Decision-making for childhood vaccination in crisis settings: a survey of practice & barriers.

Background: Children, particularly those who have received no routine vaccinations (zero-dose children), are at high risk of vaccine-preventable diseases in humanitarian crisis settings. However, the decision-making processes underlying vaccine intervention design and delivery in such settings are poorly understood. The present study investigated the decision-making practices of organisations involved in childhood vaccination in humanitarian crisis settings globally via an online survey.

Progress in the discovery and development of anticancer agents from marine cyanobacteria.

Covering 2010-April 2024There have been tremendous new discoveries and developments since 2010 in anticancer research based on marine cyanobacteria. Marine cyanobacteria are prolific sources of anticancer natural products, including the tubulin agents dolastatins 10 and 15 which were originally isolated from a mollusk that feeds on cyanobacteria. Decades of research have culminated in the approval of six antibody-drug conjugates (ADCs) and many ongoing clinical trials.

Probing a distinct druggable tubulin binding site with gatorbulins 1-7, their metabolic and physicochemical properties, and pharmacological consequences.

Microtubules, consisting of α/β-tubulin heterodimers, are prime targets for anticancer drug discovery. Gatorbulin-1 (GB1, 1a) is a recently described marine natural product that targets tubulin at a new, seventh pharmacological site at the tubulin intradimer interface. Using our previously developed robust route towards GB1 (1a), we synthesized simplified, first-generation gatorbulins, GB2-7 (1b-1g) of this highly modified cyclodepsipeptide (GB1) that does not contain any proteinogenic amino acid.

Phage Hunting in the High School Classroom: Phage Isolation and Characterization.

National science, technology, engineering, and mathematics education emphasizes science practices, such as hands-on learning. We describe a week-long activity where students participate in real-world scientific discovery, including "hunting" for bacteriophage in a variety of environmental samples. First, the students collect samples, then look for evidence of phage on "bait" bacteria, and finally amplify/purify the phages for further study.

Isolation and Characterization of the Cyanobacterial Macrolide Glycoside Moorenaside, an Anti-Inflammatory Analogue of Aurisides Targeting the Keap1/Nrf2 Pathway.

A new 14-membered ring brominated macrolide glycoside, named moorenaside (), was discovered from a marine cyanobacterial sample collected from Shands Key in Florida. The structure of was established by analysis of spectroscopic data including its relative configuration. The absolute configuration was inferred from optical rotation data and comparison with related compounds.

Queuosine salvage in Houston 1: a unique evolutionary path.

Queuosine (Q) stands out as the sole tRNA modification that can be synthesized via salvage pathways. Comparative genomic analyses identified specific bacteria that showed a discrepancy between the projected Q salvage route and the predicted substrate specificities of the two identified salvage proteins: (1) the distinctive enzyme tRNA guanine-34 transglycosylase (bacterial TGT, or bTGT), responsible for inserting precursor bases into target tRNAs; and (2) queuosine precursor transporter (QPTR), a transporter protein that imports Q precursors. Organisms such as the facultative intracellular pathogen , which possess only bTGT and QPTR but lack predicted enzymes for converting preQ to Q, would be expected to salvage the queuine (q) base, mirroring the scenario for the obligate intracellular pathogen .

Spatiotemporal Modeling of Cholera, Uvira, Democratic Republic of the Congo, 2016-2020.

We evaluated the spatiotemporal clustering of rapid diagnostic test-positive cholera cases in Uvira, eastern Democratic Republic of the Congo. We detected spatiotemporal clusters that consistently overlapped with major rivers, and we outlined the extent of zones of increased risk that are compatible with the radii currently used for targeted interventions.

Evaluation of co-culture of cellulolytic fungi for enhanced cellulase and xylanase activity and saccharification of untreated lignocellulosic material.

Bioethanol production from lignocellulosic materials is hindered by the high costs of pretreatment and the enzymes. The present study aimed to evaluate whether co-cultivation of four selected cellulolytic fungi yields higher cellulase and xylanase activities compared to the monocultures and to investigate whether the enzymes from the co-cultures yield higher saccharification on selected plant materials without thermo-chemical pretreatment. The fungal isolates, Trichoderma reesei F118, Penicillium javanicum FS7, Talaromyces sp.

Morphological profiling for drug discovery in the era of deep learning.

Morphological profiling is a valuable tool in phenotypic drug discovery. The advent of high-throughput automated imaging has enabled the capturing of a wide range of morphological features of cells or organisms in response to perturbations at the single-cell resolution. Concurrently, significant advances in machine learning and deep learning, especially in computer vision, have led to substantial improvements in analyzing large-scale high-content images at high throughput.

The Significance of Stone Culture in the Incidence of Sepsis: Results from a Prospective, Multicenter Study on Infections Post Flexible UreteroreNescopy (I-FUN) and Laser Lithotripsy for Renal Stones.

Sepsis is the most serious complication of flexible ureteroscopy (F-URS) and laser lithotripsy. We assessed the influence of positive stone culture (SC) on major infectious complications (sepsis, septic shock). This prospective study enrolled adult patients deemed suitable for F-URS and laser lithotripsy from nine centers (January 2022-August 2023).

Chemical Genetics in Identifies Anticancer Mycotoxins Chaetocin and Chetomin as Potent Inducers of a Nuclear Metal Homeostasis Response.

(clear-localized etal-esponsive) is an identical gene pair encoding a nuclear protein previously shown to be activated by cadmium and disruption of the integrator RNA metabolism complex. We took a chemical genetic approach to further characterize regulation of this novel metal response by screening 41,716 compounds and extracts for activation. The most potent activator was chaetocin, a fungal 3,6-epidithiodiketopiperazine (ETP) with promising anticancer activity.

Epigenetic small-molecule screen for inhibition and reversal of acinar ductal metaplasia in mouse pancreatic organoids.

Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development. We developed a novel morphology-based screen using organoids from wildtype and (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA). Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis.

Biosynthesis and function of 7-deazaguanine derivatives in bacteria and phages.

SUMMARYDeazaguanine modifications play multifaceted roles in the molecular biology of DNA and tRNA, shaping diverse yet essential biological processes, including the nuanced fine-tuning of translation efficiency and the intricate modulation of codon-anticodon interactions. Beyond their roles in translation, deazaguanine modifications contribute to cellular stress resistance, self-nonself discrimination mechanisms, and host evasion defenses, directly modulating the adaptability of living organisms. Deazaguanine moieties extend beyond nucleic acid modifications, manifesting in the structural diversity of biologically active natural products.

Biosynthesis of Dolastatin 10 in Marine Cyanobacteria, a Prototype for Multiple Approved Cancer Drugs.

Dolastatin 10, a potent tubulin-targeting marine anticancer natural product, provided the basis for the development of six FDA-approved antibody-drug conjugates. Through the screening of cyanobacterial environmental DNA libraries and metagenome sequencing, we identified its biosynthetic gene cluster. Functional prediction of 10 enzymes encoded in the 39 kb cluster supports the dolastatin 10 biosynthesis.

Morphological Profiling for Drug Discovery in the Era of Deep Learning.

Morphological profiling is a valuable tool in phenotypic drug discovery. The advent of high-throughput automated imaging has enabled the capturing of a wide range of morphological features of cells or organisms in response to perturbations at the single-cell resolution. Concurrently, significant advances in machine learning and deep learning, especially in computer vision, have led to substantial improvements in analyzing large-scale high-content images at high-throughput.

Queuosine Salvage in Houston 1: A Unique Evolutionary Path.

Queuosine (Q) stands out as the sole tRNA modification that can be synthesized via salvage pathways. Comparative genomic analyses identified specific bacteria that showed a discrepancy between the projected Q salvage route and the predicted substrate specificities of the two identified salvage proteins: 1) the distinctive enzyme tRNA guanine-34 transglycosylase (bacterial TGT, or bTGT), responsible for inserting precursor bases into target tRNAs; and 2) Queuosine Precursor Transporter (QPTR), a transporter protein that imports Q precursors. Organisms like the facultative intracellular pathogen , which possess only bTGT and QPTR but lack predicted enzymes for converting preQ to Q, would be expected to salvage the queuine (q) base, mirroring the scenario for the obligate intracellular pathogen .

Epigenetic Small-Molecule Screen for Inhibition and Reversal of Acinar Ductal Metaplasia in Mouse Pancreatic Organoids.

Background: Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development.

Methods: We developed a novel morphology-based screen using organoids from wildtype and p48 (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA).

Results: Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis.

Discovery and Anti-Inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway.

The monounsaturated fatty acid 7()-9-keto-hexadec-7-enoic acid () and three structurally related analogues with different oxidation states and degrees of unsaturation (-) were discovered from a marine benthic cyanobacterial mat collected from Delta Shoal, Florida Keys. Their structures were elucidated using NMR spectroscopy and mass spectrometry. The structure of contained an α,-unsaturated carbonyl system, a key motif required for the activation of the Keap1/Nrf2-ARE pathway that is involved in the activation of antioxidant and phase II detoxification enzymes.

Characterization of arrowroot () starch as a potential starch source for the food industry.

Arrowroot is an underutilized tuber crop in Sri Lanka and the characterization of starch was done to identify its nutritional, physicochemical, and functional properties to evaluate its potential for use in the food industry. This study distinctly advances the field of arrowroot starch characterization by providing more characterization techniques for starch samples from Sri Lanka. Arrowroot starch colour was closely similar to colour of wheat flour indicating that the effect of colour is minimum when replacing wheat flour.

Targeted and functional genomics approaches to the mechanism of action of lagunamide D, a mitochondrial cytotoxin from marine cyanobacteria.

Lagunamide D, a cyanobacterial cyclodepsipeptide, exhibits potent antiproliferative activity against HCT116 colorectal cancer cells (IC 5.1 nM), which were used to probe the mechanism of action. Measurements of metabolic activity, mitochondrial membrane potential, caspase 3/7 activity and cell viability indicate the rapid action of lagunamide D on mitochondrial function and downstream cytotoxic effects in HCT116 cells.

Implementation of targeted cholera response activities, Cameroon.

Objective: To describe the implementation of case-area targeted interventions to reduce cholera transmission using a rapid, localized response in Kribi district, Cameroon.

Methods: We used a cross-sectional design to study the implementation of case-area targeted interventions. We initiated interventions after rapid diagnostic test confirmation of a case of cholera.

Disruption to water supply and waterborne communicable diseases in northeast Syria: a spatiotemporal analysis.

Background: In Syria, disruption to water and sanitation systems, together with poor access to vaccination, forced displacement and overcrowding contribute to increases in waterborne diseases (WBDs). The aim of this study is to perform a spatiotemporal analysis to investigate potential associations between interruptions to water, sanitation, and hygiene (WASH) and WBDs in northeast Syria using data collected by the Early Warning Alert and Response Network (EWARN) from Deir-ez-Zor, Raqqa, Hassakeh and parts of Aleppo governorates.

Methods: We reviewed the literature databases of MEDLINE and Google Scholar and the updates of ReliefWeb to obtain information on acute disruptions and attacks against water infrastructure in northeast Syria between January 2015 and June 2021.

Rapidly adapted community health strategies to prevent treatment interruption and improve COVID-19 detection for Syrian refugees and the host population with hypertension and diabetes in Jordan.

Background: We evaluated community health volunteer (CHV) strategies to prevent non-communicable disease (NCD) care disruption and promote coronavirus disease 2019 (COVID-19) detection among Syrian refugees and vulnerable Jordanians, as the pandemic started.

Methods: Alongside medication delivery, CHVs called patients monthly to assess stockouts and adherence, provide self-management and psychosocial support, and screen and refer for complications and COVID-19 testing. Cohort analysis was undertaken of stockouts, adherence, complications and suspected COVID-19.