bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to oxacillin subinhibitory concentrations andin vitroinduction of resistance expression in heteroresistant and non-heteroresistant oxacillin-susceptiblemecA-positiveStaphylococcus aureus(OS-MRSA)
Authors: Schimidt Denise Braga , Póvoa Helvécio Cardoso Corrêa 
Published: January 2023

AbstractResistance expression can occur as a consequence of irrational use of antibiotics, since this implies dissemination of subinhibitory concentration (sub-MICs) in different environments and generates a selective pressure. The study aimed to evaluate thein vitroinfluence of selective pressure on antibiotic resistance expression in two oxacillin-susceptiblemecA-positiveStaphylococcus aureus(OS-MRSA), through exposure to oxacillin sub-MICs. One heteroresistant OS-MRSA strain and a non-heteroresistant strain, both isolated from nasal colonization were exposed to two-fold serial dilutions of oxacillin (0,125 a 256 μg/mL) during seven consecutive days. Disc diffusion test was used to determine the susceptibility to several antibiotics and population analysis profile (PAP) was used to evaluate the expression of oxacillin resistance before and after antibiotic exposure. Susceptibility to non-β-lactam antibiotics was not altered but changes in phenotypic expression of penicillin and oxacillin resistance were observed. Both OS-MRSA strains began to express homoresistance (oxacillin MIC = 256 μg/mL) and had no penicillin zone inhibition after induction, different from that was observed before oxacillin exposure, which suggested increased in β-lactamase production.In vitroselective pressure with oxacillin stimulated β-lactamase production and led phenotypic expression of oxacillin resistance in heteroresistant and non-heteroresistant OS-MRSA, which became homoresistant. This reinforces the impact that irrational use of antibiotics has on individuals colonized byS. aureusand on the population, emphasizing that the emergence and spread of resistance to antibiotics represent a process of evolution in response to selective antimicrobial pressure.
The Adr1 transcription factor directs regulation of the ergosterol pathway and azole resistance in C.albicans
Authors: Shrivastava Manjari , Kouyoumdjian Gaëlle S. , Kirbizakis Eftyhios , Ruiz Daniel , Henry Manon , Vincent Antony T , Sellam Adnane , Whiteway Malcolm 
Published: January 2023

AbstractTranscription factors play key roles in cellular regulation and are critical in the control of drug resistance in the fungal pathogenCandida albicans. We found that activation of the transcription factor C4_02500C_A (Adr1) conferred significant resistance against fluconazole. InSaccharomyces cerevisiae, Adr1 is a carbon-source-responsive zinc-finger transcription factor required for transcription of the glucose-repressed geneADH1and of genes required for ethanol, glycerol, and fatty acid utilization. Motif scanning of promoter elements suggests that Adr1 may be rewired in fungi and governs the ergosterol synthesis pathway inC. albicans. Because previous studies have identified the zinc-cluster transcription factor Upc2 as a regulator of the ergosterol pathway in both fungi, we examined the relationship of Adr1 and Upc2 in sterol biosynthesis inC. albicans. Phenotypic profiles of eitherADR1andUPC2modulation inC. albicansshowed differential growth in the presence of fluconazole; eitheradr1orupc2homozygous deletion results in sensitivity to the drug while their activation generates a fluconazole resistant strain. The rewiring from ergosterol synthesis to fatty acid metabolism involved all members of the Adr1 regulon except the alcohol dehydrogenase Adh1, which remains under Adr1 control in both circuits and may have been driven by the lifestyle ofS. cerevisiae, which requires the ability to both tolerate and process high concentrations of ethanol.
The RALF Signaling Pathway Regulates Cell Wall Integrity during Pollen Tube Growth in Maize
Authors: Zhou Liang-Zi , Wang Lele , Ge Zengxiang , Mergner Julia , Li Xingli , Küster Bernhard , Längst Gernot , Qu Li-Jia , Dresselhaus Thomas 
Published: January 2023

ABSTRACTAutocrine signaling pathways regulated by RAPID ALKALINIZATION FACTORs (RALFs) control cell wall integrity during pollen tube germination and growth in Arabidopsis. To investigate the role of pollen-specific RALFs in another plant species, we combined gene expression data with phylogenetic and biochemical studies to identify candidate orthologs in maize. We show that Clade IBZmRALF2/3mutants, but not that of Clade IIIZmRALF1/5caused cell wall instability in the sub-apical region of the growing pollen tube. ZmRALF2/3 are mainly located to the cell wall and are partially able to complement the pollen germination defect of their Arabidopsis orthologs AtRALF4/19. Mutations inZmRALF2/3compromise pectin distribution pattern leading to altered cell wall thickness, hyperphosphorylation of ZmPEX cell wall proteins and pollen tube burst. Clade IB, but not Clade III ZmRALFs are capable to interact with pollen-specific CrRLK1L receptor kinases ZmFERL4/7/9 and GPI-anchored co-receptors ZmLLG1/2 at similar binding affinities. In contrast, binding affinity to ZmPEX2/4 cell wall proteins is about five times higher. Based on these data, we now propose a dosage-dependent model showing how Clade IB RALFs act as extracellular sensors to regulate cell wall integrity and thickness during pollen tube growth in plants.One sentence summaryPollen-specific RALFs interact at different binding affinities with receptor kinases, GPI-anchored proteins and cell wall proteins to regulate cell wall integrity during pollen tube growth in maize.
Emphasis on quality in iNaturalist plant collections enhances learning and research utility
Authors: McNair Mason C. , Sexton Chelsea M. , Zenoble Mark 
Published: January 2023

AbstractFollowing the switch to remote online teaching in the wake of the COVID-19 pandemic, the plant taxonomy course at the University of Georgia (UGA) switched to iNaturalist for the specimen collection portion of the course requirements. Building off extant rubrics, the instructors designed project guidelines for a fully online plant collection experience to alleviate plant awareness disparity. Researchers collected stratified samples from the UGA iNaturalist project along with four other institutions’ projects to determine if rubrics and project guidelines could improve the quality of observations to make them useful in plant science research. The specific rubric was shown to improve quality of iNaturalist observations. Researchers found that iNaturalist increased engagement as a student-centered tool but did not enhance their manual keying skills as the app uses automatic identification. Instructors recommend continuing to use iNaturalist to supplement physical collection and keying along with a detailed rubric and guidelines for collection.
Investigating variant and expression of CVD genes associated phenotypes among high-risk Heart Failure patients
Authors: Ahmed Zeeshan , Zeeshan Saman , Persaud Nicholas , Liang Bruce T. 
Published: January 2023

AbstractCardiovascular disease (CVD) is a leading cause of premature mortality in the US and the world. CVD comprises of several complex and mostly heritable conditions, which range from myocardial infarction to congenital heart disease. Here, we report our findings from an integrative analysis of gene expression, disease-causing gene variants, and associated phenotypes among CVD populations, with a focus on high-risk Heart Failure (HF) patients. We built a cohort using electronic health records (EHR) of consented patients with available samples, and then performed high-throughput whole-genome and RNA sequencing (RNA-seq) of key genes responsible for HF and other CVD pathologies. We also incorporated a translational aspect to our study by integrating genomics findings with patient medical records. This involved linking ICD-10 codes with our gene expression and variant data to identify associations with HF and other CVDs. Our in-depth gene expression analysis revealed differentially expressed genes associated with HF (41 genes) and other CVDs (23 genes). Furthermore, a variant analysis of whole-genome sequence data of CVD patients identified genes with altered gene expression (FLNA, CST3, LGALS3, and HBA1) with functional and nonfunctional mutations in these genes. Our study highlights the importance of an integrative approach that leverages gene expression, genetic mutations, and clinical data that will allow the prioritization of key driver genes for complex diseases to improve personalized healthcare.
Ultra-fast deep-learned pediatric CNS tumor classification during surgery
Authors: Vermeulen C. , Pagès-Gallego M. , Kester L. , Kranendonk M.E.G. , Wesseling P. , van der Lugt J. , van Baarsen K. , Hoving E.W. , Tops B.B.J. , de Ridder J. 
Published: January 2023

AbstractThe primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and to reduce tumor load and mass effect. The neurosurgeon has to decide between radical resection versus a more conservative strategy to prevent surgical morbidity. The prognostic impact of a radical resection varies between tumor types. However due to a lack of pre-operative tissue-based diagnostics, limited knowledge of the precise tumor type is available at the time of surgery. Current standard practice includes preoperative imaging and intraoperative histological analysis, but these are not always conclusive. After surgery, histopathological and molecular tests are performed to diagnose the precise tumor type. The results may indicate that an additional surgery is needed or that the initial surgery could have been less radical. Using rapid Nanopore sequencing, a sparse methylation profile can be directly obtained during surgery, making it ideally suited to enable intraoperative diagnostics. We developed a state-of-the-art neural-network approach called Sturgeon, to deliver trained models that are lightweight and universally applicable across patients and sequencing depths. We demonstrate our method to be accurate and fast enough to provide a correct diagnosis with as little as 20 to 40 minutes of sequencing data in 45 out of 49 pediatric samples, and inconclusive results in the other four. In four intraoperative cases we achieved a turnaround time of 60-90 minutes from sample biopsy to result; well in time to impact surgical decision making. We conclude that machine-learned diagnosis based on intraoperative sequencing can assist neurosurgical decision making, allowing neurological comorbidity to be avoided or preventing additional surgeries.
General practitioners ending their practice and impact on patients’ health, health care use and mortality. A protocol for national registry cohort studies in Norway, 2006 to 2021
Authors: Vinjerui Kristin Hestmann , Anthun Kjartan Sarheim , Asheim Andreas , Carlsen Fredrik , Mjølstad Bente Prytz , Nilsen Sara Marie , Pape Kristine , Håkon Bjørngaard Johan 
Published: January 2023

AbstractIntroductionContinuous general practitioner (GP) and patient relations associate with positive health outcomes. Termination of GP-practice is unavoidable, while consequences of final breaks in relations are less explored. We will study how an ended GP-relation affects patient’s health care utilization and mortality, compared to patients with a continuous GP-relation.Methods and analysisLinking personal-level national registries data on GP-affiliation, sociodemographic characteristics, health care use and mortality, from 2008 to 2021, we will identify patients of GPs terminating practice, and match these GP-patient pairs on age, sex (both), immigrant status and education (patient), and number of patients and practice period (GPs), to GP-patient pairs with a continuous relationship in other municipalities, and compare acute and elective primary and specialist health care use mortality, before and after ended GP-practice, using Poisson regression with high-dimensional fixed effects. We will address expected modifying factors, such as patients with complex health care needs, quality of termination and GP-availability in the municipalities.Ethics and disseminationThis study protocol is part of the approved project Improved Decisions with Causal Inference in Health Services Research, 2016/2158/REK Midt (the Regional Committees for Medical and Health Research Ethics) and does not require consent. We will publish in peer-reviewed journals, accessible in NTNU Open, and present at scientific conferences. To reach a broader audience, we will summarize articles in the project’s web page, regular and social media, and disseminate to relevant stakeholders.Strengths and limitations of this studyThis study adds to research on GP-patient relation continuity and associations, exploring termination of relations and designing a natural experiment in register data, facilitating causal inference.The study includes the entire Norwegian population and their general practitioners (GPs) from 2008 to 2021, linking several mandatory, high-quality, healthcare, and demographic registers on a personal level.The register data include exact time points (xxx or months? xxx) for the intervention, termination of GP-relation, and the outcomes, health care utilization and death.By matching GP-patient pairs in practice period and distinct municipalities, we minimize time-varying confounders and dilution of effects.As in all observational studies, our results may be influenced by residual confounding
Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study
Authors: White Marina , Arif-Pardy Jayden , Van Mieghem Tim , Connor Kristin L 
Published: January 2023

AbstractTo improve outcomes of fetuses with spina bifida (SB), better knowledge is needed on the molecular drivers of SB and its comorbidities. We have recently shown in historical data that SB often associates with reduced fetal growth. We here use placental transcriptome sequencing and a novel nutrient-focused analysis pipeline to determine whether this association is due to placental dysfunction. We show that fetuses with SB have dysregulation in placental gene networks that play a role in nutrient transport, branching angiogenesis, and immune/inflammatory processes. Several of these networks are sensitive to multiple micronutrients, other than the well-known folic acid, and this deserves further investigation. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with SB and its comorbidities, and reveal new targets to improve fetal outcomes in this population.
The development of a guidance document for interprofessional collaborative advance care planning in dementia care
Authors: Khemai C. , Janssen D.J.A. , Van Dongen J. , Biesmans J.M.A. , Bolt S.R. , Schols J.M.G.A. , Meijers J.M.M. 
Published: January 2023

AbstractAdvance care planning (ACP) is an essential part of palliative dementia care and should embrace a collaborative approach involving persons with dementia, family members and various healthcare professionals (HCPs). This study aimed to develop a guidance document for IPC in ACP in dementia care for HCPs from nursing homes, using a mixed-method design and taking an appreciative inquiry approach comprising semi-structured focus groups and interviews with HCPs. The study participants (N=18) included certified nurses, registered nurses, a quality nurse, nurse specialists, team leaders, physicians specialized in old age medicine, psychologists, and a teacher/researcher (mean age 43.8 years; 79% female). The data analysis indicated six elements to include in the guidance document. The first three elements concerned common awareness of collaborative ACP in dementia care, role clarification for various professions, and actively working towards shared goals in collaborative ACP in dementia care. The last three themes focused on the dynamic processes in collaborative ACP in dementia care: interprofessional communication, coordination, monitoring and evaluation. This study provides a guidance document that HCPs could use in practice to identify the elements they can address to improve collaborative ACP in dementia care.
Antibody escape, the risk of serotype formation, and rapid immune waning: modeling the implications of SARS-CoV-2 immune evasion
Authors: Albright Catherine , Van Egeren Debra , Thakur Aditya , Chakravarty Arijit , White Laura F. , Stoddard Madison 
Published: January 2023

AbstractAs the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of “endemicity” or “herd immunity.” At this point, an array of viral variants has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antigenic drift resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading variants that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic.
One marine protected area is not enough: The trophic ecology of the broadnose sevengill shark (Notorynchus cepedianus) in the Southwest Atlantic
Authors: Funes Manuela , De Wysiecki Agustín M. , Bovcon Nelson D. , Jaureguizar Andrés J. , Irigoyen Alejo J. 
Published: January 2023

AbstractThe broadnose sevengill shark (Notorynchus cepedianus) has been categorized as Vulnerable by the IUCN and shows a declining population trend in the Southwest Atlantic. Bycatch and poaching are the major threats in the region.Although some ecological requirements have been described, there are still several information gaps regarding its ecology. Important aspects of its trophic ecology, like main prey items or key feeding grounds, remain uncertain and are essential to design effective conservation strategies.We applied stable isotope and stomach content analyses to describe the trophic ecology of sevengill shark within a marine protected area of Peninsula Valdés in Patagonia, Argentina.The stomach content analysis determined the southern elephant seal,Mirounga leonina, as the most frequently regurgitated prey item (70%F) during abundance peaks of both species in Península Valdes. The stable isotope analysis indicated that the overall contribution of the elephant seal to the diet of the sevengill shark was around 30% and that this percentage varied with the size of individuals.Present results strengthen the current understanding of the trophic ecology of the sevengill shark. This study confirmed the use of the marine protected area as an essential foraging ground and identified its main prey items. Also, it reinforced the critical need to expand conservation tools beyond this particular coastal protection.
Functional effects of haemoglobin can be rescued by haptoglobin in anin vitromodel of subarachnoid haemorrhage
Authors: Warming Hannah , Deinhardt Katrin , Garland Patrick , More John , Bulters Diederik , Galea Ian , Vargas-Caballero Mariana 
Published: January 2023

AbstractDuring subarachnoid haemorrhage, a blood clot forms in the subarachnoid space releasing extracellular haemoglobin (Hb), which causes oxidative damage and cell death in surrounding tissues. High rates of disability and cognitive decline in SAH survivors is attributed to loss of neurons and functional connections during secondary brain injury. Haptoglobin sequesters Hb for clearance, but this scavenging system is overwhelmed after a haemorrhage. Whilst exogenous haptoglobin application can attenuate cytotoxicity of Hb andin vivo, andin vivothe functional effects of sub-lethal Hb concentrations on surviving neurons and whether cellular function can be protected with haptoglobin treatment remain unclear. Here we use cultured neurons to investigate neuronal health and function across a range of Hb concentrations to establish the thresholds for cellular damage and investigate synaptic function. Hb impairs ATP concentrations and cytoskeletal structure. At clinically relevant but sublethal Hb concentrations, synaptic AMPAR-driven currents are reduced, accompanied by a reduction in GluA1 subunit expression. Haptoglobin co-application can prevent these deficits by scavenging free Hb to reduce it to sub-threshold concentrations and does not need to be present at stoichiometric amounts to achieve efficacy. Haptoglobin itself does not impair measures of neuronal health and function at any concentration tested. Our data highlight a role for Hb in modifying synaptic function after SAH, which may link to impaired cognition or plasticity, and support the development of haptoglobin as a therapy for subarachnoid haemorrhage.
Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410
Authors: Remm Sille , De Vecchis Dario , Schöppe Jendrik , Hutter Cedric A.J. , Gonda Imre , Hohl Michael , Newstead Simon , Schäfer Lars V. , Seeger Markus A. 
Published: January 2023

AbstractMycobacterium tuberculosisis protected from antibiotic therapy by a multi-layered hydrophobic cell envelope. Major facilitator superfamily (MFS) transporter Rv1410 and the periplasmic lipoprotein LprG are involved in transport of triacylglycerides (TAGs) that seal the mycomembrane. Here, we report a 2.7 Å structure of a mycobacterial Rv1410 homologue, which adopts an outward-facing conformation and exhibits unusual transmembrane helix 11 and 12 extensions that protrude ∼20 Å into the periplasm. A small, very hydrophobic cavity suitable for lipid transport is constricted by a unique and functionally important ion-lock likely involved in proton coupling. Combining mutational analyses and MD simulations, we propose that TAGs are extracted from the core of the inner membrane into the central cavity via lateral clefts present in the inward-facing conformation. The periplasmic helix extensions are crucial for lifting TAGs away from the membrane plane and channeling them into the lipid binding pocket of LprG.