bluuebunny/crossref_metadata_2025_split huggingface dataset:
One year monitoring of SARS-CoV-2 prevalence in a German cohort of patients with cystic fibrosis
Authors: Jaudszus Anke , Pavlova Mariya , Rasche Marius , Baier Michael , Moeser Anne , Lorenz Michael 
Published: March 2022

Abstract
Background
In Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF).

Methods
From February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data.

Results
In total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized.

Conclusions
SARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.
Discomfort, pain and stiffness: what do these terms mean to patients? A cross-sectional survey with lexical and qualitative analyses
Authors: Funabashi Martha , Wang Simon , Lee Alexander D , C. K. Duarte Felipe , Budgell Brian , Stilwell Peter , Hogg-Johnson Sheilah 
Published: March 2022

Abstract
Background
While pain is often the focus of clinical interventions, other clinical outcomes (e.g., discomfort, stiffness) might also contribute to patients’ functionality and well-being. Although researchers and clinicians may view discomfort, pain and stiffness as different constructs, it remains unclear how patients perceive and differentiate between these constructs. Therefore, the purpose of this study was to explore patients’ perceptions of pain, discomfort, and stiffness.

Methods
Chiropractic patients were invited to complete an online cross-sectional survey and describe what ‘discomfort’, ‘pain’ and ‘stiffness’ meant to them using their own words. Lexical and inductive qualitative content analyses were conducted independently and then triangulated.

Results
Fifty-three chiropractic patients (47.2% female, mean age: 39.1 ± 15.1 years) responded. The most common combinations of words to describe discomfort were “can be ignored” and “less severe than”. “Cannot be ignored” and “sharp shooting” were used to describe pain. “Limited range of motion” was used to describe stiffness. Qualitatively, five themes were developed: impact, character, feeling, intensity and temporality. Stiffness was described as limited movement/mobility. Although discomfort and stiffness impacted patients’ activities, patients remained functional; pain was described as stopping/limiting activities. Discomfort was described as dull and tingling, pain as sharp and shooting, and stiffness as tight and restricted. Patients felt displeased and annoyed when experiencing discomfort and stiffness but hurt and in danger of harm when experiencing pain. Discomfort and stiffness were described as less intense than pain, with shorter/intermittent duration; however, all constructs could be experienced constantly.

Conclusion
Patients perceived discomfort, pain and stiffness as different, yet overlapping constructs. This preliminary work advances our knowledge of how patients conceptualize these constructs, contributing to better understanding of what patients mean when reporting these experiences, potentially improving the clinician-patient communication.
A copper switch for inducing CRISPR/Cas9-based transcriptional activation tightly regulates gene expression in Nicotiana benthamiana
Authors: Garcia-Perez Elena , Diego-Martin Borja , Quijano-Rubio Alfredo , Moreno-Giménez Elena , Selma Sara , Orzaez Diego , Vazquez-Vilar Marta 
Published: March 2022

Abstract
Background
CRISPR-based programmable transcriptional activators (PTAs) are used in plants for rewiring gene networks. Better tuning of their activity in a time and dose-dependent manner should allow precise control of gene expression. Here, we report the optimization of a Copper Inducible system called CI-switch for conditional gene activation in Nicotiana benthamiana. In the presence of copper, the copper-responsive factor CUP2 undergoes a conformational change and binds a DNA motif named copper-binding site (CBS).

Results
In this study, we tested several activation domains fused to CUP2 and found that the non-viral Gal4 domain results in strong activation of a reporter gene equipped with a minimal promoter, offering advantages over previous designs. To connect copper regulation with downstream programmable elements, several copper-dependent configurations of the strong dCasEV2.1 PTA were assayed, aiming at maximizing activation range, while minimizing undesired background expression. The best configuration involved a dual copper regulation of the two protein components of the PTA, namely dCas9:EDLL and MS2:VPR, and a constitutive RNA pol III-driven expression of the third component, a guide RNA with anchoring sites for the MS2 RNA-binding domain. With these optimizations, the CI/dCasEV2.1 system resulted in copper-dependent activation rates of 2,600-fold and 245-fold for the endogenous N. benthamiana DFR and PAL2 genes, respectively, with negligible expression in the absence of the trigger.

Conclusions
The tight regulation of copper over CI/dCasEV2.1 makes this system ideal for the conditional production of plant-derived metabolites and recombinant proteins in the field.
The relationships between women’s reproductive factors: a Mendelian randomisation analysis
Authors: Prince Claire , Sharp Gemma C. , Howe Laura D. , Fraser Abigail , Richmond Rebecca C. 
Published: March 2022

Abstract
Background
Women’s reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors.

Methods
We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap.

Results
LDSC indicated that most reproductive factors are genetically correlated (rg range: |0.06–0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (rg < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = −0.38 SD, CI = −0.44, −0.32).

Conclusion
This study presents evidence that women’s reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman’s entire reproductive history, including the causal interplay between reproductive factors.
Diversity and pathogenesis of Staphylococcus aureus from bovine mastitis: current understanding and future perspectives
Authors: Campos Bruno , Pickering Amy C. , Rocha Lis Souza , Aguilar Ananda Pereira , Fabres-Klein Mary Hellen , de Oliveira Mendes Tiago Antônio , Fitzgerald J. Ross , de Oliveira Barros Ribon Andrea 
Published: March 2022

AbstractStaphylococcus aureus is a leading cause of bovine mastitis worldwide. Despite some improved understanding of disease pathogenesis, progress towards new methods for the control of intramammary infections (IMI) has been limited, particularly in the field of vaccination. Although herd management programs have helped to reduce the number of clinical cases, S. aureus mastitis remains a major disease burden. This review summarizes the past 16 years of research on bovine S. aureus population genetics, and molecular pathogenesis that have been conducted worldwide. We describe the diversity of S. aureus associated with bovine mastitis and the geographical distribution of S. aureus clones in different continents. We also describe studies investigating the evolution of bovine S. aureus and the importance of host-adaptation in its emergence as a mastitis pathogen. The available information on the prevalence of virulence determinants and their functional relevance during the pathogenesis of bovine mastitis are also discussed. Although traits such as biofilm formation and innate immune evasion are critical for the persistence of bacteria, the current understanding of the key host-pathogen interactions that determine the outcome of S. aureus IMI is very limited. We suggest that greater investment in research into the genetic and molecular basis of bovine S. aureus pathogenesis is essential for the identification of novel therapeutic and vaccine targets.
Protein interaction networks provide insight into fetal origins of chronic obstructive pulmonary disease
Authors: Röhl Annika , Baek Seung Han , Kachroo Priyadarshini , Morrow Jarrett D. , Tantisira Kelan , Silverman Edwin K. , Weiss Scott T. , Sharma Amitabh , Glass Kimberly , DeMeo Dawn L. 
Published: March 2022

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of death in adults that may have origins in early lung development. It is a complex disease, influenced by multiple factors including genetic variants and environmental factors. Maternal smoking during pregnancy may influence the risk for diseases during adulthood, potentially through epigenetic modifications including methylation.MethodsIn this work, we explore the fetal origins of COPD by utilizing lung DNA methylation marks associated with in utero smoke (IUS) exposure, and evaluate the network relationships between methylomic and transcriptomic signatures associated with adult lung tissue from former smokers with and without COPD. To identify potential pathobiological mechanisms that may link fetal lung, smoke exposure and adult lung disease, we study the interactions (physical and functional) of identified genes using protein–protein interaction networks.ResultsWe build IUS-exposure and COPD modules, which identify connected subnetworks linking fetal lung smoke exposure to adult COPD. Studying the relationships and connectivity among the different modules for fetal smoke exposure and adult COPD, we identify enriched pathways, including the AGE-RAGE and focal adhesion pathways.ConclusionsThe modules identified in our analysis add new and potentially important insights to understanding the early life molecular perturbations related to the pathogenesis of COPD. We identify AGE-RAGE and focal adhesion as two biologically plausible pathways that may reveal lung developmental contributions to COPD. We were not only able to identify meaningful modules but were also able to study interconnections between smoke exposure and lung disease, augmenting our knowledge about the fetal origins of COPD.
Construction of cell factory capable of efficiently converting l-tryptophan into 5-hydroxytryptamine
Authors: Wang Yingying , Chen Xueman , Chen Qiaoyu , Zhou Ning , Wang Xin , Zhang Alei , Chen Kequan , Ouyang Pingkai 
Published: March 2022

Abstract
Background
l-Tryptophan (l-Trp) derivatives such as 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT), N-Acetyl-5-hydroxytryptamine and melatonin are important molecules with pharmaceutical interest. Among, 5-HT is an inhibitory neurotransmitter with proven benefits for treating the symptoms of depression. At present, 5-HT depends on plant extraction and chemical synthesis, which limits its mass production and causes environmental problems. Therefore, it is necessary to develop an efficient, green and sustainable biosynthesis method to produce 5-HT.

Results
Here we propose a one-pot production of 5-HT from l-Trp via two enzyme cascades for the first time. First, a chassis cell that can convert l-Trp into 5-HTP was constructed by heterologous expression of tryptophan hydroxylase from Schistosoma mansoni (SmTPH) and an artificial endogenous tetrahydrobiopterin (BH4) module. Then, dopa decarboxylase from Harminia axyridis (HaDDC), which can specifically catalyse 5-HTP to 5-HT, was used for 5-HT production. The cell factory, E. coli BL21(DE3)△tnaA/BH4/HaDDC-SmTPH, which contains SmTPH and HaDDC, was constructed for 5-HT synthesis. The highest concentration of 5-HT reached 414.5 ± 1.6 mg/L (with conversion rate of 25.9 mol%) at the optimal conditions (substrate concentration,2 g/L; induced temperature, 25℃; IPTG concentration, 0.5 mM; catalysis temperature, 30℃; catalysis time, 72 h).

Conclusions
This protocol provided an efficient one-pot method for converting. l-Trp into 5-HT production, which opens up possibilities for the practical biosynthesis of natural 5-HT at an industrial scale.
The molecular mechanism of METTL3 promoting the malignant progression of lung cancer
Authors: Ma Chao , Ma Rui-Jie , Hu Kang , Zheng Qi-Ming , Wang Ye-Peng , Zhang Nan , Sun Zhi-Gang 
Published: March 2022

AbstractLung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.
Biochemical but not imaging parameters are predictive of outcome in septic shock: a pilot study
Authors: Belli Oriana E. , Campolo Jonica , Vallerio Paola , Musca Francesco , Moreo Antonella , Maloberti Alessandro , Parolini Marina , Bonacchini Luca , Monti Gianpaola , De Gasperi Andrea , Fumagalli Roberto , Giannattasio Cristina 
Published: March 2022

Abstract
Background
Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.

Methods
Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.

Results
The multivariate Cox’s proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000–1.034; P = 0.049). An angiopoietin-2 concentrations ≥ of 33,418 pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.

Conclusions
Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting.
Titanium nanosheet as robust and biosafe drug carrier for combined photochemo cancer therapy
Authors: Yuan Xiaoli , Zhu Ying , Li Shasha , Wu Yiqun , Wang Zhongshi , Gao Rui , Luo Shiyao , Shen Juan , Wu Jun , Ge Liang 
Published: March 2022

AbstractTwo-dimensional (2D) Titanium nanosheets (Ti NSs) have shown many excellent properties, such as nontoxicity, satisfactory photothermal conversion efficacy, etc. However, the biomedical applications of Ti NSs have not been intensively investigated. Herein, we synthesized a multifunctional Ti NS drug delivery system modified with polydopamine/polyethylene glycol (Ti@PDA-PEG) and applied simultaneously for photothermal therapy and chemotherapy. Doxorubicin (DOX) was utilized as a model drug. Ti@PDA-PEG NS shows an ultrahigh antitumor drug DOX loading (Ti@PDA-PEG-DOX). The prepared Ti@PDA-PEG-DOX NS as robust drug delivery system demonstrates great stability and excellent multi-response drug-release capabilities, including pH-responsive and near-infrared -responsive behavior and obviously high photothermal efficiency. Both in vitro and in vivo experimental results have shown high biosafety and outstanding antitumor effects. Therefore, this work exhibits the enormous potential of a multifunctional platform in the treatment of tumors and may stimulate interest in the exploration of other new 2D nanomaterials for biomedical applications.
Graphical Abstract
Psychometric properties of the end-of-life care decision inventory (EOL-CDI): a mixed-methods study
Authors: Kim Shinmi , Lee Insook , Hong Sun-Woo , Koh Su-Jin 
Published: March 2022

Abstract
Background
End-of-life care decision-making has become important to support dignity and quality of life for patients who are facing death in Korea, along with the enactment of the Life-Sustaining Treatment Act in 2018. However, it seems that the concepts and policies related to the law are not yet familiar to health care providers or the general public. This unfamiliarity can hinder efficient end-of-life care discussions. Therefore, the purpose of this study was to propose a valid and reliable tool to explore the level of understanding of concepts and attributes related to end-of-life care decisions.

Methods
This is a mixed-methods study design. A relevant law and literature analysis, expert consultation, cognitive interviews of 10 adults, and cross-sectional survey for psychometric tests using data from 238 clinical nurses were performed to update a tool developed before the life-sustaining treatment Act was enacted in Korea.

Results
29 items of the draft version were polished in terms of literacy, total length, and scoring method via cognitive interviews and finalized into 21 items through psychometric tests and expert consultations. The 21 items conformed to the Rasch unidimensional paramenters.

Conclusion
A tool to identify the level of understanding of concepts related to end-of-life care decisions was proposed through a rather rigorous process to ensure feasibility and validity/reliability. We recommend the proposed tool to apply to the adult population and nurses for evaluation and educational purposes.
Relevant HRH leadership during public health emergencies
Authors: Ferrinho Paulo , Lehman Uta , Kovacs Eszter , Poz Mario Dal 
Published: March 2022

Abstract
Background
Inadequate leadership capacity compounds the world's workforce lack of preparedness for outbreaks of all sizes, as illustrated by the COVID-19 pandemic.
Traditional human resources for health (HRH) leadership has focused on determining the health workforce requirements, often failing to fully consider the unpredictability associated with issues such as public health emergencies (PHE).

Main arguments
The current COVID-19 pandemic demonstrates that policy-making and relevant leadership have to be effective under conditions of ethical uncertainty and with inconclusive evidence. The forces at work in health labor markets (HLM) entail leadership that bridges across sectors and all levels of the health systems. Developing and applying leadership competencies must then be understood from a systemic as well as an individual perspective. To address the challenges described and to achieve universal health coverage (UHC) by 2030, countries need to develop effective HRH leaderships relevant to the complexity of HLM in the most diverse contexts, including acute surge events during PHE. In complex and rapidly changing contexts, such as PHE, leadership needs to be attentive, nimble, adaptive, action oriented, transformative, accountable and provided throughout the system, i.e., authentic, distributed and participatory. This type of leadership is particularly important, as it can contribute to complex organizational changes as required in surge events associated with PHE, even in in the absence of formal management plans, roles, and structures. To deal with the uncertainty it needs agile tools that may allow prompt human resources impact assessments.

Conclusions
The complexity of PHE requires transformative, authentic, distributed and participatory leadership of HRH. The unpredictable aspects of the dynamics of the HLM during PHE require the need to rethink, adapt and operationalize appropriate tools, such as HRH impact assessment tools, to redirect workforce operations rapidly and with precision.