bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel optimized adaptive servo-ventilation setting for a patient with severe heart failure based on the echocardiogram: a case report
Authors: Sekiguchi Haruki , Tanino Sae , Serizawa Naoki , Hagiwara Nobuhisa 
Published: February 2022

Abstract

Background
Adaptive servo-ventilation (ASV) is a non-invasive positive-pressure ventilation therapy considered beneficial for treating heart failure (HF) in patients with central sleep apnoea. However, to the best of our knowledge, there is no evidence indicating that this therapy increases the mortality in HF patients. We hypothesized that ASV settings are important for HF patients with reduced ejection fraction. Therefore, to determine the suitable ASV setting for such patients, we optimized these settings to improve the left ventricular (LV) output during the therapy.

Case summary
We present a case of HF caused by dilated cardiomyopathy in a 45-year-old man. He was hospitalized due to HF; his LV ejection fraction was ∼20%, and haemodynamics analysis revealed his HF grade was Forrester subset IV. During hospitalization, he was diagnosed with sleep apnoea; therefore, we induced ASV with our optimized setting using an echocardiogram evaluating stroke volume (SV). Using this method, we could determine the appropriate setting that increased his SV and improved his apnoea–hypopnoea index. At the 5th-year follow-up, he had no dyspnoea on effort (New York Heart Association Functional Classification I). He continued using the ASV with good adherence, and no hospitalization for ventricular arrhythmia and HF was reported.

Discussion
Our ASV optimized setting showed beneficial effects in an HF patient with reduced ejection fraction. This method improved the patient’s SV and apnoea–hypopnoea index, indicating that this novel method should be considered for HF patients with reduced ejection fraction.
Political power of the press in the Weimar Republic
Authors: Nguyen Bang Dinh 
Published: February 2022

Abstract
This paper examines how changes in newspaper circulation affected voter turnout, party vote shares, and mass polarization in Weimar Berlin. My empirical strategy exploits variation in the development of railway system across historical districts of Berlin, which influenced the circulation of newspapers. I find that an increase in newspaper circulation significantly induced higher turnout in fourteen outer districts and a higher degree of mass polarization. Partisan newspapers benefitted party vote shares, with stronger effects in federal elections than in local elections. The electoral influence of newspapers was driven by tabloids and mass newspapers, and not by elite political newspapers.
Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study
Authors: Portilla-Fernandez Eliana , Klarin Derek , Hwang Shih-Jen , Biggs Mary L , Bis Joshua C , Weiss Stefan , Rospleszcz Susanne , Natarajan Pradeep , Hoffmann Udo , Rogers Ian S , Truong Quynh A , Völker Uwe , Dörr Marcus , Bülow Robin , Criqui Michael H , Allison Matthew , Ganesh Santhi K , Yao Jie , Waldenberger Melanie , Bamberg Fabian , Rice Kenneth M , Essers Jeroen , Kapteijn Daniek M C , van der Laan Sander W , de Knegt Rob J , Ghanbari Mohsen , Felix Janine F , Ikram M Arfan , Kavousi Maryam , Uitterlinden Andre G , Roks Anton J M , Danser A H Jan , Tsao Philip S , Damrauer Scott M , Guo Xiuqing , Rotter Jerome I , Psaty Bruce M , Kathiresan Sekar , Völzke Henry , Peters Annette , Johnson Craig , Strauch Konstantin , Meitinger Thomas , O’Donnell Christopher J , Dehghan Abbas ,   VA Million Veteran Program
Published: February 2022

Abstract
Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior–posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = −0.02, SE = 0.004, P-value = 2.10 × 10−8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10−4). In exome-array single-variant analysis (P-value threshold = 9 × 10−7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10−5). In the gene-based analysis (P-value threshold = 1.85 × 10−6), PCSK5 showed an association with AAD (P-value = 8.03 × 10−7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = −0.003, P-value = 0.02), triglycerides (beta = −0.16, P-value = 0.008) and height (beta = 0.03, P-value &lt; 0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.
SegmentGeometry: A Tool for Measuring Second Moment of Area in 3D Slicer
Authors: Huie Jonathan M , Summers Adam P , Kawano Sandy M 
Published: February 2022

Synopsis
Second moment of area is a measure of how well the cross-section of a beam will resist bending because of its shape. Many have used second moment of area to investigate the mechanical adaptations of biological structures from stingray jaws to animal limb bones. In this context it is important to acknowledge the assumptions of beam theory, in which second moment of area plays a key role, if reasonable results are desired. For example, to minimize shear the structure should be at least 10 times longer than it is wide and deflection should be minimal. Analyzing the internal geometry of biological structures has never been easier or more accessible given the wide, and growing availability of micro-CT scans. Here, we offer a guide on the care that needs to be taken when interpreting second moment of area, and present open-access, open-source software that can process hundreds if not thousands of structures in a short time frame. SegmentGeometry, an extension for the open-source imaging platform 3D Slicer, iterates slice-by-slice through 3D structures to calculate second moment of area and other cross-sectional properties. We analyzed 2 case studies to demonstrate the power of this tool and to highlight interpretations that can be gleaned from second moment of area. Second moment of area is just one part of the Euler–Bernoulli beam theory and considering the full equation would greatly increase the number and diversity of questions that can be answered.
Multiple secondary outbreaks of NDM-producing Enterobacter hormaechei in the context of endemic NDM-producing Klebsiella pneumoniae
Authors: Izdebski R. , Biedrzycka M. , Urbanowicz P. , Papierowska-Kozdój W. , Dominiak M. , Żabicka D. , Gniadkowski M. 
Published: February 2022

Abstract

Background
Consecutive Polish regions have become endemic for NDM-1-producing Klebsiella pneumoniae ST11, followed by K. pneumoniae ST147. Since 2017 a significant increase in NDM-positive Enterobacter hormaechei cases has been observed.

Objectives
To investigate the origin and character of this increase in NDM-positive E. hormaechei.

Methods
The analysis included 160 NDM-producing Enterobacter cloacae complex isolates, recovered in 2015–20 in 37 centres of 9/16 regions. These were typed by PFGE and MLST, and screened by PCR-mapping for NDM-1-encoding Tn125-like elements. Forty-four isolates were sequenced by MiSeq. Species identification was based on whole-genome average nucleotide identity; clonality and phylogeny were inferred by SNP approaches. The structural plasmid analysis was done for 12 isolates sequenced by MinION.

Results
The isolates belonged to 11 STs, predominantly ST89 (65.6%), followed by ST146 (15.6%), ST198 (7.5%) and ST1303 (3.7%), representing different E. hormaechei subspecies. Most of the isolates contained the Tn125A variant of the K. pneumoniae ST11 lineage, and several had Tn125F of the ST147. Individual E. hormaechei genotypes represented various epidemiological situations, from sporadic cases to single-hospital, city and regional outbreaks, including one caused by ST89 organisms with 82 cases in 17 centres. Acquisitions of the Tn125A/Tn125F determinants by the E. hormaechei strains occurred around 10 times and were plasmid-mediated, with a significant plasmid rearrangement in case of Tn125F.

Conclusions
The increase in E. hormaechei NDM-1 cases in Poland is a consequence of the uncontrolled spread of NDM-1-producing K. pneumoniae genotypes. Several E. hormaechei lineages have acquired NDM-encoding plasmids in different locales which started ‘secondary’ progressive outbreaks.
The value, challenges and practical considerations of conducting qualitative research on antimicrobial stewardship in primary care
Authors: Wanat Marta , Santillo Marta , Borek Aleksandra J. , Butler Christopher C. , Anthierens Sibyl , Tonkin-Crine Sarah 
Published: February 2022

AbstractIn order to design appropriate antimicrobial stewardship (AMS) programmes, it is crucial to understand challenges to tackling antibiotic resistance (AMR) specific to each healthcare setting. Antibiotic prescribing in primary care accounts for most prescriptions with a significant proportion considered clinically inappropriate. Qualitative research has a long history in social sciences, but its value and contribution are still contested in medical journals including in the AMR/AMS field. However, through its focus on understanding, meaning making and explaining, qualitative research can offer insights in how to improve AMS efforts in primary care. This paper provides an overview of unique considerations, contributions and challenges related to using qualitative research in AMS to help the AMS community new to qualitative research to utilize its potential most fully. First, we discuss specific considerations for AMS in relation to the stages of conducting a qualitative study, including identifying a research question and choosing a suitable methodology; sampling appropriate participants; planning a recruitment strategy; choosing a method of data collection; and conducting data analysis. These are illustrated with examples of qualitative AMS studies in primary care. Second, we highlight the importance of patient and public involvement throughout all stages of the project and ensuring quality in qualitative AMS research. Finally, drawing on these considerations, we make a further case for the value and contribution of qualitative methodologies in AMS/AMR research while outlining future directions for both AMS and qualitative research, including the need for studies with diverse actors; interdisciplinary collaborations; and complex decisions on methodologies and timelines.
Monte Carlo simulations of multiple populations in globular clusters: constraints on the initial size of the second generation from binary stars
Authors: Sollima A , Gratton R , Lucatello S , Carretta E 
Published: February 2022

ABSTRACT
We present the result of a survey of Monte Carlo simulations of globular clusters hosting two generations of stars including a large ($f_{b}=50{{\ \rm per\ cent}}$) fraction of primordial binaries in both populations. The dynamical evolution of the two stellar populations is followed for a Hubble time taking into account the effect of the tidal field, two-body relaxation, stellar evolution, and three/four-body interactions. The fraction of surviving binaries, once accounted for the observational bias and uncertainties, is compared with the available radial velocity time-series performed in real globular clusters, and it is used to constrain the initial spatial concentration of the second generation. The fraction of second generation binaries appears to depend only on the ratio between the total cluster mass and the initial size of the second generation that determines the average velocity dispersion across the extent of this stellar population. In spite of the various uncertainties, we find that the observed fraction can be obtained only assuming a strong initial concentration of the second generation ($r_{h,S}\sim 0.1~(M/10^{6} \, \mathrm{M}_{\odot })\, \mathrm{pc}$). The evolution of the first generation binary fraction is more sensitive to the tidal field strength (with a non-negligible effect of the cluster orbital eccentricity) since the tidal field has a direct impact on the first generation structural properties.
The detailed chemical abundance patterns of accreted halo stars from the optical to infrared
Authors: Carrillo Andreia , Hawkins Keith , Jofré Paula , de Brito Silva Danielle , Das Payel , Lucey Madeline 
Published: February 2022

ABSTRACT
Understanding the assembly of our Galaxy requires us to also characterize the systems that helped build it. In this work, we accomplish this by exploring the chemistry of accreted halo stars from Gaia-Enceladus/Gaia-Sausage (GES) selected in the infrared from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) Data Release 16. We use high resolution optical spectra for 62 GES stars to measure abundances in 20 elements spanning the α, Fe-peak, light, odd-Z, and notably, the neutron-capture groups of elements to understand their trends in the context of and in contrast to the Milky Way and other stellar populations. Using these derived abundances we find that the optical and the infrared abundances agree to within 0.15 dex except for O, Co, Na, Cu, and Ce. These stars have enhanced neutron-capture abundance trends compared to the Milky Way, and their [Eu/Mg] and neutron-capture abundance ratios (e.g. [Y/Eu], [Ba/Eu], [Zr/Ba], [La/Ba], and [Nd/Ba]) point to r-process enhancement and a delay in s-process enrichment. Their [α/Fe] trend is lower than the Milky Way trend for [Fe/H] &gt; −1.5 dex, similar to previous studies of GES stars and consistent with the picture that these stars formed in a system with a lower rate of star formation. This is further supported by their depleted abundances in Ni, Na, and Cu abundances, again, similar to previous studies of low-α stars with accreted origins.
Population-Genomic Analysis Identifies a Low Rate of Global Adaptive Fixation in the Proteins of the Cyclical ParthenogenDaphnia magna
Authors: Fields Peter D , McTaggart Seanna , Reisser Céline M O , Haag Christoph , Palmer William H , Little Tom J , Ebert Dieter , Obbard Darren J 
Published: February 2022

AbstractDaphnia are well-established ecological and evolutionary models, and the interaction between D. magna and its microparasites is widely considered a paragon of the host-parasite coevolutionary process. Like other well-studied arthropods such as Drosophila melanogaster and Anopheles gambiae, D. magna is a small, widespread, and abundant species that is therefore expected to display a large long-term population size and high rates of adaptive protein evolution. However, unlike these other species, D. magna is cyclically asexual and lives in a highly structured environment (ponds and lakes) with moderate levels of dispersal, both of which are predicted to impact upon long-term effective population size and adaptive protein evolution. To investigate patterns of adaptive protein fixation, we produced the complete coding genomes of 36 D. magna clones sampled from across the European range (Western Palaearctic), along with draft sequences for the close relatives D. similis and D. lumholtzi, used as outgroups. We analyzed genome-wide patterns of adaptive fixation, with a particular focus on genes that have an a priori expectation of high rates, such as those likely to mediate immune responses, RNA interference against viruses and transposable elements, and those with a strongly male-biased expression pattern. We find that, as expected, D. magna displays high levels of diversity and that this is highly structured among populations. However, compared with Drosophila, we find that D. magna proteins appear to have a high proportion of weakly deleterious variants and do not show evidence of pervasive adaptive fixation across its entire range. This is true of the genome as a whole, and also of putative ‘arms race’ genes that often show elevated levels of adaptive substitution in other species. In addition to the likely impact of extensive, and previously documented, local adaptation, we speculate that these findings may reflect reduced efficacy of selection associated with cyclical asexual reproduction.
RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma
Authors: Mladek Ann C , Yan Huihuang , Tian Shulan , Decker Paul A , Burgenske Danielle M , Bakken Katrina , Hu Zeng , He Lihong , Connors Margaret A , Carlson Brett L , Wilson Jonathan , Bommi-Reddy Archana , Conery Andy , Eckel-Passow Jeanette E , Sarkaria Jann N , Kitange Gaspar J 
Published: February 2022

Abstract

Background
RBBP4 activates transcription by histone acetylation, but the partner histone acetyltransferases are unknown. Thus, we investigated the hypothesis that RBBP4 interacts with p300 in a complex in glioblastoma (GBM).

Methods
shRNA silencing of RBBP4 or p300 and RNAseq was used to identify genes co-regulated by RBBP4 and p300 in GBM43 patient-derived xenograft (PDX). RBBP4/p300 complex was demonstrated using proximity ligation assay (PLA) and ChIPseq delineated histone H3 acetylation and RBBP4/p300 complex binding in promoters/enhancers. Temozolomide (TMZ)-induced DNA double strand breaks (DSBs) were evaluated by γ-H2AX and proliferation by CyQuant and live cell monitoring assays. In vivo efficacy was based on survival of mice with orthotopic tumors.

Results
shRBBP4 and shp300 downregulated 4768 genes among which 1485 (31%) were commonly downregulated by both shRNAs, while upregulated genes were 2484, including 863 (35%) common genes. The pro-survival genes were the top-ranked among the downregulated genes, including C-MYC. RBBP4/p300 complex was demonstrated in the nucleus, and shRBBP4 or shp300 significantly sensitized GBM cells to TMZ compared to the control shNT in vitro (P &lt; .05). Moreover, TMZ significantly prolonged the survival of mice bearing GBM22-shRBBP4 orthotopic tumors compared with control shNT tumors (median shNT survival 52 days vs. median shRBBP4 319 days; P = .001). CREB-binding protein (CBP)/p300 inhibitor CPI-1612 suppressed H3K27Ac and RBBP4/p300 complex target proteins, including C-MYC, and synergistically sensitized TMZ in vitro. Pharmacodynamic evaluation confirmed brain penetration by CPI-1612 supporting further investigation to evaluate efficacy to sensitize TMZ.

Conclusions
RBBP4/p300 complex is present in GBM cells and is a potential therapeutic target.
Filamin A increases aggressiveness of human neuroblastoma
Authors: Bandaru Sashidar , Prajapati Bharat , Juvvuna Prasanna Kumar , Dosa Sandor , Kogner Per , Johnsen John I , Kanduri Chandrasekhar , Akyürek Levent M 
Published: February 2022

Abstract

Background
The actin-binding protein filamin A (FLNA) regulates oncogenic signal transduction important for tumor growth, but the role of FLNA in the progression of neuroblastoma (NB) has not been explored.

Methods
We analyzed FLNA mRNA expression in the R2 NB-database and FLNA protein expression in human NB tumors. We then silenced FLNA expression in human SKNBE2 and IMR32 NB cells by lentiviral vector encoding shRNA FLNA and assayed the cells for proliferation, migration, colony, spheroid formation, and apoptosis. SKNBE2 xenografts expressing or lacking FLNA in BALB/c nude mice were analyzed by both routine histopathology and immunohistochemistry.

Results
We observed shorter patient survival with higher expression of FLNA mRNA than patients with lower FLNA mRNA expression, and high-risk NB tumors expressed higher FLNA levels. Overexpression of FLNA increased proliferation of SH-SY5 NB cells. NB cell lines transfected with siRNA FLNA proliferated and migrated less, expressed lower levels of phosphorylated AKT and ERK1/2, formed smaller colonies and spheroids, as well as increased apoptosis. After inoculation of SKNBE2 cells infected with lentivirus expressing shRNA FLNA, size of NB tumors and number of proliferating cells were decreased. Furthermore, we identified STAT3 as an interacting partner of FLNA. Silencing FLNA mRNA reduced levels of NF-κB, STAT3 and MYCN, and increased levels of p53 and cleaved caspase 3.

Conclusion
Inhibition of FLNA impaired NB cell signaling and function and reduced NB tumor size in vivo, suggesting that drugs targeting either FLNA or its interaction with STAT3 may be useful in the treatment of NB.
Safety and Effectiveness of High-Dose Cefazolin in Patients With High Body Weight: A Retrospective Cohort Study
Authors: Ryu HaYoung , Mohayya Sana , Hong Thomas , Modi Mansi , Yang Jaehee , Abdul Azim Ahmed , Bhatt Pinki J , Brunetti Luigi , Narayanan Navaneeth 
Published: February 2022

Abstract

Background
Cefazolin is a commonly used antibiotic for the treatment of mild to severe infections. Despite the use of higher dose of cefazolin (3 g/dose) for surgical prophylaxis in patients with obesity, there is currently a paucity of data identifying the optimal dose to treat infections in this specific patient population.

Methods
This was a multicenter, retrospective cohort study of patients who received cefazolin at weight-based (up to 9 g/day) or standard doses (up to 6 g/day) for the treatment of bacteremia or skin and soft tissue infection (SSTI). Study groups were stratified by body weight and cefazolin dose received. Primary outcome was the composite of treatment-emergent adverse events (TEAEs) and secondary outcome was treatment failure rate.

Results
A total of 208 patients were included for study analysis. Fifty-nine patients had body weight &gt;120 kg. Of these, 33 received high-dose cefazolin while 26 received standard doses. The remaining 149 patients had body weight of ≤120 kg and received standard doses. The occurrence of TEAEs did not differ across the 3 groups. The study also did not find any difference between the rate of treatment failure between groups.

Conclusions
High-dose cefazolin (9 g/day) for the treatment of bacteremia or SSTIs in patients with high body weight was safe and well tolerated. Larger studies are needed to further explore the benefit of high-dose cefazolin in improving clinical outcomes.