bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning identifies explainable reasoning paths of mechanism of action for drug repurposing from multilayer biological network
Authors: Yang Jiannan , Li Zhen , Wu William Ka Kei , Yu Shi , Xu Zhongzhi , Chu Qian , Zhang Qingpeng 
Published: November 2022

Abstract
The discovery and repurposing of drugs require a deep understanding of the mechanism of drug action (MODA). Existing computational methods mainly model MODA with the protein–protein interaction (PPI) network. However, the molecular interactions of drugs in the human body are far beyond PPIs. Additionally, the lack of interpretability of these models hinders their practicability. We propose an interpretable deep learning-based path-reasoning framework (iDPath) for drug discovery and repurposing by capturing MODA on by far the most comprehensive multilayer biological network consisting of the complex high-dimensional molecular interactions between genes, proteins and chemicals. Experiments show that iDPath outperforms state-of-the-art machine learning methods on a general drug repurposing task. Further investigations demonstrate that iDPath can identify explicit critical paths that are consistent with clinical evidence. To demonstrate the practical value of iDPath, we apply it to the identification of potential drugs for treating prostate cancer and hypertension. Results show that iDPath can discover new FDA-approved drugs. This research provides a novel interpretable artificial intelligence perspective on drug discovery.
Monarch Butterfly Ecology, Behavior, and Vulnerabilities in North Central United States Agricultural Landscapes
Authors: Grant Tyler J , Fisher Kelsey E , Krishnan Niranjana , Mullins Alexander N , Hellmich Richard L , Sappington Thomas W , Adelman James S , Coats Joel R , Hartzler Robert G , Pleasants John M , Bradbury Steven P 
Published: November 2022

AbstractThe North American monarch butterfly (Danaus plexippus) is a candidate species for listing under the Endangered Species Act. Multiple factors are associated with the decline in the eastern population, including the loss of breeding and foraging habitat and pesticide use. Establishing habitat in agricultural landscapes of the North Central region of the United States is critical to increasing reproduction during the summer. We integrated spatially explicit modeling with empirical movement ecology and pesticide toxicology studies to simulate population outcomes for different habitat establishment scenarios. Because of their mobility, we conclude that breeding monarchs in the North Central states should be resilient to pesticide use and habitat fragmentation. Consequently, we predict that adult monarch recruitment can be enhanced even if new habitat is established near pesticide-treated crop fields. Our research has improved the understanding of monarch population dynamics at the landscape scale by examining the interactions among monarch movement ecology, habitat fragmentation, and pesticide use.
Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections
Authors: Butler Anne M , Brown Derek S , Newland Jason G , Nickel Katelin B , Sahrmann John M , O’Neil Caroline A , Olsen Margaret A , Zetts Rachel M , Hyun David Y , Durkin Michael J 
Published: November 2022

Abstract

Background
Little is known about the clinical and financial consequences of inappropriate antibiotics. We aimed to estimate the comparative risk of adverse drug events and attributable healthcare expenditures associated with inappropriate versus appropriate antibiotic prescriptions for common respiratory infections.

Methods
We established a cohort of adults aged 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral respiratory infection (influenza, viral upper respiratory infection, nonsuppurative otitis media, bronchitis) from 1 April 2016 to 30 September 2018 using Merative MarketScan Commercial Database. The exposure was an inappropriate versus appropriate oral antibiotic (ie, non-guideline-recommended vs guideline-recommended antibiotic for bacterial infections; any vs no antibiotic for viral infections). Propensity score-weighted Cox proportional hazards models were used to estimate the association between inappropriate antibiotics and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable healthcare expenditures by infection type.

Results
Among 3 294 598 eligible adults, 43% to 56% received inappropriate antibiotics for bacterial and 7% to 66% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and nausea/vomiting/abdominal pain (hazard ratio, 2.90; 95% confidence interval, 1.31–6.41 and hazard ratio, 1.10; 95% confidence interval, 1.03–1.18, respectively, for pharyngitis). Thirty-day attributable healthcare expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18–$67) and variable (−$53 to $49) for viral infections.

Conclusions
Inappropriate antibiotic prescriptions for respiratory infections were associated with increased risks of patient harm and higher healthcare expenditures, justifying a further call to action to implement outpatient antibiotic stewardship programs.
VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study
Authors: Blossey Alexandra M , Brückner Sina , May Marcus , Parzmair Gerald P , Sharma Hitt , Shaligram Umesh , Grode Leander , Kaufmann Stefan H E , Netea Mihai G , Schindler Christoph 
Published: November 2022

AbstractBackgroundBacille Calmette-Guérin (BCG) vaccination can potentially reduce the rate of respiratory infections in vulnerable populations. This study evaluates the safety and efficacy of VPM1002 (a genetically modified BCG) as prophylaxis against severe respiratory tract infections including coronavirus disease 2019 (COVID-19) in an elderly population.MethodsIn this phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy elderly volunteers (N = 2064) were enrolled, randomized (1:1) to receive either VPM1002 or placebo, and followed up remotely for 240 days. The primary outcome was the mean number of days with severe respiratory infections at hospital and/or at home. Secondary endpoints included the incidence of self-reported fever, number of hospital and intensive care unit (ICU) admissions, and number of adverse events.ResultsA total of 31 participants in the VPM1002 group reported at least 1 day with severe respiratory disease and a mean number of days with severe respiratory disease of 9.39 ± 9.28 while in the placebo group; 38 participants reported a mean of 14.29 ± 16.25 days with severe respiratory disease. The incidence of self-reported fever was lower in the VPM1002 group (odds ratio, 0.46 [95% confidence interval, .28–.74]; P = .001), and consistent trends to fewer hospitalization and ICU admissions due to COVID-19 were observed after VPM1002 vaccination. Local reactions typical for BCG were observed in the VPM1002-vaccinated group, which were mostly of mild intensity.ConclusionsVaccination with VPM1002 is well tolerated and seems to have a prophylactic effect against severe respiratory disease in the elderly.Clinical Trials RegistrationNCT04435379.
Onion Thrips (Thysanoptera: Thripidae) Host Plant Preference and Performance are Mediated by a Facultative Plant Pathogen of Onion
Authors: Constancio Natalie , Higgins Doug , Hausbeck Mary , Szendrei Zsofia 
Published: November 2022

Abstract
Insect vector and phytopathogen interactions are mediated by host plants. Insects interact with pathogens directly or indirectly and they may prefer host plants based on infection status. Performance on infected hosts varies depending on the type of pathogen involved. Species specific studies of economically important insects and phytopathogens are needed to understand how these interactions impact crop yields. Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), is an economically devastating insect pest of onions (Allium cepa L., Asparagales: Amaryllidaceae) worldwide and it co-occurs simultaneously with many different pathogens. Colletotrichum coccodes (Wallr) (Glomerellales: Glomerellaceae) is a generalist fungal pathogen that attacks onion foliage, causing tan lesions and decreasing yield. Onion thrips and C. coccodes represent two important pests of onions, but the relationship between onion thrips and C. coccodes infected onions has not been studied, and it is unclear if onion thrips contribute to the spread of C. coccodes in onion fields. A four-choice test with control, artificially injured, artificially injured + symptomatic, and inoculated-symptomatic onion suggests that onion thrips distinguish between hosts based on health status. Furthermore, a two-choice test with control, inoculated-asymptomatic, and inoculated-symptomatic onion pairings revealed that onion thrips distinguish between hosts based on infection status and prefer inoculated-symptomatic hosts. In a no-choice test, onion thrips numbers increased on inoculated-symptomatic plants compared to control or inoculated-asymptomatic plants. Overall, we found that onion thrips preferred and performed best on C. coccodes infected plants.
NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients
Authors: Rossignol P , Duarte K , Bresso E , A Åsberg , Devignes M D , Eriksson N , Girerd N , Glerup R , Jardine A G , Holdaas H , Lamiral Z , Leroy C , Massy Z , März W , Krämer B , Wu P H , Schmieder R , Soveri I , Christensen J H , Svensson M , Zannad F , Fellström B 
Published: November 2022

AbstractAimsEnd-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.Methods and resultsThe AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths.ConclusionsOur findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.
Cost-effectiveness of population screening for atrial fibrillation: the STROKESTOP study
Authors: Lyth Johan , Svennberg Emma , Bernfort Lars , Aronsson Mattias , Frykman Viveka , Al-Khalili Faris , Friberg Leif , Rosenqvist Mårten , Engdahl Johan , Levin Lars-Åke 
Published: November 2022

Abstract

Aims
Previous studies on the cost-effectiveness of screening for atrial fibrillation (AF) are based on assumptions of long-term clinical effects. The STROKESTOP study, which randomised 27 975 persons aged 75/76 years into a screening invitation group and a control group, has a median follow-up time of 6.9 years. The aim of this study was to estimate the cost-effectiveness of population-based screening for AF using clinical outcomes.

Methods and results
The analysis is based on a Markov cohort model. The prevalence of AF, the use of oral anticoagulation, clinical event data, and all-cause mortality were taken from the STROKESTOP study. The cost for clinical events, age-specific utilities, utility decrement due to stroke, and stroke death was taken from the literature. Uncertainty in the model was considered in a probabilistic sensitivity analysis. Per 1000 individuals invited to the screening, there were 77 gained life years and 65 gained quality-adjusted life years. The incremental cost was €1.77 million lower in the screening invitation group. Gained quality-adjusted life years to a lower cost means that the screening strategy was dominant. The result from 10 000 Monte Carlo simulations showed that the AF screening strategy was cost-effective in 99.2% and cost-saving in 92.7% of the simulations. In the base-case scenario, screening of 1000 individuals resulted in 10.6 [95% confidence interval (CI): −22.5 to 1.4] fewer strokes (8.4 ischaemic and 2.2 haemorrhagic strokes), 1.0 (95% CI: −1.9 to 4.1) more cases of systemic embolism, and 2.9 (95% CI: −18.2 to 13.1) fewer bleedings associated with hospitalization.

Conclusion
Based on the STROKESTOP study, this analysis shows that a broad AF screening strategy in an elderly population is cost-effective. Efforts should be made to increase screening participation.
The association between psychological factors and self-care in patients with heart failure: an integrative review
Authors: Wang Zequan , Tocchi Christine , Chyun Deborah , Kim Kyounghae , Cong Xiaomei , Starkweather Angela 
Published: November 2022

Abstract

Aims
This integrative review aims to describe the current evidence concerning the relationship between a broad range of psychological factors (depression, depressive symptoms, anxiety, stress, and type-D personality) and self-care in patients with heart failure.

Methods and results
Six electronic databases were searched and keywords were used to identify potential eligible studies published within the last 10 years. To be eligible, individuals with heart failure aged 18 years or older and who were included in any type of observational study that examined the association between psychological factors and self-care were considered. Twenty articles were included, and 16 of them reported that depression/depressive symptoms were associated with poorer self-care, after controlling for age, sex, education level, cardiac history, or comorbidities. Five studies found that self-care confidence/self-efficacy mediates the relationship between depression/depressive symptoms and self-care. The association between depression/depressive symptoms and self-care varied in assessment methods and statistical approaches. Seven studies showed an inverse association between anxiety and self-care. Four studies found a stronger association between self-care and depression compared with the relationship between self-care and other psychological factors. Stress and type-D personality were both associated with self-care in four studies.

Conclusion
Depression/depressive symptoms and anxiety were found to be inversely associated with self-care in patients with heart failure. Depression exhibited a stronger impact on self-care than other psychological factors. Limited studies assessed stress and type-D personality; the results should be considered with caution. Further studies are warranted on different psychological factors and their underlying mechanisms in individuals with heart failure.
Measles cases in Split-Dalmatia County (a Croatian tourist region), in May–July 2019: outbreak report and lessons learnt
Authors: Brzovic Milka , Barac Juretic Katija , Jurcev-Savicevic Anamarija , Mihojevic Linda , Nonkovic Diana , Rizvan Pero , Vujevic Petrovic Matea , Tonkic Marija , Kaic Bernard , Babic-Erceg Andrea , Vilibic-Cavlek Tatjana , Ivancic-Jelecki Jelena 
Published: November 2022

Abstract

Background
Measles elimination was accomplished in Croatia in 2016. Split-Dalmatia County, with population of ca. 425 000 inhabitants, is among the most important Croatian tourist areas with numerous seasonal workers coming during summer months. In both 2018 and 2019, more than 3 million tourists visited this county. In 2000–2018, there were no measles cases in this county, or their number was low (1–3 cases per year).

Methods
After measles was clinically suspected, all contacts were traced and contacted. Detection of specific IgM/IgG antibodies and real-time reverse transcription–polymerase chain reaction detection of viral RNA were used for laboratory confirmation. Sequencing and genotyping were performed for strains’ molecular epidemiology analysis.

Results
Six epidemiologically unlinked measles virus occurrences happened in Split-Dalmatia County in 15 May–19 July 2019. Causative viral strains belonged to genotypes B3 and D8. Four were single imported cases. Ten patients belonged to two separate clusters within domicile population. Multiple individual and public health measures were implemented. In total, 483 contacts were identified, 64.2% within healthcare system where two persons contracted the disease.

Conclusions
Besides the importance of timely vaccination of children, the lessons learned from this outbreak point to the need of stricter implementation of other aspects of Croatian measles prevention programme, such as checking of vaccination status in early adulthood. Despite the fact that measles elimination within domicile population in this tourist region has been accomplished and maintained for years, continuous public health workers’ efforts are still necessary for identification and diminishment of populational pockets of susceptibility.
Identification of yeasts in fermented foods and beverages using MALDI-TOF MS
Authors: Boyaci Gunduz Cennet Pelin , Agirman Bilal , Erten Huseyin 
Published: November 2022

Abstract
Yeasts are an important group of microorganisms and contribute to the fermentation of a broad range of foods and beverages spontaneously or as a starter culture. Rapid and reliable microbial species identification is essential to evaluate biodiversity in fermented foods and beverages. Nowadays, high-throughput omics technologies and bioinformatics tools produce large-scale molecular-level data in many fields. These omics technologies generate data at different expression levels and are used to identify microorganisms. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a powerful analytical technique in proteomic technology. It is a tool used to analyze the peptides or proteins of microorganisms for identification. MALDI-TOF MS has been used for the taxonomic identification of microorganisms as a fast, high-throughput, and cost-effective method. This review briefly discussed the application of MALDI-TOF MS in identifying yeasts in fermented foods and beverages.
Contrasting Norway spruce disturbance dynamics in managed forests and strict forest reserves in Slovakia
Authors: Potterf Mária , Svitok Marek , Mezei Pavel , Jarčuška Benjamín , Jakuš Rastislav , Blaženec Miroslav , Hlásny Tomáš 
Published: November 2022

AbstractForest disturbances are intensifying globally, yet regional drivers of these dynamics remain poorly understood. We investigated recent disturbance intensities in Norway spruce (Picea abies L.) forests in Slovakia (Central Europe) with different management objectives in 2000–2017 based on Landsat imagery. We focused on 122 strict reserves without any management, their actively managed surroundings (500 m and 2000 m buffers), and managed production forests beyond the buffer areas. We used generalized additive mixed models to test for differences in temporal trends of disturbance intensity among these management categories. We found that disturbance intensity was increasing in all management categories during the studied period. The increase was more pronounced in the managed forests (compound annual disturbance rate 1.76% year−1) and the 2000 m buffer (2.21% year−1) than in the strict reserves (0.58% year−1). The predicted cumulative disturbance during the 18-year period was 9.9% in the reserves and 30.5% in the 2000 m buffer. We found that forests in nature reserves can be more resistant to disturbances than forests managed for timber production, despite management efforts to control disturbances in managed forests. Our findings can help reconcile the different perceptions of natural disturbances and their management in Central Europe and support climate-adapted management strategies that consider natural disturbances as an indispensable component of ecosystem dynamics.
Muscle Endurance and Self-Perceived Fatigue Predict Decline in Gait Speed and Activities of Daily Living After 1-Year Follow-Up: Results From the BUTTERFLY Study
Authors: Knoop Veerle , Costenoble Axelle , Debain Aziz , Bravenboer Bert , Jansen Bart , Scafoglieri Aldo , Bautmans Ivan ,   Gerontopole Brussels Study Group, Bautmans Ivan , Verté Dominque , Beyer Ingo , Petrovic Mirko , De Donder Liesbeth , Kardol Tinie , Rossi Gina , Clarys Peter , Scafoglieri Aldo , Cattrysse Erik , de Hert Paul , Jansen Bart 
Published: November 2022

Abstract

Background
Fatigue might influence the losses in activities of daily living (ADL). When fatigue parameters are present before the experience of losses in ADL and gait speed, they can be used as early warning signals. This study aimed to explore the predictive value of muscle endurance and fatigue on changes in ADL and gait speed in community-dwelling older adults aged 80 and older.

Methods
Three hundred twenty four community-dwelling older adults aged 80 and older of the BUTTERFLY study were assessed after 1 year for muscle endurance, self-perceived fatigue, ADL, and gait speed. Exploratory factor analysis (EFA) was performed to explore, whether there is an underlying arrangement of the fatigue parameters. Mediating logistic regression analyses were used to investigate whether muscle endurance mediated by self-perceived fatigue predicts the decline in gait speed and ADL after 1-year follow-up.

Results
EFA indicated a 2-factor model (muscle endurance factor and self-perceived fatigue factor) and had a moderate fit (X2: 374.81, df: 2, comparative fit index; 0.710, Tucker–Lewis index (TLI): 0.961, root mean square error of approximation [90%]: 0.048 [0.00–0.90]). Muscle endurance mediated by self-perceived fatigue had an indirect effect on the prediction of decline in Basal-ADL (−0.27), Instrumental-ADL (−0.25), and gait speed (−0.28) after 1-year follow-up.

Conclusion
This study showed that low muscle endurance combined with high self-perceived fatigue can predict changes in ADL after 1-year follow-up. These parameters might be very suitable for use in evaluating intrinsic capacity and can help to reduce the limitations in clinical usage of the vitality domain in the framework of intrinsic capacity.