bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting hierarchy in medical concept embedding*
Authors: Finch Anthony , Crowell Alexander , Bhatia Mamta , Parameshwarappa Pooja , Chang Yung-Chieh , Martinez Jose , Horberg Michael 
Published: March 2021

Abstract

Objective
To construct and publicly release a set of medical concept embeddings for codes following the ICD-10 coding standard which explicitly incorporate hierarchical information from medical codes into the embedding formulation.

Materials and Methods
We trained concept embeddings using several new extensions to the Word2Vec algorithm using a dataset of approximately 600,000 patients from a major integrated healthcare organization in the Mid-Atlantic US. Our concept embeddings included additional entities to account for the medical categories assigned to codes by the Clinical Classification Software Revised (CCSR) dataset. We compare these results to sets of publicly released pretrained embeddings and alternative training methodologies.

Results
We found that Word2Vec models which included hierarchical data outperformed ordinary Word2Vec alternatives on tasks which compared naïve clusters to canonical ones provided by CCSR. Our Skip-Gram model with both codes and categories achieved 61.4% normalized mutual information with canonical labels in comparison to 57.5% with traditional Skip-Gram. In models operating on two different outcomes, we found that including hierarchical embedding data improved classification performance 96.2% of the time. When controlling for all other variables, we found that co-training embeddings improved classification performance 66.7% of the time. We found that all models outperformed our competitive benchmarks.

Discussion
We found significant evidence that our proposed algorithms can express the hierarchical structure of medical codes more fully than ordinary Word2Vec models, and that this improvement carries forward into classification tasks. As part of this publication, we have released several sets of pretrained medical concept embeddings using the ICD-10 standard which significantly outperform other well-known pretrained vectors on our tested outcomes.
Progressive failure mechanical behaviour and response characteristics of sandstone under stress-seepage coupling
Authors: Song Zhixiang , Zhang Junwen 
Published: March 2021

AbstractConventional triaxial loading tests with different confining pressures and stress-seepage coupling tests on sandstone with different confining pressures and seepage pressures were conducted. A permeability model considering strength and strain was established, which better characterized the progressive deformation mechanical behaviour of sandstone under stress-seepage coupling. The results showed the following. (i) The confining pressure not only affects the peak strength of sandstone but also affects the axial deformation under conventional triaxial loading conditions. (ii) Compared with the seepage pressure effect, the degree of the confining pressure effect on the strength of sandstone was weaker, but the degree of that on the axial, radial and volumetric deformations of sandstone was stronger under stress-seepage coupling. (iii) With increasing confining pressure, the axial strain of sandstone decreased, while the corresponding radial and volumetric strains showed progressively increasing evolution characteristics under identical seepage pressures and different confining pressures. With increasing seepage pressure, the axial strain continuously decreased, while the corresponding radial and volumetric strains showed the progressive evolution characteristic of first increasing and then decreasing under identical confining pressures and different seepage pressures. (iv) Compared with the confining pressure effect, the degree of the seepage pressure effect on the permeability progressive evolution law of sandstone was weaker under stress-seepage coupling. The research conclusions could enrich the theories for the prevention and control of water inrush accidents in coal mines.
Genome mining for drug discovery: cyclic lipopeptides related to daptomycin
Authors: Baltz Richard H 
Published: March 2021

Abstract
The cyclic lipopeptide antibiotics structurally related to daptomycin were first reported in the 1950s. Several have common lipopeptide initiation, elongation, and termination mechanisms. Initiation requires the use of a fatty acyl-AMP ligase (FAAL), a free-standing acyl carrier protein (ACP), and a specialized condensation (CIII) domain on the first NRPS elongation module to couple the long chain fatty acid to the first amino acid. Termination is carried out by a dimodular NRPS that contains a terminal thioesterase (Te) domain (CAT-CATTe). Lipopeptide BGCs also encode ABC transporters, apparently for export and resistance. The use of this mechanism of initiation, elongation, and termination, coupled with molecular target-agnostic resistance, has provided a unique basis for robust natural and experimental combinatorial biosynthesis to generate a large variety of structurally related compounds, some with altered or different antibacterial mechanisms of action. The FAAL, ACP, and dimodular NRPS genes were used as molecular beacons to identify phylogenetically related BGCs by BLASTp analysis of finished and draft genome sequences. These and other molecular beacons have identified: (i) known, but previously unsequenced lipopeptide BGCs in draft genomes; (ii) a new daptomycin family BGC in a draft genome of Streptomyces sedi; and (iii) novel lipopeptide BGCs in the finished genome of Streptomyces ambofaciens and the draft genome of Streptomyces zhaozhouensis.
Corporations, high-stakes biomedical research, and research misconduct: yes they can (and sometimes do)
Authors: Morreim E H 
Published: March 2021

Abstract
Science has long been vulnerable to research misconduct (RM). Biomedical sciences, with vast financial stakes, carry heightened temptations. However, RM is standardly seen as an undertaking of individual scientists, not as something that could be committed by an organization such as a corporation or university. Rather, organizations are generally regarded merely as supervisors to encourage scientific integrity and investigate suspected RM. Indeed, federal regulations expressly embrace this perspective, and the federal Office of Research Integrity has never deemed an organization guilty of committing RM. This article aims to rewrite this corner of research integrity: organizations can directly commit RM and should be held accountable as such. Although the conclusions apply to organizations such as universities and government agencies, the focus here is on corporations in the biomedical sciences. After defining ‘research misconduct’ in Part II, Part III describes corporate-level RM and distinguishes it from individuals’ misconduct. Part IV provides five case studies exemplifying corporate RM, while Part V discusses implications, describes ways in which federal regulations could already encompass organization-level RM, and identifies some needed legal and regulatory adjustments.
The Influence of Indoor Environmental Factors on the Prevalence of House Dust Mites as Aeroallergens in Bandar Abbas Student Dormitories, South of Iran, 2019
Authors: Zare Mehdi , Hassani-Azad Mehdi , Soleimani-Ahmadi Moussa , Majnoon Raziea 
Published: March 2021

Abstract
This study was conducted to determine the influence of environmental factors on the prevalence of house dust mites in student dormitories of Bandar Abbas city. In this study, 64 dust samples were collected from seven randomly selected dormitories located in various areas of the Bandar Abbas. The collected mites were isolated and mounted in Hoyer’s medium and identified using a morphological key. The associations between the environmental factors and the density of house dust mites were investigated. In total, 1,093 adult mites were collected and identified. They consisted of four species including Dermatophagoides pteronyssinus Trouessart (57.6%), Dermatophagoides farinae Hughes (24.3%) and Dermatophagoides evansi Fain (14.9%) (Acari: Pyroglyphidae), and Cheyletus malaccensis Oudemans (3.2%) (Acari: Cheyletidae). All of the dormitories were contaminated by more than one house dust mites species and the mean density of house dust mites in dormitories was 8.3 ± 0.2 mites/g of dust. There was a significant relationship between average house dust mites density and some of environmental factors such as relative humidity, temperature, floor covering type, and number of occupants (P &lt; 0.05). Results of this study revealed that two major allergenic dust mites, D. pteronyssinus and D. farinae, were the most prevalent and collected from all of dormitories and some of indoor environmental factors found to influence mites’ population.
Whose (Ir)Religion? Which Bioethics?
Authors: Parks Benjamin N 
Published: March 2021

Abstract
In this issue, contributors engage Timothy Murphy’s proposal for irreligious bioethics over against religious bioethics. Two essays take opposing sides in the debate, while a third seeks middle ground. Another essay questions the meaning of the words “religion,” “irreligion,” and “secular.” The final essay examines the religious nature of human existence and its implications for the debate.
Understanding Drug Development: A Primer on the Food and Drug Administration
Authors: Purandare Amol V 
Published: March 2021

Abstract
Over the past year, the Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has led to rapid advancement regarding therapeutics, vaccines, and testing. In the United States, the Food and Drug Administration (FDA) is the agency ensuring standardization, reproducibility, and meeting benchmarks of safety and efficacy for these products. Among medical professionals and the public, there are often questions about the role of regulation, product development and approval, and terminology often used in regard to the FDA. This manuscript will serve as an introduction to the FDA, clarify the steps of drug development and approval, review terms related to product use, and discuss the role of the medical community and industry.
The FDA serves as a regulatory agency ensuring safety, efficacy, and quality are met in the approval of drugs, vaccines, biologics, and testing products. Understanding the terms of development can help providers with many new products being developed.
Functionalised molybdenum disulfide nanosheets for co-delivery of doxorubicin and siRNA for combined chemo/gene/photothermal therapy on multidrug-resistant cancer
Authors: Li Guo , Meng Fayan , Lu Taicheng , Wei Liying , Pan Xin , Nong Zhenzhen , Wei Mei , Liao Chuanan , Li Xuehua 
Published: March 2021

Abstract

Objective
Molybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.

Methods
MoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed.

Key findings
The nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone.

Conclusions
Our results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.
Myofibroblastoma of the breast: two case reports and literature review
Authors: Scardina Lorenzo , Franceschini Gianluca , Biondi Ersilia , Di Leone Alba , Sanchez Alejandro Martin , D'Archi Sabatino , Mason Elena Jane , Angelico Giuseppe , Santoro Angela , Mulè Antonino , Masetti Riccardo 
Published: March 2021

ABSTRACT
Myofibroblastoma (MFB) is a relatively rare tumor of the breast parenchyma, which belongs to the family of the ‘benign stromal tumor of the breast’. Two cases of MFB of the breast are described. Radiological imaging is nonspecific in MFB, and pathological examination of needle biopsy or surgically resected specimen is necessary for the diagnosis. Surgery is recommended and considered curative without additional treatment; however, patients should be followed-up.
Genome-wide association studies reveal the coordinated regulatory networks underlying photosynthesis and wood formation in Populus
Authors: Quan Mingyang , Liu Xin , Du Qingzhang , Xiao Liang , Lu Wenjie , Fang Yuanyuan , Li Peng , Ji Li , Zhang Deqiang 
Published: March 2021

Abstract
Photosynthesis and wood formation underlie the ability of trees to provide renewable resources and perform ecological functions; however, the genetic basis and regulatory pathways coordinating these two linked processes remain unclear. Here, we used a systems genetics strategy, integrating genome-wide association studies, transcriptomic analyses, and transgenic experiments, to investigate the genetic architecture of photosynthesis and wood properties among 435 unrelated individuals of Populus tomentosa, and unravel the coordinated regulatory networks resulting in two trait categories. We detected 222 significant single-nucleotide polymorphisms, annotated to 177 candidate genes, for 10 traits of photosynthesis and wood properties. Epistasis uncovered 74 epistatic interactions for phenotypes. Strikingly, we deciphered the coordinated regulation patterns of pleiotropic genes underlying phenotypic variations for two trait categories. Furthermore, expression quantitative trait nucleotide mapping and coexpression analysis were integrated to unravel the potential transcriptional regulatory networks of candidate genes coordinating photosynthesis and wood properties. Finally, heterologous expression of two pleiotropic genes, PtoMYB62 and PtoMYB80, in Arabidopsis thaliana demonstrated that they control regulatory networks balancing photosynthesis and stem secondary cell wall components, respectively. Our study provides insights into the regulatory mechanisms coordinating photosynthesis and wood formation in poplar, and should facilitate genetic breeding in trees via molecular design.
XMMU J050722.1−684758: discovery of a new Be X-ray binary pulsar likely associated with the supernova remnant MCSNR J0507−6847
Authors: Maitra C , Haberl F , Maggi P , Kavanagh P J , Vasilopoulos G , Sasaki M , Filipović M D , Udalski A 
Published: March 2021

ABSTRACT
We report the discovery of a new high-mass X-ray binary pulsar, XMMU J050722.1−684758, possibly associated with the supernova remnant (SNR) MCSNR J0507−6847 in the Large Magellanic Cloud, using XMM–NewtonX-ray observations. Pulsations with a periodicity of 570 s are discovered from the Be X-ray binary XMMU J050722.1−684758 confirming its nature as a HMXB pulsar. The HMXB is located near the geometric centre of the SNR MCSNR J0507−6847(0.9 arcmin from the centre) which supports the XRB-SNR association. The estimated age of the SNR is 43–63 kyr years which points to a middle aged to old SNR. The large diameter of the SNR combined with the lack of distinctive shell counterparts in optical and radio indicates that the SNR is expanding into the tenuous environment of the superbubble N103. The estimated magnetic field strength of the neutron star is B ≳ 1014 G assuming a spin equilibrium condition which is expected from the estimated age of the parent remnant and assuming that the measured mass-accretion rate remained constant throughout.
The excitation of CNCN in the interstellar medium: hyperfine resolved rate coefficients and non-LTE modelling
Authors: Ndaw D , Bop C T , Dieye G , Faye N A Boye , Lique F 
Published: March 2021

ABSTRACT
The recent detections of CNCN and HNCCN+ are seen as further evidence of the large abundance of NCCN in the interstellar medium. The accurate determination of the abundance of these chemically related compounds from the observational spectra requires the prior calculation of collisional rate coefficients. In this work, we aimed at computing hyperfine resolved rate coefficients for the CNCN–He collisional system. First, we determined a new potential energy surface for the CNCN–He van der Waals complex from which we computed rotationally resolved excitation cross-sections for energies up to 800 cm−1 using the quantum mechanical close-coupling approach. Then, hyperfine resolved transitions between the 30 low-lying pure rotational levels of CNCN were computed for temperatures ranging from 5 to 150 K using an improved infinite order sudden approach. The analysis of the scattering results showed a propensity rule in favour of Δj = ΔF1 = ΔF for the hyperfine transitions and a slight dominance of the odd Δj transitions. Using these data, we carried out non-LTE radiative transfer calculations to simulate the excitation of CNCN in molecular clouds and to constrain the physical conditions of cold dark clouds. Preliminary results showed that the abundance of CNCN derived from observational spectra has to be revisited using these new collisional data.
Enhancer Pleiotropy, Gene Expression, and the Architecture of Human Enhancer–Gene Interactions
Authors: Singh Devika , Yi Soojin V 
Published: March 2021

AbstractEnhancers are often studied as noncoding regulatory elements that modulate the precise spatiotemporal expression of genes in a highly tissue-specific manner. This paradigm has been challenged by recent evidence of individual enhancers acting in multiple tissues or developmental contexts. However, the frequency of these enhancers with high degrees of “pleiotropy” out of all putative enhancers is not well understood. Consequently, it is unclear how the variation of enhancer pleiotropy corresponds to the variation in expression breadth of target genes. Here, we use multi-tissue chromatin maps from diverse human tissues to investigate the enhancer–gene interaction architecture while accounting for 1) the distribution of enhancer pleiotropy, 2) the variations of regulatory links from enhancers to target genes, and 3) the expression breadth of target genes. We show that most enhancers are tissue-specific and that highly pleiotropy enhancers account for &lt;1% of all putative regulatory sequences in the human genome. Notably, several genomic features are indicative of increasing enhancer pleiotropy, including longer sequence length, greater number of links to genes, increasing abundance and diversity of encoded transcription factor motifs, and stronger evolutionary conservation. Intriguingly, the number of enhancers per gene remains remarkably consistent for all genes (∼14). However, enhancer pleiotropy does not directly translate to the expression breadth of target genes. We further present a series of Gaussian Mixture Models to represent this organization architecture. Consequently, we demonstrate that a modest trend of more pleiotropic enhancers targeting more broadly expressed genes can generate the observed diversity of expression breadths in the human genome.
Secondhand Smoke Exposure is Associated with Prevalent Heart Failure: Longitudinal Examination of the National Health and Nutrition Examination Survey
Authors: Skipina T M , Upadhya B , Soliman E Z 
Published: March 2021

Abstract

Introduction
Serum cotinine is a sensitive and specific biomarker for tobacco exposure including second-hand smoke exposure (SHS). We sought to examine whether SHS is associated with heart failure (HF) among non-hospitalized adults.

Methods
This analysis included 11 219 non-smokers (age 48.4 ± 20.5 years, 55.9% women, 70.5% whites) from the United States Third National Health and Nutrition Examination (NHANES) years 1988–1994. SHS was defined as serum cotinine ≥1 ng/mL. To assess dose-response, cut-points of serum cotinine ≥3 ng/mL and ≥6 ng/mL were used. Multivariable logistic regression was used to examine the association between SHS and HF. The consistency of this association was tested among subgroups stratified by race, gender, and comorbidities. NHANES years 2003–2006 were examined for longitudinal comparison.

Results
18.9% (n = 2125) of participants had SHS exposure while 3.7% (n = 416) had HF. After adjusting for covariates, SHS was associated with a 35% increased odds of HF with a dose-response relationship between levels of serum cotinine and HF. This association was stronger in males than females (interaction p-value = 0.03) and those with a history of CVD versus those without (interaction p-value &lt; 0.001). This association persisted in the NHANES 2003–2006 analysis.

Conclusion
There is a dose-response relationship between SHS and HF with possible effect modification by gender and prior CVD. This is a novel finding that underscores the harmful effects of passive smoking on the cardiovascular system and highlights the needs for further prohibition of smoking in public areas and a personalized risk assessment among high-risk groups, especially in regions with less-stringent public health policies.

Implications
This study showed a novel association between secondhand smoke exposure and prevalent heart failure among non-smokers, adding to the list of harmful cardiovascular manifestations of secondhand smoke exposure. This was more apparent in men and those with a prior history of cardiovascular disease. Heart failure is a debilitating disease process, so this finding has important policy implications in low-income countries and poor communities with less-stringent health policies because they are known to have the highest levels of exposure. Smoke-free policies targeting these regions would thus yield substantial public health benefits.