bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the mechanisms driving multimorbidity in COPD to develop holistic approaches to patient-centred care
Authors: Burke H. , Wilkinson T.M.A. 
Published: June 2021

COPD is a major cause of morbidity and mortality worldwide. Multimorbidity is common in COPD patients and a key modifiable factor, which requires timely identification and targeted holistic management strategies to improve outcomes and reduce the burden of disease.We discuss the use of integrative approaches, such as cluster analysis and network-based theory, to understand the common and novel pathobiological mechanisms underlying COPD and comorbid disease, which are likely to be key to informing new management strategies.Furthermore, we discuss the current understanding of mechanistic drivers to multimorbidity in COPD, including hypotheses such as multimorbidity as a result of shared common exposure to noxious stimuli (e.g.tobacco smoke), or as a consequence of loss of function following the development of pulmonary disease. In addition, we explore the links to pulmonary disease processes such as systemic overspill of pulmonary inflammation, immune cell priming within the inflamed COPD lung and targeted messengers such as extracellular vesicles as a result of local damage as a cause for multimorbidity in COPD.Finally, we focus on current and new management strategies which may target these underlying mechanisms, with the aim of holistic, patient-centred treatment rather than single disease management.
Effects of mechanical ventilation with expiratory negative airway pressure on porcine pulmonary and systemic circulation: mechano-physiology and potential application
Authors: Hagiwara-Nagasawa Mihoko , Kambayashi Ryuichi , Goto Ai , Chiba Koki , Wada Takeshi , Nunoi Yoshio , Izumi-Nakaseko Hiroko , Takei Yoshinori , Matsumoto Akio , Lurie Keith G. , Sugiyama Atsushi 
Published: June 2021

AbstractWe studied the impact of mechanically regulated, expiratory negative airway pressure (ENAP) ventilation on pulmonary and systemic circulation including its mechanisms and potential applications. Microminipigs weighing about 10 kg were anesthetized (n = 5). First, hemodynamic variables were evaluated without and with ENAP to approximately −16 cmH2O. ENAP significantly increased heart rate and cardiac output, but decreased right atrial, pulmonary arterial and pulmonary capillary wedge pressures. Second, the evaluation was repeated following pharmacological adrenergic blockade, modestly blunting ENAP effects. Third, fluvoxamine (10 mg/kg) was intravenously administered to intentionally induce cardiovascular collapse in the presence of adrenergic blockade. ENAP was started when systolic pressure was < 40 mmHg in the animals assigned to ENAP treatment-group. Fluvoxamine induced cardiovascular collapse within 4 out of 5 animals. ENAP increased systolic pressure to > 50 mmHg (n = 2): both animals fully recovered without neurological deficit, whereas without ENAP both animals died of cardiac arrest (n = 2). ENAP may become an innovative treatment for drug-induced cardiovascular collapse.
PIKE-R2P: Protein–protein interaction network-based knowledge embedding with graph neural network for single-cell RNA to protein prediction
Authors: Dai Xinnan , Xu Fan , Wang Shike , Mundra Piyushkumar A. , Zheng Jie 
Published: June 2021

Abstract
Background
Recent advances in simultaneous measurement of RNA and protein abundances at single-cell level provide a unique opportunity to predict protein abundance from scRNA-seq data using machine learning models. However, existing machine learning methods have not considered relationship among the proteins sufficiently.

Results
We formulate this task in a multi-label prediction framework where multiple proteins are linked to each other at the single-cell level. Then, we propose a novel method for single-cell RNA to protein prediction named PIKE-R2P, which incorporates protein–protein interactions (PPI) and prior knowledge embedding into a graph neural network. Compared with existing methods, PIKE-R2P could significantly improve prediction performance in terms of smaller errors and higher correlations with the gold standard measurements.

Conclusion
The superior performance of PIKE-R2P indicates that adding the prior knowledge of PPI to graph neural networks can be a powerful strategy for cross-modality prediction of protein abundances at the single-cell level.
Identifying genomic islands with deep neural networks
Authors: Assaf Rida , Xia Fangfang , Stevens Rick 
Published: June 2021

Abstract
Background
Horizontal gene transfer is the main source of adaptability for bacteria, through which genes are obtained from different sources including bacteria, archaea, viruses, and eukaryotes. This process promotes the rapid spread of genetic information across lineages, typically in the form of clusters of genes referred to as genomic islands (GIs). Different types of GIs exist, and are often classified by the content of their cargo genes or their means of integration and mobility. While various computational methods have been devised to detect different types of GIs, no single method is capable of detecting all types.

Results
We propose a method, which we call Shutter Island, that uses a deep learning model (Inception V3, widely used in computer vision) to detect genomic islands. The intrinsic value of deep learning methods lies in their ability to generalize. Via a technique called transfer learning, the model is pre-trained on a large generic dataset and then re-trained on images that we generate to represent genomic fragments. We demonstrate that this image-based approach generalizes better than the existing tools.

Conclusions
We used a deep neural network and an image-based approach to detect the most out of the correct GI predictions made by other tools, in addition to making novel GI predictions. The fact that the deep neural network was re-trained on only a limited number of GI datasets and then successfully generalized indicates that this approach could be applied to other problems in the field where data is still lacking or hard to curate.
Metagenomic diagnosis of severe psittacosis using multiple sequencing platforms
Authors: Wang Kaiying , Liu Xiong , Liu Huiying , Li Peihan , Lin Yanfeng , Yin Dongdong , Yang Lang , Li Jinhui , Li Shenlong , Jia Leili , Bai Changqing , Jiang Yongqiang , Li Peng , Song Hongbin 
Published: June 2021

Abstract
Background
Chlamydia psittaci is an avian pathogen that can cause lethal human infections. Diagnosis of C. psittaci pneumonia is often delayed due to nonspecific clinical presentations and limited laboratory diagnostic techniques.

Results
The MinION platform established the diagnosis in the shortest time, while BGISEQ-500 generated additional in-depth sequence data that included the rapid characterization of antibiotic susceptibility. Cytopathy appeared only in cell cultures of BALF. BALF yielded a higher bacterial load than sputum or blood, and may be the most suitable clinical specimen for the genomic diagnosis of severe pneumonia.

Conclusions
This study indicated that the benefits of metagenomic sequencing include rapid etiologic diagnosis of unknown infections and the provision of additional relevant information regarding antibiotic susceptibility. The continued optimization and standardization of sampling and metagenomic analysis promise to enhance the clinical utility of genomic diagnosis.
Complete genome sequence of Arthrobacter sp. PAMC25564 and its comparative genome analysis for elucidating the role of CAZymes in cold adaptation
Authors: Han So-Ra , Kim Byeollee , Jang Jong Hwa , Park Hyun , Oh Tae-Jin 
Published: June 2021

Abstract
Background
The Arthrobacter group is a known set of bacteria from cold regions, the species of which are highly likely to play diverse roles at low temperatures. However, their survival mechanisms in cold regions such as Antarctica are not yet fully understood. In this study, we compared the genomes of 16 strains within the Arthrobacter group, including strain PAMC25564, to identify genomic features that help it to survive in the cold environment.

Results
Using 16 S rRNA sequence analysis, we found and identified a species of Arthrobacter isolated from cryoconite. We designated it as strain PAMC25564 and elucidated its complete genome sequence. The genome of PAMC25564 is composed of a circular chromosome of 4,170,970 bp with a GC content of 66.74 % and is predicted to include 3,829 genes of which 3,613 are protein coding, 147 are pseudogenes, 15 are rRNA coding, and 51 are tRNA coding. In addition, we provide insight into the redundancy of the genes using comparative genomics and suggest that PAMC25564 has glycogen and trehalose metabolism pathways (biosynthesis and degradation) associated with carbohydrate active enzyme (CAZymes). We also explain how the PAMC26654 produces energy in an extreme environment, wherein it utilizes polysaccharide or carbohydrate degradation as a source of energy. The genetic pattern analysis of CAZymes in cold-adapted bacteria can help to determine how they adapt and survive in such environments.

Conclusions
We have characterized the complete Arthrobacter sp. PAMC25564 genome and used comparative analysis to provide insight into the redundancy of its CAZymes for potential cold adaptation. This provides a foundation to understanding how the Arthrobacter strain produces energy in an extreme environment, which is by way of CAZymes, consistent with reports on the use of these specialized enzymes in cold environments. Knowledge of glycogen metabolism and cold adaptation mechanisms in Arthrobacter species may promote in-depth research and subsequent application in low-temperature biotechnology.
Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study
Authors: Moitinho-Silva Lucas , Wegener Michelle , May Sandra , Schrinner Florian , Akhtar Awais , Boysen Teide J. , Schaeffer Eva , Hansen Clint , Schmidt Timo , Rühlemann Malte C. , Hübenthal Matthias , Rausch Philipp , Kondakci Mustafa T. , Maetzler Walter , Weidinger Stephan , Laudes Matthias , Süß Philip , Schulte Dominik , Junker Ralf , Sommer Felix , Weisser Burkhard , Bang Corinna , Franke Andre 
Published: June 2021

Abstract
Background
Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models. Thus, we conducted a randomised intervention study that focused on the effects of different types of training (endurance and strength) in previously physically inactive, healthy adults in comparison to controls that did not perform regular exercise. Overall study duration was ten weeks including six weeks of intervention period. In addition to 16S rRNA gene amplicon sequencing of longitudinally sampled faecal material of participants (six time points), detailed body composition measurements and analysis of blood samples (at baseline and after the intervention) were performed to obtain overall physiological changes within the intervention period. Activity tracker devices (wrist-band wearables) provided activity status and sleeping patterns of participants as well as exercise intensity and heart measurements.

Results
Different biometric responses between endurance and strength activities were identified, such as a significant increase of lymphocytes and decrease of mean corpuscular haemoglobin concentration (MCHC) only within the strength intervention group. In the endurance group, we observed a significant reduction in hip circumference and an increase in physical working capacity (PWC). Though a large variation of microbiota changes were observed between individuals of the same group, we did not find specific collective alterations in the endurance nor the strength groups, arguing for microbiome variations specific to individuals, and therefore, were not captured in our analysis.

Conclusions
We could show that different types of exercise have distinct but moderate effects on the overall physiology of humans and very distinct microbial changes in the gut. The observed overall changes during the intervention highlight the importance of physical activity on well-being. Future studies should investigate the effect of exercise on a longer timescale, investigate different training intensities and consider high-resolution shotgun metagenomics technology.

Trial registration
DRKS, DRKS00015873. Registered 12 December 2018; Retrospectively registered.
Sarcopenia as a predictor of mortality among the critically ill in an intensive care unit: a systematic review and meta-analysis
Authors: Zhang Xiao-Ming , Chen Denghong , Xie Xiao-Hua , Zhang Jun-E , Zeng Yingchun , Cheng Andy SK 
Published: June 2021

Abstract
Background
The evidence of sarcopenia based on CT-scan as an important prognostic factor for critically ill patients has not seen consistent results. To determine the impact of sarcopenia on mortality in critically ill patients, we performed a systematic review and meta-analysis to quantify the association between sarcopenia and mortality.

Methods
We searched studies from the literature of PubMed, EMBASE, and Cochrane Library from database inception to June 15, 2020. All observational studies exploring the relationship between sarcopenia based on CT-scan and mortality in critically ill patients were included. The search and data analysis were independently conducted by two investigators. A meta-analysis was performed using STATA Version 14.0 software using a fixed-effects model.

Results
Fourteen studies with a total of 3,249 participants were included in our meta-analysis. The pooled prevalence of sarcopenia among critically ill patients was 41 % (95 % CI:33-49 %). Critically ill patients with sarcopenia in the intensive care unit have an increased risk of mortality compared to critically ill patients without sarcopenia (OR = 2.28, 95 %CI: 1.83–2.83; P < 0.001; I2 = 22.1 %). In addition, a subgroup analysis found that sarcopenia was associated with high risk of mortality when defining sarcopenia by total psoas muscle area (TPA, OR = 3.12,95 %CI:1.71–5.70), skeletal muscle index (SMI, OR = 2.16,95 %CI:1.60–2.90), skeletal muscle area (SMA, OR = 2.29, 95 %CI:1.37–3.83), and masseter muscle(OR = 2.08, 95 %CI:1.15–3.77). Furthermore, critically ill patients with sarcopenia have an increased risk of mortality regardless of mortality types such as in-hospital mortality (OR = 1.99, 95 %CI:1.45–2.73), 30-day mortality(OR = 2.08, 95 %CI:1.36–3.19), and 1-year mortality (OR = 3.23, 95 %CI:2.08 -5.00).

Conclusions
Sarcopenia increases the risk of mortality in critical illness. Identifying the risk factors of sarcopenia should be routine in clinical assessments and offering corresponding interventions may help medical staff achieve good patient outcomes in ICU departments.
The sex difference in gait speed among older adults: how do sociodemographic, lifestyle, social and health determinants contribute?
Authors: Sialino Lena D. , Schaap Laura A. , van Oostrom Sandra H. , Picavet H. Susan J. , Twisk Johannes W.R. , Verschuren W. M. Monique , Visser Marjolein , Wijnhoven Hanneke A.H. 
Published: June 2021

Abstract
Background
This study explores whether a sex difference in sensitivity to (strength of the association) and/or in exposure to (prevalence) determinants of gait speed contributes to the observed lower gait speed among older women compared to men.

Methods
Data from the Longitudinal Aging Study Amsterdam (LASA) were used. In total 2407 men and women aged 55–81 years were included, with baseline measurements in 1992/2002 and follow-up measurements every 3–4 years for 15/25 years. Multivariable mixed model analysis was used to investigate sex differences in sensitivity (interaction term with sex) and in exposure to (change of the sex difference when adjusted) socio-demographic, lifestyle, social and health determinants of gait speed.

Results
Women had a 0.054 m/s (95 % CI: 0.076 − 0.033, adjusted for height and age) lower mean gait speed compared to men. In general, men and women had similar determinants of gait speed. However, higher BMI and lower physical activity were more strongly associated with lower gait speed in women compared to men (i.e. higher sensitivity). More often having a lower educational level, living alone and having more chronic diseases, pain and depressive symptoms among women compared to men also contributed to observed lower gait speed in women (i.e. higher exposure). In contrast, men more often being a smoker, having a lower physical activity and a smaller personal network size compared to women contributed to a lower gait speed among men (i.e. higher exposure).

Conclusions
Both a higher sensitivity and higher exposure to determinants of gait speed among women compared to men contributes to the observed lower gait speed among older women. The identified (modifiable) contributing factors should be taken into account when developing prevention and/or treatment strategies aimed to enhance healthy physical aging. This might require a sex-specific approach in both research and clinical practice, which is currently often lacking.
Transitions between levels of dependency among older people receiving social care – a retrospective longitudinal cohort study in a Swedish municipality
Authors: Zingmark Magnus , Norström Fredrik 
Published: June 2021

AbstractBackgroundKnowledge is scarce on how needs for home help and special housing evolve among older people who begin to receive support from municipal social care. The purpose of this study was to describe baseline distributions and transitions over time between levels of dependency among older persons after being granted social care in a Swedish municipality.MethodsBased on a longitudinal cohort study in a Swedish municipality, data was collected retrospectively from municipal records. All persons 65 years or older who received their first decision on social care during 2010 (n = 415) were categorized as being in mild, moderate, severe, or total dependency, and were observed until the end of 2013. Baseline distributions and transitions over time were described descriptively and analysed with survival analysis, with the Kaplan-Meier estimator, over the entire follow-up period. To test potential differences in relation to gender, we used the Cox-Proportional hazards model.ResultsBaseline distributions between mild, moderate, severe, and total dependency were 53, 16, 24, and 7.7%. During the first year, between 40 and 63% remained at their initial level of dependency. Among those with mild and moderate levels of dependency at baseline, a large proportion declined towards increasing levels of dependency over time; around 40% had increased their dependency level 1 year from baseline and at the end of the follow-up, 75% had increased their dependency level or died.ConclusionsOlder people in Sweden being allocated home help are at high risk for decline towards higher levels of dependency, especially those at mild or moderate dependency levels at baseline. Taken together, it is important that municipalities make use of existing knowledge so that they implement cost-effective preventative interventions for older people at an early stage before a decline toward increasing levels of dependency.
Reducing the use of empiric antibiotic therapy in COVID-19 on hospital admission
Authors: Pettit Natasha N. , Nguyen Cynthia T. , Lew Alison K. , Bhagat Palak H. , Nelson Allison , Olson Gregory , Ridgway Jessica P. , Pho Mai T. , Pagkas-Bather Jade 
Published: June 2021

Abstract
Background
Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19.

Methods
This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics.

Results
A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p < 0.001. The median DOT in the post-intervention group was 1.3 days shorter (p < 0.001) than the pre-intervention group, and antibiotics directed at atypical bacteria DOT was reduced by 2.8 days (p < 0.001). More patients in the post-intervention group were initiated on antibiotics based on criteria consistent with our guideline (68% versus 87%, p = 0.001). There were no differences between groups in terms of clinical outcomes.

Conclusion
Following the implementation of a guideline outlining recommendations for initiating and discontinuing antibiotics for CABP among COVID-19 inpatients, we observed a reduction in antibiotic prescribing and DOT. The guideline also resulted in a significant increase in the rate of guideline-congruent empiric antibiotic initiation.