bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant versus definitive chemoradiation in locally advanced esophageal cancer for patients of advanced age or significant comorbidities
Authors: Jensen Garrett L , Hammonds Kendall P , Haque Waqar 
Published: July 2022

Summary
The addition of surgery to chemoradiation for esophageal cancer has not shown a survival benefit in randomized trials. Patients with more comorbidities or advanced age are more likely to be given definitive chemoradiation due to surgical risk. We aimed to identify subsets of patients in whom the addition of surgery to chemoradiation does not provide an overall survival (OS) benefit. The National Cancer Database was queried for patients with locally advanced esophageal cancer who received either definitive chemoradiation or neoadjuvant chemoradiation followed by surgery. Bivariate analysis was used to assess the association between patient characteristics and treatment groups. Log-rank tests and Cox proportional hazards models were performed to assess for differences in survival. A total of 15,090 with adenocarcinoma and 5,356 with squamous cell carcinoma met the inclusion criteria. Patients treated with neoadjuvant chemoradiation and surgery had significantly improved survival by Cox proportional hazards model regardless of histology if &lt;50, 50–60, 61–70, or 71–80 years old. There was no significant benefit or detriment in patients 81–90 years old. Survival advantage was also significant with a Charlson/Deyo comorbidity condition score of 0, 1, 2, and ≥3 in adenocarcinoma squamous cell carcinoma with scores of 2 or ≥3 had no significant benefit or detriment. Patients 81–90 years old or with squamous cell carcinoma and a Charlson/Deyo comorbidity score ≥ 2 lacked an OS benefit from neoadjuvant chemoradiation followed by surgery compared with definitive chemoradiation. Careful consideration of esophagectomy-specific surgical risks should be used when recommending treatment for these patients.
Influence of the healthcare pathway on the outcome of patients with infective endocarditis
Authors: Arregle Florent , Iline Nicolas , Giorgi Roch , Philip Mary , Hubert Sandrine , Gouriet Frederique , Casalta Jean Paul , Collart Frédéric , Riberi Alberto , Martel Hélène , Renard Sébastien , Camoin Laurence , Casalta Anne Claire , Lepidi Hubert , Raoult Didier , Drancourt Michel , Habib Gilbert 
Published: July 2022

Abstract

Aims
To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized.

Methods and results
In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P &lt; 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P &lt; 0.001) and had more comorbidities (P &lt; 0.001) than patients treated in referral centres.

Conclusion
Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.
Interaction between secondary mitral regurgitation and left atrial function and their prognostic implications after cardiac resynchronization therapy
Authors: Stassen Jan , Galloo Xavier , Hirasawa Kensuke , van der Bijl Pieter , Leon Martin B , Marsan Nina Ajmone , Bax Jeroen J 
Published: July 2022

AbstractAimsLeft atrial (LA) function is a strong prognostic marker in patients with heart failure and functional mitral regurgitation (MR). Although cardiac resynchronization therapy (CRT) has shown to improve MR severity, the interaction between a reduction in MR severity and an increase in LA function, as well as its association with outcomes, has not been investigated.Methods and resultsLA reservoir strain (RS) was evaluated with speckle tracking echocardiography in patients with at least moderate functional MR undergoing CRT implantation. MR improvement was defined as at least 1 grade improvement in MR severity at 6 months after CRT implantation. The primary endpoint was all-cause mortality. A total of 340 patients (mean age 66 ± 10 years, 73% male) were included, of whom 200 (59%) showed MR improvement at 6 months follow-up. On multivariable analysis, an improvement in MR severity was independently associated with an increase in LARS (odds ratio 1.008; 95% confidence interval 1.003–1.013; P = 0.002). After multivariable adjustment, including baseline and follow-up variables, an increase in LARS was significantly associated with lower mortality. MR improvers showing LARS increasement had the lowest mortality rate, whereas outcomes were not significantly different between MR non-improvers and MR improvers showing no LARS increasement (P = 0.236).ConclusionA significant reduction in MR severity at 6 months after CRT implantation is independently associated with an increase in LARS. In addition, an increase in LARS is independently associated with lower all-cause mortality in patients with heart failure and significant functional MR.
Vascular senescence in progeria: role of endothelial dysfunction
Authors: Xu Qiu , Mojiri Anahita , Boulahouache Luay , Morales Elisa , Walther Brandon K , Cooke John P 
Published: July 2022

Abstract

Aims
Hutchinson–Gilford progeria syndrome (HGPS) is a pre-mature aging disorder caused by the mutation of the LMNA gene leading to an irreversibly farnesylated lamin A protein: progerin. The major causes of death in HGPS are coronary and arterial occlusive disease. In the murine model of HGPS, vascular smooth muscle cell (VSMC) loss is the primary vascular manifestation, which is different from the arterial occlusive disease seen in older patients.

Methods and results
To identify the mechanisms of HGPS vascular disease in humans, we differentiated isogenic endothelial cells (ECs) and VSMCs from HGPS-induced pluripotent stem cells (iPSCs) and control-iPSCs. Both HGPS-ECs and HGPS-VSMCs manifested cellular hallmarks of aging, including dysmorphic nuclei, impaired proliferation, increased β-galactosidase staining, shortened telomeres, up-regulated secretion of inflammatory cytokines, increased DNA damage, loss of heterochromatin, and altered shelterin protein complex (SPC) expression. However, at similar days after differentiation, even with lower levels of progerin, HGPS-ECs manifested more severe signs of senescence, as indicated in part by a higher percentage of β-galactosidase positive cells, shorter telomere length, and more DNA damage signals. We observed increased γH2A.X binding to RAP1 and reduced TRF2 binding to lamin A in HGPS-ECs but not in HGPS-VSMCs. The expression of γH2A.X was greater in HGPS-ECs than in HGPS-VSMCs and is associated with greater telomere shortening, impaired SPC interactions, and loss of heterochromatin.

Conclusion
Although progerin expression has a deleterious effect on both ECs and VSMCs, the dysfunction is greater in HGPS-ECs compared with HGPS-VSMCs. This study suggests that an endothelial-targeted therapy may be useful for HGPS patients.
Resolving Conflicting Emotions: Obama's Quandaries on the Red Line and the Fight against ISIS
Authors: Beauregard Philippe 
Published: July 2022

AbstractThe study of emotions in foreign policymaking has emphasized dominant discrete emotions and how they each lead to specific action tendencies. Scholars often focus on one emotion to explain decisions and have an additive view of emotions. This article argues that decision-makers often feel conflicting emotions and that emotions are not simply additive. What are conflicting emotions’ consequences for foreign policymaking? How are these conflicts resolved? The cases of President Obama's response to the Syrian chemical weapon attack in 2013 and the rise of ISIS in 2014 provide an occasion to study these questions on major security issues surrounding military intervention. This article argues that when decision-makers feel conflicted emotions their anxiety level rises, and that they are likely to attempt to gain time through procrastination, to resolve their conflict by focusing their attention on new developments, and to seek support to bolster confidence in their decision.
Modular safe-harbor transgene insertion for targeted single-copy and extrachromosomal array integration in Caenorhabditis elegans
Authors: El Mouridi Sonia , Alkhaldi Faisal , Frøkjær-Jensen Christian 
Published: July 2022

Abstract
Efficient and reproducible transgenesis facilitates and accelerates research using genetic model organisms. Here, we describe a modular safe-harbor transgene insertion (MosTI) for use in Caenorhabditis elegans which improves targeted insertion of single-copy transgenes by homology directed repair and targeted integration of extrachromosomal arrays by nonhomologous end-joining. MosTI allows easy conversion between selection markers at insertion site and a collection of universal targeting vectors with commonly used promoters and fluorophores. Insertions are targeted at three permissive safe-harbor intergenic locations and transgenes are reproducibly expressed in somatic and germ cells. Chromosomal integration is mediated by CRISPR/Cas9, and positive selection is based on a set of split markers (unc-119, hygroR, and gfp) where only animals with chromosomal insertions are rescued, resistant to antibiotics, or fluorescent, respectively. Single-copy insertion is efficient using either constitutive or heat-shock inducible Cas9 expression (25–75%) and insertions can be generated from a multiplexed injection mix. Extrachromosomal array integration is also efficient (7–44%) at modular safe-harbor transgene insertion landing sites or at the endogenous unc-119 locus. We use short-read sequencing to estimate the plasmid copy numbers for 8 integrated arrays (6–37 copies) and long-read Nanopore sequencing to determine the structure and size (5.4 Mb) of 1 array. Using universal targeting vectors, standardized insertion strains, and optimized protocols, it is possible to construct complex transgenic strains which should facilitate the study of increasingly complex biological problems in C. elegans.
Quantitative evaluation of nonlinear methods for population structure visualization and inference
Authors: Ubbens Jordan , Feldmann Mitchell J , Stavness Ian , Sharpe Andrew G 
Published: July 2022

Abstract
Population structure (also called genetic structure and population stratification) is the presence of a systematic difference in allele frequencies between subpopulations in a population as a result of nonrandom mating between individuals. It can be informative of genetic ancestry, and in the context of medical genetics, it is an important confounding variable in genome-wide association studies. Recently, many nonlinear dimensionality reduction techniques have been proposed for the population structure visualization task. However, an objective comparison of these techniques has so far been missing from the literature. In this article, we discuss the previously proposed nonlinear techniques and some of their potential weaknesses. We then propose a novel quantitative evaluation methodology for comparing these nonlinear techniques, based on populations for which pedigree is known a priori either through artificial selection or simulation. Based on this evaluation metric, we find graph-based algorithms such as t-SNE and UMAP to be superior to principal component analysis, while neural network-based methods fall behind.
Tourmaline: A containerized workflow for rapid and iterable amplicon sequence analysis using QIIME 2 and Snakemake
Authors: Thompson Luke R , Anderson Sean R , Den Uyl Paul A , Patin Nastassia V , Lim Shen Jean , Sanderson Grant , Goodwin Kelly D 
Published: July 2022

Abstract

Background
Amplicon sequencing (metabarcoding) is a common method to survey diversity of environmental communities whereby a single genetic locus is amplified and sequenced from the DNA of whole or partial organisms, organismal traces (e.g., skin, mucus, feces), or microbes in an environmental sample. Several software packages exist for analyzing amplicon data, among which QIIME 2 has emerged as a popular option because of its broad functionality, plugin architecture, provenance tracking, and interactive visualizations. However, each new analysis requires the user to keep track of input and output file names, parameters, and commands; this lack of automation and standardization is inefficient and creates barriers to meta-analysis and sharing of results.

Findings
We developed Tourmaline, a Python-based workflow that implements QIIME 2 and is built using the Snakemake workflow management system. Starting from a configuration file that defines parameters and input files—a reference database, a sample metadata file, and a manifest or archive of FASTQ sequences—it uses QIIME 2 to run either the DADA2 or Deblur denoising algorithm; assigns taxonomy to the resulting representative sequences; performs analyses of taxonomic, alpha, and beta diversity; and generates an HTML report summarizing and linking to the output files. Features include support for multiple cores, automatic determination of trimming parameters using quality scores, representative sequence filtering (taxonomy, length, abundance, prevalence, or ID), support for multiple taxonomic classification and sequence alignment methods, outlier detection, and automated initialization of a new analysis using previous settings. The workflow runs natively on Linux and macOS or via a Docker container. We ran Tourmaline on a 16S ribosomal RNA amplicon data set from Lake Erie surface water, showing its utility for parameter optimization and the ability to easily view interactive visualizations through the HTML report, QIIME 2 viewer, and R- and Python-based Jupyter notebooks.

Conclusion
Automated workflows like Tourmaline enable rapid analysis of environmental amplicon data, decreasing the time from data generation to actionable results. Tourmaline is available for download at github.com/aomlomics/tourmaline.
ETS1 loss in mice impairs cardiac outflow tract septation via a cell migration defect autonomous to the neural crest
Authors: Lin Lizhu , Pinto Antonella , Wang Lu , Fukatsu Kazumi , Yin Yan , Bamforth Simon D , Bronner Marianne E , Evans Sylvia M , Nie Shuyi , Anderson Robert H , Terskikh Alexey V , Grossfeld Paul D 
Published: July 2022

Abstract
Ets1 deletion in some mouse strains causes septal defects and has been implicated in human congenital heart defects in Jacobsen syndrome, in which one copy of the Ets1 gene is missing. Here, we demonstrate that loss of Ets1 in mice results in a decrease in neural crest (NC) cells migrating into the proximal outflow tract cushions during early heart development, with subsequent malalignment of the cushions relative to the muscular ventricular septum, resembling double outlet right ventricle (DORV) defects in humans. Consistent with this, we find that cultured cardiac NC cells from Ets1 mutant mice or derived from iPS cells from Jacobsen patients exhibit decreased migration speed and impaired cell-to-cell interactions. Together, our studies demonstrate a critical role for ETS1 for cell migration in cardiac NC cells that are required for proper formation of the proximal outflow tracts. These data provide further insights into the molecular and cellular basis for development of the outflow tracts, and how perturbation of NC cells can lead to DORV.
Outcomes following surgical repair of absent pulmonary valve syndrome: 30 years of experience from a Swedish tertiary referral centre
Authors: Avdikos Vasileios , Johansson Ramgren Jens , Hanséus Katarina , Malm Torsten , Liuba Petru 
Published: July 2022

Abstract
Surgical approach with reduction pulmonary artery plasty and valved conduit in patients with respiratory compromise prior to repair is associated with excellent long-term survival at the cost of a higher reintervention rate.

OBJECTIVES
Absent pulmonary valve syndrome is a rare congenital heart defect with pulmonary artery dilatation and secondary airway compression. Although preoperative respiratory support and early surgical repair with pulmonary arterioplasty are often required in patients with airway compromise, the need for extensive plasty in these patients and for plasty in general in those with no or mild respiratory issues remains debatable.

METHODS
We performed a retrospective survey of patients with this diagnosis and repair from 1988 to 2018.

RESULTS
Twenty patients were identified. The median age and weight at repair were 0.8 (0.1–2.4) years and 7.0 (2.5–13.8) kg and included a valved conduit in 17 (85%) patients and a transannular patch in 3 patients. Five (29%) patients were ventilator-dependent prior to repair at the age of 0.3 (0.1–0.4) years. Pulmonary arterioplasty was performed in 7 patients (35%), including all 5 with ventilator dependency and 2 with respiratory symptoms due to recurrent infections. Two patients (10%) with preoperative ventilator dependency underwent extensive intrahilar arterioplasty. Preoperative ventilator dependency was associated with earlier repair and reinterventions (P &lt; 0.05). There were 3 late deaths among cases with repair after 2000 (n = 14), none with preoperative ventilator dependency.

CONCLUSIONS
The long-term outcomes of patients with this rare defect are good, comparable to those of other previous studies. Reduction pulmonary arterioplasty, which in this study was used only in patients with respiratory distress and ventilator dependency, is associated with excellent survival. Reinterventions are common in these patients.
Splitting Hairs with Transcendental Entire Functions
Authors: Pardo-Simón Leticia 
Published: July 2022

Abstract
In recent years, there has been significant progress in the understanding of the dynamics of transcendental entire functions with bounded postsingular set. In particular, for certain classes of such functions, a complete description of their topological dynamics in terms of a simpler model has been given inspired by methods from polynomial dynamics. In this paper, and for the 1st time, we give analogous results in cases when the postsingular set is unbounded. More specifically, we show that if $f$ is of finite order, has bounded criticality on its Julia set $J(f)$, and its singular set consists of finitely many critical values that escape to infinity and satisfy a certain separation condition, then $J(f)$ is a collection of dynamic rays or hairs, which split at critical points, together with their corresponding landing points. In fact, our result holds for a much larger class of functions with bounded singular set. Moreover, this result is a consequence of a significantly more general one: we provide a topological model for the action of $f$ on its Julia set.
Elliptic Stable Envelopes of Affine Type A Quiver Varieties
Authors: Dinkins Hunter 
Published: July 2022

Abstract
We generalize Smirnov’s formula for the elliptic stable envelopes of the Hilbert scheme of points in $\mathbb {C}^2$ to the case of affine type $A$ Nakajima quiver varieties constructed with positive stability condition. We allow for arbitrary choices of polarization and a fairly general choice of chamber. This paper is a companion to the Maple code developed by the author, which implements the formulas described in this paper.
Antimicrobial activity of cefepime/zidebactam (WCK 5222), a β-lactam/β-lactam enhancer combination, against clinical isolates of Gram-negative bacteria collected worldwide (2018–19)
Authors: Sader Helio S , Mendes Rodrigo E , Duncan Leonard R , Carvalhaes Cecilia G , Castanheria Mariana 
Published: July 2022

Abstract

Background
Zidebactam, a bicyclo-acyl hydrazide β-lactam ‘enhancer’ antibiotic, in combination with cefepime (WCK 5222) is under clinical development for the treatment of resistant Gram-negative infections.

Objectives
To evaluate the in vitro activity of cefepime/zidebactam and comparators against 24 220 Gram-negative bacteria.

Methods
Organisms were consecutively collected in 2018–19 from 137 medical centres located in the USA (n = 9140), Western Europe (W-EU; n = 5929), Eastern Europe (E-EU; n = 3036), the Asia-Pacific region (APAC; n = 3791) and Latin America (LATAM; n = 2324). The isolates were susceptibility tested using the broth microdilution method as part of the SENTRY Program. Cefepime/zidebactam was tested at a 1:1 ratio.

Results
Cefepime/zidebactam was highly active against Enterobacterales (MIC50/90 0.03/0.25 mg/L; 99.9% inhibited at ≤8 mg/L) and retained potent activity against carbapenem-resistant Enterobacterales (CRE) isolates (97.8% inhibited at ≤8 mg/L). CRE rates varied widely from 1.1% in the USA to 1.9% in W-EU, 3.6% in APAC and 14.6% in E-EU (3.9% overall). The most common carbapenemase genes observed overall were blaKPC (37.6% of CRE), blaOXA-48-like (30.0%) and blaNDM (23.8%). Resistance to ceftazidime/avibactam among CRE was elevated in APAC (64.8%), E-EU (25.5%) and LATAM (20.7%). Against Pseudomonas aeruginosa, cefepime/zidebactam inhibited 99.2% of isolates at ≤8 mg/L and susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was lowest in E-EU (83.9% and 82.0%, respectively). Cefepime/zidebactam exhibited good activity against Stenotrophomonas maltophilia (80.0% inhibited at ≤8 mg/L) and Burkholderia cepacia (89.4% inhibited at ≤8 mg/L).

Conclusions
Cefepime/zidebactam demonstrated potent in vitro activity against a large worldwide collection of contemporary clinical isolates of Gram-negative bacteria.