bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alirocumab after acute coronary syndrome in patients with a history of heart failure
Authors: White Harvey D , Schwartz Gregory G , Szarek Michael , Bhatt Deepak L , Bittner Vera A , Chiang Chern-En , Diaz Rafael , Goodman Shaun G , Jukema Johan Wouter , Loy Megan , Pagidipati Neha , Pordy Robert , Ristić Arsen D , Zeiher Andreas M , Wojdyla Daniel M , Steg Philippe Gabriel ,   for the ODYSSEY OUTCOMES Investigators
Published: November 2021

Abstract

Aims
Patients with heart failure (HF) have not been shown to benefit from statins. In a post hoc analysis, we evaluated outcomes in ODYSSEY OUTCOMES in patients with vs. without a history of HF randomized to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab or placebo.

Methods and results
Among 18 924 patients with recent acute coronary syndrome (ACS) receiving intensive or maximum-tolerated statin treatment, the primary outcome of major adverse cardiovascular events (MACE) was compared in patients with or without a history of HF. The pre-specified secondary outcome of hospitalization for HF was also analysed. Overall, 2815 (14.9%) patients had a history of HF. Alirocumab reduced low-density lipoprotein cholesterol and lipoprotein(a) similarly in patients with or without HF. Overall, alirocumab reduced MACE compared with placebo [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.78–0.93; P = 0.0001]. This effect was observed among patients without a history of HF (HR: 0.78; 95% CI: 0.70–0.86; P &lt; 0.0001), but not in those with a history of HF (HR: 1.17; 95% CI: 0.97–1.40; P = 0.10) (P interaction = 0.0001). Alirocumab did not reduce hospitalization for HF, overall or in patients with or without prior HF.

Conclusion
Alirocumab reduced MACE in patients without a history of HF but not in patients with a history of HF. Alirocumab did not reduce hospitalizations for HF in either group. Patients with a history of HF are a high-risk group that does not appear to benefit from PCSK9 inhibition after ACS.
Frailty and Depression in Late Life: A High-Risk Comorbidity With Distinctive Clinical Presentation and Poor Antidepressant Response
Authors: Brown Patrick J , Ciarleglio Adam , Roose Steven P , Montes Garcia Carolina , Chung Sarah , Fernandes Sara , Rutherford Bret R 
Published: November 2021

Abstract

Background
To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness.

Methods
An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score &lt;10), and frailty (non/intermediate frail [0–2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories.

Results
A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10).

Conclusions
Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.
Sources of anxiety among health care workers in Tehran during the COVID-19 pandemic
Authors: Daneshvar Elahe , Otterbach Steffen , Alameddine Mohamad , Safikhani Hamidreza , Sousa-Poza Alfonso 
Published: November 2021

Abstract
By applying multivariate regression to 2020 survey data from four Tehran hospitals, we measure eight recognized sources of Coronavirus disease 2019 (COVID-19) pandemic-related anxiety among 723 healthcare workers (HCWs) with diverse sociodemographic characteristics employed across different hospital areas and positions. The most prominent anxiety source identified is the risk of workplace COVID-19 contraction and transmission to family, followed by uncertainty about organizational support for personal and family needs in the event of worker infection. A supplemental qualitative analysis of 68 respondents in the largest hospital identifies four additional anxiety sources, namely, health, finances, workload, and leadership. This evidence of the multifaceted nature of anxiety sources among HCWs highlights the differentiated approaches that hospital policymakers must take to combat anxiety.
Barriers and facilitators affecting physical activity among adults in Saudi Arabia during COVID-19 quarantine
Authors: Alqahtani Abdulfattah S , Baattaiah Baian A , Alharbi Mutasim D , Khan Fayaz , Aldhahi Monira I 
Published: November 2021

SummaryThe quarantine period in Saudi Arabia from May to June 2020 due to the coronavirus disease (COVID-19) pandemic prevented many people from engaging in physical activity (PA), which may have had negative effects on their health. Therefore, it is important to understand the factors, barriers, and facilitators affecting PA of people during quarantine. This cross-sectional study was conducted using an electronic survey that was distributed to adults between 18 and 69 years old. The survey included demographic-related questions and the International Physical Activity Questionnaire-Short Form. The survey was completed by 1859 participants ranging in age from 18 to 69 years old (42.5% male, 57.5% female). The major factors influencing exercise were being male (odds ratio [OR] = 1.26; 95% confidence interval [CI] 1.03–1.53), being single (OR = 1.37; 95% CI 1.12–1.67), completing higher education at a Master/Doctorate level (OR = 1.83; 95% CI 1.23–2.72), and being resilient (OR = 1.05; 95% CI 1.03–1.08). The facilitators for doing regular exercise were having enough space at home (OR = 1.62), free time (OR = 1.77), good motivation (OR = 1.56), and being free from work (OR = 1.43) and family responsibilities (OR = 1.40). Sex, marital status, level of education and resilience were important factors affecting the type and level of PA during the quarantine period resulting from the COVID-19 pandemic.
The F-box protein, FBXO7, is required to maintain chromosome stability in humans
Authors: Palmer Michaela C L , Neudorf Nicole M , Farrell Ally C , Razi Tooba , Lichtensztejn Zelda , McManus Kirk J 
Published: November 2021

Abstract
Despite the high morbidity and mortality rates associated with colorectal cancer (CRC), the aberrant genes and mechanisms driving CRC pathogenesis remain poorly understood. Chromosome instability (CIN), or ongoing changes in chromosome numbers, is a predominant form of genome instability associated with ~85% of CRCs, suggesting it may be a key mechanism driving CRC oncogenesis. CIN enables the acquisition of copy number alterations conferring selective growth, proliferation and survival advantages that promote cellular transformation. Despite these associations, the aberrant genes underlying CIN remain largely unknown. Candidate CIN gene FBXO7 encodes an F-box protein, a subunit of the SKP1-CUL1-FBOX (SCF) complex that confers substrate specificity to the complex and targets proteins for subsequent degradation by the 26S proteasome. Recently, the genes encoding the three core SCF complex members were identified as CIN genes; however, it is unknown whether F-box proteins exhibit similar integral roles in maintaining chromosome stability. Using short- small interfering RNA (siRNA) and long- (CRISPR/Cas9) term approaches, we show that reduced FBXO7 expression induces CIN in various colonic epithelial cell contexts, whereas FBXO7 knockout clones also exhibit hallmarks associated with cellular transformation, namely increased clonogenic and anchorage-independent growth. Collectively, these data demonstrate that FBXO7 is required to maintain genome stability identifying FBXO7 a novel CIN gene whose reduced expression may contribute to CRC development and progression.
Hear No Evil, See No Evil: Motivated Reasoning, Drone Warfare, and the Effects of Message Framing on US Public Opinion
Authors: Rowling Charles M , Blauwkamp Joan M 
Published: November 2021

Abstract
We conducted a poll with a survey-experimental design to examine whether variations in how the US policy of drone warfare was framed significantly impacted public support. Consistent with scholarship on motivated reasoning and valence framing, we find that respondents could be primed to express significantly greater or lesser support based on questions that either affirmed or challenged: the strategic value, international legality, domestic legality, or technological capability of drone strikes or whether they cause collateral damage. While affirming the policy generally had insignificant effects on opinion reports, compared to the control group, challenges to the policy produced significant decreases in American support for drone warfare. These results illustrate the importance of exposing citizens to contested discourse on controversial public policy.
Growth of Local Height Functions Along Orbits of Self-Morphisms on Projective Varieties
Authors: Matsuzawa Yohsuke 
Published: November 2021

AbstractWe consider the limit $$ \begin{align*} & \lim_{n\to \infty} \sum_{v\in S} \lambda_{Y,v}(f^{n}(x))/h_{H}(f^{n}(x)) \end{align*}$$where $f \colon X \longrightarrow X$ is a surjective self-morphism on a smooth projective variety $X$ over a number field, $S$ is a finite set of places, $ \lambda _{Y,v}$ is a local height function associated with a proper closed subscheme $Y \subset X$, and $h_{H}$ is an ample height function on $X$. We give a geometric condition that ensures that the limit is zero, unconditionally when $\dim Y=0$ and assuming Vojta’s conjecture when $\dim Y\geq 1$. In particular, we prove (one is unconditional, one is assuming Vojta’s conjecture) dynamical Lang–Siegel type theorems, that is, the relative sizes of coordinates of orbits on ${{\mathbb {P}}}^{N}$ are asymptotically the same with trivial exceptions. These results are higher dimensional generalization of Silverman’s classical result.
Utilization of CRISPR interference to investigate the contribution of genes to pathogenesis in a macrophage model of Mycobacterium tuberculosis infection
Authors: Cheung Chen-Yi , McNeil Matthew B , Cook Gregory M 
Published: November 2021

Abstract

Objectives
There is an urgent need for novel drugs that target unique cellular pathways to combat infections caused by Mycobacterium tuberculosis. CRISPR interference (CRISPRi)-mediated transcriptional repression has recently been developed for use in mycobacteria as a genetic tool for identifying and validating essential genes as novel drug targets. Whilst CRISPRi has been applied to extracellular bacteria, no studies to date have determined whether CRISPRi can be used in M. tuberculosis infection models.

Methods
Using the human monocytic macrophage-like THP-1 cell line as a model for M. tuberculosis infection we investigated if CRISPRi can be activated within intracellular M. tuberculosis.

Results
The transcriptional repression of two candidate M. tuberculosis genes, i.e. mmpL3 and qcrB, leads to a reduction in viable M. tuberculosis within infected THP-1 cells. The reduction in viable colonies is dependent on both the level of CRISPRi-mediated repression and the duration of repression.

Conclusions
These results highlight the utility of CRISPRi in exploring mycobacterial gene function and essentiality under a variety of conditions pertinent to host infection.
Impact of Rapid Susceptibility Testing System on the Management of Gram-Negative Bacteremia in a Network of Community Hospitals
Authors: Ganapathiraju Ice , Weichman Brittani , Rogers Kathie L , Bushman Amanda M , Rosa Rossana 
Published: November 2021

Abstract

Background
Rapid initiation of optimal antimicrobial therapy is crucial for the management of Gram-negative (GN) bacteremia. We aimed to evaluate the impact of Accelerate PhenoTM (AxDx) system on change in therapy and length of stay among patients with GN bacteremia.

Methods
We conducted a retrospective cohort study of adult patients hospitalized who had at least 1 blood culture with presence of Enterobacterales. We compared clinical outcomes among patients who had their blood cultures processed through standard methods alone vs AxDx.

Results
We identified 255 bacteremia episodes among 243 unique patients. In the AxDx group, 31.1% of patients had deescalation of antibiotics within 48 h from blood culture collection compared to 20.0% of patients in the control group (P = 0.09). We found no impact of AxDx on the odds of deescalation at 48 h from blood culture collection [odds ratio (OR) 1.80 (95% CI 0.91–3.56), P = 0.09] or Gram stain report [OR 1.61 (95% CI 0.86–3.01), P = 0.14]. Escalation in therapy at 48 h from blood culture collection occurred in 16.8% and 16.9% of patients in the AxDx and control groups, respectively (P = 0.99). There was no impact on the odds of escalation at 48 h from blood culture collection [OR 0.99 (95% CI 0.47–2.11), P = 0.99] or Gram stain report [OR 1.26 (95% CI 0.57–2.80), P = 0.57]. No differences were seen in length of stay and mortality between the 2 groups.

Conclusions
The impact of rapid identification and susceptibility technologies may differ according to the setting in which they are implemented.
Virtual Reality Therapy to Control Burn Pain: Systematic Review of Randomized Controlled Trials
Authors: de Jesus Catalã Cristina Antonia , Pan Raquel , Rossetto Kron-Rodrigues Meline , de Oliveira Freitas Noélle 
Published: November 2021

Abstract
Virtual reality therapy has been shown to be an excellent alternative to non-pharmacological treatment for the control of burn pain. The objective was to evaluate the effects of virtual reality therapy on pain control in people who have suffered burns published in the scientific literature. Systematic review carried out as recommended by Cochrane. The search was carried out in the Embase, PubMed, Lilacs, and Cochrane Library databases, in the period from March 2021. Randomized clinical trials were included without language restriction and year of publication. The risk of bias was assessed using the Cochrane tool. Of the 3755 articles found, only 17 articles were selected for reading in full. Of these, only four articles met the inclusion criteria. The results of the studies showed that the use of virtual reality therapy reduced the intensity of pain in children and adolescents with burns, despite the fact that most results are not statistically significant. No selected study had a high risk of bias. Virtual reality therapy has been shown to be effective in controlling pain, reducing the time spent thinking about it and greater distraction during the procedures. However, most randomized clinical trials results were not statistically significant in at least one of the moments when pain was assessed. It is noteworthy that randomized clinical trials are still necessary to administer virtual reality therapy, especially in adults.
Are genome-edited micro-organisms covered by Directive 2009/41/EC?—implications of the CJEU’s judgment in the case C-528/16 for the contained use of genome-edited micro-organisms
Authors: Dederer Hans-Georg , Hamburger David 
Published: November 2021

Abstract
In its judgement of July 25, 2018, the Court of Justice of the European Union (CJEU) in the case C-528/16, Confédération paysanne and Others, held that organisms obtained by techniques of mutagenesis are ‘genetically modified organisms’ (GMOs). It follows from the Court’s reasoning that genome-edited organisms, ie organisms resulting from techniques of directed mutagenesis, are GMOs as well and are fully regulated by Directive 2001/18/EC. However, Directive 2001/18/EC only stipulates rules for the deliberate release and placing on the market of GMOs. By contrast, the European Union (EU) has adopted a separate set of rules laid down in Directive 2009/41/EC, which apply to the so-called ‘contained use’ of ‘genetically modified micro-organisms’ (GMMs). Whether also genome-edited micro-organisms are GMMs and, thus, subject to Directive 2009/41/EC is of crucial importance since contained use activities with genome-edited micro-organisms are currently carried out extensively, eg in laboratories and research facilities. An in-depth legal analysis shows that the CJEU’s interpretation of Directive 2001/18/EC can be extended to Directive 2009/41/EC which means that, in the end, genome-edited micro-organisms are GMMs invariably subject to Directive 2009/41/EC.
System parameters of three short-period cataclysmic variable stars
Authors: Wild J F , Littlefair S P , Ashley R P , Breedt E , Brown A J , Dhillon V S , Dyer M J , Green M J , Kerry P , Marsh T R , Parsons S G , Sahman D I 
Published: November 2021

ABSTRACT
Using photometric ULTRACAM observations of three new short-period cataclysmic variables (CVs), we model the primary eclipse light curves to extract the orbital separation, masses, and radii of their component stars. We find donor masses of $0.060\pm 0.008\, {\rm M_\odot }$, $0.042\pm 0.001\, {\rm M_\odot }$, and $0.042\pm 0.004\, {\rm M_\odot }$, two being very low-mass sub-stellar donors, and one within 2σ of the hydrogen burning limit. All three of the new systems lie close to the empirical evolutionary sequence that has emerged from observations of the last decade. We briefly re-evaluate the long-standing discrepancy between observed donor mass and radius data, and theoretical CV evolutionary tracks. By looking at the difference in the observed period at each mass and the period predicted by the modelled evolutionary sequences, we qualitatively examine the form of excess angular momentum loss that is missing from the models below the period gap. We show indications that the excess angular momentum loss missing from CV models grows in importance relative to gravitational losses as the period decreases. Detailed CV evolutionary models are necessary to draw more quantitative conclusions in the future.
Ensembl Genomes 2022: an expanding genome resource for non-vertebrates
Authors: Yates Andrew D , Allen James , Amode Ridwan M , Azov Andrey G , Barba Matthieu , Becerra Andrés , Bhai Jyothish , Campbell Lahcen I , Carbajo Martinez Manuel , Chakiachvili Marc , Chougule Kapeel , Christensen Mikkel , Contreras-Moreira Bruno , Cuzick Alayne , Da Rin Fioretto Luca , Davis Paul , De Silva Nishadi H , Diamantakis Stavros , Dyer Sarah , Elser Justin , Filippi Carla V , Gall Astrid , Grigoriadis Dionysios , Guijarro-Clarke Cristina , Gupta Parul , Hammond-Kosack Kim E , Howe Kevin L , Jaiswal Pankaj , Kaikala Vinay , Kumar Vivek , Kumari Sunita , Langridge Nick , Le Tuan , Luypaert Manuel , Maslen Gareth L , Maurel Thomas , Moore Benjamin , Muffato Matthieu , Mushtaq Aleena , Naamati Guy , Naithani Sushma , Olson Andrew , Parker Anne , Paulini Michael , Pedro Helder , Perry Emily , Preece Justin , Quinton-Tulloch Mark , Rodgers Faye , Rosello Marc , Ruffier Magali , Seager James , Sitnik Vasily , Szpak Michal , Tate John , Tello-Ruiz Marcela K , Trevanion Stephen J , Urban Martin , Ware Doreen , Wei Sharon , Williams Gary , Winterbottom Andrea , Zarowiecki Magdalena , Finn Robert D , Flicek Paul 
Published: November 2021

AbstractEnsembl Genomes (https://www.ensemblgenomes.org) provides access to non-vertebrate genomes and analysis complementing vertebrate resources developed by the Ensembl project (https://www.ensembl.org). The two resources collectively present genome annotation through a consistent set of interfaces spanning the tree of life presenting genome sequence, annotation, variation, transcriptomic data and comparative analysis. Here, we present our largest increase in plant, metazoan and fungal genomes since the project's inception creating one of the world's most comprehensive genomic resources and describe our efforts to reduce genome redundancy in our Bacteria portal. We detail our new efforts in gene annotation, our emerging support for pangenome analysis, our efforts to accelerate data dissemination through the Ensembl Rapid Release resource and our new AlphaFold visualization. Finally, we present details of our future plans including updates on our integration with Ensembl, and how we plan to improve our support for the microbial research community. Software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license). Data updates are synchronised with Ensembl's release cycle.
Sensory neuron transcriptomes reveal complex neuron-specific function and regulation of mec-2/Stomatin splicing
Authors: Liang Xiaoyu , Calovich-Benne Canyon , Norris Adam 
Published: November 2021

Abstract
The function and identity of a cell is shaped by transcription factors controlling transcriptional networks, and further shaped by RNA binding proteins controlling post-transcriptional networks. To overcome limitations inherent to analysis of sparse single-cell post-transcriptional data, we leverage the invariant Caenorhabditis elegans cell lineage, isolating thousands of identical neuron types from thousands of isogenic individuals. The resulting deep transcriptomes facilitate splicing network analysis due to increased sequencing depth and uniformity. We focus on mechanosensory touch-neuron splicing regulated by MEC-8/RBPMS. We identify a small MEC-8-regulated network, where MEC-8 establishes touch-neuron isoforms differing from default isoforms found in other cells. MEC-8 establishes the canonical long mec-2/Stomatin isoform in touch neurons, but surprisingly the non-canonical short isoform predominates in other neurons, including olfactory neurons, and mec-2 is required for olfaction. Forced endogenous isoform-specific expression reveals that the short isoform functions in olfaction but not mechanosensation. The long isoform is functional in both processes. Remarkably, restoring the long isoform completely rescues mec-8 mutant mechanosensation, indicating a single MEC-8 touch-neuron target is phenotypically relevant. Within the long isoform we identify a cassette exon further diversifying mec-2 into long/extra-long isoforms. Neither is sufficient for mechanosensation. Both are simultaneously required, likely functioning as heteromers to mediate mechanosensation.