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cell division machinery drives cell- specific gene activation during differentiation in Bacillus subtilis

PROcEEDINGS OF THE NATIONAL AcADEMY OF ScIENcES OF THE UNITED STATES OF AMERIcA 2024年第13期121卷 e2400584121-e2400584121页

作者： chareyre, Sylvia Li, Xuesong Anjuwon, Brandon R. Updegrove, Taylor B. clifford, Sarah Brogan, Anna P. Su, Yijun Zhang, Lixia chen, Jiji Shroff, Hari Ramamurthia, Kumaran S. NCI Mol Biol Lab NIH Bethesda MD 20892 USA Natl Inst Biomed Imaging & Bioengn Lab High Resolut Opt Imaging NIH Bethesda MD 20892 USA HHMI Ashburn VA 20147 USA NIH Adv Imaging & Microscopy Resource Bethesda MD 20892 USA

When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor aF is exclusively activated in the smaller daughter cell. compartment- specific activation of aF requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates aF in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that the core components of the redeployed cell division machinery drive the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.

关键词： c difficile E coli | RacA MincD

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A matching-adjusted indirect comparison of results from REDUcE and RESPEcT-two randomized trials on patent foramen ovale closure devices to prevent recurrent cryptogenic stroke

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 337-343页

作者： Kasner, Scott E. Sondergaard, Lars Nakum, Mitesh Gomez Montero, Melissa Hashim, Mahmoud Landaas, Erik J. Univ Penn Dept Neurol Philadelphia PA 19104 USA Abbott Struct Heart Santa Clara CA USA WL Gore & Associates Phoenix AZ USA Cytel Rotterdam Netherlands

AimsTwo randomized clinical trials, REDUcE and RESPEcT, demonstrated that patent foramen ovale (PFO) closure in combination with antithrombotic therapy was more effective for the prevention of recurrent ischemic stroke compared with antithrombotic therapy alone. The aim of this study was to determine the relative efficacy and safety of the PFO closure devices used in REDUcE (HELEX and cARDIOFORM Septal Occluders) compared with the device used in RESPEcT (Amplatzer PFO Occluder).MethodsAn unanchored matching-adjusted indirect comparison (MAIc) of the PFO closure arms of the REDUcE and RESPEcT trials was performed using patient-level data from REDUcE weighted to match baseline characteristics from RESPEcT. comparisons of the following outcomes were made between the devices assessed in the trials: risk of recurrent ischemic stroke;recurrent ischemic stroke one year after randomization;any serious adverse event (SAE) related to the procedure or device;and atrial fibrillation or atrial flutter as an SAE related to the procedure or *** conducting the MAIc, baseline characteristics were well-matched between the two trials. compared to RESPEcT, PFO closure using the devices from REDUcE resulted in a hazard ratio of 0.46 (95% confidence interval [cI] 0.15-1.43;p = 0.17) for the risk of recurrent stroke. For the recurrence of stroke after one year, SAE related to the procedure or device, and atrial fibrillation or atrial flutter as SAE related to the procedure or device, the MAIc resulted in a rate difference of -0.68 (95%cI -2.06 to 0.70;p = .34), -1.29 (95%cI -3.82 to 1.25;p = .32), and -0.19 (95%cI -1.16 to 0.78;p = .71), respectively. These findings were consistent across scenario *** MAIc analysis found no statistically significant differences in efficacy and safety outcomes between PFO closure with the HELEX and cARDIOFORM Septal Occluders versus the Amplatzer PFO Occluder, as used in the REDUcE and RESPEcT trials. The individual eff

关键词： Patent foramen ovale cryptogenic stroke PFO closure matching-adjusted indirect comparison comparative effectiveness I10 I1 I c00 c c10 c1

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Veterinary bacteriology in Denmark from the 1880s to 2022

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APMIS 2024年第1期132卷 31-42页

作者： Leisner, Jorgen J. Larsen, Jens Laurits Univ Copenhagen Fac Hlth & Med Sci Dept Vet & Anim Sci Copenhagen Denmark Abildgaard Soc Fredensborg Denmark Univ Copenhagen Fac Hlth & Med Sci Dept Vet & Anim Sci Gronnegardsvej 15 DK-1870 Frederiksberg C Denmark

This paper gives an account of the history of veterinary bacteriology including clinical veterinary bacteriology as well as the area of veterinary public health in Denmark from the 1880s to 2022. We describe key persons, including B. Bang, c.O. Jensen, K.A. Jensen and others who made important contributions to the development of these areas of microbiological expertise, and we discuss how challenges ranging from bovine tuberculosis to bacterial antimicrobial resistance have been met. Further, we describe progress in research on important bacterial pathogens both with regard to animal clinical aspects and zoonotic food-related aspects. Finally, we describe current issues in relation to One Health and research organization.

关键词： Antimicrobial resistance Bernhard Bang c O Jensen Mycobacterium bovis Mycoplasma pathogen Salmonella Serum Laboratory veterinary microbiology

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cost-effectiveness of a novel urethral catheter safety device in preventing catheterization injuries in the UK

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 154-164页

作者： croghan, Stefanie M. Malcolm, Robert Flood, Hugh D. Mealing, Stuart Avey, Brooke Leonard, Gavin Wright, James Davis, Niall F. Walsh, Michael T. Royal Coll Surg Ireland RCSI Dept Surg Dublin Ireland York Hlth Econ Consortium Heslington England Class Med Ltd Limerick Ireland MedTech Connect Ltd Derby England Univ Limerick Bernal Inst Limerick Ireland Univ Limerick Hlth Res Inst Limerick Ireland

AimsIntraurethral catheter balloon inflation is a substantial contributor to significant catheter-related urethral injury. A novel safety valve has been designed to prevent these balloon-inflation injuries. The purpose of this evaluation was to assess the cost-effectiveness of urethral catheterisation with the safety valve added to a Foley catheter versus the current standard of care (Foley catheter alone).Materials and methodsThe analysis was conducted from the UK public payer perspective on a hypothetical cohort of adults requiring transurethral catheterization. A decision tree was used to capture outcomes in the first 30 days following transurethral catheterization, followed by a Markov model to estimate outcomes over a person's remaining lifetime. clinical outcomes included catheter balloon injuries [cBIs], associated short-term complications, urethral stricture disease, life years and QALYs. Health-economic outcomes included total costs, incremental cost-effectiveness ratio, net monetary benefit (NMB) and net health *** a person's lifetime, the safety valve was predicted to reduce cBIs by 0.04 per person and cBI-related short-term complications by 0.03 per person, and nearly halve total costs. The safety valve was dominant, resulting in 0.02 QALYs gained and relative cost savings of 93.19 pound per person. Probabilistic sensitivity analysis indicated that the safety valve would be cost-saving in 97% of simulations run versus standard of *** addition of a novel safety valve aiming to prevent cBIs during transurethral catheterization to current standard of care was estimated to bring both clinical benefits and cost savings.

关键词： catheter balloon injury transurethral catheterization economic evaluation cost-effectiveness analysis urethral safety valve I00 I c02 c

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cost-effectiveness analysis of sodium zirconium cyclosilicate for hyperkalemia among patients with chronic kidney disease or heart failure in Kuwait

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 253-265页

作者： Elsisi, Gihan Hamdy Mahmoud, Mohamed M. Ibrahim Al-Humood, Khaldoon Al-Yousef, Anas HTA Off LLC Cairo Egypt Amer Univ Cairo Hlth Econ Cairo Egypt Jaber Al Ahmed Armed Forces Hosp Dept Med Kuwait Minist Def Kuwait Kuwait Amiri Hosp Head Nephrol Dept Nephrol Dept Kuwait Kuwait Adan Hosp Cardiol Dept MOH Kuwait Kuwait Amer Univ Cairo HTA Off LLC Hlth Econ 51 Helmy Hassan Aly St Cairo Egypt

IntroductionOur model was conducted from Kuwaiti payer's perspective to provide evidence on the cost-effectiveness of Sodium zirconium cyclosilicate (SZc) versus patiromer to correct and maintain serum potassium (K+) in combination with renin-angiotensin-aldosterone system inhibitors (RAASis) with different dose titration in patients with chronic kidney disease/heart failure (cKD/HF) with/without renal replacement therapy (RRT).MethodologyThe model was developed as a patient-level, fixed-time increment stochastic simulation to simulate the complexity of disease, including multiple coexisting and competing conditional risks. This model was established to compare SZc versus patiromer as a treatment for hyperkalemia (HK) among adult populations with underlying conditions of advanced cKD stages 3a-5 or HF to correct and maintain serum K + over a lifetime horizon. The clinical outcomes of SZc and patiromer were demonstrated through arm-specific K + trajectories extracted from the HARMONIZE trial and OPAL-HK trial, respectively. The utility data was captured from different studies. Direct medical cost was captured from local data from Kuwaiti hospitals. Sensitivity analyses were conducted to assess the uncertainty in the *** different scenarios of cKD/HF, SZc was a cost-saving option, with/without RRT, whether one-off administration or repeated administration, except for one-off treatment administration among the HF cohort, which generated an incremental cost effectiveness ratio of KWD 331/quality adjusted life year (QALY). The incremental QALY of SZc ranged from 0.007 to 0.202. In addition, the savings observed with SZc fall within a range of KWD -60 to KWD -1,235 at serum K+ >= 5.1 mmol/*** evidence generated by our model recommends the inclusion of SZc as a treatment option to correct HK and maintain normal serum K + level for cKD/HF patients within the Kuwaiti healthcare system. The costs saved from reducing frequent HK episodes, RAASis dis

关键词： chronic kidney disease heart failure cost-effectiveness analysis sodium zirconium cyclosilicate c52 c5 c E47 E4 E

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Light changes Promote Distinct Responses of Plastid Protein Acetylation Marks

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MOLEcULAR & cELLULAR PROTEOMIcS 2024年第11期23卷 100845页

作者： Eirich, Juergen Boyer, Jean-Baptiste Armbruster, Laura Ivanauskaite, Aiste De La Torre, carolina Meinnel, Thierry Wirtz, Markus Mulo, Paula Finkemeier, Iris Giglione, carmela Univ Munster Inst Plant Biol & Biotechnol Plant Physiol Munster Germany Univ Paris Saclay Inst Integrat Biol Cell I2BC CEA CNRS Gif Sur Yvette France Heidelberg Univ Ctr Organismal Studies Heidelberg Heidelberg Germany Univ Turku Dept Life Technol Mol Plant Biol Turku Finland Heidelberg Univ Med Fac Mannheim NGS Core Facil Mannheim Germany

Protein acetylation is a key co- and post-translational modification. However, how different types of acetylation respond to environmental stress is still unknown. To address this, we investigated the role of a member of the newly discovered family of plastid acetyltransferases (GNAT2), which features both lysine- and N-terminal acetyltransferase activities. Our study aimed to provide a holistic multi-omics acetylation-dependent view of plant acclimation to short-term light changes. We found that both the yield and coverage of the N-terminal acetylome remained unchanged in WT and gnat2-KO backgrounds after 2 h of exposure to high light or darkness. Similarly, no differences in transcriptome or adenylate energy charge were observed between the genotypes under the tested light conditions. In contrast, the lysine acetylome proved to be sensitive to the changes in light conditions, especially in the gnat2 background. This suggests unique strategies of plant acclimation for quick responses to environmental changes involving lysine, but not N-terminal, GNAT2-mediated acetylation activity.

关键词： acetyltransferase acetylation quantitative proteomics light acclimation Arabidopsis thaliana acK acetylation of lysine side chains c control light cV compensation voltage D darkness GNAT GcN5 family HL high light HSP heat shock protein KAT lysine acetyltransferase LcH light harvesting complex NAT N-terminal acetyltransferase NTA acetylation of N-termini PS photosystem TMT tandem mass tags UPLc ultra-performance liquid chromatography

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Estimated impact and value of blood-based colorectal cancer screening at varied adherence compared with stool-based screening

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 746-753页

作者： Kisiel, John B. Fendrick, A. Mark Ebner, Derek W. Ozbay, A. Burak Vahdat, Vahab Estes, chris Limburg, Paul J. Mayo Clin Div Gastroenterol & Hepatol Rochester MN USA Univ Michigan Div Gen Med North Campus Res Complex2800 Plymouth RdBldg 16 Ann Arbor MI 48109 USA Exact Sci Corp Madison WI USA

ObjectiveThis analysis estimated the outcomes of triennial blood-based colorectal cancer (cRc) screening at various adherence, including perfect adherence, compared with triennial multi-target stool DNA (mt-sDNA) screening at the reported real-world adherence *** validated cRc-AIM model simulated a US cohort of average-risk individuals receiving triennial screening with mt-sDNA or blood-based test from ages 45 to 75 years. Modeled specificity and sensitivity were based on reported data. Adherence was set at a real-world rate of 65.6% for mt-sDNA and at 65.6%, relative 10% incremental increases from 65.6%, or 100% for the blood-based test. costs of mt-sDNA and the blood-based test were based on prices for clinically available tests ($508.87 and $895, respectively). Value-based pricing was estimated at a willingness-to-pay threshold of $100,*** tests resulted in life-years gained (LYG), reduced cRc cases, and reduced deaths versus no screening. With adherence for mt-sDNA set at 65.6% and for blood-based test set at 100%, mt-sDNA resulted in 30% more LYG, 52% more averted cRc cases, and 32% more averted cRc deaths. At reported sensitivity and specificity rates, mt-sDNA at 65.6% adherence dominates (is more effective and less costly) the blood-based test at any adherence. There was no price at which triennial screening with the blood-based test at any adherence was cost-effective compared with mt-sDNA at 65.6% *** screening with mt-sDNA resulted in better clinical outcomes at a lower cost compared with the modeled blood-based test even at perfect adherence, supporting application of blood-based tests only as a secondary screening option. Blood-based colorectal cancer screening has lower diagnostic accuracy, lower clinical and health outcomes, and is more expensive than mt-sDNA, even with perfect blood-based screening participation. Although better than no screening at all, blood-based testing is unlikely to exceed perfo

关键词： Liquid biopsy colorectal neoplasms computer simulation early detection of cancer feces/chemistry I10 I1 I c31 c3 c

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Executability and connexivity in an Interpretation of Griss

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STUDIA LOGIcA 2024年第1-2期112卷 459-509页

作者： Ferguson, Thomas M. M. Univ Amsterdam ILLC Amsterdam Netherlands Czech Acad Sci Inst Philosophy & Comp Sci Prague Czech Republic

Although the work of G.F.c. Griss is commonly understood as a program of negationless mathematics, close examination of Griss's work suggests a more fundamental feature is its executability, a requirement that mental constructions are possible only if corresponding mental activity can be actively carried out. Emphasizing executability reveals that Griss's arguments against negation leave open several types of negation-including D. Nelson's strong negation-as compatible with Griss's intuitionism. Reinterpreting Griss's program as one of executable mathematics, we iteratively develop a pair of bilateral constructive logics and argue for their adequacy as accounts of the propositional basis of Griss's work. We conclude by observing connexive features exhibited by the two bilateral logics and by investigating the difficulties connexive principles reveal for the development of executable mathematics.

关键词： connexive logic constructive logic G F c Griss Executable logic

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Geroprotective potential of microbiome modulators in the caenorhabditis elegans model

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GEROScIENcE 2024年第1期46卷 129-151页

作者： Miller, Brandi c. Mathai, Megha Yadav, Hariom Jain, Shalini Univ S Florida Microbiomes Inst USF Ctr Microbiome Res 12901 Bruce B Downs BlvdMDC 78 Tampa FL 33612 USA Univ S Florida Dept Neurosurg & Brain Repair Tampa FL USA

Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Emerging evidence suggests that gut microbiota dysbiosis is a hallmark of aging-related diseases and microbiome modulators, such as probiotics (live bacteria) or postbiotics (non-viable bacteria/bacterial byproducts) may be promising geroprotectors. However, because they are strain-specific, the geroprotective effects of probiotics and postbiotics remain poorly understood and understudied. Drosophila melanogaster, caenorhabditis elegans, and rodents are well-validated preclinical models for studying lifespan and the role of probiotics and/or postbiotics, but each have their limitations, including cost and their translation to human aging biology. c. elegans is an excellent model for large-scale screening to determine the geroprotective potential of drugs or probiotics/postbiotics due to its short lifecycle, easy maintenance, low cost, and homology to humans. The purpose of this article is to review the geroprotective effects of microbiome modulators and their future scope, using c. elegans as a model. The proposed geroprotective mechanisms of these probiotics and postbiotics include delaying immune system senescence, preventing or reducing mitochondrial dysfunction, and regulating food intake (dietary restriction) and metabolism. More studies are warranted to understand the geroprotective potential of probiotics and postbiotics, as well as other microbiome modulators, like prebiotics and fermented foods, and use them to develop effective therapeutics to extend lifespan and reduce the risk of debilitating aging-related diseases.

关键词： Geroscience Aging Microbiome Gut c elegans Probiotics Postbiotics

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A cost-consequence model of using the 21-gene assay to identify patients with early-stage node-positive breast cancer who benefit from adjuvant chemotherapy in the Netherlands

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JOURNAL OF MEDIcAL EcONOMIcS 2024年第1期27卷 445-454页

作者： Simons, Martijn J. H. G. Machielsen, Peter M. Spoorendonk, Jelle A. Ignacio, Tim Drost, Pieter B. Jacobs, Tim de Jongh, Felix E. OPEN Hlth Evidence & Access Rotterdam Netherlands Exact Sci Lindenstr 2 CH-6340 Baar Switzerland Ikazia Ziekenhuis Rotterdam Rotterdam Netherlands

BackgroundPatients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1-3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (AcT). Many patients have no benefit from AcT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from AcT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence *** validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent AcT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 *** for the total population amounted to euro8.0 million (M), euro16.2 M, and euro9.5 M, and cost per patient amounted to euro13,540, euro27,455, and euro16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to euro8.2 M versus no GEP testing and euro1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving AcT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and *** Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system. Early-stage invasive breast cancer patients often undergo surgery followed by adjuvant che

关键词： 21-gene gene expression profiling early stage hormone receptor human epidermal growth factor receptor 2 breast cancer lymph node positive adjuvant chemotherapy cost-consequence analysis A11 A1 A c21 c2 c c51 c5

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