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For more than 30 years, Peter Senge's theory of learning organizations has influenced the study of leadership and organizations. Researchers have studied various components of his framework: team cognition and mental models, team learning, shared vision, systems thinking, and personal mastery. But few articles have explored what it looks like in practice when the five disciplines of the learning organization are enacted in an organization. This article explores the ways in which these disciplines influenced the implementation and outcomes of a collection diversity audit at Sonoma State University Library. The authors discuss the ways that Senge's learning organization framework enabled them to create a sustainable model for evaluating diversity in selection and acquisition practices.

Abstract Background Komagataella phaffii (K. phaffii), formerly known as Pichia pastoris, is a widely utilized yeast for recombinant protein production. However, due to the formation of overflow metabolites, carbon yields may be reduced and product recovery becomes challenging. This study investigates the impact of oxygen availability, different glucose concentrations and feeding strategies on overflow metabolite formation and recombinant protein production in K. phaffii. Results High glucose concentrations in batch fermentation, as applied in literature, lead to substantial ethanol accumulation, adversely affecting biomass yield and product formation. Increasing dissolved oxygen setpoints does not significantly reduce ethanol formation, indicating that glucose surplus, rather than oxygen availability, drives overflow metabolism. Decreasing the initial glucose concentration to 5 g/L and adapting the feeding strategy of the fed-batch phase, effectively mitigates overflow metabolite formation, improving biomass yield by up to 9% and product concentration by 40% without increasing process time. Conclusions These findings underscore the importance of a suitable glucose-feeding strategy in K. phaffii fermentation processes and highlight the detrimental effects of overflow metabolites on productivity. By optimizing carbon source utilization, it is possible to enhance fermentation efficiency and recombinant protein production with K. phaffii.

Abstract Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.

Abstract The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.

Abstract Objective In the present work we investigate how individual differences in at least occasionally using distinct social media platforms is linked to social networks use disorder (SNUD) tendencies. A final sample of n = 2200 participants filled in the AICA-C-9 measure to get insights into individual differences in overuse of social media and participants also indicated which platforms they used at least once a month. Results The analysis revealed a robust positive association between number of at least occasionally used social media apps and SNUD tendencies (r = .44, p

Abstract Sudden aggravations of chronic inflammatory airway diseases are difficult-to-foresee life-threatening episodes for which advanced prognosis-systems are highly desirable. Here we present an experimental chip-based fluidic system designed for the rapid and sensitive measurement of biomarkers prognostic for potentially imminent asthma or COPD exacerbations. As model biomarkers we chose three cytokines (interleukin-6, interleukin-8, tumor necrosis factor alpha), the bacterial infection marker C-reactive protein and the bacterial pathogen Streptococcus pneumoniae—all relevant factors in exacerbation episodes. Assay protocols established in laboratory environments were adapted to 3D-printed fluidic devices with emphasis on short processing times, low reagent consumption and a low limit of detection in order to enable the fluidic system to be used in point-of-care settings. The final device demonstrator was validated with patient sample material for its capability to detect endogenous as well as exogenous biomarkers in parallel.

Rationale & Objective: Estimates of the incidence of hyperkalemia in patients with chronic kidney disease (CKD) vary widely. Our objective was to estimate hyperkalemia incidence in patients with CKD from routine clinical care, including by level of kidney damage or function and among important patient subgroups. Study Design: Retrospective cohort study. Setting & Participants: 1,771,900 patients with stage 1-4 CKD identified from the US Optum De-Identified electronic health records database. Exposures or Predictors: Impaired kidney damage or function level at baseline based on urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), respectively, and selected patient subgroups. Outcomes: Hyperkalemia: 2 elevated serum potassium values (≥5.5 mmol/L) from the inpatient setting (2-24 hours apart) or outpatient setting (maximum 7 days apart), or 1 elevated serum potassium value plus pharmacotherapy initiation or hyperkalemia diagnosis (maximum 3 days apart). Analytical Approach: Incidence rates of hyperkalemia were calculated. Estimates were stratified by UACR and eGFR level at baseline and patient subgroups. Results: Over a mean follow-up of 3.9 years, the incidence of hyperkalemia was 3.37 events/100 person-years (95% confidence intervals, 3.36-3.38). Higher incidence rates were observed with increased UACR and lower eGFR. Highest rates were observed with UACR ≥3,500 (up to 19.1/100 person-years) irrespective of decreased eGFR level. High rates also occurred in patients with type 2 diabetes mellitus (T2DM, 5.43/100 person-years), heart failure (8.7/100 person-years), and those prescribed steroidal mineralocorticoid receptor antagonists (sMRAs, 7.7/100 person-years). Limitations: Potential misclassification of variables from possible medical coding errors; potential data incompleteness issues if patients received care at institutions not included in Optum. Conclusions: Hyperkalemia is a frequent occurrence in CKD, particularly in patients with T2DM, heart failure, or prescribed sMRAs, indicating the need for regular serum potassium and UACR monitoring in this patient population to help mitigate risk. Plain-Language Summary: People with chronic kidney disease (CKD) have a higher risk of illness, hospitalization, and death than those without CKD. Medicines that are commonly used to slow down CKD progression can sometimes lead to hyperkalemia, where levels of potassium in the blood are higher than normal and which can be potentially dangerous. Concerns about hyperkalemia have led some people with CKD to stop taking their medication. Our study of 1.7 million patients from the United States found that patients with severe kidney damage, as well as those with type 2 diabetes mellitus or heart failure, have a higher risk of hyperkalemia than other patients, indicating they are priority groups for having their potassium levels and level of kidney damage checked regularly.

Summary: Background: The HVTN 705 Imbokodo trial of 2636 people without HIV and assigned female sex at birth, conducted in southern Africa, evaluated a heterologous HIV-1 vaccine regimen: mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) at Months 0, 3, 6, 12 and alum-adjuvanted clade C gp140 at Months 6, 12. Per-protocol vaccine efficacy (VE) against HIV-1 diagnosis from seven to 24 months was 14.1% (95% CI: −22.0% to 39.5%). Immune correlates analysis was performed for markers selected based on prior evidence in efficacy trials and/or nonhuman primate models. Methods: Humoral and cellular immune response markers at Month 7 were evaluated as immune correlates of risk and of protection in a breakthrough case–control cohort (n = 52 cases, 246 non-cases). Primary markers were IgG binding to vaccine-strain gp140, IgG3 binding to diverse Env antigens (IgG3 Env breadth), IgG3 binding to diverse V1V2 antigens (IgG3 V1V2 breadth), antibody-dependent phagocytosis against the vaccine-strain gp140, Env-specific CD4+ and CD8+ T-cell responses, and multi-epitope functions. Findings: No immune markers were statistically significant correlates of risk. IgG3 V1V2 breadth trended toward an inverse association: hazard ratio 0.70 (95% CI: 0.36 to 1.35; p = 0.29) per 10-fold increase and 0.51 (95% CI: 0.21 to 1.24; p = 0.14) in a Cox model with all primary markers. The VE estimate was 11.8% (95% CI: −17.9% to 34.0%) at all IgG3 V1V2 breadth values below 667 weighted geometric mean net MFI; just above this value, the VE estimate sharply increased to 62.6% (95% CI: −17.9% to 89.6%), and further increased to 80.9% (95% CI: −17.9% to 99.5%) at 1471 MFI, the 95th percentile of the marker distribution. Mediation analysis yielded a VE of 35.7% (95% CI: 15.0% to 51.3%) attributable to the vaccine's impact on this marker. Interpretation: The trend in association of greater IgG3 V1V2 antibody breadth with lower likelihood of HIV acquisition is consistent with the identification of antibodies against V1V2 as immune correlates in three other HIV vaccine efficacy trials and suggests that a greater emphasis should be placed on studying this region in the HIV-1 envelope as a vaccine immunogen. Funding: National Institute of Allergy and Infectious Diseases and Janssen Vaccines & Prevention BV.

Botrytis cinerea is a well-known pathogen that can be challenging to control in crops, such as wine grapes. To adapt to the increasing problems of climate change and strain resistance, it is important to find new methods to detect Botrytis cinerea and differentiate strains. These methods include strain differentiation and classification by simple sequence repeats (SSRs) and early detection of the fungus by qPCR. Various strains were analysed using SSR markers and either agarose gel electrophoresis or capillary sequencing via PCR. A sensitive qPCR method was refined to achieve an early detection method for the pathogen. The results demonstrate promising ways to distinguish between strains using both agarose gel electrophoresis and capillary sequencing as well as to detect infection before it becomes visible on grapes. This can be used to further understand and analyse different Botrytis cinerea strain characteristics such as laccase activity, regional or annual effects. The early detection method can be used to better prepare growers for an impending infection so that targeted efforts can be made.

Abstract One of the strategies towards an effective HIV-1 vaccine is to elicit broadly neutralizing antibody responses that target the high HIV-1 Env diversity. Here, we present an HIV-1 vaccine candidate that consists of cobalt porphyrin-phospholipid (CoPoP) liposomes decorated with repaired and stabilized clade C HIV-1 Env trimers in a prefusion conformation. These particles exhibit high HIV-1 Env trimer decoration, serum stability and bind broadly neutralizing antibodies. Three sequential immunizations of female rabbits with CoPoP liposomes displaying a different clade C HIV-1 gp140 trimer at each dosing generate high HIV-1 Env-specific antibody responses. Additionally, serum neutralization is detectable against 18 of 20 multiclade tier 2 HIV-1 strains. Furthermore, the peak antibody titers induced by CoPoP liposomes can be recalled by subsequent heterologous immunization with Ad26-encoded membrane-bound stabilized Env antigens. Hence, a CoPoP liposome-based HIV-1 vaccine that can generate cross-clade neutralizing antibody immunity could potentially be a component of an efficacious HIV-1 vaccine.

Abstract The transcellular propagation of the aberrantly modified protein tau along the functional brain network is a key hallmark of Alzheimer's disease and related tauopathies. Inoculation-based tau propagation models can recapitulate the stereotypical spread of tau and reproduce various types of tau inclusions linked to specific tauopathy, albeit with varying degrees of fidelity. With this systematic review, we underscore the significance of judicious selection and meticulous functional, biochemical, and biophysical characterization of various tau inocula. Furthermore, we highlight the necessity of choosing suitable animal models and inoculation sites, along with the critical need for validation of fibrillary pathology using confirmatory staining, to accurately recapitulate disease-specific inclusions. As a practical guide, we put forth a framework for establishing a benchmark of inoculation-based tau propagation models that holds promise for use in preclinical testing of disease-modifying drugs.

This work studies mathematical foundations for optimal boundary control of mixers which mix two fluid phases. Existence of optima is proved and the influence of common objective functionals is discussed.

Background: Previous research has reported mental health variables and maladaptive cognitive emotion processes to be associated with severity of problematic social networking site use (PSNSU) and problematic smartphone use (PSU). The present study examined trait and state fear of missing out (FOMO) dimensions and their potential mediating roles in explaining relations between PSNSU and PSU severity. Method: A sample of 461 participants (mean age = 24.15, SD = 7.78) completed an online survey protocol measuring trait and state FOMO, PSU, and PSNSU. Results: Structural equation modelling revealed that trait and state FOMO were significantly associated with PSNSU severity, and PSNSU severity was associated with PSU severity. State (but not trait) FOMO mediated relations between PSNSU and PSU severity. Conclusions: The study demonstrates the role of FOMO, especially state FOMO, in association with PSNSU and PSU severity.

IntroductionInterleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation.MethodsWe reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models.ResultsWe first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model.DiscussionAltogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19.

Despite powerful DNA repair systems, oxidative damage/modification to DNA is an inevitable side effect of metabolism, ionizing radiation, lifestyle habits, inflammatory pathologies such as type-2 diabetes or metabolic syndrome, cancer and natural aging.One of the most common oxidative DNA modifications is 8-OHdG (8‑hydroxy-2′-deoxyguanosine), which is the most widely used marker in research and clinical diagnostics. 8-OHdG is easily and specifically detectable in various samples such as urine, plasma, cells and tissues via a large variety of methods like ELISA, HPLC, chromatographic methods, and immunochemistry.Formed by oxidation of guanine and being representative for the degree of DNA damage, 8-OHdG can be also used as biomarker for risk assessment of various cancers as well as degenerative diseases.Here, we present a highly specific, self-developed 8-OHdG antibody in successful comparison to a commercially one, tested in cells (FF95, HCT116, and HT22) and intestinal tissue, focusing on automatized evaluation via fluorescence/confocal microscopy.