Cost-informed Bayesian reaction optimization.

Bayesian optimization (BO) is an efficient method for solving complex optimization problems, including those in chemical research, where it is gaining significant popularity. Although effective in guiding experimental design, BO does not account for experimentation costs: testing readily available reagents under different conditions could be more cost and time-effective than synthesizing or buying additional ones. To address this issue, we present cost-informed BO (CIBO), an approach tailored for the rational planning of chemical experimentation that prioritizes the most cost-effective experiments.

A multi-nozzle nebuliser does not improve tissue drug delivery during PIPAC.

Background: Multi-nozzle nebulisers for pressurised intraperitoneal aerosol chemotherapy (PIPAC) are implemented in clinical practice to improve the homogeneity of tissue drug delivery. Nonetheless, the advantages of such devices over one-nozzle nebulisers have not been demonstrated thus far. In this study, we compared the performance of multi- and one-nozzle nebulisers by conducting physical and ex vivo pharmacological experiments.

Evolutionary Monte Carlo of QM Properties in Chemical Space: Electrolyte Design.

Optimizing a target function over the space of organic molecules is an important problem appearing in many fields of applied science but also a very difficult one due to the vast number of possible molecular systems. We propose an evolutionary Monte Carlo algorithm for solving such problems which is capable of straightforwardly tuning both exploration and exploitation characteristics of an optimization procedure while retaining favorable properties of genetic algorithms. The method, dubbed MOSAiCS (etropolis ptimization by ampling daptively n hemical pace), is tested on problems related to optimizing components of battery electrolytes, namely, minimizing solvation energy in water or maximizing dipole moment while enforcing a lower bound on the HOMO-LUMO gap; optimization was carried out over sets of molecular graphs inspired by QM9 and Electrolyte Genome Project (EGP) data sets.

The role of AJB35136 and fdtA genes in biofilm formation by avian pathogenic Escherichia coli.

Background: Infections caused by avian pathogenic Escherichia coli (APEC) result in significant economic losses in poultry industry. APEC strains are known to form biofilms in various conditions allowing them to thrive even under harsh and nutrient-deficient conditions on different surfaces, and this ability enables them to evade chemical and biological eradication methods. Despite knowing the whole genome sequences of various APEC isolates, little has been reported regarding their biofilm-associated genes.

Microbiological Findings and Clinical Outcomes in Ugandan Patients with Infected Burn Wounds.

Nosocomial wound infections are a dreaded complication in patients with burns. However, access to the necessary microbiological diagnostics is impaired in low-resource settings. This prospective observational cohort study aimed to describe the bacterial pathogens, resistance profiles and clinical outcomes of patients with wound infections admitted to the largest specialized unit for burns and plastic surgery in Uganda.

Ab initio machine learning of phase space averages.

Equilibrium structures determine material properties and biochemical functions. We here propose to machine learn phase space averages, conventionally obtained by ab initio or force-field-based molecular dynamics (MD) or Monte Carlo (MC) simulations. In analogy to ab initio MD, our ab initio machine learning (AIML) model does not require bond topologies and, therefore, enables a general machine learning pathway to obtain ensemble properties throughout the chemical compound space.

Machine learning of free energies in chemical compound space using ensemble representations: Reaching experimental uncertainty for solvation.

Free energies govern the behavior of soft and liquid matter, and improving their predictions could have a large impact on the development of drugs, electrolytes, or homogeneous catalysts. Unfortunately, it is challenging to devise an accurate description of effects governing solvation such as hydrogen-bonding, van der Waals interactions, or conformational sampling. We present a Free energy Machine Learning (FML) model applicable throughout chemical compound space and based on a representation that employs Boltzmann averages to account for an approximated sampling of configurational space.

Investigation of Commensal Populations of Cormorant Hatchlings in the Absence of Anthropogenic Impacts in Remote Areas of West Mongolia.

To increase our understanding of bacterial intestinal colonization in animal populations lacking substantial anthropogenic influence we studied the diversity of in cormorants from the pristine West-Mongolian steppe. were isolated from individual birds of two cormorant colonies located on small islands in lakes at least 100 km away from human settlements. Diversity of the isolates was studied using pulsed-field gel electrophoresis (PFGE).

Novel Avian Pathogenic Escherichia coli Genes Responsible for Adhesion to Chicken and Human Cell Lines.

Avian pathogenic (APEC) is a major bacterial pathogen of commercial poultry contributing to extensive economic losses and contamination of the food chain. One of the initial steps in bacterial infection and successful colonization of the host is adhesion to the host cells. A random transposon mutant library ( = 1,300) of APEC IMT 5155 was screened phenotypically for adhesion to chicken (CHIC-8E11) and human (LoVo) intestinal epithelial cell lines.

Phylogenetic Characterization and Multilocus Sequence Typing of Extended-Spectrum Beta Lactamase-Producing from Food-Producing Animals, Beef, and Humans in Southwest Nigeria.

Multidrug-resistant extended-spectrum beta lactamase (ESBL)-producing strains are emerging globally in both humans and animals. Antimicrobial susceptibility testing and ESBL screening were performed on pure cultures of 216 isolates from human and animal fecal samples as well as beef. Polymerase chain reaction was performed for the detection of resistance genes.

Adhesion of to Pancreatic Secretory Granule Membrane Major Glycoprotein GP2 of Human and Porcine Origin Depends on FimH Sequence Variation.

Bacterial host tropism is a primary determinant of the range of host organisms they can infect. serotypes are differentiated into host-restricted and host-adapted specialists, and host-unrestricted generalists. In order to elucidate the underlying molecular mechanisms of host specificity in infection, we investigated the role of the intestinal host cell receptor zymogen granule membrane glycoprotein 2 (GP2), which is recognized by FimH adhesin of type 1 fimbriae found in .

Multiple Drug Resistance and Virulence Profiling of Salmonella enterica Serovars Typhimurium and Enteritidis from Poultry Farms of Faisalabad, Pakistan.

The zoonotic serovars of Salmonella enterica particularly Typhimurium and Enteritidis pose a continuous global threat to poultry industry and public health. We report the prevalence of Salmonella Typhimurium and Salmonella Enteritidis serovars in local poultry, phenotypic antimicrobial resistance profiling, and molecular detection of antimicrobial resistance and virulence genes. A total of 340 clinical samples were collected and 239 carried Salmonella, which were identified by genus-specific PCR (invA gene) and by matrix-assisted laser desorption/ionization time-of-flight.

Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro.

We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. The experiments were designed to reflect the conditions of intraperitoneal chemotherapy.

Genotypic and Phenotypic Characteristics Associated with Biofilm Formation by Human Clinical Escherichia coli Isolates of Different Pathotypes.

Bacterial biofilm formation is a widespread phenomenon and a complex process requiring a set of genes facilitating the initial adhesion, maturation, and production of the extracellular polymeric matrix and subsequent dispersal of bacteria. Most studies on biofilm formation have investigated nonpathogenic K-12 strains. Due to the extensive focus on laboratory strains in most studies, there is poor information regarding biofilm formation by pathogenic isolates.

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies with application of cytostatic drugs such as oxaliplatin (OX) after cytoreductive surgery. Despite its increased use, evidence for optimal drug dosage, and notably duration of HIPEC, is scarce.

Methods: In this study, OX distribution was comprehensively assessed in nine patients during HIPEC (300 mg OX/m body surface area in Physioneal solution for 30 min).

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing.

Aim: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.

Methods: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc).

Growth and Chemosensitivity of Gastric Adenocarcinoma and Non-Malignant Cell Lines in Response to Novel Anti-Cancer Drug Combinations.

Background: To design novel polychemotherapy regimens for gastric adenocarcinoma therapy with wider therapeutic windows using a novel duplex drug (D-D).

Methods: Two gastric adenocarcinoma (MKN-45 and 23132/87) and 2 non-malignant (NHDF and CCL-241) cell lines were treated with different drug regimens that included different doses of the standard triple-drug combination epirubicin (E) + cisplatin (C) + 5-fluorouracil (5-FU, F), i.e.

Assessment of species and antimicrobial resistance among Enterobacteriaceae isolated from mallard duck faeces.

Mallard ducks have demonstrated to be a likely reservoir for zoonotic E. coli strains; thus, it is possible that these ducks could also act as a reservoir for other Enterobacteriaceae members. The present study was initiated to evaluate the species distribution of Enterobacteriaceae other than E.

Intestinal Escherichia coli colonization in a mallard duck population over four consecutive winter seasons.

We report the population structure and dynamics of one Escherichia coli population of wild mallard ducks in their natural environment over four winter seasons, following the characterization of 100 isolates each consecutive season. Macro-restriction analysis was used to define isolates variously as multi- or 1-year pulsed-field gel electrophoresis (PFGE) types. Isolates were characterized genotypically based on virulence-associated genes (VAGs), phylogenetic markers, and phenotypically based on haemolytic activity, antimicrobial resistance, adhesion to epithelial cells, microcin production, motility and carbohydrate metabolism.

Adhesion patterns of commensal and pathogenic Escherichia coli from humans and wild animals on human and porcine epithelial cell lines.

Background: Different strategies of colonization or infection by E. coli result in formation of certain adhesion patterns which help also in classifying intestinal E. coli into pathotypes.

Adhesion of human and animal Escherichia coli strains in association with their virulence-associated genes and phylogenetic origins.

Intestinal colonization is influenced by the ability of the bacterium to inhabit a niche, which is based on the expression of colonization factors. Escherichia coli carries a broad range of virulence-associated genes (VAGs) which contribute to intestinal (inVAGs) and extraintestinal (exVAGs) infection. Moreover, initial evidence indicates that inVAGs and exVAGs support intestinal colonization.

Porcine E. coli: virulence-associated genes, resistance genes and adhesion and probiotic activity tested by a new screening method.

We established an automated screening method to characterize adhesion of Escherichia coli to intestinal porcine epithelial cells (IPEC-J2) and their probiotic activity against infection by enteropathogenic E. coli (EPEC). 104 intestinal E.

Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites.

The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'→5')ECyd.