bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tool Adaptation Workshop for Moral Distress in Military Critical Care Nurses
Authors: Wilson Melissa A. 
Published: June 2021

Purpose
The US military healthcare services provide the highest level of trusted medical care to its members and to the world population during catastrophic events. These services can be difficult, making moral and ethical situations commonplace. Moral distress results when actions are inconsistent with personal or professional beliefs, resulting in a loss of moral integrity. Moral distress research is well established in the civilian literature and results in poor outcomes and increased expenses. There is little research studying moral distress in military providers.

Description of the Project
A clinical nurse specialist–led workshop was conducted with military and civilian experts. The expert panel reviewed the literature, examined instruments, and reviewed tool items for applicability to military healthcare providers.

Outcome
The team determined the existing civilian moral distress tool was applicable to military providers. Twelve additional items were added to the modified tool. A tool testing plan was developed to test the tool in military critical care nurses on the last day of the workshop for the next phase of this project.

Conclusion
The civilian moral distress tool was adapted for a military version and will be tested in the next phase of the project.
Replication of an open-access deep learning system for screening mammography: Reduced performance mitigated by retraining on local data
Authors: Condon J.J.J. , Oakden-Rayner L. , Hall K.A. , Reintals M. , Holmes A. , Carneiro G. , Palmer L.J. 
Published: June 2021

ABSTRACTAimTo assess the generalisability of a deep learning (DL) system for screening mammography developed at New York University (NYU), USA (1, 2) in a South Australian (SA) dataset.Methods and MaterialsClients with pathology-proven lesions (n=3,160) and age-matched controls (n=3,240) were selected from women screened at BreastScreen SA from January 2010 to December 2016 (n clients=207,691) and split into training, validation and test subsets (70%, 15%, 15% respectively). The primary outcome was area under the curve (AUC), in the SA Test Set 1 (SATS1), differentiating invasive breast cancer or ductal carcinoma in situ (n=469) from age-matched controls (n=490) and benign lesions (n=44). The NYU system was tested statically, after training without transfer learning (TL), after retraining with TL and without (NYU1) and with (NYU2) heatmaps.ResultsThe static NYU1 model AUCs in the NYU test set (NYTS) and SATS1 were 83.0%(95%CI=82.4%-83.6%)(2) and 75.8%(95%CI=72.6%-78.8%), respectively. Static NYU2 AUCs in the NYTS and SATS1 were 88.6%(95%CI=88.3%-88.9%)(2) and 84.5%(95%CI=81.9%-86.8%), respectively. Training of NYU1 and NYU2 without TL achieved AUCs in the SATS1 of 65.8% (95%CI=62.2%-69.1%) and 85.9%(95%CI=83.5%-88.2%), respectively. Retraining of NYU1 and NYU2 with TL resulted in AUCs of 82.4%(95%CI=79.7-84.9%) and 86.3%(95%CI=84.0-88.5%) respectively.ConclusionWe did not fully reproduce the reported performance of NYU on a local dataset; local retraining with TL approximated this level of performance. Optimising models for local clinical environments may improve performance. The generalisation of DL systems to new environments may be challenging.Key ContributionsIn this study, the original performance of deep learning models for screening mammography was reduced in an independent clinical population.Deep learning (DL) systems for mammography require local testing and may benefit from local retraining.An openly available DL system approximates human performance in an independent dataset.There are multiple potential sources of reduced deep learning system performance when deployed to a new dataset and population.
Detection of Human Papillomaviruses DNA in paired peripheral blood and cervix samples patients with cervical lesions and healthy individuals
Authors: do Nascimento Kamylla Conceição Gomes , de Lima Elyda Gonçalves , da Mota Nunes Zhilbelly , Barros Júnior Marconi Rêgo , de Aragão Batista Marcus Vinícius , Lucena Antônio Roberto , da Costa Silva Neto Jacinto , Chagas Barbara Simas , Gurgel Ana Pavla Almeida Diniz , de Freitas Antonio Carlos 
Published: June 2021

AbstractThis study evaluated the presence of HPV DNA in the cervix and peripheral blood of women with cervical intraepithelial neoplasia (CIN I, II, and III) and healthy individuals. Overall, 139 paired peripheral blood and cervix samples of healthy women and women with CIN I, II, and III (n= 68) were tested for HPV DNA by using standard procedures. PCR-sequencing determined HPV types. Quantification of HPV16 E6 and E2 genes was performed to determine viral load and physical state. HPV DNA was detected in the cervix (21.1% in healthy individuals; 48.8-55.5% in CIN patients), blood (46.4% in healthy individuals; 44.1-77.7% in CIN patients), and paired peripheral blood and cervix samples (24% in healthy individuals; 32.5-44.4% in CIN patients). The most frequent types found in the cervix were HPV16, 18, 31, 33, 58, and 70, while HPV16, 18, 33, 58, and 66 were the most frequent types found in the blood. HPV DNA in the cervix was associated with previous sexually transmitted infections (STIs) (P=0.023; OR: 2.978; CI:1.34-7.821), HPV DNA in the blood (P=0.000; OR: 8.283; CI:3.700-18.540), and cervical lesions (CIN I/II or III) (P=0.007). Binomial logistic regression showed that HPV DNA in the blood (P=0.000; OR: 9.324; CI:3.612-24.072) and cervical lesions (P=0.011; OR: 3.622; CI:1.338-9.806) were associated with HPV DNA in the cervix. However, we did not find an association between HPV DNA in the blood and cervical lesions (P=0.385). Our results showed that only HPV DNA found in the cervix was associated with cervical lesions.
Overexpression of long non coding RNA OR3A4 is associated with altered p38 signalling, morphological and phenotypic changes, and reduced immunogenicity in Barrett’s Oesophagus
Authors: Nieto Tom , Sinha Yash , Zhuang Qin Qin , Coleman Mathew , Stockton Joanne , Whalley Celina , Hejmadi Rahul , Dilworth Mark , Stoldona Agata , Pestinger Valerie , Tucker Olga , Beggs Andrew D 
Published: June 2021

ABSTRACTBackgroundBarrett’s Oesophagus (BO) presents a particular pathological dilemma, in that patients who have no dysplasia within their BO experience a small but significant risk of malignant progression each year. Screening programmes have attempted to reduce the mortality from BO associated oesophageal adenocarcinoma but cannot predict which BO patients will progress to invasive malignancy. We have previously identified the long non coding RNA, OR3A4, is differentially hypomethylated in progressive BO. We aimed to understand its role in BO pathogenicityMethodsThe stable BO cell line CP-A, as well as the oesophageal adenocarcinoma cells line OE-33 was transfected with a lentiviral OR3A4 over-expression vector, and underwent high resolution microscopy, immunofluorescence, RT-qPCR, RNA sequencing, and targeted drug screening with the p38-MAPK inhibitor domipramod to understand the effects of OR3A4 expression on progression. We then compared progressive vs. non-progressive BO samples using quantitative multi-fluorophore (Vectra) immunohistochemistry.ResultsOver-expression of OR3A4 in CP-A lines resulted in a hyperproliferative, dysplastic cellular phenotype, with strong over-expression of MAPK and anti-apoptotic pathways at the RNA and protein level, which was sensitive to the p38-MAPK inhibitor domipramod. Vectra immunohistochemistry demonstrated that progressive BO had reduced visibility associated with a reduction in CD8+ T-cells and CD68+ macrophages and reduced CD4+ T-cells in the stomal compartment.ConclusionThe overexpression of OR3A4, which we have previously shown is associated with progressive BO leads to a proliferative dysplastic cellular phenotype associated with increased, reversible MAPK signalling and loss of immune visibility.
The effect of hypersensitivity pneumonitis guideline on the pathologic diagnosis of interstitial pneumonia
Authors: Ozasa Mutsumi , Bychkov Andrey , Zaizen Yoshiaki , Tabata Kazuhiro , Uegami Wataru , Yamano Yasuhiko , Kataoka Kensuke , Johkoh Takeshi , Mukae Hiroshi , Kondoh Yasuhiro , Fukuoka Junya 
Published: June 2021

ABSTRACTHypersensitivity pneumonitis (HP) and interstitial pneumonia (IP) have several overlapping characteristics, and a high diagnostic concordance rate of HP is rarely obtained. New guideline, highly influenced by pathology, were devised for its diagnosis. We recently reported that the 2020 HP guideline may result in a possible overdiagnosis of fibrotic HP (fHP) through multidisciplinary discussion. Here, we attempted to investigate the impact of the 2020 HP guideline on the pathological diagnosis of cases previously diagnosed as IP. We classified 247 cases with fibrotic IP diagnoses sourced from 2014–2019 into three categories according to the 2020 HP guideline: typical, probable, and indeterminate HP. The original pathological diagnosis and categorization based on the 2020 HP guideline were compared. The clinical data including serum data and pulmonary function tests were compared among groups. The number of cases that changed to HP from an original diagnosis other than HP based on the guideline was 56 (23%). The clinical data of these cases bore a greater resemblance to cases diagnosed as indeterminate for HP than those diagnosed as typical or probable. The ratio of typical and probable HP to the total cases was significantly lower when using a transbronchial lung cryobiopsy (TBLC). Based on the new guideline, the pathological diagnosis of HP efficiently excluded HP cases but increased the rate of HP diagnosis for cases with fibrotic IP that may not suit an HP diagnosis. Thus, a TBLC may not be useful when imparting findings for fibrotic HP diagnosis using the new criteria.Key messagesWhat is the key question? >Does the 2020 HP Guideline improve pathological diagnosis?What is the bottom line? >By applying the new guideline, about 1/4 of the pathological diagnoses were changed from not chronic HP to probable or typical fHP, but most of the changed cases showed a clinical picture closer to not chronic HP.Why read on? >To understand that simple application of the pathological criteria of the HP guideline may cause a misleading diagnosis.
Digital embryos – A novel technical approach to investigate perceptual categorization in pigeons (Columba livia) using machine learning
Authors: Pusch Roland , Packheiser Julian , Koenen Charlotte , Iovine Fabrizio , Güntürkün Onur 
Published: June 2021

AbstractPigeons are classic model animals to study perceptual category learning. A theoretical understanding of the cognitive mechanisms of categorization requires a careful consideration of the employed stimulus material. Optimally, stimuli should not consist of real-world objects that might be associated with prior experience. The number of exemplars should be theoretically infinite and easy to produce. In addition, the experimenter should have the freedom to produce 2D- and 3D-versions of the stimuli and, finally, the stimulus set should provide the opportunity to identify the diagnostic elements that the animals use. To this end, we used the approach of “virtual phylogenesis” of “digital embryos” to produce two stimulus sets of objects that meet these criteria. In our experiment pigeons learned to categorize these stimuli in a forced-choice procedure. In addition, we used peck tracking to identify where on the stimulus the animals pecked to signal their choice. Pigeons learned the task and transferred successfully to novel exemplars. Using a k-nearest neighbor classifier, we were able to predict the presented stimulus class based on pecking location indicating that pecks are related to features of interest. We further identified potential strategies of the pigeons through this approach, namely that they were either learning one or two categories to discriminate between stimulus classes. These strategies remained stable during category transfer, but differed between individuals indicating that categorization learning is not limited to a single learning strategy.
Foregut organ progenitors and their niche display distinct viscoelastic properties in vivo during early morphogenesis stages
Authors: Dzementsei Aliaksandr , Barooji Younes F. , Ober Elke A. , Oddershede Lene B. 
Published: June 2021

AbstractMaterial properties of living matter play an important role for biological function and development. Yet, quantification of material properties of internal organs in vivo, without causing physiological damage, remains challenging. Here, we present a non-invasive approach based on modified optical tweezers for quantifying sub-cellular material properties deep inside living zebrafish. Material properties of cells within the gut region of living zebrafish are quantified as deep as 150 μm into the biological tissue. The measurements demonstrate differential mechanical properties of the developing foregut organs progenitors: Gut progenitors are more elastic than any of the neighboring cell populations at the time when the developing organs undergo substantial displacements during morphogenesis. The higher elasticity of gut progenitors correlates with an increased cellular concentration of microtubules. The results infer a role of material properties during morphogenesis and the approach paves the way for quantitative material investigations in vivo of embryos, explants, or organoids.
Systematic identification of a CDYL1-dependent decrease in lysine crotonylation at DNA double-strand break sites functionally uncouples transcriptional silencing and repair
Authors: Abu-Zhayia Enas R. , Machour Feras E. , Bishara Laila A. , Ben-Oz Bella M. , Ayoub Nabieh 
Published: June 2021

SummaryPreviously, we showed that CDYL1 is recruited to DNA double-strand breaks (DSBs) to promote homology-directed repair (HDR) and foster transcriptional silencing. Yet, how CDYL1 elicits DSB-induced silencing is not fully understood. Here, we systematically identify a CDYL1-dependent local decrease in the transcriptionally active marks lysine crotonylation (PanKcr) and crotonylated histone residue H3K9cr at AsiSI-induced DSBs, which correlates with transcriptional silencing. Mechanistically, we reveal that CDYL1 crotonyl-CoA hydratase activity counteracts PanKcr and H3K9cr at AsiSI sites, which triggers the eviction of the transcriptional elongation factor ENL and foster transcriptional silencing. Furthermore, genetic inhibition of CDYL1 hydratase activity blocks the reduction in H3K9cr and alleviates DSB-induced silencing, while HDR efficiency unexpectedly remains intact. Therefore, our results functionally uncouple the repair and silencing activity of CDYL1 at DSBs. In a broader context, we address a long-standing question concerning the functional relationship between HDR and DSB-induced transcriptional silencing, suggesting that they may occur independently.HighlightsSystematic identification of a local decrease in lysine crotonylation PanKcr and H3K9cr at AsiSI-induced DSBs that correlates with transcriptional silencing.CDYL1 crotonyl-CoA hydratase activity downregulates Kcr at DSBs.Kcr reduction at DSBs promotes ENL eviction and fosters transcriptional silencing.CDYL1 roles in DSB-induced transcriptional silencing and HDR are functionally uncoupled.
COVID-19 Mortality is Associated with Impaired Innate Immunity in Pre-existing Health Conditions
Authors: Lee Matthew E. , Chang Yung , Ahmadinejad Navid , Johnson-Agbakwu Crista E. , Bailey Celeste , Liu Li 
Published: June 2021

AbstractBackgroundCOVID-19 poses a life-threatening endangerment to individuals with chronic diseases. However, not all comorbidities affect COVID-19 prognosis equally. Some increase the risk of COVID-19 related death by more than six folds while others show little to no impact. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities in common health conditions that predispose patients to poor prognoses. In this study, we aim to discover some of these molecular risk factors by associating gene expression dysregulations in common health conditions with COVID-19 mortality rates in different cohorts.MethodsWe focused on fourteen pre-existing health conditions, for which age-and-sex-adjusted hazard ratios of COVID-19 mortality have been documented. For each health condition, we analyzed existing transcriptomics data to identify differentially expressed genes (DEGs) between affected individuals and unaffected individuals. We then tested if fold changes of any DEG in these pre-existing conditions were correlated with hazard ratios of COVID-19 mortality to discover molecular risk factors. We performed gene set enrichment analysis to identify functional groups overrepresented in these risk factor genes and examined their relationships with the COVID-19 disease pathway.ResultsWe found that upregulated expression of 70 genes and downregulated expression of 181 genes in pre-existing health conditions were correlated with increased risk of COVID-19 related death. These genes were significantly enriched with endoplasmic reticulum (ER) function, proinflammatory reaction, and interferon production that participate in viral transcription and immune responses to viral infections.ConclusionsImpaired innate immunity in pre-existing health conditions are associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic interventions.
Infection of mouse neural progenitor cells by Toxoplasma gondii affects in vitro proliferation, differentiation and migration
Authors: Pires Luiza Bendia , Barbosa Helene Santos , Santiago Marcelo Felippe , Adesse Daniel 
Published: June 2021

ABSTRACTCongenital toxoplasmosis constitutes a major cause of pre- and post-natal complications. Fetal infection with Toxoplasma gondii influences development and can lead to microcephaly, encephalitis, and neurological abnormalities. Few studies have attempted to explain the impact of T. gondii infection on the physiology of mature nerve cells, and no systematic study concerning the effect of infection of neural progenitor cells by T. gondii in the biology of these progenitors is available. We infected cortical intermediate progenitor cell cultivated as neurospheres obtained from E16.5 Swiss Webster mice with T. gondii (Me49 strain) tachyzoites to mimic the developing mouse cerebral cortex in vitro. Infection decreased cell proliferation as detected by Ki67 staining at 48 and 72 hours post infection (hpi) in floating neurospheres, resulting in reduced cellularity at 96 hpi. Neurogenic and gliogenic potential, assessed in plated neurospheres, was shown to be impaired in infected cultures, as indicated by neurofilament heavy chain (NF-200) and GFAP staining, respectively. To further investigate the impact of infection on neuronal differentiation, Neuro2a neuroblasts were infected and after 24 hpi, neurogenic differentiation was induced with serum withdrawal. We confirmed that infection induces a decrease in neuroblast-neuron differentiation rates in cells stained for NF-200, with reduced neuritogenesis. Migration rates were analyzed in plated neurospheres. At 120 h after plating, infected cultures exhibited decreased overall migration rates and altered the radial migration of nestin-, GFAP- and NF-200-positive cells. These findings indicate that T. gondii infection of neural progenitor cells may lead to reduced neuro/gliogenesis due to an imbalance in cell proliferation alongside an altered migratory profile. If translated to the in vivo situation, these data could explain, in part, the cortical malformations observed in congenitally infected individuals.
Development, validation, and application of the ribosome separation and reconstitution system for protein translation in vitro
Authors: Trainor Brandon M. , Pestov Dimitri G. , Shcherbik Natalia 
Published: June 2021

ABSTRACTThe conventional view regarding regulation of gene expression is based on transcription control. However, a growing number of recent studies has revealed the important additional impact of translational regulation. Eukaryotic translational machinery appears to be capable of reprogramming mRNA translation to generate proteins required to maintain a healthy cellular proteostasis under particular physiological conditions or to adapt to stress. Although the mechanisms of such remarkable regulation are beginning to emerge, recent studies have identified the ribosome as one of the major constituents of translation-dependent control of gene expression that is especially important during stress. Built of RNA and proteins, ribosomes are susceptible to environmental and intracellular stresses. How stress-modified ribosomes regulate translation and whether they play a role in stress-induced gene expression remain largely elusive. This knowledge gap is likely due to the lack of an appropriate experimental system. Canonical approaches based on exposing cells or cell-free extracts to stressors provide inconclusive results due to off-target effects of modifying agents. Here we describe a robust and simple in vitro assay that allows separation of yeast ribosomes from other translational machinery constituents, followed by reconstitution of the translation reaction. This ribosome separation and reconstitution assay (RSR) is highly advantageous, as it allows modification of ribosomes without compromising other key translational components, followed by supplementing the ribosomes back into translation reactions containing undamaged, translationally-competent yeast lysate. Besides addressing the impact of ribosome-derived stress on translation, RSR can also be used to characterize mutated ribosomes and ribosomes devoid of associated factors.
Exoskeleton cloud-brain platform and its application in safety assessment
Authors: Xu Fashu , Huang Rui , Cheng Hong , Fan Min , Qiu Jing 
Published: June 2021

Purpose
This paper aims at the problem of attaching the data of doctors, patients and the real-time sensor data of the exoskeleton to the cloud in intelligent rehabilitation applications. This study designed the exoskeleton cloud-brain platform and validated its safety assessment.

Design/methodology/approach
According to the dimension of data and the transmission speed, this paper implements a three-layer cloud-brain platform of exoskeleton based on Alibaba Cloud's Lambda-like architecture. At the same time, given the human–machine safety status detection problem of the exoskeleton, this paper built a personalized machine-learning safety detection module for users with the multi-dimensional sensor data cloned by the cloud-brain platform. This module includes an abnormality detection model, prediction model and state classification model of the human–machine state.

Findings
These functions of the exoskeleton cloud-brain and the algorithms based on it were validated by the experiments, they meet the needs of use.

Originality/value
This thesis innovatively proposes a cloud-brain platform for exoskeletons, beginning the digitalization and intelligence of the exoskeletal rehabilitation process and laying the foundation for future intelligent assistance systems.