Bioproduction and optimization of newly characterized melanin pigment from Streptomyces djakartensis NSS-3 with its anticancer, antimicrobial, and radioprotective properties.

BACKGROUND: Melanin is a natural pigment that is considered a promising biomaterial for numerous biotechnological applications across several industries. Melanin has biomedical applications as antimicrobial, anticancer, and antioxidant properties. Additionally, in the pharmaceutical and cosmetic industries, it is used in drug delivery and as a radioprotective agent. Also, melanin has environmental uses in the fields of bioremediation and the food industry. The biosynthesis of melanin pigment is an area of interest for researchers due to its multifunctionality, high compatibility, and biodegradability. Therefore, our present work is the first attempt to characterize and optimize the productivity of melanin pigment from Streptomyces djakartensis NSS-3 concerning its radioprotection and biological properties. RESULTS: Forty isolates of soil actinobacteria were isolated from the Wadi Allaqui Biosphere Reserve, Egypt. Only one isolate, ACT3, produced a dark brown melanin pigment extracellularly. This isolate was identified according to phenotypic properties and molecular phylogenetic analysis as Streptomyces djakartensis NSS-3 with accession number OP912881. Plackett-Burman experimental design (PBD) and response surface methodology (RSM) using a Box-Behnken design (BBD) were performed for optimum medium and culturing conditions for maximum pigment production, resulting in a 4.19-fold improvement in melanin production (118.73 mg/10 mL). The extracted melanin pigment was purified and characterized as belonging to nitrogen-free pyomelanin based on ultraviolet-visible spectrophotometry (UV-VIS), Fourier transform infrared (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and NMR studies. Purified melanin demonstrated potent scavenging activity with IC50 values of 18.03 µg/mL and revealed high potency as sunscreens (in vitro SPF = 18.5). Moreover, it showed a nontoxic effect on a normal cell line (WI38), while it had a concentration-dependent anticancer effect on HCT116, HEPG, and MCF7 cell lines with IC50 = 108.9, 43.83, and 81.99 µg/mL, respectively. Also, purified melanin had a detrimental effect on the tested MDR bacterial strains, of which PA-09 and SA-04 were clearly more susceptible to melanin compared with other strains with MICs of 6.25 and 25 µg/mL, respectively. CONCLUSION: Our results demonstrated that the newly characterized pyomelanin from Streptomyces djakartensis NSS-3 has valuable biological properties due to its potential photoprotective, antioxidant, anticancer, antimicrobial, and lack of cytotoxic activities, which open up new prospects for using this natural melanin pigment in various biotechnological applications and avoiding chemical-based drugs.

Translation and linguistic validation of 24 PROMIS item banks into French.

PURPOSE: The Patient-Reported Outcome Measurement Information System (PROMIS®) was developed to provide reliable, valid, and normed item banks to measure health. The item banks provide standardized scores on a common metric allowing for individualized, brief assessment (computerized adaptive tests), short forms (e.g. heart failure specific), or profile assessments (e.g. PROMIS-29). The objective of this study was to translate and linguistically validate 24 PROMIS adult item banks into French and highlight cultural nuances arising during the translation process. METHODS: We used the FACIT translation methodology. Forward translation into French by two native French-speaking translators was followed by reconciliation by a third native French-speaking translator. A native English-speaking translator fluent in French then completed a back translation of the reconciled version from French into English. Three independent reviews by bilingual translators were completed to assess the clarity and consistency of terminology and equivalency across the English source and French translations. Reconciled versions were evaluated in cognitive interviews for conceptual and linguistic equivalence. RESULTS: Twenty-four adult item banks were translated: 12 mental health, 10 physical health, and two social health. Interview data revealed that 577 items of the 590 items translated required no revisions. Conceptual and linguistic differences were evident for 11 items that required iterations to improve conceptual equivalence and two items were revised to accurately reflect the English source. CONCLUSION: French translations of 24 item banks were created for routine clinical use and research. Initial translation supported conceptual equivalence and comprehensibility. Next steps will include validation of the item banks.

Implementation of an integrated primary care prevention and management program for chronic low back pain (LBP): patient-reported outcomes and predictors of pain interference after six months.

BACKGROUND: Integrated primary care programs for patients living with chronic pain which are accessible, interdisciplinary, and patient-centered are needed for preventing chronicity and improving outcomes. Evaluation of the implementation and impact of such programs supports further development of primary care chronic pain management. This study examined patient-reported outcomes among individuals with low back pain (LBP) receiving care in a novel interdisciplinary primary care program. METHODS: Patients were referred by primary care physicians in four regions of Quebec, Canada, and eligible patients received an evidence-based interdisciplinary pain management program over a six-month period. Patients were screened for risk of chronicity. Patient-reported outcome measures of pain interference and intensity, physical function, depression, and anxiety were evaluated at regular intervals over the six-month follow-up. A multilevel regression analysis was performed to evaluate the association between patient characteristics at baseline, including risk of chronicity, and change in pain outcomes. RESULTS: Four hundred and sixty-four individuals (mean age 55.4y, 63% female) completed the program. The majority (≥ 60%) experienced a clinically meaningful improvement in pain intensity and interference at six months. Patients with moderate (71%) or high risk (81%) of chronicity showed greater improvement in pain interference than those with low risk (51%). Significant predictors of improvement in pain interference included a higher risk of chronicity, younger age, female sex, and lower baseline disability. CONCLUSION: The outcomes of this novel LBP program will inform wider implementation considerations by identifying key components for further effectiveness, sustainability, and scale-up of the program.

Collaborative sustainability planning for an outcome measure in outpatient stroke rehabilitation: A qualitative description study.

RATIONALE: Evidence suggests that sustainability planning and the use of a collaborative approach to planning result in better sustainability outcomes and more relevant knowledge. Yet, both approaches appear to be underutilized. A detailed description of collaborative sustainability planning may encourage the use of these two impactful strategies. AIMS AND OBJECTIVES: To explore the collaborative sustainability planning process for a single outcome measure in three rehabilitation sites. METHODOLOGY: Within the Mayo-Portland Adaptability Inventory-version 4 (MPAI-4) implementation project, we conducted a qualitative description study. We used data from 12 core sustainability planning meetings and 108 follow-up meetings that included a total of 31 clinical and research team participants. Sustainability planning was informed by an MPAI-4-specific implementation guide, and by the results from a realist review of the sustainability of rehabilitation practices and the Clinical Sustainability Assessment Tool. We analyzed qualitative data using thematic content analysis. RESULTS: Three themes describe the collaborative sustainability planning process: (1) "collaboration as a driver for sustainability" which captures the active collaboration underpinning sustainability planning; (2) "co-creation of a sustainability plan to achieve shared objectives" which captures the identified barriers and facilitators, and selected sustainability strategies linked to one of six collaboratively identified shared objectives; and (3) "the iterative nature of sustainability planning" which captures the necessity of an agile and responsive sustainability planning process. CONCLUSION: Identified strategies may be useful to support (collaborative) sustainment. Future research could investigate the effect of collaborative sustainability planning on sustainability objectives, and the relationship between these objectives.

Sustainability of an outcome measure in outpatient stroke rehabilitation: A realist evaluation.

RATIONALE: Only half of newly implemented evidence-based practices are sustained. Though poor sustainment can lead to negative consequences for clinical teams, organizations and patients, the causal explanations of sustainment are largely unknown. AIMS AND OBJECTIVES: We aimed to ascertain how (mechanisms) and in what circumstances (context) a newly implemented outcome measure in rehabilitation was sustained or not (outcome). METHODOLOGY: Informed by an integrated knowledge translation approach, we conducted a realist evaluation using a mixed method, embedded single case study design with data collection up to 18 months following the implementation of the Mayo-Portland Adaptability Inventory - version 4 (MPAI-4), a rehabilitation outcome measure. Quantitative data (survey and patient charts) was analysed using descriptive statistics, then integrated with qualitative data (interviews with 10 key informants) and analysed using inductive and deductive retroduction. We integrated the data to develop a case description and ultimately, to refine the programme theory to better understand the sustainability of the MPAI-4. RESULTS: We linked context, mechanisms and outcomes, and also emphasized sustainability strategies in 18 explanations of how sustainability works. These explanations provide evidence for four overarching patterns: (1) implementation and sustainability phases are interconnected, (2) outcomes build on each other recursively, with patient benefits as the keystone outcome, (3) sustainment is achieved to varying levels across different sustainability outcomes [e.g., high level (e.g., rate of MPAI-4 scoring: 77.7%) to low level (e.g., rate of MPAI-4 application to clinical decision-making: 3.7%)] and (4) the work of sustaining the MPAI-4 is shared amongst different stakeholders. CONCLUSION: Implementation teams can draw from this programme theory to improve the sustainment of outcomes measures while researchers could continue to refine the theory. Continued investigation of sustainability, including diverse and continuous sustainability outcomes, is needed to understand how to maintain improvements in quality of care and patient outcomes.

Enrollment and dropout rates of individuals with chronic obstructive pulmonary disease approached for telehealth interventions: A systematic review and meta-regression analysis.

Introduction: Telehealth interventions have the potential of improving health outcomes for individuals with chronic obstructive pulmonary disease (COPD). However, the precise impact of telehealth on exacerbation and hospital readmissions remains inconclusive. This lack of knowledge on the effectiveness of telehealth for COPD care might be due to lack of clarity regarding which variables are most strongly associated with enrolment and dropout rates. Objectives: Among individuals with COPD in telehealth studies, we aimed to: (1) estimate the extent to which trial-related variables are associated with enrolment and dropout rates, and identify reasons for dropouts; (2) estimate the extent to which patients-related and intervention-related variables are associated with dropout rates; (3) estimate the effect of enrolment rate and dropout rate on effect size; (4) estimate the effect of trial-related, patient-related, and intervention-related variables on effect size. Methods: A systematic literature search was conducted using four electronic databases. Two independent reviewers screened all retrieved titles, abstracts and full texts according to the inclusion criteria and extracted the data. A random-effect meta-regression analysis was conducted to estimate the overall enrolment and dropout rates, and estimated the different variables' effects on the enrolment rate, dropout rate, and effect sizes in the studies included in the review. Results: A total of 56 studies comprising 7530 participants were identified. The estimated enrolment and dropout rates were 50.3 % and 14.9 %, respectively. Trial-related variables influence enrollment and dropout rates, including RCT designs and the recruitments. The patient-related variables, including age and severity of the disease, and intervention-related variables, including the components of the intervention and mode of delivery, influence dropout rates. Studies with low dropout rates had a bigger effect size by 0.23. The main reported reasons for dropping out of the intervention were related to death (21 %) followed by lost to follow-up (14 %). Conclusion: Trial, patient, and intervention-related variables were found to influence the enrolment and dropout rates. This would help plan and develop a more appealing telehealth intervention that patients can easily accept and incorporate into their everyday lives. Registration information: International Prospective Register of Systematic Reviews (PROSPERO); ID: CRD42017078541.

Resveratrol-based Delivery Systems as Contemporary Nominees for Combating Pulmonary Diseases: A Comprehensive Review.

Exploiting different formulation approaches, each designed to improve the clinical use of resveratrol (RES) in treating several lung diseases. Accentuating the rationale for using RESbased delivery systems in different clinical applications in pulmonary diseases. Resveratrol (RES), a well-known natural polyphenol stilbenoid, possesses tremendous potential to treat various lung diseases owing to its anti-inflammatory, antioxidant, antiapoptotic, antiviral, and anticancer activities. Its physicochemical properties have restricted the beneficial activities of resveratrol, as it is characterized by low aqueous solubility, bioavailability and stability in addition to high photosensitivity. With the growing understanding of the effectiveness of RES in treating lung diseases, the need for attempts and advances in RES formulations should be evolved to enhance its involvement in pharmaceutical applications. This review discusses the role of RES in treating several pulmonary illnesses. For the first time, different approaches and strategies to evade its limitations and allow its clinical applications via various routes for managing a variety of respiratory ailments are presented rigorously.

Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets.

Obesity, characterized by excessive body fat, is closely linked to endoplasmic reticulum (ER) stress, leading to insulin resistance and type 2 diabetes. Inflammatory pathways like c-Jun N-terminal kinase (JNK) worsen insulin resistance, impacting insulin signaling. Moreover, ER stress plays a substantial role in cancer, influencing tumor cell survival and growth by releasing factors like vascular endothelial growth factor (VEGF). The unfolded protein response (UPR) is pivotal in this process, offering both pro-survival and apoptotic pathways. This review offers an extensive exploration of the sophisticated connection between ER stress provoked by obesity and its role in both the onset and advancement of cancer. It delves into the intricate interplay between oncogenic signaling and the pathways associated with ER stress in individuals who are obese. Furthermore, this review sheds light on potential therapeutic strategies aimed at managing ER stress induced by obesity, with a focus on addressing cancer initiation and progression. The potential to alleviate ER stress through therapeutic interventions, which may encompass the use of small molecules, FDA-approved medications, and gene therapy, holds great promise. A more in-depth examination of pathways such as UPR, ER-associated protein degradation (ERAD), autophagy, and epigenetic regulation has the potential to uncover innovative therapeutic approaches and the identification of predictive biomarkers.

View-shuffled clustering via the modified Hungarian algorithm.

In the majority of existing multi-view clustering methods, the prerequisite is that the data have the correct cross-view correspondence. However, this strong assumption may not always hold in real-world applications, giving rise to the so-called View-shuffled Problem (VsP). To address this challenge, we propose a novel multi-view clustering method, namely View-shuffled Clustering via the Modified Hungarian Algorithm (VsC-mH). Specifically, we first establish the cross-view correspondence of the shuffled data utilizing strategies of the global alignment and modified Hungarian algorithm (mH) based intra-category alignment. Subsequently, we generate the partition of the aligned data employing matrix factorization. The fusion of these two processes facilitates the interaction of information, resulting in improved quality of both data alignment and partition. VsC-mH is capable of handling the data with alignment ratios ranging from 0 to 100%. Both experimental and theoretical evidence guarantees the convergence of the proposed optimization algorithm. Extensive experimental results obtained on six practical datasets demonstrate the effectiveness and merits of the proposed method.

Thymoquinone-protoflavone hybrid molecules as potential antitumor agents.

We describe herein the synthesis of eight new ester-coupled hybrid compounds from thymoquinone and protoflavone building blocks, and their bioactivity testing against multiple cancer cell lines. Among the hybrids, compound 14 showed promising activities in all cell lines studied. The highest activities were recorded against breast cancer cell lines with higher selectivity to MDA-MB-231 as compared to MCF-7. Even though the hybrids were found to be completely hydrolysed in 24 h under cell culture conditions, compound 14 demonstrated a ca. three times stronger activity against U-87 glioblastoma cells than a 1:1 mixture of its fragments. Further, compound 14 showed good tumour selectivity: it acted 4.4-times stronger on U-87 cells than on MRC-5 fibroblasts. This selectivity was much lower, only ca. 1.3-times, when the cells were co-treated with a 1:1 mixture of its non-coupled fragments. Protoflavone-thymoquinone hybrids may therefore serve as potential new antitumor leads particularly against glioblastoma.

Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells.

BACKGROUND: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs. Herein, we investigate ASC homeostasis and regenerative potential in the diabetic milieu. METHODS: We conducted data collection and functional enrichment analysis to investigate the differential gene expression profile of MSCs in the diabetic microenvironment. Next, ASCs were cultured in a medium containing diabetic serum (DS) or normal non-diabetic serum (NS) for six days and one-month periods. Proteomic analysis was carried out, and ASCs were then evaluated for apoptosis, changes in the expression of surface markers and DNA repair genes, intracellular oxidative stress, and differentiation capacity. The crosstalk between the ASCs and the diabetic microenvironment was determined by the expression of pro and anti-inflammatory cytokines and cytokine receptors. RESULTS: The enrichment of MSCs differentially expressed genes in diabetes points to an alteration in oxidative stress regulating pathways in MSCs. Next, proteomic analysis of ASCs in DS revealed differentially expressed proteins that are related to enhanced cellular apoptosis, DNA damage and oxidative stress, altered immunomodulatory and differentiation potential. Our experiments confirmed these data and showed that ASCs cultured in DS suffered apoptosis, intracellular oxidative stress, and defective DNA repair. Under diabetic conditions, ASCs also showed compromised osteogenic, adipogenic, and angiogenic differentiation capacities. Both pro- and anti-inflammatory cytokine expression were significantly altered by culture of ASCs in DS denoting defective immunomodulatory potential. Interestingly, ASCs showed induction of antioxidative stress genes and proteins such as SIRT1, TERF1, Clusterin and PKM2. CONCLUSION: We propose that this deterioration in the regenerative function of ASCs is partially mediated by the induced oxidative stress and the diabetic inflammatory milieu. The induction of antioxidative stress factors in ASCs may indicate an adaptation mechanism to the increased oxidative stress in the diabetic microenvironment.

Sonophoresis mediated diffusion of caffeine loaded Transcutol® enriched cerosomes for topical management of cellulite.

The goal of this research was to augment the deposition of caffeine loaded Transcutol® enriched cerosomes (TECs) gel for efficient topical treatment of cellulite utilizing the sonophoresis technique. Caffeine-loaded TECs were prepared using thin film hydration method applying 23 factorial design to study the impact of different factors, each with two levels on the entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of the formulated TECs. The studied factors were cetyl trimethyl ammonium bromide (CTAB) amount (mg) (X1), phosphatidylcholine (PC) amount (mg) (X2), and Transcutol® amount (mg) (X3). Design-Expert® software was utilized to determine the optimum TECs formulation. Afterward, the optimum TECs formulation was loaded into a gel and subjected to extra investigations. The optimum TECs formulation was (TEC5) which was prepared using 10 mg of CTAB, 150 mg of PC, and 10 mg of Transcutol®. TEC5 presented EE% of 87.44 ± 0.14 %, PS of 308.60 ± 13.38 nm, PDI of 0.455 ± 0.030, and ZP of 50.20 ± 1.55 mV. TEC5 had a fiber-like morphology, with elongated tubules of ceramide. Further, the optimum TECs formulation showed a high stability profile. Moreover, an in vivo dermatokinetic study showed superior deposition of caffeine from TEC5 gel coupled with the sonophoresis on rat skin compared to TEC5 gel and caffeine gel. Moreover, the histopathological study of TEC5 on rat skin confirmed the non-irritant nature of TEC 5 gel mediated by ultrasonic waves through the skin. Overall, the outcomes exposed the obvious superiority of sonophoresis delivered TECs-gel for topical delivery of caffeine for cellulite management.

Hepatocellular carcinoma patients serum modulates the regenerative capacities of adipose mesenchymal stromal cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers causing the highest mortality rate worldwide. Treatment options of surgery, radiation, cytotoxic drugs and liver transplantation suffer significant side effects and a high frequency of relapse. Stem cell therapy has been proposed as a new effective therapy, however, controversial reports are emerging on the role of mesenchymal stem cells in cancer. In this work, we aimed to assess the regenerative capacities of adipose mesenchymal stem cells when exposed to serum from HCC patients, by assessing the effect of the sera on modulating the regenerative capacities of h-AMSCs and the cancer properties in HCC cells. This will pave the way for maximizing the efficacy of MSCs in cancer therapy. Our data show that HCC serum-treated hA-MSCs suffered oncogene-induced senescence as shown by their altered morphology and ameliorated proliferation and differentiation. The cells were enlarged with small irregular nuclei, swollen rough endoplasmic reticulum cisternae, and aging lysosomes typified by dark residual bodies. HCC serum-treated Huh-7 cancer cells on the other hand displayed higher tumor aggressiveness as depicted by altered morphology, increased cellular proliferation and migration, and decreased percentage of early and late apoptotic cells. Our findings provide evidence that exposure of hA-MSCs to the serum of HCC patients decreases their regenerative capacities and should be considered when employed as a potential therapy in HCC patients.

The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

BACKGROUND: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. METHODS: PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients. The functionality of PCs was analyzed after 6, 14, and 30 days. RESULTS: Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin-related protein 2/3 complex, and downregulated COL21A1 protein expression. These cells suffered more pronounced apoptosis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein, serine/threonine protein phosphatase, and caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 TERF2, and upregulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. Further, DS-treated cells also showed disruption in the expression of the focal adhesion and binding proteins TSP1, TGF-ß, fibronectin, and PCDH7. Interestingly, DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maintaining the intracellular reactive oxygen species (ROS) level and upregulation of extracellular matrix (ECM) organizing proteins as vinculin, IQGAP1, and tubulin beta chain. CONCLUSION: These data showed that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of T2DM. Nevertheless, PCs have shown remarkable protective mechanisms when initially exposed to DS and thus they could provide a promising cellular therapy for T2DM.

Application of simultaneous uncertainty quantification and segmentation for oropharyngeal cancer use-case with Bayesian deep learning.

BACKGROUND: Radiotherapy is a core treatment modality for oropharyngeal cancer (OPC), where the primary gross tumor volume (GTVp) is manually segmented with high interobserver variability. This calls for reliable and trustworthy automated tools in clinician workflow. Therefore, accurate uncertainty quantification and its downstream utilization is critical. METHODS: Here we propose uncertainty-aware deep learning for OPC GTVp segmentation, and illustrate the utility of uncertainty in multiple applications. We examine two Bayesian deep learning (BDL) models and eight uncertainty measures, and utilize a large multi-institute dataset of 292 PET/CT scans to systematically analyze our approach. RESULTS: We show that our uncertainty-based approach accurately predicts the quality of the deep learning segmentation in 86.6% of cases, identifies low performance cases for semi-automated correction, and visualizes regions of the scans where the segmentations likely fail. CONCLUSIONS: Our BDL-based analysis provides a first-step towards more widespread implementation of uncertainty quantification in OPC GTVp segmentation.

Radiotherapy is used as a treatment for people with oropharyngeal cancer. It is important to distinguish the areas where cancer is present so the radiotherapy treatment can be targeted at the cancer. Computational methods based on artificial intelligence can automate this task but need to be able to distinguish areas where it is unclear whether cancer is present. In this study we compare these computational methods that are able to highlight areas where it is unclear whether or not cancer is present. Our approach accurately predicts how well these areas are distinguished by the models. Our results could be applied to improve the computational methods used during radiotherapy treatment. This could enable more targeted treatment to be used in the future, which could result in better outcomes for people with oropharyngeal cancer.

Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.

Antibiotic resistance and evasion are incompletely understood and complicated by the fact that murine interval dosing models do not fully recapitulate antibiotic pharmacokinetics in humans. To better understand how gastrointestinal bacteria respond to antibiotics, we colonized germ-free mice with a pan-susceptible genetically barcoded Escherichia coli clinical isolate and administered the antibiotic cefepime via programmable subcutaneous pumps, allowing closer emulation of human parenteral antibiotic dynamics. E. coli was only recovered from intestinal tissue, where cefepime concentrations were still inhibitory. Strikingly, "some" E. coli isolates were not cefepime resistant but acquired mutations in genes involved in polysaccharide capsular synthesis increasing their invasion and survival within human intestinal cells. Deleting wbaP involved in capsular polysaccharide synthesis mimicked this phenotype, allowing increased invasion of colonocytes where cefepime concentrations were reduced. Additionally, "some" mutant strains exhibited a persister phenotype upon further cefepime exposure. This work uncovers a mechanism allowing "select" gastrointestinal bacteria to evade antibiotic treatment.

Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation.

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of segmentation quality. The experimental results revealed a low interrater agreement (Krippendorff α, 0.34) in experts' segmentation quality perception. Furthermore, the correlations between the ratings and commonly used quantitative quality metrics were low (Kendall tau between Dice score and mean rating, 0.23; Kendall tau between Hausdorff distance and mean rating, 0.51), with large variability among the experts. Conclusion The results demonstrate that quality ratings are prone to variability due to the ambiguity of tumor boundaries and individual perceptual differences, and existing metrics do not capture the clinical perception of segmentation quality. Keywords: Brain Tumor Segmentation, Deep Learning Algorithms, Glioblastoma, Cancer, Machine Learning Clinical trial registration nos. NCT00756106 and NCT00662506 Supplemental material is available for this article. © RSNA, 2023.

Euglycemic diabetic ketoacidosis in a pregnant woman.

Background: Euglycemic diabetic ketoacidosis (EDKA) carries serious risks for mortality and morbidity for both the mother and the baby, and it is essential to recognize it early and start immediate treatment. Case Presentation: We present a case of EDKA in a 28-week pregnant woman known to have type 1 diabetes. She was found to have severe acidosis with a blood sugar level of 10.6 mmol/L (190.8 mg/dL) and normal anion gap. She was found to have EDKA, which was confirmed later with a depressed venous pH and bicarbonate level and an increased serum ketone level. The patient's acidosis was not improving significantly with 0.05 units/kg/h of insulin infusion, so a full dose of 0.1 unit/kg/h of insulin infusion was started following a full diabetic ketoacidosis (DKA) protocol regardless of her blood sugar level. The patient showed gradual improvement and was discharged home after 4 days, with follow-up with endocrinology and obstetrics. Conclusion: In conclusion, EDKA is a critical complication of diabetes, especially in pregnant women. Therefore, it is crucial to treat it early and potentially consider following a full DKA protocol using 0.1 unit/kg/h insulin infusion instead of 0.05 unit/kg/h.