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The emergence of bacterial resistance has a negative impact on the conventional antimicrobial treatments, and research into the development of the new antimicrobial materials is of great significance. Multimodal synergistic antimicrobial materials exert better antimicrobial effects compared with a single modality. In recent years, Polyoxometalate (POM) has shown great potential in the biomedical field due to its high catalytic activity and high photothermal conversion ability. However, owing to its small surface area, its applications have been greatly limited. Herein, we designed a H2O2 self‐supplied CDT and PTT bimodal nanogeneration material (i.e., CaO2/POM@MOF) possessing a larger surface area for the treatment of the bacterial infections, in which CaO2 could release O2 and H2O2 in the weakly acidic microenvironment of bacterial infection and the dual catalytic site of POM@MOF could enhance the CDT reaction to generate ROS, resulting in the bacterial oxidative stress and the leakage of the bacterial contents, and the exposure to the NIR light generates localized high temperature that cause the rupture of bacterial cell membranes and the denaturation of their proteins. Meanwhile, the superior stability of POM@MOF can release fewer metal ions to improve its biocompatibility. The in vitro antimicrobial experiments demonstrated that CaO2/POM@MOF possessed the combined CDT and PTT effect and exhibited excellent antimicrobial efficacy. This work presents a promising strategy to combat the bacterial infections. [ABSTRACT FROM AUTHOR]

A 40-year-old woman presented with a 4-week history of headache, facial swelling, and dyspnea. Computed tomography (CT) scan of the chest showed marked narrowing of the superior vena cava (SVC) with surrounding hypodense soft tissue and prominent collateral circulation in mediastinum, and the diagnosis of fibrosing mediastinitis was made. Biopsy suggested active fungal infection and she was treated with oral antifungal therapy. She reported persistent symptoms even after medical management; hence, she was taken for endovascular treatment with placement of a 16 × 60 mm stent (Optimed sinus-XL) in SVC. The patient complained of aggravation in symptoms immediately the next day, and a diagnostic venogram revealed acute total in-stent thrombosis. On an emergency basis, the patient was taken for catheter-directed thrombolysis (CDT) with tissue plasminogen activator (tPA) infusion. She was followed up with CT after1 year, which showed patent stent and no residual or recurrent thrombosis. She is on follow-up with marked relief in symptoms and improved quality of life. Catheter-directed thrombolysis is an emergent treatment modality with limited albeit growing evidence to treat acute in-stent thrombosis. CDT with tPA can be used to effectively treat acute thrombosis with promising results. [ABSTRACT FROM AUTHOR]

Alcohol abuse poses an important challenge to public health and is associated with a shorter lifespan, numerous disorders, and social and economic problems. Methods to identify heavy drinkers are necessary for choosing the prevention and treatment strategies in medicine and are in demand in forensics. Alcohol consumption is often underestimated in self-reported data, and objective laboratory tests are therefore essential to employ in diagnosing chronic alcohol abuse and acute alcoholic excess. Carbohydrate-deficient transferrin (CDT) is one of the most specific biomarkers of alcohol abuse. CDT is a set of transferrin isoforms with a lower content of sialic acid residues and is found when glycosylation is impaired by ethanol metabolites. Oxidation of exogenous ethanol to acetaldehyde by alcohol dehydrogenase 1B (ADH1B) is a major pathway of ethanol metabolism. This study showed for the first time that carriers of the allele ADH1B*48His (rs1229984), which determines acetaldehyde production to higher concentrations, have greater CDT levels as compared with noncarriers, alcohol consumption being the same. The difference should be taken into account in medicine, forensics, and studies where Mendelian randomization with respect to the polymorphic locus rs1229984 is performed to address the effects of drinking alcohol. [ABSTRACT FROM AUTHOR]

The advancement of rational nano drug delivery systems offers robust tools for achieving synergistic therapeutic outcomes in tumor treatment. In this study, we present the development of pH and near-infrared laser dual-responsive nanoparticles (DOX-CuS@CaCO 3 @PL-PEG, DCCP NPs) based on calcium carbonate, utilizing a one-pot gas diffusion reaction. These nanoparticles enable combined photothermal therapy (PTT), chemodynamic therapy (CDT), chemotherapy, and Ca2+-overloading synergistic therapy. Doxorubicin (DOX) and copper sulfide (CuS) NPs were co-loaded in CaCO 3 , followed by PEG surface functionalization. The presence of PEG enhanced the stability of DCCP NPs in aqueous environments. Controlled release of DOX, CuS NPs, and Ca2+ occurs specifically in the acidic tumor microenvironment. Released DOX enhances chemotherapy efficiency, while CuS NPs, upon laser irradiation, induce thermal damage, promoting further drug release and cellular uptake. Additionally, CuS NPs in our system consume excess GSH and generate toxic hydroxyl radicals (·OH) through a Fenton-like reaction, contributing to CDT. These radicals not only directly eliminate tumor cells but also disrupt mitochondrial Ca2+ buffering capacity. Furthermore, Ca2+ released from CaCO 3 induces Ca2+-overloading, intensifying mitochondrial disruption and oxidative damage. The synergistic combination of PTT, CDT, chemotherapy, and Ca2+-overloading showcases significant therapeutic potential, indicating broad applications in tumor therapy. This multifaceted approach holds promise for advancing the field of tumor therapeutics. pH and NIR laser dual-responsive multimodal nanoplatform DCCP NPs can achieve Ca2+-overloading therapy, PTT, CDT and chemotherapy after entering tumor tissues and irradiated by NIR laser. Photothermal light improves chemotherapy effect and CDT efficiency, while ROS generated by CDT disrupts Ca2+ buffer capacity and synergizes with CaCO 3 degradation to release large amount of Ca2+, leading to Ca2+-overloading. [Display omitted] • CuS NPs produce effective thermal ablation under NIR laser irradiation. • Photothermal promotes CuS-mediated Fenton-like catalytic activityto generate ROS. • The large amount of Ca2+ released by CaCO 3 degradation causes Ca2+-overloading to damage mitochondria. • Dual-responsive multimodal nanoplatform achieves enhanced cancer therapeutic effects. [ABSTRACT FROM AUTHOR]

Escherichia albertii and Escherichia fergusonii are recognized as emerging pathogens with zoonotic potential. Despite their increasing importance, there is a paucity of data on the cytotoxicity of these two pathogens. Therefore, in the present study, we investigated the cytotoxic potentials of the cell-free supernatants from 10 E. albertii and 15 E. fergusonii isolates for their cytotoxic effects on four different cell lines (CHO, Vero, HeLa, and MDCK). All E. albertii isolates (100%) and all but one E. fergusonii (93.33%) were cytotoxic. E. albertii isolates produced similar cytotoxicity titres across the cell lines, whereas the Vero cell was found to be the most sensitive to toxins produced by E. fergusonii (p < 0.05), followed by HeLa and CHO cells. MDCK was the least sensitive cell line to E. fergusonii toxins (p < 0.05). PCR detection of cytotoxicity-associated genes (cdtB, stx1, and stx2) indicated uniform possession of cdtB gene by all E. albertii isolates, while stx1 and stx2 genes were harboured neither by E. albertii, nor E. fergusonii. Taken together, our results provided experimental evidence of the cytotoxic effects of these two emerging pathogens, and Vero cells were identified as an optimal candidate to study the cytotoxic effects of E. albertii and E. fergusonii. [ABSTRACT FROM AUTHOR]

Eliciting anti-tumor immune responses and improving the tumor microenvironment crucial for boosting the effectiveness of anti-PD-1 immunotherapy. Tumor-associated macrophages (TAMs), the primary types of immune cells infiltrating tumors, play a critical role in the formation of an immunosuppressive microenvironment. In this study, we constructed a novel Evans Blue (EB)-based in vivo self-assembled nanocarrier system, mUNO-EB-ICG-Fc@Alb nanoparticles (designated as MA NPs), for targeted imaging and clearance of M2-TAMs to elicit antitumor immunotherapy of PD-1 inhibitor. In vitro experiments demonstrated the specific fluorescence imaging and killing effect of MA NPs on M2-TAMs. In vivo experiments shown that MA NPs-induced chemodynamic therapy (CDT) successfully reversed the tumor immunosuppressive microenvironment (ITM), promoted intratumoral infiltration of T lymphocytes, and ultimately enhancing the anti-tumor immunotherapy effect of PD-1 inhibitors. This study might provide good inspiration for improving the therapeutic efficacy of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. Objectives: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. Method: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. Results: For sub‐massive PE, CDT plus AC significantly reduced in‐hospital, 30‐day, and 12‐month mortality compared to AC alone, odds ratio (OR) of −0.99 (95% CI [−1.32 to −0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [−0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all‐cause or in‐hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. Conclusion: The addition of CDT to AC improves mortality outcomes for sub‐massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] An injectable hydrogel dressing, Zr/Fc-MOF@CuO 2 @FH, was constructed by combing acid-triggered chemodynamic treatment (CDT) with low-temperature photothermal treatment (LT-PTT) to effectively eliminate bacteria without harming the surrounding normal tissues. The Zr/Fc-MOF acts as both photothermal reagent and nanozyme to generate reactive oxygen species (ROS). The CuO 2 nanolayer can be decomposed by the acidic microenvironment of the bacterial infection to release Cu2+ and H 2 O 2 , which not only induces Fenton-like reaction but also enhances the catalytic capability of the Zr/Fc-MOF. The generated heat augments ROS production, resulting in highly efficient bacterial elimination at low temperature. Precisely, injectable hydrogel dressing can match irregular wound sites, which shortens the distance of heat dissipation and ROS diffusion to bacteria, thus improving sterilization efficacy and decreasing non-specific systemic toxicity. Both in vitro and in vivo experiments validated the predominant sterilization efficiency of drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) and kanamycin-resistant Escherichia coli (KREC), presenting great potential for application in clinical therapy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study was designed to give a comprehensively updated bibliometric summary of employee performance when faced with cognitive dissonance in light of recent imperatives and expanding scholarly interest. OBJECTIVE: This research provided a deep knowledge of references, cited sources, countries through network map, relevant sources map with table, relevant authors map with table, frequent keywords used by authors network map, citations per year graph, and co-occurrence of network with networking map. METHOD: In the study, the Scopus database was used to analyse large data. Biblioshiny software was also used for the analysis and verified using a VOS viewer. A mixed (combination of several) techniques is the main focus of the methodological procedure. 400 Scopus-indexed articles and 5 conference papers have been taken to prepare this bibliometrics review with the help of biblioshiny and Vos viewer software. RESULT: The results reveal that employee performance depends on their beliefs and attitudes. These two factors fall under cognitive dissonance theory (CDT). CONCLUSION: It is also fruitful for organizations to study CDT theory for organizational development and employee performance growth. [ABSTRACT FROM AUTHOR]

Simple Summary: The postoperative complication rate is high (30–64%) among patients undergoing major surgery for bladder cancer, and significantly increased for patients with a high alcohol use at the time of surgical intervention. Several markers have been used to estimate alcohol use—including questionnaires and biomarkers. The aim of this study was to evaluate the accuracy for identifying preoperative alcohol use of four markers (one questionnaire and three biomarkers) relative to the standard method (Timeline Follow Back interviews). This was done in a sample of 94 patients scheduled for major bladder cancer surgery. We found none of the tested markers were sufficiently reliable to identify preoperative risky alcohol use and, for now, the standard procedure seems preferable. Background: The postoperative complication rate is 30–64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. Methods: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT–C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P–CDT), phosphatidyl-ethanol in blood (B–PEth), and ethyl glucuronide in urine (U–EtG). Results: The correlation between TLFB and AUDIT–C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55–0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B–PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79–100%), but low negative predictive values (42–55%). Conclusions: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use. [ABSTRACT FROM AUTHOR]

In the treatment of various cancers, photodynamic therapy (PDT) has been extensively studied as an effective therapeutic modality. As a potential alternative to conventional chemotherapy, PDT has been limited due to the low Reactive Oxygen Species (ROS) yield of photosensitisers. Herein, a nanoplatform containing mesoporous Fe3O4@TiO2 microspheres was developed for near-infrared (NIR)-light-enhanced chemodynamical therapy (CDT) and PDT. Titanium dioxide (TiO2) has been shown to be a very effective PDT agent; however, the hypoxic tumour microenvironment partly affects its in vivo PDT efficacy. A peroxidase-like enzyme, Fe3O4, catalyses the decomposition of H2O2 in the cytoplasm to produce O2, helping overcome tumour hypoxia and increase ROS production in response to PDT. Moreover, Fe2+ in Fe3O4 could catalyse H2O2 decomposition to produce cytotoxic hydroxyl radicals within tumour cells, which would result in tumour CDT. The photonic hyperthermia of Fe3O4@TiO2 could not only directly damage the tumour but also improve the efficiency of CDT from Fe3O4. Cancer-killing effectiveness has been maximised by successfully loading the chemotherapeutic drug DOX, which can be released efficiently using NIR excitation and slight acidification. Moreover, the nanoplatform has high saturation magnetisation (20 emu/g), making it suitable for magnetic targeting. The in vitro results show that the Fe3O4@TiO2/DOX nanoplatforms exhibited good biocompatibility as well as synergetic effects against tumours in combination with CDT/PDT/PTT/chemotherapy. [ABSTRACT FROM AUTHOR]

Iron boride nanomaterials based on BCN substrates (FeB/BCN), with good antitumor effects and biosafety, were obtained via complexing the organic ligand(1,10-phenanthroline) with boron cluster (closo -[B 12 H 12 ]2–) and calcination. [Display omitted] Chemodynamic therapy (CDT) is an emerging treatment strategy that inhibits tumor growth by catalyzing the generation of reactive oxygen species (ROS), such as hydroxyl radicals (•OH), using specific nanomaterials. Herein, we have developed a new class of iron-based nanomaterials, i.e., iron-based borides (FeB), using the superchaotropic effect of a boron cluster (closo- [B 12 H 12 ]2–) and organic ligands, followed by high-temperature calcination. Experimental data and theoretical calculations revealed that FeB nanoparticles exhibit a Fenton-like effect, efficiently decomposing hydrogen peroxide into •OH and thus increasing the concentration of ROS. FeB nanomaterials demonstrate excellent catalytic performance, efficiently generate ROS, and exert significant antitumor effects in cell experiments and animal models. Therefore, FeB nanomaterials have considerable potential for application in tumor treatment and offer new insights for the development of novel and efficient cancer therapy strategies. [ABSTRACT FROM AUTHOR]

Escherichia albertii and Escherichia fergusonii are recognized as emerging pathogens with zoonotic potential. Despite their increasing importance, there is a paucity of data on the cytotoxicity of these two pathogens. Therefore, in the present study, we investigated the cytotoxic potentials of the cell-free supernatants from 10 E. albertii and 15 E. fergusonii isolates for their cytotoxic effects on four different cell lines (CHO, Vero, HeLa, and MDCK). All E. albertii isolates (100%) and all but one E. fergusonii (93.33%) were cytotoxic. E. albertii isolates produced similar cytotoxicity titres across the cell lines, whereas the Vero cell was found to be the most sensitive to toxins produced by E. fergusonii (p < 0.05), followed by HeLa and CHO cells. MDCK was the least sensitive cell line to E. fergusonii toxins (p < 0.05). PCR detection of cytotoxicity-associated genes (cdtB, stx1, and stx2) indicated uniform possession of cdtB gene by all E. albertii isolates, while stx1 and stx2 genes were harboured neither by E. albertii, nor E. fergusonii. Taken together, our results provided experimental evidence of the cytotoxic effects of these two emerging pathogens, and Vero cells were identified as an optimal candidate to study the cytotoxic effects of E. albertii and E. fergusonii.

Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device. [ABSTRACT FROM AUTHOR]

Nowadays, countries face a multitude of electronic threats that have permeated almost all business sectors, be it private corporations or public institutions. Among these threats, advanced persistent threats (APTs) stand out as a well-known example. APTs are highly sophisticated and stealthy computer network attacks meticulously designed to gain unauthorized access and persist undetected threats within targeted networks for extended periods. They represent a formidable cybersecurity challenge for governments, corporations, and individuals alike. Recognizing the gravity of APTs as one of the most critical cybersecurity threats, this study aims to reach a deeper understanding of their nature and propose a multi-stage framework for automated APT detection leveraging time series data. Unlike previous models, the proposed approach has the capability to detect real-time attacks based on stored attack scenarios. This study conducts an extensive review of existing research, identifying its strengths, weaknesses, and opportunities for improvement. Furthermore, standardized techniques have been enhanced to enhance their effectiveness in detecting APT attacks. The learning process relies on datasets sourced from various channels, including journal logs, traceability audits, and systems monitoring statistics. Subsequently, an efficient APT detection and prevention system, known as the composition-based decision tree (CDT), has been developed to operate in complex environments. The obtained results demonstrate that the proposed approach consistently outperforms existing algorithms in terms of detection accuracy and effectiveess. [ABSTRACT FROM AUTHOR]

In this paper, we propose an abstract domain-neutral architecture for a cognitive digital twin (CDT) and a software platform to develop such CDTs, including machine reasoning capabilities. Sustainable development refers here to an abstract model that enables a holistic view of limiting resources and has an ability to adapt to different application domains while reusing existing resources. The proposed solution allows for a unified abstract representation and the development of a wide range of diverse digital twins, as well as facilitating their interoperability. The abstract architecture consists of a four-layer structure (observation/actuation layer, data management layer, reasoning layer, and simulation layer) with an upper ontology to which the domain ontology of the specific CDT is mapped. The architecture relies on semantic web technologies, including ontology-based reasoning using OWL, and a loosely coupled, component-based service-oriented software architecture. The platform utilizes a microservice architecture that enables separate, loosely coupled services on each layer, message queues to provide asynchronous communication, and possesses cloud technologies to achieve scalability. The proposed approach was validated by implementing a software platform prototype and demonstrating its key features through two dissimilar scenarios. The first scenario demonstrates simple sustainable energy management through IoT systems inside smart buildings, while the second one demonstrates knowledge quality management based on knowledge space theory. [ABSTRACT FROM AUTHOR]

The electric vehicle technology is vacillating at remarkable rates. Thus, the enhancements of the associated fluids and their associated additives are also changing. Varying conditions, depending on the EV system and usage albeit passenger car or heavy duty, can cause the formation of conductive deposits and corrosion within drivetrains. Corrosion is a wellknown entity and tools to evaluate under these conditions are imperative. However, the formation of conducting layer deposits, a corrosion product, has also been identified as a failure mechanism for current electric motor designs. Different drivetrain base stocks along with additive formulations may have inherently different corrosion rates producing conducting layer deposits in both solution and vapor phases. To help resolve these issues, a group of industry experts involving both OEM's and lubricant experts from across the globe, have developed bench tests to better predict these conductive and corrosion deposits. The apparatus' developed are the conductive deposit test and the wire corrosion test. This paper covers several different aspects of the EV drivetrains and fluids performing in the CDT and WCT that show both field correlation and repeatability. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT), a non-invasive cancer treatment strategy, selectively induces cancer cell death without harming normal cells. However, CDT's efficacy is limited by the inadequate levels of endogenous hydrogen peroxide (H2O2) in tumor cells and the powerful antioxidant system glutathione (GSH). To overcome this obstacle, the study introduces a nanointelligent platform (IrOx-CaP@PTX NPs) incorporating paclitaxel (PTX), a cytotoxic agent, employing glucose oxidase (GOx) as a scaffold to generate degradable calcium phosphate (CaP) nanoparticles doped with iridium oxide (IrOx) via physisorption. To stabilize the nanosystems and enable them to target tumor cells, hyaluronic acid (HA) was finally modified on their surface. By conducting both in vitro and in vivo experiments, it was revealed that GOx functioned as an enzymatic accelerator, producing H2O2 and gluconic acid through glucose metabolism within cancerous cells. This process starved the tumor cells but also provided a continuous supply of H2O2 and an acidic environment for the subsequent CDT. Furthermore, the released IrOx used its peroxidase activity (POD) to generate hydroxyl radicals (•OH) from H2O2 and consume intracellular reducing GSH through its valence exchange, thus further enhancing the efficacy of CDT. Finally, PTX acted synergistically with CDT as a chemotherapeutic agent for treatment. In summary, the IrOx-CaP@PTX NPs accomplished a multimodal treatment strategy encompassing GOx-mediated metabolic restriction, self-generation of H2O2, enhanced elimination of GSH for improved CDT, and PTX-induced chemotherapy. This comprehensive approach demonstrated superior tumor growth inhibition and reduced adverse effects in vivo studies. In conclusion, this study provides a non-invasive therapeutic strategy for the synergistic treatment of cancer. [ABSTRACT FROM AUTHOR]

Metal–phenolic networks (MPNs) are a new type of nanomaterial self-assembled by metal ions and polyphenols that have been developed rapidly in recent decades. They have been widely investigated, in the biomedical field, for their environmental friendliness, high quality, good bio-adhesiveness, and bio-compatibility, playing a crucial role in tumor treatment. As the most common subclass of the MPNs family, Fe-based MPNs are most frequently used in chemodynamic therapy (CDT) and phototherapy (PTT), where they are often used as nanocoatings to encapsulate drugs, as well as good Fenton reagents and photosensitizers to improve tumor therapeutic efficiency substantially. In this review, strategies for preparing various types of Fe-based MPNs are first summarized. We highlight the advantages of Fe-based MPNs under the different species of polyphenol ligands for their application in tumor treatments. Finally, some current problems and challenges of Fe-based MPNs, along with a future perspective on biomedical applications, are discussed. [ABSTRACT FROM AUTHOR]

T lymphocyte recruitment and infiltration promises to suppress the most devastating metastatic tumors for immunotherapy. However, the immune privilege and low vaccine immunogenicity usually reduces the presence of lymphocytes in tumors, especially for invading metastatic clusters. Here, an adhesive catalytic nanoreservoir (CN) containing manganese dioxide (MnO2) and catechol‐functionalized magnetic metal organic framework for the antigens capture and delivery is reported. The intravenously injected CN accumulates at tumor via the marginated target and in situ forming gel for antigen capture. At tumor site, CN releases Mn2+ for redox reactions by depleting glutathione (GSH) and Fenton‐like activity, i.e., chemodynamic therapy (CDT). Accompanying with hyperthermia, CDT promote the tumor to release the tumor‐associated antigens including neoantigens and damage‐associated molecular patterns. Then, the gels with catechol groups act as antigen reservoirs and deliver the autologous tumor‐associated antigens to dendritic cells, achieving sustained immune stimulation. The in situ‐forming catalytic nanoreservoir at lung metastasis as a magnetothermal‐induced antigen reservoir effectively inhibited the tumor in 60 days and increased the survival rate. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis reports the outcomes of catheter directed thrombolysis (CDT) in patients with not immediately threatening (Rutherford I) acute lower limb ischaemia (ALI). PubMed, Embase, and the Cochrane Library. A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify observational studies and trials published between 1990 and 2022 reporting on the results of CDT in patients with Rutherford I ALI. A meta-analysis was performed using a random effects model with 95% confidence intervals (CIs). The outcomes of interests were treatment duration, angiographic success, bleeding complications, amputation and mortality rates, primary and secondary patency, and functional outcome expressed as pain free walking distance. Thirty-nine studies were included, comprising 1 861 patients who received CDT for not immediately threatening ALI. Funnel plots showed an indication of publication bias, and heterogeneity was substantial. Data from 5 to 13 studies were included in the meta-analysis. The pooled treatment duration was 2 days (95% CI 1 – 2), with an angiographic success rate of 80% (95% CI 73 – 86) and a 30 day freedom of amputation rate of 98% (95% CI 92 – 100). The major bleeding rate was 5% (95% CI 2 – 14), with a 30 day mortality rate of 3% (95% CI 1 – 5). The amputation free survival rate was 71% (95% CI 62 – 80) at the one year and 63% (95% CI 51 – 73) at the three year follow up. Long term patency rates were retrieved from four studies: 48% at one year (95% CI 27 – 70). No data could be retrieved on patient walking distance. Although CDT in the treatment of not immediately threatening ALI showed high angiographic success, the long term outcomes were relatively poor, with low patency and a substantial risk of major amputation. Further research is required to interpret the outcome of CDT in the context of potential confounders such as age and comorbidities. [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection. Methods To determine the contribution of the separate components of CDT during infection, we developed strains of C difficile expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness. Results Although expression of CDTb without CDTa did not induce significant disease in a mouse model of C difficile infection, we found that complementation of a CDT-deficient C difficile strain with CDTb alone restored virulence in a hamster model of C difficile infection. Conclusions Overall, this study demonstrates that the binding component of C difficile binary toxin, CDTb, contributes to virulence in a hamster model of infection. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and β-lapachone (Lap) (CLH) for lung tumor treatment.Methods: The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu2+) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu2+ consumes the overexpressed GSH in TME and the generated Cu+ further exploits the TME characteristics to initiate nanocatalytic reactions for generating highly toxic hydroxyl radicals. In addition, in cancer cells overexpressing Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase 1 (NQO1), Lap can catalyze the generation of hydrogen peroxide (H2O2) through futile redox cycles. H2O2 is further converted into highly toxic hydroxyl radicals via the Fenton-like reaction, leading to a burst of reactive oxygen species in TME, which further enhances the therapeutic effect of chemokines.Results: Analysis of the antitumor efficacy in a subcutaneous A549 lung tumor model mice showed a significant delay in tumor growth and no systemic toxicity was detected.Discussion: In conclusion, we have established a CLH nanodrug platform that enables efficient lung tumor therapy through combined photothermal/chemodynamic therapy (CDT) treatment and self-supplying H2O2 to achieve cascade catalysis, leading to explosive amplification of oxidative stress.

Background: Breast cancer-related lymphedema (BCRL) after primary therapy is a common condition, causing physical and psychological distress. Decongestive lymphedema therapy (DLT) using multi-layered compression bandages is an effective treatment. We conducted a randomized controlled trial evaluating the use of a specific mobilizing bandage (Mobiderm®) on lymphedema volume reduction during the intensive phase of DLT. Methods and Results: Fifty female BCRL patients were randomized to receive either conventional multi-layered bandages or mobilizing bandaging by using Mobiderm. Affected limb volume and excess volume were evaluated at baseline (D0) and after 15 days. The primary outcome was change in affected limb volume after adjustment for baseline. Symptom scores were evaluated by visual analogue scale (VAS); safety and tolerability were also assessed. Baseline characteristics were comparable. Affected limb volume reduction was observed in both study groups after 15 days: by 19.0% in the Mobiderm arm and 8.6% in controls (adjusted values). The between-group mean difference in adjusted volume reduction at day 15 was 256 mL (95% confidence interval [CI], 92.5 to 421.3 mL; p = 0.003) favoring Mobiderm. Reductions in excess volume of 57.3% (Mobiderm) and 25.1% (controls) were observed (adjusted values); with between-group mean difference in adjusted excess volume of 220.2 mL (95% CI, 69.3 to 371.3 mL; p = 0.006) favoring Mobiderm. Pain/heaviness VAS scores fell significantly in both groups, with mean reductions of 1.84 (Mobiderm) versus 0.83 (control; p = 0.001). Both regimens were well tolerated. Conclusion: The use of Mobiderm in multilayer compression bandaging shows benefit in lymphedema reduction and in alleviating functional symptoms/pain in patients with BRCL. [ABSTRACT FROM AUTHOR]

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS 2 /CuO 2) is rationally constructed by simply decorating ultrasmall CuO 2 nanodots onto lamellar MoS 2 platelets of hydrangea-like MoS 2 nanocarrier via a covalent Cu-S bond. The MoS 2 /CuO 2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H 2 O 2 produced by acid-triggered decomposition of the decorated CuO 2 into hydroxyl radical (•OH). Meanwhile, the MoS 2 /CuO 2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced CDT. More importantly, MoS 2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H 2 O 2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS 2 /CuO 2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H 2 O 2 and consuming GSH. Importantly, MoS 2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS 2 /CuO 2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The clock drawing test (CDT) is a neuropsychological test for the screening of global cognitive functioning. The test requires use of multiple cognitive domains including executive functions, visuospatial abilities and semantic memory and can be a suitable tool for screening cognitive decline in participants in the early stages of Parkinson's Disease (PD). Behavioral performance on the CDT has been studied in depth, however, neural activation during real-time performance has not been extensively investigated. In this study we explored changes in prefrontal cortex (PFC) activation during the performance of CDT in participants with PD compared to healthy controls (HC) and assessed the correlations between PFC activation and CDT performance.Methods: The study included 60 participants, 29 PD and 31 HC participants whom performed a digital CDT (DCTclock) in conjunction with a Functional Near-Infrared Spectroscopy (fNIRS) system measuring neural activation in the PFC.Results: HbO2 signals derived from the fNIRS during the CDT revealed that PD participants showed more moderate slopes than the HC in the right hemisphere in the command (p = 0.042) and copy task (p = 0.009). Better score on the measurement of information processing correlated with steeper right hemisphere HbO2 slope in the copy task in the PD group (p = 0.003).Conclusion: Our results reflect slower PFC activation in participants with PD which correlates with behavioral measures. In addition, the findings of the study indicate the importance of performing the CDT copy task condition that detect early cognitive decline in participants with PD. [ABSTRACT FROM AUTHOR]

Triangulation algorithms that conform to a set of non-intersecting input segments typically proceed in an incremental fashion, by inserting points first, and then segments. Inserting a segment amounts to: (1) deleting all the triangles it intersects; (2) filling the so generated hole with two polygons that have the wanted segment as shared edge; (3) triangulate each polygon separately. In this article we prove that these polygons are such that all their convex vertices but two can be used to form triangles in an earcut fashion, without the need to check whether other polygon points are located within each ear. The fact that any simple polygon contains at least three convex vertices guarantees the existence of a valid ear to cut, ensuring convergence. Not only this translates to an optimal deterministic linear time triangulation algorithm, but such algorithm is also trivial to implement. We formally prove the correctness of our approach, also validating it in practical applications and comparing it with prior art. [ABSTRACT FROM AUTHOR]

Contemporary data on catheter-directed thrombolysis (CDT) utilization trends and associated hospital outcomes in pulmonary embolism (PE) n the US is limited. Using the nationwide inpatient sample database, we identified patients hospitalized for acute PE treated with CDT from January 1, 2008, to December 31, 2018. Cochrane-Armitage test was used to evaluate the temporal trends in utilization, hospital mortality, and major bleeding rates. Multivariate logistic regression was used to compare differences in the outcomes across race/ethnicity, 4444 patients (unweighted hospitalizations) underwent CDT during the study period. The mean age ± standard deviation of the population was 58 ± 16 years and the majority were males (54%). 3269 (73.6%) patients were non-Hispanic White (NHW), 802 (18.0%) patients were non-Hispanic Black (NHB), and 373 (8.4%) patients were of 'other' races/ethnicities. There was a more than tenfold increase in CDT use in 2018 compared to 2008. The total mortality and bleeding rates were approximately 7 and 10% respectively. Hospital mortality rates trended down across all races/ethnicities during the study period. A similar downward trend in bleeding rates was noted in NHB only (28.6% vs 10.7%, p = 0.04). In-hospital mortality and major bleeding odds were comparable across all races/ethnicities were comparable. NHB patients and other races were more likely to require blood transfusion and incur higher hospitalization costs compared with NHW patients. CDT use increased significantly in the US during the study period with a corresponding downward trend in in-hospital mortality across all races, and bleeding rates in NHB. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) with cor pulmonale causes considerable mortality and morbidity. Randomized trials have failed to show a mortality difference between treatment modalities including anticoagulation (AC), Catheter directed thrombolysis (CDT) and systemic tPA (tissue plasminogen activator). Methods: This is a cross-sectional retrospective case-control study utilizing the 2017 National Inpatient Sample (NIS). Patients admitted with acute PE with cor pulmonale were divided into groups based on whether they received anticoagulation, CDT or systemic tPA based on appropriate ICD-10 PCS codes. The AC group and CDT group were compared using univariate and multivariate analyses after adjusting for age, gender, race, comorbidities, insurance status and Charlson comorbidity index (CCI). Secondary outcomes included factors influencing length of stay (LOS) and total charges incurred. Similar analyses were done to compare the CDT group with the tPA group. Results: In 2017, 13240 patients were admitted with acute PE and cor pulmonale, of whom 18% underwent CDT, 10% underwent systemic tPA and 72% underwent AC alone. Patients who received CDTover AC alone were significantly younger (61.5 vs. 65.5, p=0.00). Mortality rate overall was 4.8% with tPA group, CDT group and AC alone group having a 11.2%, 3.0% and 4.4% mortality rate respectively. On multivariate analyses, there was no significant mortality difference between the CDT and AC groups (aOR 0.61, 0.34-1.1 95%CI, p=0.103). Patients with liver disease had significantly higher mortality while obese patients had a significantly lower mortality after adjusting for treatment strategy and confounders. Length of stay (LOS) was not signifi- cantly different between the groups however, compared to AC alone, patients who underwent CDTor tPA incurred significantly higher total hospital charges. Conclusions: CDT offers an attractive alternative to tPA therapy; however, our study does not show an in-hospital mortality benefit. More studies are required to guide patient selection prior to establishing treatment protocols. [ABSTRACT FROM AUTHOR]

Chemotherapy, as one main strategy to relieve tumor progression, has a weak effect on triple-negative breast cancer (TNBC) chest wall metastasis. The development of near-infrared (NIR) light-responsive nanomaterials for chemodynamic therapy (CDT) and photothermal therapy (PTT) is a promising platform but still challenging in biomedicine. This study reports a peroxidase mimicking nanozyme (Fe-N-C SAzyme) against TNBC by CDT and PTT. Fe-N-C SAzyme generated reactive oxygen species (ROS) by decomposing H2O2 into hydroxyl radicals (•OH) and also induced light-to-heat conversion under the exposure of 808 nm laser irradiation. With these biological characteristics, the obtained Fe-N-C SAzymes displayed enhanced cell cytotoxicity and inhibition of cancer cell proliferation both in vitro and in vivo at a low dose of nanoagent and a moderate NIR laser power density. Besides, Fe-N-C nanoagent with its excellent ROS generation brought metabolic reprogramming of elevated glycolysis in tumor cells. In vivo experiments, when combined with PTT, the enhanced antitumor effect was found by the elimination of M-MDSC in tumor microenvironment. Fe-N-C SAzymes can serve as a new synergistic CDT and PTT nanoagent to simultaneously reprogram tumor metabolism and tumor microenvironment. It will provide prospects for chemodynamic/photothermal combined cancer therapy for TNBC chest wall metastasis based on the use of a single nanosystem.

Background: Vascular dementia is a cognitive decline with functional deterioration caused by cerebrovascular disease. It is the second leading cause of dementia. A number of screening questionnaires and models have been developed to help in assessing cognitive function and activity daily living (ADL) in patients with dementia. Mini Mental State Examination (MMSE), Clock Drawing Test (CDT) and Barthel Index are instruments to evaluate cognitive function and ADL of vascular dementia patients. Objective: To determine the role of achetylcholine-esterase inhibitor therapy on cognitive function and ADL in patients with vascular dementia in Saiful Anwar General Hospital. Methods: This study is an analytical study assessing the improvement of cognitive function and ADL of patients with vascular dementia after administration of acethylcholine-esterase inhibitor by assessing the MMSE, CDT and Barthel Index scoring in 1, 3, 6 and 12 month period consecutively. Results: From 15 study subjects, individuals who have been given treatment for 12 months consecutively have the highest increase in MMSE and CDT whilst for Barthel Index has shown highest improvement in one month period. Conclusion: The administration of acetylcholine-esterase inhibitor drugs has the potential to improve and maintain cognitive function and improve ADL. The limited number of study subjects and the many confounding factors that we did not evaluate were the drawbacks of this study. The results of this study cannot be generalized to all patients with vascular dementia and only apply to 15 patients who were the subjects of this study.

• A new intelligent semi-salamo-type copper complex (CuL1) was synthesized to consume excess glutathione (GSH) in tumor cells for enhanced CDT. • CuL1 can be degraded GSH and produced highly toxic •OH, which further increased the efficacy of CDT. • The semi-salamo-type complex can be utilized to create more intelligent metal-based anticancer drugs and improve the effectiveness of tumor CDT. Due to its high selectivity, chemokinetic therapy (CDT), which uses Fenton catalyst to kill cancer cells by converting intracellular H 2 O 2 into highly toxic hydroxyl radicals (·OH), has shown potential application in the treatment of tumors. Nevertheless, the presence of overexpressed glutathione (GSH) in tumor cells limits the lethal effect of this treatment on tumors. Herein, an intelligent semi-salamo-type copper complex (CuL1) was synthesized to consume excess glutathione (GSH) in tumor cells for enhanced CDT. Research on the crystal structure of CuL1 indicates that the formed complex self-assembles through intermolecular hydrogen bonding interactions, resulting in a three-dimensional supramolecular shape that can be infinitely stretched inward. After being internalized by tumor cells, CuL1 can be degraded and reduced by GSH, resulting in the generation of high concentrations of Cu (I). The subsequent Fenton-like reaction resulted in excessive Cu (I) ions binding with H 2 O 2 to produce highly toxic ·OH, increasing the efficacy of CDT. Our findings can be utilized to create more intelligent metal-based anticancer drugs and improve the effectiveness of tumor CDT. A intelligent semi-salamo-type copper complex (CuL1) was prepared and characterized. Such CuL1 could enhance the specificity, high efficiency and biosecurity of CDT in inhibition of cancer cell growth. [Display omitted] [ABSTRACT FROM AUTHOR]

• Mn with Fenton-like effect as metal node to prepare a biocompatibility Mn-CPP. • Mn2+ reacted with H 2 O 2 to produce ROS to realize chemodynamic therapy through Fenton-like reaction. • Mn-CPP loaded chemotherapeutic drug DOX to construct a system for combined chemodynamic therapy and chemotherapy. A Mn-based metal-organic framework Mn-CPP was synthesized and showed excellent chemodynamic therapy (CDT) effect. DOX was selected and loaded into Mn-CPP obtaining DOX@Mn-CPP to improve the therapeutic properties. DOX@Mn-CPP exhibited better drug release behaviors in the tumor environment than that in normal environment. Besides, the material displayed good biocompatibility to L929 cells and significant effect of lethality on 4T1 cells and Hela cells. The successful fabrication of DOX@Mn-CPP provided the potential application for the combination therapy of chemodynamic therapy and chemotherapy. A Mn-based metal-organic framework Mn-CPP with good Fenton-like effect was synthesized and showed excellent CDT effect. The anticancer drug DOX was loaded to provide chemotherapeutic effect, which showed the potential application in combination therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Clostridioides difficile ist bei gesunden Neugeborenen und Kleinkindern häufiger Teil der Magen-Darm-Flora als bei Erwachsenen. Dennoch gibt es auch bei Kindern immer öfter symptomatische und rezidivierende Infektionen. Die Teststrategien für Kinder unterscheiden sich nicht von denjenigen für Erwachsene; die Interpretation positiver Testergebnisse stellt aber unter anderem aufgrund des möglichen Vorkommens hoher Toxin-Konzentrationen im Stuhl gesunder Kinder eine Herausforderung dar. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) represents a significant burden on the health care system, one that is exacerbated by the emergence of binary toxin (CDT)-producing hypervirulent C. difficile strains. Previous work from our laboratory has shown that Toll-like receptor 2 (TLR2) recognizes CDT to induce inflammation. Here we explore the interactions of CDT with TLR2 and the impact on host immunity during CDI. We found that the TLR2/6 heterodimer, not TLR2/1, is responsible for CDT recognition, and that gene pathways including nuclear factor-κB and MAPK downstream of TLR2/6 are upregulated in mice with intact TLR2/6 signaling during CDI. [ABSTRACT FROM AUTHOR]

Background The incidence of Clostridioides difficile infection (CDI) has increased over the past 2 decades and is considered an urgent threat by the Centers for Disease Control and Prevention. Hypervirulent strains such as ribotype 027, which possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality. Methods We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed quantitative PCR (PCR) DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT-positive samples had an altered fecal microbiota. Results We found that patients with CdtB, the pore-forming component of CDT, detected in their stool by ELISA, were more likely to have severe disease with higher 90-day mortality. CDT-positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT-positive and -negative patients. Conclusions Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and testing for C. difficile toxins A and B may not reveal the entire picture when diagnosing CDI; detection of CDT-expressing strains is valuable in identifying patients at risk of more severe disease. [ABSTRACT FROM AUTHOR]

Las fluctuaciones del tronco son indicadores del balance hídrico y crecimiento de la planta. El objetivo de este estudio fue determinar qué fluctuaciones del tronco pueden ser utilizadas para evaluar el estado hídrico y crecimiento real de la vid. Se utilizó dendrómetros a nivel de brazo, con medición cada 30 minutos, para evaluar la contracción máxima diaria del tronco (CDT), la tasa de crecimiento potencial diaria (TCP) y la tasa de crecimiento real diaria (TCR), se utilizó como parámetros de comparación el déficit de presión de vapor (DPV) y la evapotranspiración del cultivo (ETc). Los datos obtenidos se sometieron a un análisis de coeficiente de correlación de Pearson (P-valor ≤ 0,05) para ver la relación que existe entre parámetros derivados de la fluctuación, el DVP y la ETc. se observó que CDT, TCP y TCR presentaron un porcentaje de determinación con el DPV de 15%, 29%, y 28%; y con la ETc de 3%, 76%, y 77%, respectivamente, el porcentaje de determinación del DPV y ETc fue de 35%. Los resultados mostraron que CDT es un indicador de estrés hídrico, a excepción del agostamiento, dónde ETc y CDT tiene correlación negativa. TCR indica el crecimiento real del diámetro del tronco.

The major toxins of Clostridioides difficile (TcdA, TcdB, CDT) are chromosomally encoded in nearly all known strains. Following up on previous findings, we identified 5 examples of a family of putative conjugative plasmids with tcdB and cdtAB in clinical C. difficile isolates from multilocus sequence typing clades C-I, 2, and 4.

Climate services can contribute to alleviating a range of climate-sensitive development challenges, including those of agricultural production and food security. However, the use of climate data for research and applications in Africa has been scanty, mainly due to poor availability of and access to quality climate data. Weather stations are sparse, and their number has been declining. Access to existing climate data is a challenge mainly because of national data policies, low financial investment, lack of dissemination capacity and tools, and high access costs. The ENACTS (Enhancing National Climate Services) initiative led by the International Research Institute for Climate and Society (IRI) at Columbia University has been tackling this problem by working with National Meteorological Services (NMS) in Africa and in other developing countries. This initiative helps NMS to improve data availability and quality, by combining quality-controlled data from national observation networks with satellite estimates for rainfall and climate model reanalysis products for temperature. This requires access to an easy-to-use and freely available tool for preforming the tasks required to generate the data, as well as using the generated data. Most NMS in Africa do not have access to such a tool. To meet this significant need, the IRI developed such a tool in-house. This is the Climate Data Tool (CDT), which is an open-source, R-based software with an easy-to-use a graphical user interface (GUI). It can be used for data organization, quality control, combining station data with satellite and reanalysis data, evaluating merged and inputs datasets, performing an array of analyses, and visualization. The CDT software has been evolving over that last seven years with inputs from the NMS themselves. Now, it has become a powerful and user-friendly tool, and has been installed in over 20 countries in Africa alone.

Campylobacter jejuni is a major cause of food poisoning worldwide, and remains the main infective agent in gastroenteritis and related intestinal disorders in Europe and the USA. As with all bacterial infections, the stages of adhesion to host tissue, survival in the host and eliciting disease all require the synthesis of proteinaceous virulence factors on the ribosomes of the pathogen. Here, we describe how C. jejuni virulence is attenuated by altering the methylation of its ribosomes to disrupt the composition of its proteome, and how this in turn provides a means of identifying factors that are essential for infection and pathogenesis. Specifically, inactivation of the C. jejuni Cj0588/TlyA methyltransferase prevents methylation of nucleotide C1920 in the 23S rRNA of its ribosomes and reduces the pathogen’s ability to form biofilms, to attach, invade and survive in host cells, and to provoke the innate immune response. Mass spectrometric analyses of C. jejuni TlyA-minus strains revealed an array of subtle changes in the proteome composition. These included reduced amounts of the cytolethal distending toxin (CdtC) and the MlaEFD proteins connected with outer membrane vesicle (OMV) production. Inactivation of the cdtC and mlaEFD genes confirmed the importance of their encoded proteins in establishing infection. Collectively, the data identify a subset of genes required for the onset of human campylobacteriosis, and serve as a proof of principle for use of this approach in detecting proteins involved in bacterial pathogenesis.

Campylobacter jejuni is a major cause of food poisoning worldwide, and remains the main infective agent in gastroenteritis and related intestinal disorders in Europe and the USA. As with all bacterial infections, the stages of adhesion to host tissue, survival in the host and eliciting disease all require the synthesis of proteinaceous virulence factors on the ribosomes of the pathogen. Here, we describe how C. jejuni virulence is attenuated by altering the methylation of its ribosomes to disrupt the composition of its proteome, and how this in turn provides a means of identifying factors that are essential for infection and pathogenesis. Specifically, inactivation of the C. jejuni Cj0588/TlyA methyltransferase prevents methylation of nucleotide C1920 in the 23S rRNA of its ribosomes and reduces the pathogen's ability to form biofilms, to attach, invade and survive in host cells, and to provoke the innate immune response. Mass spectrometric analyses of C. jejuni TlyA-minus strains revealed an array of subtle changes in the proteome composition. These included reduced amounts of the cytolethal distending toxin (CdtC) and the MlaEFD proteins connected with outer membrane vesicle (OMV) production. Inactivation of the cdtC and mlaEFD genes confirmed the importance of their encoded proteins in establishing infection. Collectively, the data identify a subset of genes required for the onset of human campylobacteriosis, and serve as a proof of principle for use of this approach in detecting proteins involved in bacterial pathogenesis. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is the major cause of antibiotic-associated colitis (CDAC) with increasing prevalence in morbidity and mortality. Severity of CDAC has been attributed to hypervirulent C. difficile strains, which in addition to toxin A and B (TcdA, TcdB) produce the binary toxin C. difficile transferase (CDT). However, the link between these toxins and host immune responses as potential drivers of immunopathology are still incompletely understood. Here, we provide first experimental evidence that C. difficile toxins efficiently activate human mucosal-associated invariant T (MAIT) cells. Among the tested toxins, CDT and more specifically, the substrate binding and pore-forming subunit CDTb provoked significant MAIT cell activation resulting in selective MAIT cell degranulation of the lytic granule components perforin and granzyme B. CDT-induced MAIT cell responses required accessory immune cells, and we suggest monocytes as a potential CDT target cell population. Within the peripheral blood mononuclear cell fraction, we found increased IL-18 levels following CDT stimulation and MAIT cell response was indeed partly dependent on this cytokine. Surprisingly, CDT-induced MAIT cell activation was found to be partially MR1-dependent, although bacterial-derived metabolite antigens were absent. However, the role of antigen presentation in this process was not analyzed here and needs to be validated in future studies. Thus, MR1-dependent induction of MAIT cell cytotoxicity might be instrumental for hypervirulent C. difficile to overcome cellular barriers and may contribute to pathophysiology of CDAC. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is the major cause of antibiotic-associated colitis (CDAC) with increasing prevalence in morbidity and mortality. Severity of CDAC has been attributed to hypervirulent C. difficile strains, which in addition to toxin A and B (TcdA, TcdB) produce the binary toxin C. difficile transferase (CDT). However, the link between these toxins and host immune responses as potential drivers of immunopathology are still incompletely understood. Here, we provide first experimental evidence that C. difficile toxins efficiently activate human mucosal-associated invariant T (MAIT) cells. Among the tested toxins, CDT and more specifically, the substrate binding and pore-forming subunit CDTb provoked significant MAIT cell activation resulting in selective MAIT cell degranulation of the lytic granule components perforin and granzyme B. CDT-induced MAIT cell responses required accessory immune cells, and we suggest monocytes as a potential CDT target cell population. Within the peripheral blood mononuclear cell fraction, we found increased IL-18 levels following CDT stimulation and MAIT cell response was indeed partly dependent on this cytokine. Surprisingly, CDT-induced MAIT cell activation was found to be partially MR1-dependent, although bacterial-derived metabolite antigens were absent. However, the role of antigen presentation in this process was not analyzed here and needs to be validated in future studies. Thus, MR1-dependent induction of MAIT cell cytotoxicity might be instrumental for hypervirulent C. difficile to overcome cellular barriers and may contribute to pathophysiology of CDAC.

Background: Acinetobacter baumannii (A. baumannii) is a Gram-negative, aerobic coccobacillus. It causes life-threatening nosocomial infections, particularly in immunocompromised patients. Carbapenem-resistant A. baumannii are prevalent worldwide mostly caused by carbapenemase synthesis. Metallo β-lactamases (MBLs) include imipenemase (IMP), New Delhi metallo- β-lactamases (NDM) and Verona integrin metallo- β-lactamase (VIM). We aimed to investigate the prevalence of MBLs genes expression in carbapenem-resistant A. baumannii isolated from ICU patients as a reliable method for reducing the morbidity & mortality of these patients. Methods: Using conventional methods, 87 A. baumannii isolates were identified from 103 ICU patient specimens. Metallo β-lactamases were detected phenotypically in imipenem-resistant strains using a combined disc test (CDT). Real-time PCR was used to quantitate the expression of the blaIPM, blaNDM & blaVIM genes. Results: Imipenem resistance was identified in 82.8% of patients. Combined disc test was positive in 44.4% of imipenemresistant isolates. For metallo-lactamases gene expression, blaVIM had a higher median value than blaNDM and blaIPM (0.5, 0.1 and 0 respectively). Combined disc test was found to have a statistically significant relationship with both NDM and VIM gene expression, which was considerably higher in isolates with positive CDT. Both NDM and VIM gene expression had a statistically non-significant correlation with CDT value, but their expression had a statistically significant negative correlation with CD zone of inhibition value. Conclusion: The expression of blaVIM and blaNDM genes is directly correlated with the level of MBLs production and the level of these enzymes can be detected phenotypically depending on its negative correlation with the CD zone of inhibition diameter. [ABSTRACT FROM AUTHOR]