bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of 2-amino benzothiazoles with bactericidal activity againstMycobacterium tuberculosis
Authors: Bonnett Shilah , Jee Jo-Ann , Chettiar Somsundaram , Ovechkina Yulia , Korkegian Aaron , Greve Eric , Odingo Joshua , Parish Tanya 
Published: September 2022

ABSTRACTWe identified an amino-benzothiazole scaffold from a whole cell screen against recombinantMycobacterium tuberculosisunder expressing the essential signal peptidase LepB. The seed molecule had two-fold higher activity against the LepB hypomorph. Through a combination of purchase and chemical synthesis we explored the structure activity relationship for this series; 34 analogs were tested for anti-tubercular activity and for cytotoxicity against eukaryotic cells. We identified molecules with improved potency and reduced cytotoxicity. However, molecules did not appear to target LepB directly and did not inhibit protein secretion. Key compounds showed good permeability, low protein binding, and lack of CYP inhibition, but metabolic stability was poor with short half-lives. The seed molecule showed good bactericidal activity against both replicating and non-replicating bacteria, as well as potency against intracellularM. tuberculosisin murine macrophages. Overall, the microbiological properties of the series are attractive if metabolic stability can be improved, and identification of the target could assist in development of this series.
Spurious off-target signals from potential lncRNAs by 10X Visium probes
Authors: Prakrithi P. , Juwayria  , Jain Deepali , Malik Prabhat Singh , Gupta Ishaan 
Published: September 2022

AbstractSpatial transcriptomics has revolutionized molecular profiling of tissues in a spatial context, especially in the study of cancer heterogeneity. 10X Genomics facilitates spatial gene expression profiling platforms to help work with fresh-frozen (FF) and formalin fixed paraffin embedded (FFPE) tissues. FF analysis is based on polyA capture of RNAs while FFPE analysis uses a pre-designed set of probes to capture transcripts of coding genes. Previously, we used FFPE spatial data as a ‘negative control’ in a study to identify novel non-coding RNAs in FF data. Interestingly, we find and report that certain target probes used in FFPE show off-target signals from lncRNAs. The Space Ranger pipeline of 10X Visium counts the expression of these potential off-targets to be that of the corresponding target gene, some of which have known implications in cancer and its diagnosis. Therefore, relying on this technology is not ideal to investigate expression of the genes reported in this study. We hereby recommend excluding those genes in any downstream analysis of FFPE datasets and to design probes with better specificity, considering the sequence similarity between genes and non-coding RNAs.
SmartGate is a spatial metabolomics tool for resolving tissue structures
Authors: Xiao Kaixuan , Wang Yu , Dong Kangning , Zhang Shihua 
Published: September 2022

AbstractImaging mass spectrometry (IMS) is one of the powerful tools in spatial metabolomics for obtaining metabolite data and probing the internal microenvironment of organisms. It has dramatically advanced the understanding of the structure of biological tissues and the drug treatment of diseases. However, the complexity of IMS data hinders the further acquisition of biomarkers and the study of certain specific activities of organisms. To this end, we introduce an artificial intelligence tool SmartGate to enable automatic peak picking and spatial structure identification in an iterative manner. SmartGate selects discriminative m/z features from the previous iteration by differential analysis and employs a graph attention auto-encoder model to perform spatial clustering for tissue segmentation using the selected features. We applied SmartGate to diverse IMS data at multicellular or subcellular spatial resolutions and compared it with four competing methods to demonstrate its effectiveness. SmartGate can significantly improve the accuracy of spatial segmentation and identify biomarker metabolites based on tissue structure-guided differential analysis. For multiple consecutive IMS data, SmartGate can effectively identify structures with spatial heterogeneity by introducing three-dimensional spatial neighbor information.
Complex scaffold remodeling in plant triterpene biosynthesis
Authors: De La Peña Ricardo , Hodgson Hannah , Liu Jack C.T. , Stephenson Michael J. , Martin Azahara C. , Owen Charlotte , Harkess Alex , Leebens-Mack Jim , Jimenez Luis E. , Osbourn Anne , Sattely Elizabeth S. 
Published: September 2022

AbstractTriterpenes with complex scaffold modifications are widespread in plants yet little is known regarding biosynthesis. Limonoids are an exemplary family that includes the bitter taste in citrus (e.g., limonin) and the active constituents in neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite limonoid commercial value, a complete biosynthetic route has not been described. Here, we report the discovery of 22 enzymes that catalyze 12 unique reactions including the 4-carbon scission and furan installation that are a signature of the limonoid family and a pair of sterol isomerases previously unknown in plants. This gene set is then used for the total biosynthesis of kihadalactone A and azadirone in a heterologous plant. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations.
The impact of digitalization on firm performance: examining the role of digital culture and the effect of supply chain capability
Authors: Hautala-Kankaanpää Tuire 
Published: September 2022

PurposeThe study examines the impact of digital platforms and supply chain capability on operational performance and tests the mediation effect of supply chain capability. Further, the purpose is to examine the moderating effect of digital culture and sharpen our knowledge of how organizational culture as a contextual factor affects the firm's digitalization.Design/methodology/approachThe data were harvested from 194 Finnish manufacturing companies, and structural equation modeling was used to test the hypotheses.FindingsThe findings show that digital platforms positively and significantly affect supply chain capability. Moreover, supply chain capability mediates the relation between digital platforms and operational performance. Further, this study confirms that digital culture is a contextual factor that explains the differences in the effects of digital platforms on firm performance.Originality/valueThis study is one of the first attempts to examine the effect of digital culture in the context of digital platforms, supply chain capabilities, and operational performance.
Light and storage time influence the microbial quality of minimally processed rocket
Authors: Zappia Angela , Malacrinò Antonino , Belgacem Imen , Abdelfattah Ahmed , Piscopo Amalia 
Published: September 2022

AbstractReady‐to‐eat minimally processed fruits and vegetables are an ideal substrate for the growth of microorganisms, including human pathogens and mycotoxin‐producing species, which question their quality and safety for customers. While we are aware of the importance of production workflows in structuring the products' microbial communities, we still know little about the factors that shape microbiomes during the timeframe products are available to customers, and beyond this timeframe. Here, we study the influence of storage light condition (light or dark) on microbiological and physico‐chemical parameters of minimally processed rocket leaves at different shelf life timepoints (the day the product becomes available to consumers, expiration date, 3 days after the expiration date). Our results suggest that the total microbial load increases from the day the product becomes available to consumers, to the expiry date and after the product's expiration. However, when studying the composition of the fungal microbiome, we did not observe significant changes in its structure as the effect of product shelf life or storage light condition. We also found that products stored under light condition had a higher total bacterial load compared to those stored in darkness. Our results might be helpful in crafting improved workflows for product's storage during its shelf life, which might ultimately lead to a re‐evaluation of storage times resulting in reduced food waste due to product spoilage or expiration.
RNA sequencing of single allergen‐specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect
Authors: McKenzie Craig I. , Varese Nirupama , Aui Pei Mun , Reinwald Simone , Wines Bruce D. , Hogarth P. Mark , Thien Francis , Hew Mark , Rolland Jennifer M. , O'Hehir Robyn E. , van Zelm Menno C. 
Published: September 2022

AbstractBackgroundSublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen‐specific IgG4. IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B‐cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen‐specific Bmem subsets induced by SLIT for grass pollen allergy.MethodsBlood samples were collected twice outside the pollen season from twenty‐seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4‐month pre‐seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single‐cell RNA sequencing was performed on FACS‐purified Lol p 1‐specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort.ResultsFour months of SLIT increased RGP‐specific IgE and IgG4 in serum and induced two Lol p 1‐specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4, CD23, and CD29 after SLIT.ConclusionsA clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface‐expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.
The panorama of cerebral palsy in Sweden part XIII shows declining prevalence in birth‐years 2011–2014
Authors: Himmelmann Kate , Påhlman Magnus 
Published: September 2022

AbstractAimTo describe epidemiology and characteristics of cerebral palsy (CP) in western Sweden 1954–2014.MethodsPopulation‐based study covering 105 935 live births in the area in 2011–2014. Birth characteristics, neuroimaging findings and outcome were analysed and prevalence calculated. Non‐parametric methods were used for group comparisons.ResultsCP was diagnosed in 192 children. Crude prevalence had decreased to 1.81 per 1000 live births (p = 0.0067). Gestational age‐specific prevalence for <28 gestational weeks was 74.8 per 1000 live births, 46.6 for 28–31 weeks, 5.8 for 32–36 weeks and 1.1 per 1000 for >36 weeks of gestation. Hemiplegia, found in 36.2%, had declined (p = 0.03). Diplegia was found in 36.2% and tetraplegia 5.3%. Dyskinetic CP accounted for 18.6% and ataxia for 3.7%. Neuroimaging revealed maldevelopments in 14%, white matter lesions in 44%, cortical/subcortical lesions in 13% and basal ganglia lesions in 17%. Prenatal aetiology was considered in 34%, peri‐ or neonatal in 48%, while in 18% aetiological period remained unclassified. Motor outcome in children who needed neonatal care had improved (p = 0.04). Motor function in dyskinetic CP had improved compared to previous cohorts (p = 0.008).ConclusionThe prevalence of CP has declined, mainly in term‐born and in hemiplegia, and motor severity has changed compared to previous cohorts.
A patient with bullous pemphigoid presenting with haemorrhagic oral erosions, oral haematoma and haemoptysis
Authors: Phuan Zhen Yu Crystal , Lee Xiu Hue , Tay Hui Ming , Rajaratnam Ratna , Ang Chia Chun 
Published: September 2022

Abstract
We present a case of a patient with bullous pemphigoid presenting with acquired haemophilia A. This is characterized by formation of antibodies or inhibitors against coagulation Factor VIII, leading to a prolonged activated partial thromboplastin time with normal prothrombin time and international normalized ratio. Our case emphasizes the need for increased awareness among dermatologists of this uncommon and potentially life-threatening condition.
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Three‐Dimensional tooth models for better teaching and treatment outcomes
Authors: Fakhr Mohamed , Nagy Mohamed Mokhtar 
Published: September 2022

AbstractIntroductionThe aim of this study was to fabricate 3‐Dimensional (3D) tooth models to overcome procedural errors that occur during treatment and to improve endodontic management of teeth with complex pulp morphology and dental anomalies.Materials and MethodsThree natural teeth were used to fabricate resinous tooth models (n = 90) and 90 natural teeth were used during root canal treatment. Models were fabricated from 1 mandibular canine (n = 30) and 2 maxillary molars (n = 60). Natural teeth were 30 mandibular canines, 30 mandibular molars and 30 maxillary molars.ResultsNatural teeth and opaque resin models were significantly better than the clear resin models during access preparation (p = .003). In addition, the clear resin models were significantly better than the natural teeth and opaque resin models during shaping, obturation and as an educational tool (p < .001, p < .001 and p < .001 respectively).ConclusionsAlthough it takes more time and effort to produce 3D (3D) tooth models from each natural tooth used in the study, it can give more accurate results during evaluation.
Pulmonary function is a strong predictor of 2‐year overall survival and non‐relapse mortality after allogenic hematopoietic cell transplantation
Authors: Schierbeck Frederikke , Mortensen Jann , Andersen Niels S. , Friis Lone S. , Kornblit Brian , Petersen Søren L. , Schjødt Ida , Sengeløv Henrik 
Published: September 2022

AbstractObjectivesThe purpose of the study was to assess the validity of the hematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) and of pulmonary comorbidity prior to HCT in terms of predicting non‐relapse mortality (NRM) and overall survival (OS).MethodsIn this retrospective single‐center study of 663 consecutive adult recipients of HCT, we stratified patients into groups by pulmonary comorbidity: low‐risk, intermediate‐risk, and high‐risk. The predictive value of this pulmonary comorbidity score (PCS) was compared to HCT‐CI.ResultsIn univariate analysis, the HCT‐CI and the PCS were associated with OS after transplantation when comparing patients in high‐risk groups with patients in low‐risk groups. Using the PCS, the hazard ratios (HRs) of the 2‐year OS in the entire population and in the myeloablative conditioning (MAC) group were 1.98 (p < .001) and 3.27 (p < .001), respectively, whereas the HRs using the HCT‐CI were 1.83 (p < .001) and 2.57 (p = .002). The 2‐year NRM incidence in the three risk‐groups in the entire population was significant using both indexes. In the MAC group, the 2‐year NRM was significant using the PCS (p = .003), but not using the HCT‐CI (p = .23).ConclusionsOur study suggest that pulmonary function alone is a strong predictor of 2‐year OS and NRM after HCT.
The incidence, complications, and treatment of iron deficiency in pregnancy
Authors: Benson Ashley E. , Shatzel Joseph J. , Ryan Kim S. , Hedges Madeline A. , Martens Kylee , Aslan Joseph E. , Lo Jamie O. 
Published: September 2022

AbstractIron deficiency and/or iron deficiency anemia (IDA) complicate nearly 50% of pregnancies globally, negatively impacting both maternal and fetal outcomes. Iron deficiency can cause a range of symptoms that range from aggravating to debilitating including fatigue, poor quality of life, pagophagia, and restless leg syndrome. Iron deficiency and IDA are also associated with maternal complications including preterm labor, increased rates of cesarean delivery, postpartum hemorrhage, and maternal death. Fetal complications include increased rates of low birth weight and small for gestational age newborns. Prenatal maternal anemia has also been associated with autism spectrum disorders in the neonate, although causation is not established. Deficiency in the newborn is associated with compromised memory, processing, and bonding, with some of these deficits persisting into adulthood. Despite the prevalence and consequences associated with iron deficiency in pregnancy, data show that it is routinely undertreated. Due to the physiologic changes of pregnancy, all pregnant individuals should receive oral iron supplementation. However, the bioavailability of oral iron is poor and it is often ineffective at preventing and treating iron deficiency. Likewise, it frequently causes gastrointestinal symptoms that can worsen the quality of life in pregnancy. Intravenous iron formulations administered in a single or multiple dose series are now available. There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.
Exosome‐associated mitochondrial DNA from patients with myalgic encephalomyelitis/chronic fatigue syndrome stimulates human microglia to release IL‐1β
Authors: Tsilioni Irene , Natelson Benjamin , Theoharides Theoharis C. 
Published: September 2022

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise, and cognitive problems. The pathogenesis of ME/CFS is presently unknown, and serum levels of potential biomarkers have been inconsistent. Here, we show that mitochondrial DNA (mtDNA) associated with serum exosomes, is increased in ME/CFS patients only after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant release of IL‐1β from cultured human microglia. These results provide evidence that activation of microglia by serum‐derived exosomes may serve as a potential novel pathogenetic factor and target for treatment of ME/CFS.
Thermal sensitivity modulates temporal patterns of ecosystem functioning by freshwater mussels
Authors: van Ee Brian C. , Johnson Paul D. , Atkinson Carla L. 
Published: September 2022

Abstract

The continued global loss of biodiversity highlights the importance of understanding how species loss may impact ecosystem function. Shifting temperatures will accelerate species loss, but will affect species differently.

We investigated effects of temperature (10°C, 20°C, or 30°C) on resource acquisition and assimilation (clearance rate, respiration rate, N and P excretion) for 11 freshwater mussel species from a species‐rich assemblage in the Sipsey River, Alabama, U.S.A., to evaluate how temperatures impact co‐occurring species and the ecosystem processes they facilitate. Mussels are assigned to the same guild (i.e., filter‐feeding bivalves), but span a breadth of evolutionary lineages and have a diversity of life history strategies from short‐lived, quickly maturing species to long‐lived, slow‐growing species.

Our results indicated that four species (Cyclonaias asperata, Elliptio arca, Lampsilis ornata, and Obovaria unicolor) were thermally sensitive at 30°C, using more energy than they were acquiring. These species spanned three phylogenetic tribes and two different life‐history strategies suggesting thermal tolerance may not necessarily be linked to life history strategy or phylogenetic constraints.

When laboratory clearance and excretion rates were scaled to a natural mussel community over a year, we found that relative contributions by the proportion of thermally tolerant and sensitive species to total ecosystem function varied temporally across temperature and flow regimes. Thermal stress enhanced contributions by sensitive species' during summer, as individuals attempted to meet metabolic demands by increasing clearance rates and use of energy stores that increased ammonia excretion. River discharge and background nutrient concentrations also modulated the impact of ecosystem functioning facilitated by mussels. High river discharge in winter and high background nutrient concentrations in the summer decreased the relative contribution of the mussel community.

Although mussel species are commonly grouped in a single guild, species‐specific thermal traits modulate their role in the community. As biodiversity decreases, even biomass replacement by surviving mussel species is unlikely to support comparable ecosystem function due to the loss of unique species traits.
Trophic ecology of three stingrays (Myliobatoidei: Dasyatidae) off the Brazilian north‐eastern coast: Habitat use and resource partitioning
Authors: Queiroz Aristóteles Philippe Nunes , Araújo Maria Lúcia Góes , Hussey Nigel E. , Lessa Rosângela P. T. 
Published: September 2022

AbstractUnderstanding the ecological role of species with overlapping distributions is central to inform ecosystem management. Here we describe the diet, trophic level and habitat use of three sympatric stingrays,Hypanus guttatus,H. marianaeandH. berthalutzae, through combined stomach content and stable isotope (δ13C and δ15N) analyses. Our integrated approach revealed thatH. guttatusis a mesopredator that feeds on a diverse diet of benthic and epibenthic marine and estuarine organisms, principally bivalve molluscs,Alpheusshrimp and teleost fishes. Isotopic data supported movement of this species between marine and estuarine environments.H. berthalutzaeis also a marine generalist feeder, but feeds primarily on teleost fishes and cephalopods, and consequently occupies a higher trophic level. In contrast,H. marianaeis a mesopredator specialized on shrimps and polychaetas occurring only in the marine environment and occupying a low niche breadth. While niche overlap occurred, the three stingrays utilized the same prey resources at different rates and occupied distinct trophic niches, potentially limiting competition for resources and promoting coexistence. These combined data demonstrate that these three mesopredators perform different ecological roles in the ecosystems they occupy, limiting functional redundancy.
The role of bank lenders in firm leverage adjustments
Authors: Gao Wenlian , Zhu Feifei , Chen Kai 
Published: September 2022

AbstractIn this article we examine the impact of bank loan characteristics on firm leverage adjustments, with a special focus on the conflicts of interest between shareholders and creditors. The results show that, on average, more bank loans slow down leverage adjustments. The subsample analysis reveals that bank loans slow down leverage adjustments in underlevered firms but speed up adjustments in overlevered firms. This finding suggests that bank lenders are able to limit their risk exposure in borrowers and protect their own rights. Further evidence indicates that the effect of bank loans is more notable during the global financial crisis and when a firm is financially constrained. Bank loan concentration and maturity have a significant impact on leverage adjustments as well.