bluuebunny/crossref_metadata_2025_split huggingface dataset:
SuperMICE: An Ensemble Machine Learning Approach to Multiple Imputation by Chained Equations
Authors: Laqueur Hannah S , Shev Aaron B , Kagawa Rose M C 
Published: November 2021

AbstractResearchers often face the problem of how to address missing data. Multiple imputation is a popular approach, with multiple imputation by chained equations (MICE) being among the most common and flexible methods for execution. MICE iteratively fits a predictive model for each variable with missing values, conditional on other variables in the data. In theory, any imputation model can be used to predict the missing values. However, if the predictive models are incorrectly specified, they may produce biased estimates of the imputed data, yielding inconsistent parameter estimates and invalid inference. Given the set of modeling choices that must be made in conducting multiple imputation, in this paper we propose a data-adaptive approach to model selection. Specifically, we adapt MICE to incorporate an ensemble algorithm, Super Learner, to predict the conditional mean for each missing value, and we also incorporate a local kernel-based estimate of variance. We present a set of simulations indicating that this approach produces final parameter estimates with lower bias and better coverage than other commonly used imputation methods. These results suggest that using a flexible machine learning imputation approach can be useful in settings where data are missing at random, especially when the relationships among the variables are complex.
AI-based forecasting of ethanol fermentation using yeast morphological data
Authors: Itto-Nakama Kaori , Watanabe Shun , Kondo Naoko , Ohnuki Shinsuke , Kikuchi Ryota , Nakamura Toru , Ogasawara Wataru , Kasahara Ken , Ohya Yoshikazu 
Published: November 2021

ABSTRACT
Several industries require getting information of products as soon as possible during fermentation. However, the trade-off between sensing speed and data quantity presents challenges for forecasting fermentation product yields. In this study, we tried to develop AI models to forecast ethanol yields in yeast fermentation cultures, using cell morphological data. Our platform involves the quick acquisition of yeast morphological images using a nonstaining protocol, extraction of high-dimensional morphological data using image processing software, and forecasting of ethanol yields via supervised machine learning. We found that the neural network algorithm produced the best performance, which had a coefficient of determination of &gt;0.9 even at 30 and 60 min in the future. The model was validated using test data collected using the CalMorph-PC(10) system, which enables rapid image acquisition within 10 min. AI-based forecasting of product yields based on cell morphology will facilitate the management and stable production of desired biocommodities.
Development and Validation of a Stability-Indicating Reversed-Phase Ultra High Pressure Liquid Chromatography Method for Assay of Delmopinol Hydrochloride and Estimation of Its Related Substances in Commercial Bulk Batches
Authors: Zhuang Jinyou , Rustum Abu M 
Published: November 2021

Abstract
Delmopinol hydrochloride is widely used as an active ingredient (AI) in many human oral hygiene products. To the best of our knowledge (via literature search), there is no stability-indicating liquid chromatography method available in the public domain for assay and estimation of related substances of Delmopinol hydrochloride. A fast stability-indicating Reversed-Phase Ultra High-Performance Liquid Chromatography (RP-UHPLC) method has been developed and validated for identification, assay and estimation of related substances in commercial bulk batches of this AI. The major peak of the AI and its related compounds are adequately separated in 6 min by a gradient elution on a hybrid silica-based C18 column (Waters Acquity UPLC® BEH C18, 50mm × 2.1 mm I.D., 1.7 μm particle size) maintained at 50°C. Mobile phase-A is composed of aqueous 10 mM NH4OH and mobile phase-B is ACN. The AI and its related compounds are detected with UV detection at 220 nm and quantitated by an external Delmopinol hydrochloride reference standard. The quantitation limit of the method is 0.1% of the target analytical concentration. This UHPLC method is fast and green and has been demonstrated to be specific, accurate, linear, precise, sensitive and robust as per ICH guidelines.
A phase II, Multicentre, Randomised, Double-Blind, Placebo-controlled Study to Evaluate Safety, Tolerability, and Efficacy of Amiselimod in Patients with Moderate to Severe Active Crohn’s Disease
Authors: D’Haens Geert , Danese Silvio , Davies Martin , Watanabe Mamoru , Hibi Toshifumi 
Published: November 2021

Abstract

Background and Aims
Amiselimod is an oral selective S1P1 receptor modulator with potentially fewer adverse effects than fingolimod. We evaluated the safety, tolerability, and clinical efficacy of amiselimod in participants with moderate to severe active Crohn’s disease.

Methods
This was a phase IIa, multicentre, randomised, double-blind, parallel group, placebo-controlled study comparing amiselimod 0.4 mg with placebo over a 14-Week treatment period. The primary endpoint of the study was the proportion of participants with clinical response (Crohn’s Disease activity Index [CDAI] 100) from baseline at Week 12.

Results
A total of 180 patients were screened and 78 were randomised [40 to amiselimod 0.4 mg and 38 to placebo]. There was no significant difference in the proportion of patients achieving CDAI 100 at Week 12 on amiselimod 0.4 mg and on placebo [48.7% vs. 54.1%, respectively] (odds ratio [OR] [95% confidence interval]: 0.79 [0.31, 1.98]). The results from the secondary endpoint analyses supported the results of the primary endpoint analysis. Treatment with amiselimod 0.4 mg was generally well tolerated, with 71.8% of participants completing the 14-week treatment period. Seven participants had serious adverse events and four discontinued treatment in the amiselimod group.

Conclusions
Amiselimod 0.4 mg for 12 weeks was not superior to placebo for the induction of clinical response [CDAI 100] in Crohn’s disease. Treatment with amiselimod 0.4 mg was generally well tolerated and no new safety concerns related to amiselimod were reported in this study.
Prognosis of epidermal growth factor receptor-mutated stage I lung adenocarcinoma with radiologically solid features
Authors: Hattori Aritoshi , Matsunaga Takeshi , Fukui Mariko , Takamochi Kazuya , Suzuki Kenji 
Published: November 2021

Abstract

OBJECTIVES
The prognostic role of the epidermal growth factor receptor (EGFR) mutation remains controversial, especially in early-stage lung adenocarcinoma with a solid appearance. We evaluated the oncological outcomes of clinical stage I (c-stage I) radiologically invasive lung adenocarcinoma by EGFR mutation status.

METHODS
Between 2008 and 2013, the data from 463 surgically resected c-stage I radiologically invasive, i.e. solid-dominant lung adenocarcinomas subjected to EGFR mutant analysis, were evaluated. Oncological outcomes were assessed using multivariable Cox regression analysis. Recurrence-free survival (RFS) was estimated using Kaplan–Meier analysis and the log-rank test.

RESULTS
A total of 229 (49%) samples harboured the EGFR-mutant adenocarcinoma. Overall, the 5-year RFS did not differ significantly between the EGFR-mutant and EGFR wild-type groups (67.3% vs 64.9%; P = 0.639). However, among the clinical T1c/T2a tumour subset (n = 177), a multivariable Cox hazard model revealed that radiologically pure-solid tumour (P = 0.024), EGFR-mutant (P = 0.027) and pathological stage II/III (P &lt; 0.001) were significant predictors of a poor RFS. Furthermore, in the c-T1c/T2a radiologically pure-solid lung adenocarcinoma subset, the EGFR-mutant group showed marginally lower 5-year RFS compared to that with the EGFR wild-type group (n = 134; 34.9% vs 53.0%; P = 0.062). Among them, multivariable Cox regression analysis revealed that EGFR mutant (P = 0.037) and pathological stage II/III (P = 0.011) were independently and significantly prognostic for worse RFS.

CONCLUSIONS
Among the c-stage I radiologically invasive lung adenocarcinomas, the EGFR mutation-positive type was correlated with an increased risk of recurrence in the c-T1c/T2a radiologically pure-solid tumour subset. When considering the prognostic value of EGFR mutations in early-stage lung adenocarcinoma, it is necessary to stratify them based on the presence of a ground-glass opacity component.
Pre-term delivery and long-term risk of heart failure in women: a national cohort and co-sibling study
Authors: Crump Casey , Sundquist Jan , McLaughlin Mary Ann , Dolan Siobhan M , Sieh Weiva , Sundquist Kristina 
Published: November 2021

Abstract

Aims
Women who deliver pre-term have higher future risks of hypertension and ischaemic heart disease, but long-term risks of heart failure (HF) are unknown. We examined these risks in a large national cohort.

Methods and results
All 2 201 284 women with a singleton delivery in Sweden during 1973–2015 were followed up for inpatient or outpatient HF diagnoses through 2015. Cox regression was used to compute hazard ratios (HRs) for HF associated with pregnancy duration, adjusting for other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and/or environmental) factors. In 48.2 million person-years of follow-up, 19 922 women were diagnosed with HF (median age: 60.7 years). Within 10 years after delivery, the adjusted HR was 2.96 [95% confidence interval (CI): 2.48–3.53] for HF associated with pre-term (gestational age: &lt;37 weeks) compared with full-term (39–41 weeks) delivery. Stratified HRs were 4.27 (2.54–7.17) for extremely pre-term (22–27 weeks), 3.39 (2.57–4.48) for moderately pre-term (28–33 weeks), 2.70 (2.19–3.32) for late pre-term (34–36 weeks), and 1.70 (1.45–1.98) for early term (37–38 weeks). These HRs declined but remained elevated at 10–19 years (pre-term vs. full term: HR: 2.19; 95% CI: 1.94–2.46), 20–29 years (1.80; 1.67–1.95), and 30–43 years (1.56; 1.47–1.66) after delivery, and were not explained by shared familial factors.

Conclusion
Pre-term and early term delivery were associated with markedly increased future hazards for HF, which persisted after adjusting for other maternal and familial factors and remained elevated 40 years later. Pre-term and early-term delivery should be recognized as risk factors for HF across the life course.

Key Question
What are the long-term hazards for heart failure (HF) across the life course in women who deliver preterm?

Key Finding
Preterm and early term delivery were associated with ∼3- and 1.7-fold adjusted hazards for HF in the next 10 years vs. full-term delivery. These hazards declined but remained elevated 40 years later, and were not explained by shared familial factors.

Take Home Message
Preterm and early term delivery were associated with increased future hazards for HF, which persisted for 40 years after adjusting for other maternal and familial factors. Preterm and early term delivery should be recognized as lifelong risk factors for HF.
Miniseries 1—Part III: ‘Behind the scenes’ in the triangle of Koch
Authors: Tretter Justin T , Spicer Diane E , Sánchez-Quintana Damián , Back Sternick Eduardo , Farré Jerónimo , Anderson Robert H 
Published: November 2021

Abstract

Aims
To take full advantage of the knowledge of cardiac anatomy, structures should be considered in their correct attitudinal orientation. Our aim was to discuss the triangle of Koch in an attitudinally appropriate fashion.

Methods and results
We reviewed our material prepared by histological sectioning, along with computed tomographic datasets of human hearts. The triangle of Koch is the right atrial surface of the inferior pyramidal space, being bordered by the tendon of Todaro and the hinge of the septal leaflet of the tricuspid valve, with its base at the inferior cavotricuspid isthmus. The fibro-adipose tissues of the inferior pyramidal space separate the atrial wall from the crest of the muscular interventricular septum, thus producing an atrioventricular muscular sandwich. The overall area is better approached as a pyramid rather than a triangle. The apex of the inferior pyramidal space overlaps the infero-septal recess of the subaortic outflow tract, permitting the atrioventricular conduction axis to transition directly to the crest of the muscular ventricular septum. The compact atrioventricular node is formed at the apex of the pyramid by union of its inferior extensions, which represent the slow pathway, with the septal components formed in the buttress of the atrial septum, thus providing the fast pathway.

Conclusions
To understand its various implications in current cardiological catheter interventions, the triangle of Koch must be considered in conjunction with the inferior pyramidal space and the infero-septal recess. It is better to consider the overall region in terms of a pyramidal area of interest.
Miniseries 1—Part IV: How frequent are fasciculo-ventricular connections in the normal heart?
Authors: Macías Yolanda , Tretter Justin T , Anderson Robert H , Sánchez-Quintana Damián , Soares Correa Frederico , Farré Jerónimo , Back Sternick Eduardo 
Published: November 2021

Abstract

Aims
Seeking to account for accessory atrioventricular conduction potentially leading to ventricular pre-excitation, Mahaim in the mid-20th century had described pathways between the atrioventricular conduction axis and the muscular ventricular septum. We aimed to look for such ‘paraspecific’ connections in adult human hearts.

Methods and results
We serially sectioned 21 hearts, covering the triangle of Koch and the aortic root, and assessing the atrioventricular node, the penetration of the conduction axis, and the bundle branches in our search for fasciculo-ventricular connections. We also calculated the length of the non-branching bundle, and if present the origin of the fasciculo-ventricular connections. The non-branching bundle was 3.6 ± 1.7 mmin length, varying from 1.7 mm to 7.2 mm. Fasciculo-ventricular connections were found in more than half of the hearts, making direct contact with the muscular septum at an average of 3.5 ± 1.7 mm from the origin of the left bundle branch, with the site of origin varying from 1.1 mm to 5.5 mm from the first fascicle of the left bundle branch. In three hearts, additional fasciculo-fascicular connections were observed in the left bundle branch. Two loops were small, but one loop extended over 9.5 mm.

Conclusion
We endorse the finding of Mahaim that fasciculo-ventricular pathways exist in most human hearts. We presume the identified connections had the capability of producing ventricular pre-excitation. More studies are needed to determine the potential clinical manifestations.
Miniseries 2—Septal and paraseptal accessory pathways—Part II: Para-Hisian accessory pathways—so-called anteroseptal pathways revisited
Authors: Farré Jerónimo , Anderson Robert H , Sánchez-Quintana Damián , Mori Shumpei , Rubio José-Manuel , García-Talavera Camila , Bansal Raghav , Lokhandwala Yash , Cabrera José-Angel , Wellens Hein J J , Sternick Eduardo Back 
Published: November 2021

Abstract
Surgeons, when dividing bypass tracts adjacent to the His bundle, considered them to be ‘anteroseptal’. The area was subsequently recognized to be superior and paraseptal, although this description is not entirely accurate anatomically, and conveys little about the potential risk during catheter interventions. We now describe the area as being para-Hisian, and it harbours two types of accessory pathways. The first variant crosses the membranous septum to insert into the muscular ventricular septum without exiting the heart, and hence being truly septal. The second variant inserts distally in the paraseptal components of the supraventricular crest, and consequently is crestal. The site of ventricular insertion determines the electrocardiographic expression of pre-excitation during sinus rhythm, with the two types producing distinct patterns. In both instances, the QRS and the delta wave are positive in leads I, II, and aVF. In crestal pathways, however, the QRS is ≥ 140 ms, and exhibits an rS configuration in V1–2. The delta wave in V1–2 precedes by 20–50 ms the apparent onset of the QRS in I, II, III, and aVF. In the true septal pathways, the QRS complex occupies ∼120 ms, presenting a QS, W-shaped, morphology in V1–2. The delta wave has a simultaneous onset in all leads. Our proposed terminology facilitates the understanding of the electrocardiographic manifestations of both types of para-Hisian pathways during pre-excitation and orthodromic tachycardia, and informs on the level of risk during catheter ablation.
Miniseries 2—Septal and paraseptal accessory pathways—Part IV: Inferior paraseptal accessory pathways—lessons from surgical and catheter ablation
Authors: Farré Jerónimo , Anderson Robert H , Rubio José-Manuel , Tretter Justin T , Sánchez-Quintana Damián , García-Talavera Camila , Bansal Raghav , Lokhandwala Yash Yahya , Cabrera José-Angel , Wellens Hein J J , Back Sternick Eduardo 
Published: November 2021

Abstract
Surgeons and electrophysiologists performing accessory pathway ablation procedures have used the term ‘posteroseptal’ region. This area, however, is neither septal nor posterior, but paraseptal and inferior; paraseptal because it includes the fibro-adipose tissues filling the pyramidal space and not the muscular septum itself and inferior because it is part of the heart adjacent to the diaphragm. It should properly be described, therefore, as being inferior and paraseptal. Pathways in this region can be ablated at three areas, which we term right inferior, mid-inferior, and left inferior paraseptal. The right- and left inferior paraseptal pathways connect the right and left atrial vestibules with the right and left paraseptal segments of the parietal ventricular walls. The mid-inferior paraseptal pathways take a subepicardial course from the myocardial sleeves surrounding the coronary sinus and its tributaries. Our review addresses the evolution of the anatomical concept of the inferior paraseptal region derived from surgical and catheter ablation procedures. We also highlight the limitations of the 12-lead electrocardiogram in identifying, without catheter electrode mapping, which are the pathways that can be ablated without a coronary sinus, or left heart approach.
Genetic characterization of ESBL/pAmpC-producing Escherichia coli isolated from forest, urban park and cereal culture soils
Authors: Benlabidi Saloua , Raddaoui Anis , Achour Wafa , Hassen Bilel , Torres Carmen , Abbassi Mohamed Salah , Ghrairi Taoufik 
Published: November 2021

ABSTRACT
Little is known about the role of forestland and non-fertilized agriculture soils as reservoirs of extended-spectrum beta-lactamase (ESBL) and plasmid-borne AmpC (pAmpC)-producing Escherichia coli isolates. Thus, in the present study, 210 soil samples from various origins (forest of Oued Zen (Ain Drahem), non-agriculture soils from different park gardens in Tunis City, cereal culture soils and home gardens) were investigated to characterize cefotaxime-resistant E. coli isolates. A total of 22 ESBL/pAmpC-producing E. coli were collected, and all harbored variants of the blaCTX-M gene (15 blaCTX-M-1, 5 blaCTX-M-55 and 2 blaCTX-M-15). A total of seven and two isolates harbored also blaEBC and blaDHA-like genes, respectively. Resistances to tetracycline, sulfonamides and fluoroquinolones were encoded by tetA (n = 4)/tetB (n = 12), sul1 (n = 17)/sul2 (n = 19) and aac(6’)-Ib-cr (n = 2)/qnrA (n = 1)/qnrS (n = 1) genes, respectively. A total of seven isolates were able to transfer by conjugation cefotaxime-resistance in association or not with other resistance markers. PFGE showed that ten and two isolates were clonally related (pulsotypes P1 and P2). The 10 P1 isolates had been collected from forestland, cereal culture soils and an urban park garden in Tunis City, arguing for a large spread of clonal strains. Our findings highlight the occurrence of ESBL/pAmpC-E. coli isolates in soils under limited anthropogenic activities and the predominance of CTX-M enzymes that are largely disseminated in E. coli from humans and animals in Tunisia.
Temporal and spatial transcriptomic dynamics across brain development in Xenopus laevis tadpoles
Authors: Ta Aaron C , Huang Lin-Chien , McKeown Caroline R , Bestman Jennifer E , Van Keuren-Jensen Kendall , Cline Hollis T 
Published: November 2021

Abstract
Amphibian metamorphosis is a transitional period that involves significant changes in the cell-type populations and biological processes occurring in the brain. Analysis of gene expression dynamics during this process may provide insight into the molecular events underlying these changes. We conducted differential gene expression analyses of the developing Xenopus laevis tadpole brain during this period in two ways: first, over stages of the development in the midbrain and, second, across regions of the brain at a single developmental stage. We found that genes pertaining to positive regulation of neural progenitor cell proliferation as well as known progenitor cell markers were upregulated in the midbrain prior to metamorphic climax; concurrently, expression of cell cycle timing regulators decreased across this period, supporting the notion that cell cycle lengthening contributes to a decrease in proliferation by the end of metamorphosis. We also found that at the start of metamorphosis, neural progenitor populations appeared to be similar across the fore-, mid-, and hindbrain regions. Genes pertaining to negative regulation of differentiation were upregulated in the spinal cord compared to the rest of the brain, however, suggesting that different programs may regulate neurogenesis there. Finally, we found that regulation of biological processes like cell fate commitment and synaptic signaling follow similar trajectories in the brain across early tadpole metamorphosis and mid- to late-embryonic mouse development. By comparing expression across both temporal and spatial conditions, we have been able to illuminate cell-type and biological pathway dynamics in the brain during metamorphosis.