The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy.

BACKGROUND: Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. RESULTS: We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. Video Abstract CONCLUSIONS: These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.

Selective CO2 Reduction Electrocatalysis Using AgCu Nanoalloys Prepared by a "Host-Guest" Method.

Multimetallic nanoalloy catalysts have attracted considerable interest for enhancing the efficiency and selectivity of many electrochemically driven chemical processes. However, the preparation of homogeneous bimetallic alloy nanoparticles remains a challenge. Here, we present a room-temperature and scalable, host-guest approach for synthesis of dilute Cu in Ag alloy nanoparticles. In this approach, an ionic silver bromide precursor harboring exogenous Cu cations is reduced to yield ∼20 nm diameter AgCu alloy nanoparticles wherein the % Cu loading can be tuned precisely. AgCu nanoparticles with a 5% nominal loading of Cu exhibit peak activity (-0.23 mA/cm2 normalized partial current density) and selectivity (83.2% faradaic efficiency) for CO product formation from electrocatalytic reduction of CO2 at mild overpotentials. These AgCu nanoalloys exhibit a higher mass activity compared to Ag- and Cu-containing nanomaterials used for similar electrocatalytic transformations. Our host-guest synthesis platform holds promise for production of other nanoalloys with relevance in electrocatalysis and optics.

Learning & motivational talk in smoking cessation interventions: An examination of session language in two randomized trials.

OBJECTIVES: Motivational Interviewing (MI), a client-centered approach that seeks to evoke and resolve ambivalence, and health education (HE), which provides health information and advice, may both provide some benefit to unmotivated smokers. In HE, it is possible that client language reflective of new learning, or "learning talk" (LT), and rejection of health advice, or "rejection talk," (RT), may uniquely reflect intent of subsequent behavior change. METHODS: This project utilized MI and HE sessions from two randomized clinical trials (RCTs), one in a low-income, diverse community civilian sample of 255 unmotivated smokers, and the other in a sample of Veterans with mental illness who were unmotivated smokers (n = 55). Mixed methods approaches were utilized to reliably code sessions using the Motivational Interviewing Skill Code 2.5 (MISC 2.5)1 and a refined Learning Talk coding system2. RESULTS: Reliability of LT and RT codes ranged from fair to excellent (ICCs from 0.43-0.93). CONCLUSION: LT appears to be a unique construct and its impact on post-session changes in smoking is warranted. PRACTICE IMPLICATIONS: This system can be used in a study to code existing interventions for smokers using both MI and HE techniques and relate in-session client LT to subsequent smoking behaviors.

Event-level associations among THC, CBD, social context, and subjective effects during Cannabis use episodes.

BACKGROUND: Limited research considers the quantity and potency of cannabis products along with social context on the subjective effects of real-world cannabis use. AIMS: This study examined the subjective effects of acute use as a function of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) doses and social context during cannabis use episodes. METHOD: Ninety-six participants (43.75% male, Mage = 35.73) reporting weekly cannabis use completed a baseline self-report battery assessing cannabis use. Then, THC and CBD potency and quantity of the cannabis product, social context, and subjective experience were assessed through self-initiated surveys after cannabis use episodes during a 14-day ecological momentary assessment (EMA). RESULTS: Greater feeling high and liking were significantly associated with a higher THC dose than one's average (b = 0.03, p < 0.001; b = 0.02, p < 0.001) and social use (b = 0.38, p < 0.001; b = 0.20, p = 0.01). A higher CBD dose than one's average (b = 0.01, p = 0.04) was significantly associated with greater liking. A significant interaction effect of THC dose and social context (b = 0.01, p = 0.02) was observed such that solitary use had a negative association between THC dose and disliking (b = -0.01, p = 0.04), and social use had a null association (b = 0.003, p = 0.25). Individuals with greater cannabis problems reported lower liking (b = -0.18, p = 0.03) and higher disliking (b = 0.08, p = 0.02), but not feeling high, on average, across the EMA protocol. CONCLUSION: Social context plays an important role in the subjective experience of cannabis use. Interventions targeting cannabis problems could highlight the evidence that individuals with greater cannabis problems might experience less liking but more disliking in general across use episodes to effectively challenge expectancies/motives of use.

Venom Component Allergen IgE Measurement in the Diagnosis and Management of Insect Sting Allergy.

Accurate identification of allergy-eliciting stinging insect(s) is essential to ensuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy. Diagnostic testing using whole-venom extracts with skin tests and serologic-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in patients with a positive clinical history. As a second-level evaluation, serologic testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 vs yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from interspecies cross-reactivity (hyaluronidases [Api m 2, Ves v 2, and Pol d 2] and dipeptidyl peptidases IV [Api m 5, Ves v 3, and Pol d 3]). Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole-venom and molecular venom allergens (highlighted earlier) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom-allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (interassay coefficient of variation <10%). Emerging oligoplex and multiplex (fixed-panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient's clinical history, combined with proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.

Chromothripsis-mediated small cell lung carcinoma.

Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here we performed detailed clinicopathologic, genomic and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis - massive, localized chromosome shattering - recurrently involving chromosomes 11 or 12, and resulting in extrachromosomal (ecDNA) amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers.

Impact of Intrapatient Immunosuppression Variability in Liver Transplantation Outcomes: A Systematic Review and Meta-analysis.

Background: To investigate the impact of intrapatient variability (IPV) in the levels of immunosuppressant drugs on health outcomes after liver transplantation. Methods: A comprehensive systematic review and meta-analysis were conducted, examining literature from MEDLINE/PubMed, Embase, Web of Science, Cochrane Reviews, and Cochrane CENTRAL. Results: The analysis focused on acute rejection, graft survival, acute kidney injury, and cancer risk as health outcomes. Of 2901 articles screened, 10 met the inclusion criteria. The results indicate a 19% reduction in the risk of acute rejection in patients with lower IPV (RR = 0.81; 95% confidence interval, 0.66-0.99), although 6 studies found no significant association between high IPV and acute rejection. Contrasting results were observed for graft survival, with 1 study indicating worse outcomes for high IPV, whereas another reported no significant difference. High IPV was consistently associated with acute kidney injury across 3 studies. One study suggested a link between high IPV and hepatocellular carcinoma, although a meta-analysis for these outcomes was not feasible. Conclusions: These findings point to a marginal but statistically significant association between high IPV and an increased risk of acute rejection, highlighting the importance of precise management of immunosuppressive drugs in liver transplant recipients to enhance patient outcomes.

Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?

Background: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed. Methods: A murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome. Results: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels. Conclusion: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

One-Pot Biosynthesis of Acetone from Waste Poly(hydroxybutyrate).

The plastic waste crisis is catalyzing change across the plastics life cycle. Central to this is increased production and application of bioplastics and biodegradable plastics. In particular, poly(hydroxybutyrate) (PHB) is a biodegradable bioplastic that can be produced from various renewable and waste feedstocks and is a promising alternative to some petrochemical-derived and non-biodegradable plastics. Despite its advantages, PHB biodegradation depends on environmental conditions, and the effects of degradation into microplastics, oligomers, and the 3-hydroxybutyrate (3-HB) monomer on soil microbiomes are unknown. We hypothesized that the ease of PHB biodegradation renders this next-generation plastic an ideal feedstock for microbial recycling into platform chemicals currently produced from fossil fuels. To demonstrate this, we report the one-pot degradation and recycling of PHB into acetone using a single strain of engineered Escherichia coli. Following strain development and initial bioprocess optimization, we report maximum titers of 123 mM acetone (7 g/L) from commercial PHB granules after 24 h fermentation at 30 °C. We further report biorecycling of an authentic sample of post-consumer PHB waste at a preparative scale. This is the first demonstration of biological recycling of PHB into a second-generation chemical, and it demonstrates next-generation plastic waste as a novel feedstock for the circular bioeconomy.

Targeted proteomic profiling of cardiogenic shock in the cardiac intensive care unit.

AIMS: We sought to characterize circulating protein biomarkers associated with cardiogenic shock (CS) using highly multiplex proteomic profiling. METHODS AND RESULTS: This analysis employed a cross-sectional case-control study design using a biorepository of patients admitted to a cardiac intensive care unit between 2017 and 2020. Cases were patients adjudicated to have CS, and controls were those presenting for cardiac critical care without shock, including subsets of patients with isolated hypotension or heart failure (HF). The Olink platform was used to analyse 359 biomarkers with Bonferroni correction. The analysis included 239 patients presenting for cardiac critical care (69 cases with CS, 170 non-shock controls). A total of 63 biomarkers (17.7%) were significantly associated with CS after Bonferroni correction compared with all controls. Of these, nine biomarkers remained significantly associated with CS when separately cross-validated in subsets of controls presenting with isolated hypotension and HF: cathepsin D, fibroblast growth factor (FGF)-21 and -23, growth differentiation factor (GDF)-15, insulin-like growth factor-binding protein-1, N-terminal pro-B-type natriuretic peptide, osteopontin, oncostatin-M-specific receptor subunit beta (OSMR), and soluble ST2 protein (sST2). Four biomarkers were identified as providing complementary information for CS diagnosis with development of a multi-marker model: sST2, FGF-23, CTSD, and GDF-15. CONCLUSION: In this pilot study of targeted proteomic profiling in CS, we identified nine biomarkers significantly associated with CS when cross-validated against non-shock controls including those with HF or isolated hypotension, illustrating the potential application of a targeted proteomic approach to identify novel candidates that may support the diagnosis of CS.

Survey of Animal Neoplastic Cases Diagnosed in Nigerian Veterinary Teaching Hospitals, 2000-2017.

Incidence data from 17-year veterinary neoplasm surveillance and registration were reviewed. Most of the neoplastic cases diagnosed in Nigerian veterinary teaching hospitals (VTHs) were in the avian (49%) and canine species (44%). Fewer cases were recorded in the equine (3.2%), bovine (2.4%), ovine (1.5%), caprine (0.3%) and porcine (0.15%) species. Marek's disease was the most prevalently diagnosed neoplastic disease of domestic animals in Nigerian VTHs from 2000-2017. Also, the Nigerian local breed had a higher mean distribution than any other dog breed and this was statistically significant (p < 0.05). Nearly all of the neoplastic cases diagnosed, were found in females (60.4%) and so the mean distribution of sex was statistically significant (p < 0.05). The digestive system, with 296 (46.25%) cases, was the anatomic location where the majority of the neoplastic cases were found. However, the mean distribution of different neoplastic anatomic sites was not statistically significant (p > 0.05). In conclusion, little emphasis is given to the appropriate diagnosis and recording of neoplastic cases that are diagnosed. The study provides information regarding the prevalence and distribution of tumours in different animal species consulted in Nigeria veterinary teaching hospitals. To illustrate all of this, ArcGIS software was used. Veterinary clinicians, pathologists and epidemiologists from Nigeria may benefit from the results of this study by freely accessing some specific data regarding the breed, the age group or the gender of some animal species diagnosed with different tumours.

Increasing the efficiency of cone-beam CT based delta-radiomics using automated contours to predict radiotherapy-related toxicities in prostate cancer.

Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient's anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients' data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Brief emotion regulation strategies to reduce alcohol craving: Mediating role of state difficulties in emotion regulation.

OBJECTIVE: This study experimentally compared the effects of emotion regulation (ER) strategies on alcohol craving and examined the mediating effect of state difficulties in emotion regulation (S-DER) on the relationship between negative/positive emotion and alcohol craving. METHOD: 417 participants (76.74% women, Mage = 20.76 years) endorsing past-month heavy/binge drinking were randomly assigned to one of four ER conditions (positive reappraisal, distancing, distraction, and acceptance). Participants completed state assessments, including negative/positive emotion, S-DER, and alcohol craving, prior to (T0) and after (T1) engaging in a negative emotion induction task. Subsequently, participants completed an ER strategy task based on their assigned ER strategy condition and completed a third state assessment (T2). RESULTS: Time had a significant quadratic effect on alcohol craving, such that craving increased from T0 to T1 and decreased from T1 to T2. There was no significant effect of ER strategy condition on craving. Change in S-DER mediated the relationship between the change in negative/positive emotion and the change in craving, with emotional modulation and emotional acceptance facets of S-DER dominating the mediating effect during negative emotion induction and ER strategy induction, respectively. CONCLUSIONS: Results suggest interventions targeting S-DER's emotional modulation and acceptance facets could reduce acute craving when experiencing undesired emotions.

Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients.

PURPOSE: Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma. METHODS: Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses. RESULTS: We included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46-0.81], p = 0.001). CONCLUSION: Sarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.

Tuning conductivity while maintaining mechanical properties in perylene bisimide hydrogels at physiological pH.

By using different salts as a method to achieve gelation of two different amino-acid-functionalised perylene bisimides, we were able to tune reduction potentials while maintaining the mechanical and optical properties of the system all at pH 7.4.