but not future COPD exacerbations.
Reliability of maximum oxygen uptake in cardiopulmonary exercise testing with continuous laryngoscopy
Authors: Engan Mette , Hammer Ida Jansrud , Bekken Marianne , Halvorsen Thomas , Fretheim-Kelly Zoe Louise , Vollsæter Maria , Bovim Lars Peder Vatshelle , Røksund Ola Drange , Clemm Hege 
Published: December 2020

AimsA cardiopulmonary exercise test (CPET) is the gold standard to evaluate symptom-limiting exercise intolerance, while continuous laryngoscopy performed during exercise (CLE) is required to diagnose exercise-induced laryngeal obstruction. Combining CPET with CLE would save time and resources; however, the CPET data may be distorted by the extra equipment. We therefore aimed to study whether CPET with CLE influences peak oxygen uptake (V′O2peak) and other gas exchange parameters when compared to a regular CPET.MethodsForty healthy athletes without exercise-related breathing problems, 15–35 years of age, performed CPET to peak exercise with and without an added CLE set-up, in randomised order 2–4 days apart, applying an identical computerised treadmill protocol.ResultsAt peak exercise, the mean difference (95% confidence interval) between CPET with and without extra CLE set-up forV′O2peak, respiratory exchange ratio (RER), minute ventilation (V′E) and heart rate (HR) was 0.2 (−0.4 to 0.8) mL·kg−1·min−1, 0.01(−0.007 to 0.027) units, 2.6 (−1.3 to 6.5) L·min−1and 1.4 (−0.8 to 3.5) beats·min−1, respectively. Agreement (95% limits of agreement) forV′O2peak, RER andV′Ewas 0.2 (±3.7) mL·kg−1·min−1, 0.01 (±0.10) units and 2.6 (±24.0) L·min−1, respectively. No systematic or proportional bias was found except for the completed distance, which was 49 m (95% CI 16 to 82 m) longer during CPET.ConclusionParameters of gas exchange, includingV′O2peak and RER, obtained from a maximal CPET performed with the extra CLE set-up can be used interchangeably with data obtained from standard CPET, thus preventing unnecessary additional testing.
COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia
Authors: Pedersen Eva S.L. , Collaud Eugénie N.R. , Mozun Rebeca , Ardura-Garcia Cristina , Lam Yin Ting , Harris Amanda , Lucas Jane S. , Copeland Fiona , Manion Michele , Rindlisbacher Bernhard , Silberschmidt Hansruedi , Goutaki Myrofora , Kuehni Claudia E. 
Published: December 2020

COVID-PCD is a participatory study initiated by people with primary ciliary dyskinesia (PCD) who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real-time from people with PCD throughout the pandemic to describe incidence of coronavirus disease 2019 (COVID-19), symptoms and course of disease; identify risk factors for prognosis; and assess experiences, wishes and needs.The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, current symptoms, social contact behaviour and physical activity. Occasional thematic questionnaires are sent out focussing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online.The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians and researchers.
Glucose-lactose mixture feeds in industry-like conditions: a gene regulatory network analysis on the hyperproducing Trichoderma reesei strain Rut-C30
Authors: Pirayre Aurélie , Duval Laurent , Blugeon Corinne , Firmo Cyril , Perrin Sandrine , Jourdier Etienne , Margeot Antoine , Bidard Frédérique 
Published: December 2020

AbstractBackgroundThe degradation of cellulose and hemicellulose molecules into simpler sugars such as glucose is part of the second generation biofuel production process. Hydrolysis of lignocellulosic substrates is usually performed by enzymes produced and secreted by the fungusTrichoderma reesei. Studies identifying transcription factors involved in the regulation of cellulase production have been conducted but no overview of the whole regulation network is available. A transcriptomic approach with mixtures of glucose and lactose, used as a substrate for cellulase induction, was used to help us decipher missing parts in the network ofT. reeseiRut-C30.ResultsExperimental results on the Rut-C30 hyperproducing strain confirmed the impact of sugar mixtures on the enzymatic cocktail composition. The transcriptomic study shows a temporal regulation of the main transcription factors and a lactose concentration impact on the transcriptional profile. A gene regulatory network built using BRANE Cut software reveals three sub-networks related toi) a positive correlation between lactose concentration and cellulase production,ii) a particular dependence of the lactose onto theβ-glucosidase regulation andiii) a negative regulation of the development process and growth.ConclusionsThis work is the first investigating a transcriptomic study regarding the effects of pure and mixed carbon sources in a fed-batch mode. Our study expose a co-orchestration ofxyr1,clr2andace3for cellulase and hemicellulase induction and production, a fine regulation of theβ-glucosidase and a decrease of growth in favor of cellulase production. These conclusions provide us with potential targets for further genetic engineering leading to better cellulase-producing strains in industry-like conditions.
Selective cytotoxic and anti-metastatic activity in DU-145 prostate cancer cells induced by Annona muricata L. bark extract and phytochemical, annonacin
Authors: Foster Kimberley , Oyenihi Omolola , Rademan Sunelle , Erhabor Joseph , Matsabisa Motlalepula , Barker James , Langat Moses K. , Kendal-Smith Amy , Asemota Helen , Delgoda Rupika 
Published: December 2020

AbstractBackgroundAnnona muricataL. was identified as a popular medicinal plant in treatment regimens among cancer patients in Jamaica by a previously conducted structured questionnaire. Ethnomedically used plant parts, were examined in this study against human prostate cancer cells for the first time and mechanisms of action elucidated for the most potent of them, along with the active phytochemical, annonacin.MethodsNine extracts of varying polarity from the leaves and bark ofA. muricatawere assessed initially for cytotoxicity using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on PC-3 prostate cancer cells and the ethyl acetate bark (EAB) extract was identified as the most potent. EAB extract was then standardized for annonacin content using High-performance Liquid Chromatography - Mass Spectrometry (HPLC-MS) and shown to be effective against a second prostate cancer cell line (DU-145) also. The mode of cell death in DU-145 cells were assessed via several apoptotic assays including induction of increased reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, activation of caspases and annexin V externalization combined with morphological observations using confocal microscopy. In addition, the potential to prevent metastasis was examined via inhibition of cell migration, vascular endothelial growth factor (VEGF) and angiogenesis using the chorioallantoic membrane assay (CAM).ResultsAnnonacin and EAB extract displayed selective and potent cytotoxicity against the DU-145 prostate carcinoma cells with IC50values of 0.1 ± 0.07 μM and 55.501 ± 0.55 μg/mL respectively, without impacting RWPE-1 normal prostate cells, in stark contrast to chemotherapeutic docetaxel which lacked such selectivity. Docetaxel’s impact on the cancerous DU-145 was improved by 50% when used in combination with EAB extract. Insignificant levels of intracellular ROS content, depolarization of mitochondrial membrane, Caspase 3/7 activation, annexin V content, along with stained morphological evaluations, pointed to a non-apoptotic mode of cell death. The extract at 50 μg/mL deterred cell migration in the wound-healing assay, while inhibition of angiogenesis was displayed in the CAM and VEGF inhibition assays for both EAB (100 μg /mL) and annonacin (0.5 μM).ConclusionsTaken together, the standardized EAB extract and annonacin appear to induce selective and potent cell death via a necrotic pathway in DU-145 cells, while also preventing cell migration and angiogenesis, which warrant further examinations for mechanistic insights and validity in-vivo.
Medical students’ self-reported gender discrimination and sexual harassment over time
Authors: Kisiel Marta A. , Kühner Sofia , Stolare Karin , Lampa Erik , Wohlin Martin , Johnston Nina , Rask-Andersen Anna 
Published: December 2020

Abstract
Background
Gender discrimination (GD) and sexual harassment (SH) occur at all academic institutions worldwide. Medical students report high prevalence of GD and SH, which may negatively affect their education and health. There are indications that policies and reforms on reducing GD/SH are insufficient. Swedish medical students’ experiences of GD/SH are monitored by course-evaluations and bi-annual student union evaluations; however, the response rate is usually low. The aim of this study was to compare the exposure to and context of self-reported GD/SH over an 11-year period amongst medical students at a Swedish university.

Methods
In 2002, a questionnaire (n = 622) was mailed to medical students’ home addresses. It was repeated in 2013 and then distributed during mandatory lectures (n = 856). The questions used a behavioristic approach and asked about specific GH/SH experiences. Participation was voluntary and anonymous. The changes in prevalence over time were calculated by sampling weights in order to obtain comparable estimates, representative of both cohorts.

Results
The response frequency was 55% (62% women) in 2002 and 81% (59% women) in 2013. The prevalence of GD tended to decrease for male and clinical students in comparison to female and pre-clinical peers. However, the prevalence of SH increased for female compared to male students. The ratio of SH for female pre-clinical students doubled in many instances; most often, the mistreatment occurred in the clinic. Medical doctors were indicated as perpetrators up to five times more often by all students in 2013.

Conclusion
Our results show a disproportional change in exposure to GD/SH between female and male medical students, resulting in a widening of the gender gap regarding prevalence of GD and SH between 2002 and 2013. In particular, personal experiences of SH increased for both sexes. It is proof that institutional efforts to fight mistreatment might be ineffective.
Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality in the general population: results from the prospective Lifelines-MINUTHE study
Authors: Riphagen Ineke J. , Minović Isidor , Groothof Dion , Post Adrian , Eggersdorfer Manfred L. , Kootstra-Ros Jenny E. , de Borst Martin H. , Navis Gerjan , Muskiet Frits A. J. , Kema Ido P. , Heiner-Fokkema M. Rebecca , Bakker Stephan J. L. 
Published: December 2020

Abstract
Background
Methylmalonic acid (MMA) is best known for its use as a functional marker of vitamin B12 deficiency. However, MMA concentrations not only depend on adequate vitamin B12 status, but also relate to renal function and endogenous production of propionic acid. Hence, we aimed to investigate to what extent variation in MMA levels is explained by vitamin B12 and eGFR and whether MMA levels are associated with mortality if vitamin B12 and eGFR are taken into account.

Methods
A total of 1533 individuals (aged 60–75 years, 50% male) were included from the Lifelines Cohort and Biobank Study. Individuals were included between 2006 and 2013, and the total follow-up time was 8.5 years.

Results
Median [IQR] age of the study population was 65 [62–69] years, 50% was male. At baseline, median MMA concentration was 170 [138–216] nmol/L, vitamin B12 290 [224–362] pmol/L, and eGFR 84 [74–91] mL/min/1.73 m2. Log2 vitamin B12, log2 eGFR, age, and sex were significantly associated with log2 MMA in multivariable linear regression analyses (model R2 = 0.22). After a total follow-up time of 8.5 years, 72 individuals had died. Log2 MMA levels were significantly associated with mortality (hazard ratio [HR] 1.67 [95% CI 1.25–2.22], P < 0.001). Moreover, we found a significant interaction between MMA and eGFR with respect to mortality (Pinteraction < 0.001).

Conclusions
Only 22% of variation in MMA levels was explained by vitamin B12, eGFR, age, and sex, indicating that a large part of variation in MMA levels is attributable to other factors (e.g., catabolism, dietary components, or gut microbial production). Higher MMA levels are associated with an increased risk for mortality, independent of vitamin B12, eGFR, and sex. This association was more pronounced in individuals with impaired renal function.
Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature
Authors: Zhang Qiang , Qin Zailong , Yi Shang , Wei Hao , Zhou Xun Zhao , Su Jiasun 
Published: December 2020

Abstract
Background
Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13.

Case presentation
A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605_606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed.

Conclusions
This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations.
The C allele of the reactive oxygen species modulator 1 (ROMO1) polymorphism rs6060566 is a biomarker predicting coronary artery stenosis in Slovenian subjects with type 2 diabetes mellitus
Authors: Tibaut Miha , Mankoč Ramuš Sara , Petrovič Daniel 
Published: December 2020

Abstract
Background
We aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (ROMO1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).

Methods
A total of 1072 subjects with T2DM were enrolled in this cross-sectional case–control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). The genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO1 expression according to their genotype.

Results
There were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO1 rs6060566 had a threefold increased likelihood of having 50–75% coronary artery stenosis (Adjusted OR = 3.27, 95% CI 1.16–9.20). Subjects with two affected coronary arteries had a 3.72 fold higher prevalence of MI (OR = 3.72, 95% CI 1.27–10.84). With CAD in LMCA or LAD, MI prevalence was about 3.5-fold higher (p = 0.07 for LMCA and p = 0.01 for LAD). Furthermore, the carriers of the rs6060566 C allele showed higher number of positive cells for ROMO1 expression in endarterectomy samples of coronary arteries.

Conclusions
According to our study, the rs6060566 polymorphism of the ROMO1 gene is not a risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had non-obstructive CAD. Moreover, C allele carriers showed a statistically higher number of cells positive for ROMO1 compared with T allele carriers in coronary endarterectomy samples.