Skin repair and infection control in diabetic, obese mice using bioactive laser-activated sealants.

Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice. Although lower recovery of epidermal structure and function was seen with AgNPr-LASE sealing, likely because of the hyperthermia induced by laser and presence of this material in the wound space, this approach resulted in higher enhancement in recovery of skin biomechanical strength compared to sutures and Cu-LASEs in diabetic, obese mice. Histological and immunohistochemical analyses revealed that AgNPr-LASEs resulted in significantly lower neutrophil migration to the wound compared to Cu-LASEs and sutures, indicating a more muted inflammatory response. Cu-LASEs resulted in local tissue toxicity likely because of effects of copper ions as manifested in the form of a significant epidermal gap and a 'depletion zone', which was a region devoid of viable cells proximal to the wound. Compared to sutures, LASE-mediated sealing, in later stages of healing, resulted in increased angiogenesis and diminished myofibroblast activation, which can be indicative of lower scarring. AgNPr-LASE loaded with vancomycin, an antibiotic drug, significantly lowered methicillin-resistant Staphylococcus aureus (MRSA) load in a pathogen challenge model in diabetic and obese mice and also reduced post-infection inflammation of tissue compared to antibacterial sutures. Taken together, these attributes indicate that AgNPr-LASE demonstrated a more balanced quality of tissue sealing and repair in diabetic and obese mice and can be used for combating local infections, that can result in poor healing in these individuals.

M. tuberculosis PrrA binds the dosR promoter and regulates mycobacterial adaptation to hypoxia.

The PrrAB two-component system (TCS) is essential for Mycobacterium tuberculosis viability. Previously, it was demonstrated that PrrA binds DNA in the absence of PrrB-mediated transphosphorylation and that non-cognate serine/threonine-kinases phosphorylate PrrA threonine-6 (T6). Therefore, we investigated the differential binding affinity and regulatory properties of the M. tuberculosis-derived wild-type PrrA, PrrA phosphomimetic (D58E, T6E), and PrrA phosphoablative (D58A, T6A) proteins with the prrAMtb, dosRMtb, and cydAMtb genes. While we hypothesized greater DNA binding affinity and more pronounced regulation by PrrA phosphomimetic variants, recombinant, wild-type PrrAMtb bound DNA with greatest affinity. Collectively, wild-type PrrAMtb recombinant protein displayed the highest binding affinity to the dosRMtb promoter (KD 3.46 ± 2.09 nM), followed by the prrAMtb promoter (KD 9.00 ± 2.66 nM). To establish PrrAMtb regulatory activity, we constructed M. smegmatis ΔprrABMsmeg::prrAMtb strains with each of the PrrAMtb variants and extrachromosomal prrAMtb, dosRMtb, and cydAMtb promoter-mCherry reporter fusions. Our findings showed that PrrAMtb is autoregulatory and induces dosRMtb expression only during in vitro, hypoxic growth. Combined expression of prrABMtb in M. smegmatis ΔprrAB significantly induced cydAMtb promoter-mCherry expression. Our studies advanced the understanding of PrrA function and PrrAB phosphorylation-mediated regulatory mechanisms and control of mycobacterial dosR and cydA hypoxic and low-oxygen responsive genes.

Higher prevalence of sacbrood virus in Apis mellifera (Hymenoptera: Apidae) colonies after pollinating highbush blueberries.

Highbush blueberry pollination depends on managed honey bees (Apis mellifera) L. for adequate fruit sets; however, beekeepers have raised concerns about the poor health of colonies after pollinating this crop. Postulated causes include agrochemical exposure, nutritional deficits, and interactions with parasites and pathogens, particularly Melisococcus plutonius [(ex. White) Bailey and Collins, Lactobacillales: Enterococcaceae], the causal agent of European foulbrood disease, but other pathogens could be involved. To broadly investigate common honey bee pathogens in relation to blueberry pollination, we sampled adult honey bees from colonies at time points corresponding to before (t1), during (t2), at the end (t3), and after (t4) highbush blueberry pollination in British Columbia, Canada, across 2 years (2020 and 2021). Nine viruses, as well as M. plutonius, Vairimorpha ceranae, and V. apis [Tokarev et al., Microsporidia: Nosematidae; formerly Nosema ceranae (Fries et al.) and N. apis (Zander)], were detected by PCR and compared among colonies located near and far from blueberry fields. We found a significant interactive effect of time and blueberry proximity on the multivariate pathogen community, mainly due to differences at t4 (corresponding to ~6 wk after the beginning of the pollination period). Post hoc comparisons of pathogens in near and far groups at t4 showed that detections of sacbrood virus (SBV), which was significantly higher in the near group, not M. plutonius, was the primary driver. Further research is needed to determine if the association of SBV with highbush blueberry pollination is contributing to the health decline that beekeepers observe after pollinating this crop.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Patients' acceptability of self-selected digital health services to support diet and exercise among people with complex chronic conditions: Mixed methods study.

Objective: The acceptability of being offered a choice from a suite of digital health service options to support optimal diet and exercise behaviors in adults with complex chronic conditions was evaluated. This study sought to understand many areas of acceptability including satisfaction, ease of use, usefulness and user appropriateness and perceived effectiveness. Methods: This mixed-methods study was embedded within a randomized-controlled feasibility trial providing digital health services managing diet and exercise for adults from specialist kidney and liver disease clinics. Post study surveys and semistructured interviews were used to determine patients' acceptability of the trial interventions. Quantitative (surveys) and qualitative (surveys and interviews) results were merged using integrative analysis and mapped to each construct of the modified version of the Theoretical Framework of Acceptability. Results: Seventeen interviews (intervention group) and 50 surveys (n = 24 intervention, n = 26 comparator) completed from a possible 67 participants were analyzed. In the intervention group, the survey results revealed high areas of acceptability for the digital health services including overall support received, ease of use, timely advice and feeling safe. The interviews also revealed high areas of acceptability including convenience, ability to adopt healthier behaviors and having regular interactions with health professionals. However, the interviews also revealed lower areas of acceptability as a result of absence of individualization, low digital literacy, and limitations from life circumstances. Conclusions: Recipients of digital health services that supported diet and exercise interventions found these useful, effective, and safe. Individualized care, technical support and patient confidence remain important to improve the acceptability of digital health service interventions.

A transmission assay of 'Candidatus Liberibacter asiaticus' using citrus phloem sap and topical feeding to its insect vector, Diaphorina citri.

'Candidatus Liberibacter asiaticus', the putative causal agent of citrus greening disease is transmitted by the Asian citrus psyllid, Diaphorina citri in a propagative, circulative, and persistent manner. Unfortunately, 'Ca. L. asiaticus' is not yet available in pure culture to carry out Koch's postulates and to confirm its etiology. When a pure culture is available, an assay to test its infectivity in both the insect vector and the plant host will be crucial. Herein, we described a transmission assay based on the use of phloem sap extracted from infected citrus plants and topical feeding to D. citri nymphs. Phloem sap was collected by centrifugation, diluted with 0.1 M phosphate buffer pH 7.4 containing 20% (w/v) sucrose and 0.1% ascorbic acid (w/v) as an antioxidant, and delivered to third through fifth instar nymphs by placing droplets on the mouthparts. Nymphs unfolded the stylets and acquired the phloem sap containing the bacterial pathogen. Nymphs were then placed onto Citrus macrophylla seedlings (ten nymphs/seedling) for an inoculation period of two weeks. A transmission rate of up to 80% was recorded at six months post-inoculation. The method could be a powerful tool to test the transmissibility of the bacterial pathogen after various treatments to reduce the viability of the bacteria or to block its transmission. In addition, it might be a potent assay to achieve Koch's postulates if a pure culture of 'Ca. L. asiaticus' becomes available.

Timing determines zooplankton community responses to multiple stressors.

Human activities and climate change cause abiotic factors to fluctuate through time, sometimes passing thresholds for organismal reproduction and survival. Multiple stressors can independently or interactively impact organisms; however, few studies have examined how they interact when they overlap spatially but occur asynchronously. Fluctuations in salinity have been found in freshwater habitats worldwide. Meanwhile, heatwaves have become more frequent and extreme. High salinity pulses and heatwaves are often decoupled in time but can still collectively impact freshwater zooplankton. The time intervals between them, during which population growth and community recovery could happen, can influence combined effects, but no one has examined these effects. We conducted a mesocosm experiment to examine how different recovery times (0-, 3-, 6-week) between salt treatment and heatwave exposure influence their combined effects. We hypothesized that antagonistic effects would appear when having short recovery time, because previous study found that similar species were affected by the two stressors, but effects would become additive with longer recovery time since fully recovered communities would respond to heatwave similar to undisturbed communities. Our findings showed that, when combined, the two-stressor joint impacts changed from antagonistic to additive with increased recovery time between stressors. Surprisingly, full compositional recovery was not achieved despite a recovery period that was long enough for population growth, suggesting legacy effects from earlier treatment. The recovery was mainly driven by small organisms, such as rotifers and small cladocerans. As a result, communities recovering from previous salt exposure responded differently to heatwaves than undisturbed communities, leading to similar zooplankton communities regardless of the recovery time between stressors. Our research bolsters the understanding and management of multiple-stressor issues by revealing that prior exposure to one stressor has long-lasting impacts on community recovery that can lead to unexpected joint effects of multiple stressors.

Anticoagulation and vascular anomalies.

A State of the Art lecture titled "Anticoagulation and Vascular Anomalies" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2023. Vascular anomalies have been classified by the International Society for the Study of Vascular Anomalies into vascular tumors and vascular malformations. Although some vascular tumors, such as tufted angioma and kaposiform hemangioendothelioma, and other vascular malformations can present with coagulation aberrancies, these are not generally managed with anticoagulation. A subclassification of vascular malformations includes slow-flow vascular malformations. It is this subgroup specifically that has a high risk of venous thromboembolism (VTE) and morbidity associated with coagulopathy that may be present. In these select cases, anticoagulation may be indicated to reduce the risk of VTE, treat VTE, or manage localized thrombosis in the malformation that causes significant pain and reduced quality of life. There are established risk factors for VTE in these patients that will be reviewed. Finally, we summarize relevant new data on this topic presented during the 2023 ISTH Congress.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective.

INTRODUCTION: The prevalence, health and socioeconomic burden of metabolic dysfunction-associated fatty liver disease (MAFLD) is growing, increasing the need for novel evidence-based lifestyle approaches. Lifestyle is the cornerstone for MAFLD management and co-existing cardiometabolic dysfunction. The aim of this review was to evaluate the evidence for lifestyle management of MAFLD, with a specific lens on 24-hour integrated behaviour and provide practical recommendations for implementation of the evidence. RESULTS: Weight loss ≥ 7-10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss. Lifestyle intervention for MAFLD should consider an integrated '24-h' approach that is cognisant of diet, physical activity/exercise, sedentary behavior, smoking, alcohol intake and sleep. Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered. Increasing physical activity and reducing sedentary behavior can prevent MAFLD, with strongest evidence in MAFLD supporting regular structured moderate-vigorous aerobic exercise for 150-240 min/week. Resistance training in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and/or pharmacological approaches and those with sarcopenia, to minimise bone and lean mass loss. Limited evidence suggests that sleep is important for MAFLD prevention. Emerging novel approaches to diet and exercise may address some of the key barriers to behaviour change (e.g. lack of time, access to resources and social support). FUTURE DIRECTIONS: Large-scale multidisciplinary trials in people with MAFLD with long-term follow-up, that can be scaled up into mainstream healthcare, are required. Future management guidelines should consider the heterogeneity of MAFLD and specialised models of care that coordinate the health workforce to manage the increased and growing MAFLD population.

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites.

Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level. Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics. Results: SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS. Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

Physical activity volume, frequency, and intensity: Associations with hypertension and obesity over 21 years in Australian women.

BACKGROUND: Optimal patterns of accrual of recommended levels of physical activity (PA) for prevention of hypertension and obesity are not known. The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years. Specifically, we investigated whether, for the same weekly volume of PA, the number of sessions (frequency) and vigorousness of PA (intensity) were associated with a reduction in the occurrence of hypertension and obesity in women. METHODS: Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed (n = 20,588; 12%-16% with a Bachelor's or higher degree). Self-reported PA, hypertension, height, and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021. Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume (metabolic equivalent min/week) (none; 33-499; 500-999; ≥1000, weekly frequency (none; 1-2 times; 3-4 times; 5-7 times; ≥8 times), and the proportion of vigorous PA to total volume of PA (none; 0%; 1%-33%; 34%-66%; 67%-100%) with odds of hypertension and obesity from 2000 to 2021. RESULTS: The cumulative incidence of hypertension was 6% in the 1973-1978 and 23% in the 1946-1951 cohort; 27% of women in the 1973-1978; and 15% in the 1946-1951 cohort developed obesity over the period. Overall, a higher volume of PA was associated with reduced odds of hypertension and obesity. When the volume of PA was considered, the odds of hypertension did not vary according to the frequency or intensity of PA. However, increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obesity. CONCLUSION: PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity. Incorporating more sessions, particularly of vigorous-intensity PA, may provide extra benefits for the prevention of obesity.

Evaluating the Potential of a Novel Metabolic Syndrome Severity Score to Inform Exercise Interventions for People with Complex Chronic Conditions.

Aims: Exercise interventions positively affect numerous cardiometabolic risk factors. To better evaluate the health effects of exercise training, it may be more appropriate to evaluate risk factors together. The Metabolic Syndrome Severity Score (MetSSS) is a composite score representing cardiometabolic risk. Purpose: To evaluate the relationships between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS in a heterogenous sample of people with complex chronic disease. Material and Methods: Fifty-three people with kidney or liver disease and at least one feature of the metabolic syndrome (MetS) were included. Pearson correlations were conducted between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS. Linear regressions were performed for multi-level categorical variables. Independent variables with an association with MetSSS (P ≤ 0.2) were included in a multiple regression analysis. Results: The 6-minute walk test (6MWT) distance was inversely and independently associated with MetSSS [standardized beta coefficient (ß) = -0.31, P = 0.04]. No relationship was found between MetSSS and physical activity or neuromuscular fitness. Mean 6MWT in the highest tertile was 550 m (range: 505-620 m) and 346 m (range: 233-408 m) in the lowest. The analysis showed a medium-large between-group effect for the difference in MetSSS for the lowest and highest tertile of 6MWT [Eta squared (η2) = 0.16, P = 0.01]. Conclusions: Exercise capacity was inversely and independently associated with MetSSS in people with complex chronic disease. Clinical trials with exercise interventions are needed to further investigate if improvements in exercise capacity result in clinically significant changes in the MetSSS.

Honey bee stressor networks are complex and dependent on crop and region.

Honey bees play a major role in crop pollination but have experienced declining health throughout most of the globe. Despite decades of research on key honey bee stressors (e.g., parasitic Varroa destructor mites and viruses), researchers cannot fully explain or predict colony mortality, potentially because it is caused by exposure to multiple interacting stressors in the field. Understanding which honey bee stressors co-occur and have the potential to interact is therefore of profound importance. Here, we used the emerging field of systems theory to characterize the stressor networks found in honey bee colonies after they were placed in fields containing economically valuable crops across Canada. Honey bee stressor networks were often highly complex, with hundreds of potential interactions between stressors. Their placement in crops for the pollination season generally exposed colonies to more complex stressor networks, with an average of 23 stressors and 307 interactions. We discovered that the most influential stressors in a network-those that substantively impacted network architecture-are not currently addressed by beekeepers. Finally, the stressor networks showed substantial divergence among crop systems from different regions, which is consistent with the knowledge that some crops (e.g., highbush blueberry) are traditionally riskier to honey bees than others. Our approach sheds light on the stressor networks that honey bees encounter in the field and underscores the importance of considering interactions among stressors. Clearly, addressing and managing these issues will require solutions that are tailored to specific crops and regions and their associated stressor networks.

Application of deep learning on mammographies to discriminate between low and high-risk DCIS for patient participation in active surveillance trials.

BACKGROUND: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296-2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA),  L. E. Elshof et al., Eur J Cancer, 51, 1497-510, 2015). Low-risk is defined as grade I or II DCIS. Because DCIS grade is a major eligibility criteria in these trials, it would be very helpful to assess DCIS grade on mammography, informed by grade assessed on DCIS histopathology in pre-surgery biopsies, since surgery will not be performed on a significant number of patients participating in these trials. OBJECTIVE: To assess the performance and clinical utility of a convolutional neural network (CNN) in discriminating high-risk (grade III) DCIS and/or Invasive Breast Cancer (IBC) from low-risk (grade I/II) DCIS based on mammographic features. We explored whether the CNN could be used as a decision support tool, from excluding high-risk patients for active surveillance. METHODS: In this single centre retrospective study, 464 patients diagnosed with DCIS based on pre-surgery biopsy between 2000 and 2014 were included. The collection of mammography images was partitioned on a patient-level into two subsets, one for training containing 80% of cases (371 cases, 681 images) and 20% (93 cases, 173 images) for testing. A deep learning model based on the U-Net CNN was trained and validated on 681 two-dimensional mammograms. Classification performance was assessed with the Area Under the Curve (AUC) receiver operating characteristic and predictive values on the test set for predicting high risk DCIS-and high-risk DCIS and/ or IBC from low-risk DCIS. RESULTS: When classifying DCIS as high-risk, the deep learning network achieved a Positive Predictive Value (PPV) of 0.40, Negative Predictive Value (NPV) of 0.91 and an AUC of 0.72 on the test dataset. For distinguishing high-risk and/or upstaged DCIS (occult invasive breast cancer) from low-risk DCIS a PPV of 0.80, a NPV of 0.84 and an AUC of 0.76 were achieved. CONCLUSION: For both scenarios (DCIS grade I/II vs. III, DCIS grade I/II vs. III and/or IBC) AUCs were high, 0.72 and 0.76, respectively, concluding that our convolutional neural network can discriminate low-grade from high-grade DCIS.

Feasibility and acceptability of chaplain decision coaching on Periviable resuscitation decision quality: A pilot study.

Objective: To pilot test and assess the feasibility and acceptability of chaplain-led decision coaching alongside the GOALS (Getting Optimal Alignment around Life Support) decision support tool to enhance decision-making in threatened periviable delivery. Methods: Pregnant people admitted for threatened periviable delivery and their 'important other' (IO) were enrolled. Decisional conflict, acceptability, and knowledge were measured before and after the intervention. Chaplains journaled their impressions of training and coaching encounters. Descriptive analysis and conventional content analysis were completed. Results: Eight pregnant people and two IOs participated. Decisional conflict decreased by a mean of 6.7 (SD = 9.4) and knowledge increased by a mean of 1.4 (SD = 1.8). All rated their experience as "good" or "excellent," and the amount of information was "just right." Participants found it "helpful to have someone to talk to" and noted chaplains helped them reach a decision. Chaplains found the intervention a valuable use of their time and skillset. Conclusion: This is the first small-scale pilot study to utilize chaplains as decision coaches. Our results suggest that chaplain coaching with a decision support tool is feasible and well-accepted by parents and chaplains. Innovations: Our findings recognize chaplains as an underutilized, yet practical resource in value-laden clinical decision-making.

Acquired Hemophilia: A Rare Complication of Pediatric Idiopathic Multicentric Castleman Disease.

Acquired hemophilia is caused by acquired autoantibodies to 1 of the factors of the coagulation cascade, usually factor VIII or IX, and is an exceedingly rare phenomenon in children. The finding of an acquired factor VIII inhibitor in a pediatric patient with idiopathic multicentric Castleman disease has never been reported. Patients with acquired hemophilia can have life-threatening bleeds that are refractory to blood product support, requiring bypassing agents to manage bleeding symptoms. We present the novel finding of acquired hemophilia resulting from an autoantibody to factor VIII in a pediatric patient with idiopathic multicentric Castleman disease and discuss the optimal management of bleeding in a patient with acquired hemophilia.

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.e. the number of maternal tissue layers between placental tissue and maternal blood). The villi in these species therefore serve as a compelling evolutionary case study to explore whether placentas have developed structural adaptations to respond to the challenge of reduced nutrient availability in less invasive placentas. Here, we use three-dimensional X-ray microfocus computed tomography and electron microscopy to quantitatively evaluate key structures involved in exchange in human and equid placental villi. We find that equid villi have a higher surface area to volume ratio and deeper trophoblastic vessel indentation than human villi. Using illustrative computational models, we propose that these structural adaptations have evolved in equids to boost nutrient transfer to compensate for reduced invasiveness into maternal tissue. We discuss these findings in relation to the 'maternal-fetal conflict hypothesis' of placental evolution.