bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sc2Mol: a scaffold-based two-step molecule generator with variational autoencoder and transformer
Authors: Liao Zhirui , Xie Lei , Mamitsuka Hiroshi , Zhu Shanfeng 
Published: December 2022

Abstract

Motivation
Finding molecules with desired pharmaceutical properties is crucial in drug discovery. Generative models can be an efficient tool to find desired molecules through the distribution learned by the model to approximate given training data. Existing generative models (i) do not consider backbone structures (scaffolds), resulting in inefficiency or (ii) need prior patterns for scaffolds, causing bias. Scaffolds are reasonable to use, and it is imperative to design a generative model without any prior scaffold patterns.

Results
We propose a generative model-based molecule generator, Sc2Mol, without any prior scaffold patterns. Sc2Mol uses SMILES strings for molecules. It consists of two steps: scaffold generation and scaffold decoration, which are carried out by a variational autoencoder and a transformer, respectively. The two steps are powerful for implementing random molecule generation and scaffold optimization. Our empirical evaluation using drug-like molecule datasets confirmed the success of our model in distribution learning and molecule optimization. Also, our model could automatically learn the rules to transform coarse scaffolds into sophisticated drug candidates. These rules were consistent with those for current lead optimization.

Availability and implementation
The code is available at https://github.com/zhiruiliao/Sc2Mol.

Supplementary information
Supplementary data are available at Bioinformatics online.
Graph lesion-deficit mapping of fluid intelligence
Authors: Cipolotti Lisa , Ruffle James K , Mole Joe , Xu Tianbo , Hyare Harpreet , Shallice Tim , Chan Edgar , Nachev Parashkev 
Published: December 2022

AbstractFluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated ‘multiple demand’ frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it.We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven’s Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects.Impaired performance was confined to patients with frontal lesions [F(2,387) = 18.491; P &lt; 0.001; frontal worse than non-frontal and healthy participants P &lt; 0.01, P &lt;0.001], more marked on the right than left [F(4,385) = 12.237; P &lt; 0.001; right worse than left and healthy participants P &lt; 0.01, P &lt; 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses.Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven’s Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction.
Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia
Authors: Mohammed Turab , Bowe Michael , Plant Alexandria , Perez Mario , Alvarez Carlos A , Mortensen Eric M 
Published: December 2022

Abstract

Background
Recent studies suggest that metformin use may be associated with improved infectious disease–related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia.

Methods
We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002–2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1.

Results
We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P &lt; .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P &lt; .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78–.95) and 90-day (RR: .85; 95% CI: .79–.92) mortality was significantly lower for metformin users.

Conclusions
Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.
Testing for Mycoplasma genitalium and Using Doxycycline as First-Line Therapy at Initial Presentations for Non-Gonococcal Urethritis (NGU) Correlate With Reductions in Persistent NGU
Authors: Johnson Kelly A , Sankaran Madeline , Kohn Robert P , Bacon Oliver , Cohen Stephanie E 
Published: December 2022

Abstract
We found that the odds of return clinic visits for persistent non-gonococcal urethritis (NGU) were significantly lower (odds ratio: .4; 95% confidence interval: .3–.6; P &lt; .0001) after implementing (1) testing for Mycoplasma genitalium during initial evaluations for NGU and (2) switching from azithromycin to doxycycline as first-line NGU treatment.
Wall shear stress–related plaque growth of lipid-rich plaques in human coronary arteries: an near-infrared spectroscopy and optical coherence tomography study
Authors: Hartman Eline M J , De Nisco Giuseppe , Kok Annette M , Tomaniak Mariusz , Nous Fay M A , Korteland Suze-Anne , Gijsen Frank J H , den Dekker Wijnand K , Diletti Roberto , van Mieghem Nicolas M D A , Wilschut Jeroen M , Zijlstra Felix , van der Steen Anton F W , Budde Ricardo P J , Daemen Joost , Wentzel Jolanda J 
Published: December 2022

Abstract

Aims
Low wall shear stress (WSS) is acknowledged to play a role in plaque development through its influence on local endothelial function. Also, lipid-rich plaques (LRPs) are associated with endothelial dysfunction. However, little is known about the interplay between WSS and the presence of lipids with respect to plaque progression. Therefore, we aimed to study the differences in WSS-related plaque progression between LRPs, non-LRPs, or plaque-free regions in human coronary arteries.

Methods and results
In the present single-centre, prospective study, 40 patients who presented with an acute coronary syndrome successfully underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) of at least one non-culprit vessel at baseline and completed a 1-year follow-up. WSS was computed applying computational fluid dynamics to a three-dimensional reconstruction of the coronary artery based on the fusion of the IVUS-segmented lumen with a CT-derived centreline, using invasive flow measurements as boundary conditions. For data analysis, each artery was divided into 1.5 mm/45° sectors. Plaque growth based on IVUS-derived percentage atheroma volume change was compared between LRPs, non-LRPs, and plaque-free wall segments, as assessed by both OCT and NIRS. Both NIRS- and OCT-detected lipid-rich sectors showed a significantly higher plaque progression than non-LRPs or plaque-free regions. Exposure to low WSS was associated with a higher plaque progression than exposure to mid or high WSS, even in the regions classified as a plaque-free wall. Furthermore, low WSS and the presence of lipids had a synergistic effect on plaque growth, resulting in the highest plaque progression in lipid-rich regions exposed to low shear stress.

Conclusion
This study demonstrates that NIRS- and OCT-detected lipid-rich regions exposed to low WSS are subject to enhanced plaque growth over a 1-year follow-up. The presence of lipids and low WSS proves to have a synergistic effect on plaque growth.
Abaloparatide and teriparatide enhance mandibular growth in adolescent rats with site-specific and mechano-related effects
Authors: Wang Ruyi , Qiao Hui , Qian Yuran , Zhen Gehua , Zhao Zhihe , Li Yu 
Published: December 2022

SummaryObjectiveTeriparatide (TPTD) and abaloparatide (ABL) are two osteoanabolic drugs targeting parathyroid hormone (PTH)1R signalling. This study aimed to investigate the effects of TPTD and ABL on the adolescent mandibular growth.MethodIn total, 70 4-week-old male Sprague-Dawley rats were randomly divided into 14 groups, treated with intermittent TPDT or ABL at various doses, accompanied by mandibular advancement (MA) or not. 3D printing was used to fabricate an innovative splint for MA. After a 4-week treatment, morphological measurement, histological and immunohistochemical analysis were performed. Mandibular condylar chondrocytes (MCCs) were treated with TPTD or ABL, followed by CCK-8 assay, alcian blue staining, real time–PCR and immunofluorescent staining.ResultIn vivo, TPTD or ABL alone increased the condylar length and cartilage thickness, with up-regulated SOX9 and COL II, whilst down-regulated COL X; however, when combined with MA, the promotive effects were attenuated. TPTD or ABL alone increased the mandibular body height and mandibular angle width, whilst increased the mandibular body length and alveolar bone width when combined with MA. In vitro, TPTD or ABL enhanced the MCC proliferation, glycosaminoglycan synthesis, COL II and SOX9 expression, whilst down-regulated COL X, Ihh and PTH1R expression.ConclusionBoth ABL and TPTD enhance mandibular growth in adolescent rats with site-specific and mechano-related effects, including propelling chondrogenesis at the condylar cartilage and promoting bone apposition at other mechano-responsive sites. They behave as promising drugs for mandibular growth modification, and in general ABL seems more potent than TPTD in this context.
Escaping one’s disadvantage? Neighbourhoods, socioeconomic origin and children’s adult life outcomes
Authors: Brandén Maria , Haandrikman Karen , Birkelund Gunn Elisabeth 
Published: December 2022

Abstract
This study investigates if neighbourhoods can alter the strong relationship between parental background and children’s adult outcomes. In particular, we examine if neighbourhood effects are heterogeneous in such a way that they are particularly important for children from disadvantaged backgrounds, and if school quality has a mediating effect in this equation. Using register data and individualized neighbourhoods, we follow five full birth cohorts of individuals born from 1983 to 1987. We examine the interaction between social background and neighbourhoods in shaping (i) the risk of children relying on social welfare when they are aged 30, and (ii) the probability of belonging to the highest income decile at age 30–34. Growing up in a resource-rich neighbourhood is associated with better life outcomes. Contrary to what several neighbourhood theories predict, we find that neighbourhood effects operate similarly regardless of social background. Differences in peer composition of schools does not explain these local neighbourhood effects, whereas own school results attenuate neighbourhood effects substantially. Our findings are in contrast to results from the United States studies but are in line with historical Swedish studies; and contribute to further disentangling the various mechanisms through which the neighbourhood operates.
Application of the fission yeast Schizosaccharomyces pombe in human nutrition
Authors: Chen Ee Sin 
Published: December 2022

Abstract
Fission yeast Schizosaccharomyces pombe (S. pombe) is renowned as a powerful genetic model for deciphering cellular and molecular biological phenomena, including cell division, chromosomal events, stress responses, and human carcinogenesis. Traditionally, Africans use S. pombe to ferment the beer called ‘Pombe’, which continues to be consumed in many parts of Africa. Although not as widely utilized as the baker's yeast Saccharomyces cerevisiae, S. pombe has secured several niches in the food industry for human nutrition because of its unique metabolism. This review will explore three specific facets of human nutrition where S. pombe has made a significant impact: namely, in wine fermentation, animal husbandry and neutraceutical supplementation coenzyme Q10 production. Discussions focus on the current gaps in these areas, and the potential research advances useful for addressing future challenges. Overall, gaining a better understanding of S. pombe metabolism will strengthen production in these areas and potentially spearhead novel future applications.
Anti-restriction protein ArdA promotes clinical Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae spread and its molecular mechanism
Authors: Chen Huimin , Tao Shuan , Li Na , Zhu Qing , Liu Liping , Fang Yeiwei , Xu Yao , Liang Wei 
Published: December 2022

Abstract

Background
Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has spread worldwide and has become a major threat to public health. The restriction modification system provides an innate defence of bacteria against plasmids or transposons, while many different types of plasmid encoding the anti-restriction protein ArdA can specifically affect the restriction activity in bacteria.

Objectives
To detect the codistribution of ArdA and blaKPC-2 plasmids in KPC-KP and explore the molecular mechanism of ArdA promoting KPC-KP spread.

Methods
We collected 65 clinical CRKP isolates from Ningbo, China, and 68 cases of plasmid complete sequences in GenBank to determine the prevalence of ArdA gene on the K. pneumoniae blaKPC-2 plasmid. The anti-restriction function of ArdA in promoting horizontal gene transfer (HGT) was verified by transformation, conjugation and transduction methods, and the pull-down experiment was used to investigate the molecular mechanism of ArdA protein in vitro.

Results
We found that ArdA was widely distributed in KPC-KP in 100% of cases, which was detected in 0% of drug susceptible K. pneumoniae, and the plasmids containing the ArdA gene in 90% of the 30 cases randomly retrieved from the database. We also verified that ArdA has a good anti-restriction function (P &lt; 0.05) through two aspects of HGT (transformation, transduction), and explored the non-occurrence interaction of ArdA and the hsdM subunit protein of EcoKI enzyme from the perspective of protein molecules.

Conclusions
These findings suggest that the coexistence advantage of ArdA with the blaKPC-2 plasmids may provide KPC-producing K. pneumoniae with a very efficient evasion of the restriction of type I systems, which not only favours ArdA-containing mobile genetic elements in the same species HGT between bacteria also facilitates HGT between other bacterial species.
Household Preferences and Child Labor in Rural Ethiopia
Authors: Basu Arnab , Dimova Ralitza 
Published: December 2022

Abstract
This paper revisits the causes behind child labor supply by focusing on an aspect that has received little attention: the link between the household head's risk and time preferences and observed child labor supply. We develop a theoretical model and empirically test for this link using data from the seventh round of the Ethiopian Rural Household Survey. We find child labor at the extensive and intensive margins to be increasing in both higher adult discount rates and higher degrees of risk aversion, and this finding is robust across alternative empirical specifications. While higher time discount rates are supposed to favor child labor at the expense of schooling, the explanation of the positive link between risk aversion of the household head and observed child labor supply is nuanced. The most plausible explanation is that risk averse parents react to uncertain returns to education by combining child labor and schooling as opposed to substituting schooling for child labor.
Multi-horizon predictive models for guiding extracorporeal resource allocation in critically ill COVID-19 patients
Authors: Xue Bing , Shah Neel , Yang Hanqing , Kannampallil Thomas , Payne Philip Richard Orrin , Lu Chenyang , Said Ahmed Sameh 
Published: December 2022

AbstractObjectiveExtracorporeal membrane oxygenation (ECMO) resource allocation tools are currently lacking. We developed machine learning (ML) models for predicting COVID-19 patients at risk of receiving ECMO to guide patient triage and resource allocation.Material and MethodsWe included COVID-19 patients admitted to intensive care units for &gt;24 h from March 2020 to October 2021, divided into training and testing development and testing-only holdout cohorts. We developed ECMO deployment timely prediction model ForecastECMO using Gradient Boosting Tree (GBT), with pre-ECMO prediction horizons from 0 to 48 h, compared to PaO2/FiO2 ratio, Sequential Organ Failure Assessment score, PREdiction of Survival on ECMO Therapy score, logistic regression, and 30 pre-selected clinical variables GBT Clinical GBT models, with area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics.ResultsECMO prevalence was 2.89% and 1.73% in development and holdout cohorts. ForecastECMO had the best performance in both cohorts. At the 18-h prediction horizon, a potentially clinically actionable pre-ECMO window, ForecastECMO, had the highest AUROC (0.94 and 0.95) and AUPRC (0.54 and 0.37) in development and holdout cohorts in identifying ECMO patients without data 18 h prior to ECMO.Discussion and ConclusionsWe developed a multi-horizon model, ForecastECMO, with high performance in identifying patients receiving ECMO at various prediction horizons. This model has potential to be used as early alert tool to guide ECMO resource allocation for COVID-19 patients. Future prospective multicenter validation would provide evidence for generalizability and real-world application of such models to improve patient outcomes.
The effect of harvest time of forage on carbohydrate digestion in horses quantified by in vitro and mobile bag techniques
Authors: Stang Frida Lindskov , Bjerregaard Rikke , Müller Cecilia Elisabeth , Ergon Åshild , Halling Magnus , Thorringer Nana Wentzel , Kidane Alemayehu , Jensen Rasmus Bovbjerg 
Published: December 2022

Abstract
Carbohydrates in forages constitute an important part of the feed ration for all horses. The aim of the present study was to investigate the effect of harvest time on carbohydrate composition and digestion of various grass species. The experiment was divided into three parts 1) characterization of the chemical composition of experimental feeds (6 grass species: meadow fescue [MF], cocksfoot [CF], perennial ryegrass [PR], smooth bromegrass [SB], tall fescue [TF], and timothy [TI], and 3 harvest times: early, medium, and late first cut), 2) measurements of the in vitro digestion of selected experimental feeds (the 6 grass species, and 2 harvest times [early and late]) measured by in vitro gas production, and 3) in vivo digestion of selected experimental feeds (2 grass species: CF and PR, 2 harvest times [early and late]) measured by the mobile bag technique using caecum cannulated horses. An experimental field was established with plots containing each of the grass species in three replicate blocks. Grass samples were cut between 1200 and 1400 h at 4th of June (early first cut), 17th of June (medium first cut), and 1st of July (late first cut) and analyzed for crude protein (CP), neutral detergent fiber with heat stable amylase and free of residual ash (aNDFom) and water-soluble carbohydrates (WSC). The in vitro fermentation was investigated using the ANKOM RF gas production technique, where feeds were incubated for 48 h using horse caecal fluid as an inoculum. Gas production was modeled, and maximum gas production (MGP) was used to evaluate the potential digestibility of the feeds. Based on the chemical analyses and the in vitro experiment, early and late harvested CF and PR were selected for the in vivo experiment, which was conducted as a randomized 4 × 4 Latin square design including four periods, four horses and four feeds. In general, the CP content decreased whereas the aNDFom content increased as the grasses matured. The content of WSC increased in SB and TI, but decreased in CF, and fructans increased in SB, TI, PR, and TF as they matured. The in vitro MGP showed a clearer difference between harvest times than between grass species. Harvest time had larger effect on digestibility than grass species, and a high precaecal disappearance of the WSC fraction was measured by the mobile bag technique. Cocksfoot was identified as a grass species with potentially low digestibility and low WSC content and could potentially be used more for horses.
Geographic Dependence and Diversification in House Price Returns: The Role of Leverage
Authors: Heinen Andréas , Kim Mi Lim , Hamadi Malika 
Published: December 2022

Abstract
We analyze the time variation in the average dependence within a set of regional monthly house price index returns in a regime-switching multivariate copula model with a high and a low dependence regime. Using equidependent Gaussian copulas, we show that the dependence of house price returns varies across time with changes in credit market conditions, which reduces the gains from the geographic diversification of real estate and mortgage portfolios. More specifically, we show that a decrease in leverage, measured by the loan-to-value ratio, and to a lesser extent an increase in mortgage rates, are associated with a higher probability of moving to and staying in the high dependence regime.