bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of urine microbiota in patients with lower urinary tract symptoms
Authors: Lee Hsiang-Ying , Wang Jiunn‐Wei , Juan Yung-Shun , Li Ching-Chia , Liu Chung-Jung , Cho Sung Yong , Yeh Hsin-Chih , Chueh Kuang-Shun , Wu Wen-Jeng , Wu Deng‐Chyang 
Published: April 2021

Abstract
Introduction
Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS).

Materials and methods
We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at − 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson’s correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples.

Results
We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman’s correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05).

Conclusion
Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.
mRNA therapeutics in cancer immunotherapy
Authors: Beck Jan D. , Reidenbach Daniel , Salomon Nadja , Sahin Ugur , Türeci Özlem , Vormehr Mathias , Kranz Lena M. 
Published: April 2021

AbstractSynthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.
Determining the psychometric properties of a novel questionnaire to measure “preparedness for the future” (Prep FQ)
Authors: Heyland Daren K. , Pope J. Paige , Jiang Xuran , Day Andrew G. 
Published: April 2021

Abstract
Background
People are living longer than ever before. However, with living longer comes increased problems that negatively impact on quality of life and the quality of death. Tools are needed to help individuals assess whether they are practicing the best attitudes and behaviors that are associated with a future long life, high quality of life, high quality of death and a satisfying post-death legacy. The purpose of paper is to describe the process we used to develop a novel questionnaire (“Preparedness for the Future Questionnaire™ or Prep FQ”) and to define its psychometric properties.

Methods
Using a multi-step development procedure, items were generated, for the new questionnaire after which the psychometric properties were tested with a heterogeneous sample of 502 Canadians. Using an online polling panel, respondents were asked to complete demographic questions as well as the Prep-FQ, Global Rating of Life Satisfaction, the Keyes Psychological Well-Being scale and the Short-Form 12.

Results
The final version of the questionnaire contains 34 items in 8 distinct domains (“Medico-legal”, “Social”, “Psychological Well-being”, “Planning”, “Enrichment”, “Positive Health Behaviors”, “Negative Health Behaviors”, and “Late-life Planning”). We observed minimum missing data and good usage of all response options. The average overall Prep FQ score is 51.2 (SD = 13.3). The Cronbach alphas assessing internal reliability for the Prep FQ domains ranged from 0.33 to 0.88. The intra-class correlation coefficient (ICC) used to assess the test–retest reliability had an overall score of 0.87. For the purposes of establishing construct validity, all the pre-specified relationships between Prep FQ and the other questionnaires were met.

Conclusion
Analyses of this novel measure offered support for its face validity, construct validity, test–retest reliability, and internal consistency. With the development of this useful and valid scale, future research can utilize this measure to engage people in the process of comprehensively assessing and improving their state of preparedness for the future, tracking their progress along the way. Ultimately, this program of research aims to improve the quality and quantity of peoples live by helping them ‘think ahead’ and ‘plan ahead’ on the aspects of their daily life that matter to their future.
Current status and recent advances in resection cavity irradiation of brain metastases
Authors: Minniti Giuseppe , Niyazi Maximilian , Andratschke Nicolaus , Guckenberger Matthias , Palmer Joshua D. , Shih Helen A. , Lo Simon S. , Soltys Scott , Russo Ivana , Brown Paul D. , Belka Claus 
Published: April 2021

AbstractDespite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.
Risk factors associated with surgical site infections after thoracic or lumbar surgery: a 6-year single centre prospective cohort study
Authors: Spatenkova Vera , Bradac Ondrej , Jindrisek Zdenek , Hradil Jan , Fackova Daniela , Halacova Milada 
Published: April 2021

Abstract
Background
Surgical site infection (SSI) is a risk in every operation. Infections negatively impact patient morbidity and mortality and increase financial demands. The aim of this study was to analyse SSI and its risk factors in patients after thoracic or lumbar spine surgery.

Methods
A six-year single-centre prospective observational cohort study monitored the incidence of SSI in 274 patients who received planned thoracic or lumbar spinal surgery for degenerative disease, trauma, or tumour. They were monitored for up to 30 days postoperatively and again after 1 year. All patients received short antibiotic prophylaxis and stayed in the eight-bed neurointensive care unit (NICU) during the immediate postoperative period. Risk factors for SSI were sought using multivariate logistic regression analysis.

Results
We recorded 22 incidences of SSI (8.03%; superficial 5.84%, deep 1.82%, and organ 0.36%). Comparing patients with and without SSI, there were no differences in age (p=0.374), gender (p=0.545), body mass index (p=0.878), spine diagnosis (p=0.745), number of vertebrae (p=0.786), spine localization (p=0.808), implant use (p=0.428), American Society of Anesthesiologists (ASA) Score (p=0.752), urine catheterization (p=0.423), drainage (p=0.498), corticosteroid use (p=0.409), transfusion (p=0.262), ulcer prophylaxis (p=0.409) and diabetes mellitus (p=0.811). The SSI group had longer NICU stays (p=0.043) and more non-infectious hospital wound complications (p<0.001). SSI risk factors according to our multivariate logistic regression analysis were hospital wound complications (OR 20.40, 95% CI 7.32–56.85, p<0.001) and warm season (OR 2.92, 95% CI 1.03–8.27, p=0.044).

Conclusions
Contrary to the prevailing literature, our study did not identify corticosteroids, diabetes mellitus, or transfusions as risk factors for the development of SSI. Only wound complications and warm seasons were significantly associated with SSI development according to our multivariate regression analysis.
Lessons learned from implementation of a national hotline for Ebola virus disease emergency preparedness in South Sudan
Authors: Lopez Velma K. , Shetty Sharmila , Kouch Angelo Thon , Khol Matthew Tut , Lako Richard , Bili Alexandre , Ayuen Anyang David , Jukudu Agnes , Kug Ajak Ater , Mayen Atem David , Nyawel Emmanuel , Berta Kibebu , Olu Olushayo , Clarke Kevin , Bunga Sudhir 
Published: April 2021

Abstract
Background
The world’s second largest Ebola outbreak occurred in the Democratic Republic of Congo from 2018 to 2020. At the time, risk of cross-border spread into South Sudan was very high. Thus, the South Sudan Ministry of Health scaled up Ebola preparedness activities in August 2018, including implementation of a 24-h, toll-free Ebola virus disease (EVD) hotline. The primary purpose was the hotline was to receive EVD alerts and the secondary goal was to provide evidence-based EVD messages to the public.

Methods
To assess whether the hotline augmented Ebola preparedness activities in a protracted humanitarian emergency context, we reviewed 22 weeks of call logs from January to June 2019. Counts and percentages were calculated for all available data.

Results
The hotline received 2114 calls during the analysis period, and an additional 1835 missed calls were documented. Callers used the hotline throughout 24-h of the day and were most often men and individuals living in Jubek state, where the national capital is located. The leading reasons for calling were to learn more about EVD (68%) or to report clinical signs or symptoms (16%). Common EVD-related questions included EVD signs and symptoms, transmission, and prevention. Only one call was documented as an EVD alert, and there was no documentation of reported symptoms or whether the person met the EVD case definition.

Conclusions
Basic surveillance information was not collected from callers. To trigger effective outbreak investigation from hotline calls, the hotline should capture who is reporting and from where, symptoms and travel history, and whether this information should be further investigated. Electronic data capture will enhance data quality and availability of information for review. Additionally, the magnitude of missed calls presents a major challenge. When calls are answered, there is potential to provide health communication, so risk communication needs should be considered. However, prior to hotline implementation, governments should critically assess whether their hotline would yield actionable data and if other data sources for surveillance or community concerns are available.
Machine learning and statistical approaches for classification of risk of coronary artery disease using plasma cytokines
Authors: Saharan Seema Singh , Nagar Pankaj , Creasy Kate Townsend , Stock Eveline O. , Feng James , Malloy Mary J. , Kane John P. 
Published: April 2021

AbstractBackgroundAs per the 2017 WHO fact sheet, Coronary Artery Disease (CAD) is the primary cause of death in the world, and accounts for 31% of total fatalities. The unprecedented 17.6 million deaths caused by CAD in 2016 underscores the urgent need to facilitate proactive and accelerated pre-emptive diagnosis. The innovative and emerging Machine Learning (ML) techniques can be leveraged to facilitate early detection of CAD which is a crucial factor in saving lives. The standard techniques like angiography, that provide reliable evidence are invasive and typically expensive and risky. In contrast, ML model generated diagnosis is non-invasive, fast, accurate and affordable. Therefore, ML algorithms can be used as a supplement or precursor to the conventional methods. This research demonstrates the implementation and comparative analysis of K Nearest Neighbor (k-NN) and Random Forest ML algorithms to achieve a targeted “At Risk” CAD classification using an emerging set of 35 cytokine biomarkers that are strongly indicative predictive variables that can be potential targets for therapy. To ensure better generalizability, mechanisms such as data balancing, repeated k-fold cross validation for hyperparameter tuning, were integrated within the models. To determine the separability efficacy of “At Risk” CAD versus Control achieved by the models, Area under Receiver Operating Characteristic (AUROC) metric is used which discriminates the classes by exhibiting tradeoff between the false positive and true positive rates.ResultsA total of 2 classifiers were developed, both built using 35 cytokine predictive features. The best AUROC score of .99 with a 95% Confidence Interval (CI) (.982,.999) was achieved by the Random Forest classifier using 35 cytokine biomarkers. The second-best AUROC score of .954 with a 95% Confidence Interval (.929,.979) was achieved by the k-NN model using 35 cytokines. Ap-value of less than 7.481e-10 obtained by an independent t-test validated that Random Forest classifier was significantly better than the k-NN classifier with regards to the AUROC score.Presently, as large-scale efforts are gaining momentum to enable early, fast, reliable, affordable, and accessible detection of individuals at risk for CAD, the application of powerful ML algorithms can be leveraged as a supplement to conventional methods such as angiography. Early detection can be further improved by incorporating 65 novel and sensitive cytokine biomarkers. Investigation of the emerging role of cytokines in CAD can materially enhance the detection of risk and the discovery of mechanisms of disease that can lead to new therapeutic modalities.
Clinical characteristics of children infected with SARS-CoV-2 in Italy
Authors: De Jacobis Isabella Tarissi , Vona Rosa , Cittadini Camilla , Marchesi Alessandra , Cursi Laura , Gambardella Lucrezia , Villani Alberto , Straface Elisabetta 
Published: April 2021

Abstract
Background
Since December 2019 coronavirus disease (COVID-19) emerged in Wuhan and spread rapidly worldwide. Despite the high number of people affected, data on clinical features and prognostic factors in children and adolescents are limited. We propose a retrospective study aimed to evaluate clinical characteristics of children infected with SARS-CoV-2 in Italy.

Methods
A pediatric population admitted with COVID-19 to Bambino Gesù Children’s Hospital of Rome (Italy) in the period from the end of February to July 2020 has been studied. Medical history, comorbidities, symptoms and laboratory findings were obtained from patients’ electronic medical records.

Results
In 66 patients (35 males and 31 females) we found that: i) fever and cough were the dominant symptoms, while vomit and convulsions were rare symptoms; and ii) all ages of childhood were susceptible to COVID-19. Furthermore, we found that, compared to females, males with COVID-19, although not significantly, had higher values of inflammatory markers such as C-reactive protein (CRP) and ESR. Conversely, we found that COVID-19 positive females were older than males and required more days of hospitalization. Both males and females COVID-19 positives had procalcitonin values within the normal range and D-Dimer values slightly higher than the normal range. With regard to this latter marker, the value measured in females, although not significant, was higher than that measured in males. Interestingly, the presence of leukopenia was found in both sexes.

Conclusions
Compared to the adults we found that COVID-19 infection in children is a non-severe inflammatory disease in both males and females. In any case, many detailed studies should be conducted.
Mechanisms of enhancer action: the known and the unknown
Authors: Panigrahi Anil , O’Malley Bert W. 
Published: April 2021

AbstractDifferential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic and phylogenetic diversity of cell types. A key regulator of differential gene expression programs are the enhancers, the gene-distalcis-regulatory sequences that govern spatiotemporal and quantitative expression dynamics of target genes. Enhancers are widely believed to physically contact the target promoters to effect transcriptional activation. However, our understanding of the full complement of regulatory proteins and the definitive mechanics of enhancer action is incomplete. Here, we review recent findings to present some emerging concepts on enhancer action and also outline a set of outstanding questions.
Risk of gout among Taiwanese adults with ALDH-2 rs671 polymorphism according to BMI and alcohol intake
Authors: Liu Yu-Ruey , Tantoh Disline Manli , Lin Chuan-Chao , Hsiao Chih-Hsuan , Liaw Yung-Po 
Published: April 2021

AbstractBackgroundGout stems from both modifiable and genetic sources. We evaluated the risk of gout among Taiwanese adults with aldehyde dehydrogenase-2 (ALDH2) rs671 single nucleotide polymorphism (SNP) according to body mass index (BMI) and alcohol drinking.MethodsWe obtained information of 9253 individuals having no personal history of cancer from the Taiwan Biobank (2008–2016) and estimated the association between gout and independent variables (e.g., rs671, BMI, and alcohol drinking) using multiple logistic regression.ResultsAlcohol drinking and abnormal BMI were associated with a higher risk of gout whereas the rs671 GA+AA genotype was associated with a lower risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were 1.297 and 1.098–1.532 for alcohol drinking, 1.550 and 1.368–1.755 for abnormal BMI, and 0.887 and 0.800–0.984 for GA+AA. The interaction between BMI and alcohol on gout was significant for GG (p-value = 0.0102) and GA+AA (p-value = 0.0175). When we stratified genotypes by BMI, alcohol drinking was significantly associated with gout only among individuals with a normal BMI (OR; 95% CI = 1.533; 1.036–2.269 for GG and 2.109; 1.202–3.699 for GA+AA). Concerning the combination of BMI and alcohol drinking among participants stratified by genotypes (reference, GG genotype, normal BMI, and no alcohol drinking), the risk of gout was significantly higher in the following categories: GG, normal BMI, and alcohol drinking (OR, 95% CI = 1.929, 1.385–2.688); GG, abnormal BMI, and no alcohol drinking (OR, 95% CI, = 1.721, 1.442–2.052); GG, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.941, 1.501–2.511); GA+AA, normal BMI, and alcohol drinking (OR, 95% CI = 1.971, 1.167–3.327); GA+AA, abnormal BMI, and no alcohol drinking (OR, 95% CI = 1.498, 1.256–1.586); and GA+AA, abnormal BMI, and alcohol drinking (OR, 95% CI = 1.545, 1.088–2.194).ConclusionsAlcohol and abnormal BMI were associated with a higher risk of gout, whereas the rs671 GA+AA genotype was associated with a lower risk. Noteworthy, BMI and alcohol had a significant interaction on gout risk. Stratified analyses revealed that alcohol drinking especially among normal-weight individuals might elevate the risk of gout irrespective of the genotype.
Snail mucus from the mantle and foot of two land snails, Lissachatina fulica and Hemiplecta distincta, exhibits different protein profile and biological activity
Authors: Noothuan Nattaphop , Apitanyasai Kantamas , Panha Somsak , Tassanakajon Anchalee 
Published: April 2021

AbstractObjectiveSnails secrete different types of mucus that serve several functions, and are increasingly being exploited for medical and cosmetic applications. In this study, we explored the protein pattern and compared the biological properties of the mucus secreted from the mantle collar and foot of two snail species,Lissachatina fulicaandHemiplecta distincta.ResultProtein profile showed a different pattern between the two species and between the two secretory parts. The mantle-specific protein bands were further characterized and among them was an antibacterial protein, achacin. Accordingly, the mucus from the mantle exhibited the higher antibacterial activity than that from the foot in both snail species. The mucus fromH. distincta, first reported here, also showed antibacterial properties, but with a lower activity compared to that forL. fulica. Snail mucus also exhibited anti-tyrosinase activity and antioxidant activity but with no significant difference between the foot and mantle mucus. These results indicate some different protein compositions and biological activities of snail slime from the mantle and foot, which might be associated with their specific functions in the animal and are useful for medical applications.