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Background: Children's interactions are inherently multimodal. Accordingly, when children engage in science in classroom communities, their interactions are grounded in material and embodied aspects of interactions with teachers and their peers. Purpose: This study explores the nature of children's science interactions in a classroom community where students are working in a language they are also learning through examination of the ways in which open-ended pedagogical approaches mediated embodied and material science participation and sense-making. Study and method: We employed multimodal interaction analysis layered with a critical ethnographic perspective to explore the embodied and materially-grounded experiences of a student working in an early-childhood classroom with peers and teachers in science through a language he is also working to learn. Results: Multimodal interaction analysis allowed us to build views of how the classroom interactional spaces afforded embodied and material participation and learning in science, and uncovered the multimodal ways in which this mediated his engagement in science and communication of science meanings and wonderings. Conclusions: Open-ended pedagogical approaches afforded spaces in which this student was able to engage with phenomena, materials, and embodied interactions, regardless of his verbal participation. This embodied participation and materially grounded interactions entangle and unfold to become learning. Pedagogical implications for the teaching and learning of science with all children, and in particular with plurilingual children, through the use of open-approaches that afford resource-rich embodied engagement and learning are discussed.

Abstract Cities and other human settlements are major contributors to climate change and are highly vulnerable to its impacts. They are also uniquely positioned to reduce greenhouse gas emissions and lead adaptation efforts. These compound challenges and opportunities require a comprehensive perspective on the public policy of human settlements. Drawing on core literature that has driven debate around cities and climate over recent decades, we put forward a set of boundary objects that can be applied to connect the knowledge of epistemic communities and support an integrated urbanism. We then use these boundary objects to develop the Goals-Intervention-Stakeholder-Enablers (GISE) framework for a public policy of human settlements that is both place-specific and provides insights and tools useful for climate action in cities and other human settlements worldwide. Using examples from Berlin, we apply this framework to show that climate mitigation and adaptation, public health, and well-being goals are closely linked and mutually supportive when a comprehensive approach to urban public policy is applied.

Background People living with Long COVID (PWLC), which is still a poorly understood disease, often face major issues accessing proper care and frequently feel abandoned by the healthcare system. PWLC frequently report impaired quality of life because of the medical burden, the variability and intensity of symptoms, and insecurity toward the future. These particular needs justify the development of innovative, minimally disruptive solutions to facilitate the monitoring of this complex and fluctuating disease. Voice-based interactions and vocal biomarkers are promising digital approaches for such health monitoring. Methods Based on a mixed-method approach, this study describes the entire co-design process of Long COVID Companion, a voice-based digital health app to monitor Long COVID symptoms. Potential end-users of the app, both PWLC and healthcare professionals (HCP) were involved to (1) understand the unmet needs and expectations related to Long COVID care and management, (2) to assess the barriers and facilitators regarding a health monitoring app, (3) to define the app characteristics, including future potential use of vocal biomarkers and (4) to develop a first version of the app. Results This study revealed high needs and expectations regarding a digital health app to monitor Long COVID symptoms and the readiness to use vocal biomarkers from end-users. The main expectations included improved care and daily life, and major concerns were linked to accessibility and data privacy. Long COVID Companion was developed as a web application and is composed of a health monitoring component that allows auto-evaluation of symptoms, global health, and scoring relevant symptoms and quality of life using standardized questionnaires. Conclusions The Long COVID Companion app will address a major gap and provide day-to-day support for PWLC. However, further studies will be needed following its release, to evaluate its acceptability, usability and effectiveness.

Abstract Gut microbiome differences between people with Parkinson’s disease (PD) and control subjects without Parkinsonism are widely reported, but potential alterations related to PD with mild cognitive impairment (MCI) have yet to be comprehensively explored. We compared gut microbial features of PD with MCI (n = 58) to cognitively unimpaired PD (n = 60) and control subjects (n = 90) with normal cognition. Our results did not support a specific microbiome signature related to MCI in PD.

Abstract Background Antimicrobial resistance has been identified as a major threat to global health. The pig food chain is considered an important source of antimicrobial resistance genes (ARGs). However, there is still a lack of knowledge on the dispersion of ARGs in pig production system, including the external environment. Results In the present study, we longitudinally followed one swine farm located in Italy from the weaning phase to the slaughterhouse to comprehensively assess the diversity of ARGs, their diffusion, and the bacteria associated with them. We obtained shotgun metagenomic sequences from 294 samples, including pig feces, farm environment, soil around the farm, wastewater, and slaughterhouse environment. We identified a total of 530 species-level genome bins (SGBs), which allowed us to assess the dispersion of microorganisms and their associated ARGs in the farm system. We identified 309 SGBs being shared between the animals gut microbiome, the internal and external farm environments. Specifically, these SGBs were characterized by a diverse and complex resistome, with ARGs active against 18 different classes of antibiotic compounds, well matching antibiotic use in the pig food chain in Europe. Conclusions Collectively, our results highlight the urgency to implement more effective countermeasures to limit the dispersion of ARGs in the pig food systems and the relevance of metagenomics-based approaches to monitor the spread of ARGs for the safety of the farm working environment and the surrounding ecosystems.

Background: This technical note presents a novel minimally invasive exoscope assisted coccygectomy to treat chronic refractory coccydynia. Traditional treatments often fail to provide adequate relief for this debilitating condition, prompting the need to explore surgical approaches. Case Description: A 40-year-old female patient with persistent pain unresponsive to conservative treatments underwent this advanced procedure. Utilizing the Synaptive exoscope-microscope system, the surgery allowed for precise dissection and removal of affected coccygeal segments, with a focus on minimizing skin and soft tissue disruption to optimize wound healing and surgical site pain. Conclusion: Postoperative recovery showcased significant pain reduction and improved quality of life, emphasizing the method's potential for better outcomes and fewer complications. Despite the promising results, the limitations of a single-case study necessitate further research to establish long-term effectiveness across a broader patient population.

ABSTRACTChronic digestive disorders are of increasing incidence worldwide with expensive treatments and no available cure. Available therapeutic schemes mainly rely on symptom relief, with large degrees of variability in patients’ response to such treatments, underlining the need for new therapeutic strategies. There are strong indications that the gut microbiota’s contribution seems to be a key modulator of disease activity and patients’ treatment responses. Hence, efforts have been devoted to understanding host–microbe interactions and the mechanisms underpinning such variability. Animal models, being the gold standard, provide valuable mechanistic insights into host–microbe interactions. However, they are not exempt from limitations prompting the development of alternative methods. Emerging microfluidic technologies and gut-on-chip models were shown to mirror the main features of gut physiology and disease state, reflect microbiota modification, and include functional readouts for studying host responses. In this commentary, we discuss the relevance of animal models in understanding host–microbe interactions and how gut-on-chip technology holds promises for addressing patient variability in responses to chronic digestive disease treatment.

Abstract In healthy individuals, the intestinal epithelium forms a tight barrier to prevent gut bacteria from reaching blood circulation. To study the effect of probiotics, dietary compounds and drugs on gut barrier formation and disruption, human gut epithelial and bacterial cells can be cocultured in an in vitro model called the human microbial crosstalk (HuMiX) gut-on-a-chip system. Here, we present the design, fabrication and integration of thin-film electrodes into the HuMiX platform to measure transepithelial electrical resistance (TEER) as a direct readout on barrier tightness in real-time. As various aspects of the HuMiX platform have already been set in their design, such as multiple compressible layers, uneven surfaces and nontransparent materials, a novel fabrication method was developed whereby thin-film metal electrodes were first deposited on flexible substrates and sequentially integrated with the HuMiX system via a transfer-tape approach. Moreover, to measure localized TEER along the cell culture chamber, we integrated multiple electrodes that were connected to an impedance analyzer via a multiplexer. We further developed a dynamic normalization method because the active measurement area depends on the measured TEER levels. The fabrication process and system setup can be applicable to other barrier-on-chip systems. As a proof-of-concept, we measured the barrier formation of a cancerous Caco-2 cell line in real-time, which was mapped at four spatially separated positions along the HuMiX culture area.

This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.

This study evaluated the inter-reader agreement of tumor apparent diffusion coefficient (ADC) measurements performed on breast diffusion-weighted imaging (DWI) for assessing treatment response in a multi-center clinical trial of neoadjuvant chemotherapy (NAC) for breast cancer. DWIs from 103 breast cancer patients (mean age: 46 ± 11 years) acquired at baseline and after 3 weeks of treatment were evaluated independently by two readers. Three types of tumor regions of interests (ROIs) were delineated: multiple-slice restricted, single-slice restricted and single-slice tumor ROIs. Compared to tumor ROIs, restricted ROIs were limited to low ADC areas of enhancing tumor only. We found excellent agreement (intraclass correlation coefficient [ICC] ranged from 0.94 to 0.98) for mean ADC. Higher ICCs were observed in multiple-slice restricted ROIs (range: 0.97 to 0.98) than in other two ROI types (both in the range of 0.94 to 0.98). Among the three ROI types, the highest area under the receiver operating characteristic curves (AUCs) were observed for mean ADC of multiple-slice restricted ROIs (0.65, 95% confidence interval [CI]: 0.52-0.79 and 0.67, 95% CI: 0.53-0.81 for Reader 1 and Reader 2, respectively). In conclusion, mean ADC values of multiple-slice restricted ROI showed excellent agreement and similar predictive performance for pathologic complete response between the two readers.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.

The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1). Organic cation and anion transport were studied using the fluorescent substrates 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) and 6-carboxyfluorescein (6-CF), respectively. The level and rate of intracellular ASP accumulation in PTL following basolateral application were slightly lower but within a 3-fold range compared to primary PTEC and RPTEC/TERT1 cells. The basolateral uptake of ASP and its subsequent apical efflux could be inhibited by basolateral exposure to quinidine in all models. Of the three models, only PTL showed a modest preferential basolateral-to-apical 6-CF transfer. These results show that organic cation transport could be demonstrated in all three models, but more research is needed to improve and optimise organic anion transporter expression and functionality.

Aim: The purpose of the present study is the three-dimensional (3D) analysis of molar and incisor movements that occur during the correction of the upper midline deviation by using the Mesial-Distalslider appliance. Materials and Methods: A total of 20 consecutive patients (12 women and 8 men; mean age 19.6 ± 11.1 years) were selected from the Orthodontic Department of Heinrich-Heine University of Düsseldorf. To correct the upper midline deviation (>2 mm), the patients were treated with asymmetric mechanics (mesialization on one side and distalization on the contralateral side) with the aid of Mesial-Distalslider. Dental casts were taken for each patient before (T0) and after the treatment (T1). The casts were 3D digitized and the models were superimposed on the palatal anterior region. Three-dimensional molar movements and sagittal incisor movements (proclination and retroclination) were assessed for T0 and T1. Results: At the end of the treatment, the total movements of the molars resulted in 4.5 ± 2.2 mm (antero-posterior direction), −0.4 ± 2.4 mm (transverse direction) and 0.3 ± 0.9 mm (vertical direction) on the mesialization side, and −2.4 ± 1.7 mm (antero-posterior direction), −0.5 ± 1.5 mm (transverse direction) and 0.2 ± 1.4 mm (vertical direction) on the distalization side. Incisor displacement was 0.9 mm ± 1.7 (mesialization side) and 0.6 mm ± 0.7 (distalization side). Conclusion: The Mesial-Distalslider appliance could be considered a valuable tool in orthodontic treatment for upper midline correction. Within the limits of a retrospective study, asymmetric molar movements appeared possible without clinically relevant anchorage loss.

Abstract Background The introduction of bone-anchored maxillary protraction eliminated the side effects of facemask in the early treatment of patients with maxillary retrusion. This study aimed to evaluate the effects of miniscrew-anchored maxillary protraction (MAMP) and compare them with the growth changes in an untreated control group in growing patients with Class III malocclusion. Methods Forty growing patients with Class III malocclusion and retrognathic maxilla were randomly allocated into two groups: treated and control groups. In the treated group, patients were treated with full-time intermaxillary Class III elastics (C3E) anchored by a hybrid hyrax (HH) in the maxilla and a bone-supported bar in the mandible. Protraction was stopped after obtaining a positive overjet. Cephalometric radiographs were acquired before and after the treatment. Data were statistically analyzed on an intention-to-treat basis. Intergroup comparisons were also made using analysis of covariance with the readings at T0 as a covariate. Results Forty patients agreed to participate, and 30 of them completed the study (treated group, n = 17; control group, n = 13). The average treatment duration was 11.9 months. MAMP resulted in a significant maxillary advancement (A-VR, 4.34 mm) with significant control over the mandibular growth. No significant increase in the mandibular plane angle was found in the treated group compared with the control group. The upper and lower incisors showed significant protrusion in the treated group. Conclusions Within the limitations of this study and high attrition rate, the MAMP protocol can effectively increase maxillary forward growth with good control over the growth of the mandible antero-posteriorly and vertically.

Cross-domain interactions are an integral part of the success of biofilms in natural environments but remain poorly understood. Here, we describe cross-domain interactions in stream biofilms draining proglacial floodplains in the Swiss Alps. These streams, as a consequence of the retreat of glaciers, are characterised by multiple environmental gradients and perturbations (e.g., changes in channel geomorphology, discharge) that depend on the time since deglaciation. We evaluate co-occurrence of bacteria and eukaryotic communities along streams and show that key community members have disproportionate effects on the stability of community networks. The topology of the networks, here quantified as the arrangement of the constituent nodes formed by specific taxa, was independent of stream type and their apparent environmental stability. However, network stability against fragmentation was higher in the streams draining proglacial terrain that was more recently deglaciated. We find that bacteria, eukaryotic photoautotrophs, and fungi are central to the stability of these networks, which fragment upon the removal of both pro- and eukaryotic taxa. Key taxa are not always abundant, suggesting an underlying functional component to their contributions. Thus, we show that there is a key role played by individual taxa in determining microbial community stability of glacier-fed streams.

Background Communication gaps, whether incomplete or fragmented communication, have been the cause of many disasters in human civilisation. Coordination of healthcare is directly related to proper communication and handoffs among multidisciplinary teams throughout multiple shifts during a patient’s hospitalisation.Local problem Patient surveys and direct patient feedback at Mayo Clinic Health System in Mankato, Minnesota, indicated that patient communication with physicians and nurses had declined in 2017 and 2018. Viewing this as an opportunity for improvement, our leadership initiated several changes to increase physician and nurse communication with patients, which resulted in no notable improvements.Methods A systematic quality improvement approach was implemented by using Six Sigma methodology. Stakeholders from multidisciplinary teams were assembled as the project team. The five steps of Six Sigma methodology (Define, Measure, Analyse, Improve and Control) were followed to create a quality improvement intervention.Intervention We developed a standardised and easy-to-use bedside team rounding tool to improve patient communication with physicians and nurses.Results Postintervention patient satisfaction top-box scores exceeded target improvements for both physician (from 78.5% to 82.0%, p