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Nocturnal sympathetic overdrive is an early indicator of cardiovascular (CV) disease, emphasizing the importance of reliable remote patient monitoring (RPM) for autonomic function during sleep. To be effective, RPM systems must be accurate, non-intrusive, and cost-effective. This review evaluates non-invasive technologies, metrics, and algorithms for tracking nocturnal autonomic nervous system (ANS) activity, assessing their CV relevance and feasibility for integration into RPM systems. A systematic search identified 18 relevant studies from an initial pool of 169 publications, with data extracted on study design, population characteristics, technology types, and CV implications. Modalities reviewed include electrodes (e.g., electroencephalography (EEG), electrocardiography (ECG), polysomnography (PSG)), optical sensors (e.g., photoplethysmography (PPG), peripheral arterial tone (PAT)), ballistocardiography (BCG), cameras, radars, and accelerometers. Heart rate variability (HRV) and blood pressure (BP) emerged as the most promising metrics for RPM, offering a comprehensive view of ANS function and vascular health during sleep. While electrodes provide precise HRV data, they remain intrusive, whereas optical sensors such as PPG demonstrate potential for multimodal monitoring, including HRV, SpO2, and estimates of arterial stiffness and BP. Non-intrusive methods like BCG and cameras are promising for heart and respiratory rate estimation, but less suitable for continuous HRV monitoring. In conclusion, HRV and BP are the most viable metrics for RPM, with PPG-based systems offering significant promise for non-intrusive, continuous monitoring of multiple modalities. Further research is needed to enhance accuracy, feasibility, and validation against direct measures of autonomic function, such as microneurography.

Teacher noticing has been identified as central to enacting responsive and equitable mathematics instruction. Mathematics teachers' noticing is shaped by institutional and sociopolitical narratives and ideologies that persistently marginalize culturally, socially, linguistically, and neuro-diverse learners. Gaining insight into how one's noticing is related to these narratives can enable a teacher to identify and reflect on how they frame, attend to, and interpret classroom activity, and how that in turn can perpetuate or disrupt inequitable mathematics instruction. We conjectured that learning to systematically analyze and reflect on their own noticing can enable preservice mathematics teachers to develop their awareness of themselves as noticers to support more responsive and equitable instructional practice. Using data from summative assignments in a course focused on learning from teaching, we investigate whether and how preservice teachers (PSTs) take up frameworks for responsive and equitable teaching to narrate their noticing, and examine what their narrations reveal about how they frame mathematics instruction. Analysis reveals PSTs problematized instruction to adopt aspirational frames for equitable practice, while also re-narrating classroom interactions from dominant perspectives. These findings have implications for PSTs' learning to notice for equity and for designing teacher education experiences for this purpose.

This study investigates challenges of enactment teachers notice when analyzing artifacts of teaching in a professional development focused on supporting the enactment of NGSS-aligned modeling instruction. Five secondary science teachers participated in a semester-long video club. Transcripts of the segments of their meetings in which they analyzed artifacts of practice were coded to characterize what they noticed in videos and student work samples from their own and others' classrooms of students engaging in sensemaking. Through an inductive and iterative approach, three main linguistic challenges were identified related to the teachers' noticing of students' disciplinary thinking: learning how to communicate with precision using modeling conventions, how to communicate with precision using scientific vocabulary, and how to support students explaining and defending their models. The findings of this study extend and affirm prior research on teachers' noticing of student thinking by highlighting the integrated nature of disciplinary noticing and the entanglement of learning science concepts and the language of science. The results also indicate that artifact-rich professional development designed to improve science teachers' interpretation of their students' thinking can support teachers as they work through problems of practice they encounter in their attempts to enact responsive science teaching.

Learning to teach is rife with challenges. Preservice teachers' self-efficacy can potentially mitigate the stress of these challenges, and teacher education programs are fundamental in helping them build this important resource. As such, understanding the foundations of self-efficacy is important for researchers and teacher educators alike. Grounding our study in social network theory, we explored the relationship between sense of belonging to a teacher education program, network centrality, and self-efficacy. Our sample included 245 preservice teachers in three university teacher education programs. We found that sense of belonging to the program and network centrality (in-degree and out-degree) were significantly and positively related to preservice teachers' self-efficacy beliefs. This study builds on a growing literature that explores the relationships between preservice teachers' social networks and their beliefs and practices.

This study aims to examine coherence in a teacher preparation program relative to equity. Using performance assessments and artifacts from coursework, we explore how candidates define equity, what equitable practices they enact in their field placements, and whether a relationship exists between their conceptualizations and their practice. We found that candidates' conceptualizations of equity were characterized by five categories; however, their conceptualizations were varied and wide ranging. Findings also show that candidates emphasized attention to student thinking in their teaching, a practice often described in frameworks for ambitious mathematics teaching. Lastly, we found little evidence of consistency between candidates' conceptualizations and their instructional practices. The findings suggest a need to examine the coherence among various features of the teacher education program design and the experiences offered to candidates in these programs.

Background: Rare coagulation factor deficiencies and disorders of fibrinolysis (defined as rare bleeding disorders [RBDs]) present with a heterogeneous bleeding phenotype, and bleeding severity is difficult to predict. Objectives: Describe underlying rare genetic variants in the Dutch RBD population and investigate the relationship between genotype, laboratory phenotype, and clinical phenotype. Methods: The Rare Bleeding Disorders in the Netherlands is a cross-sectional, nationwide study conducted between October 1, 2017, and November 30, 2019. Bleeding scores and blood samples were collected during a single study visit. Coagulation factor levels were measured centrally, and targeted exome analysis was performed on 156 genes involved in thrombosis and hemostasis. Pathogenicity was assigned according to the Association for Clinical Genetic Science guidelines. Results: Rare genetic variants specific to the diagnosed RBD were found in 132 of 156 patients (85%). Of the 214 rare genetic variants identified, 57% (n = 123) were clearly pathogenic, 19% (n = 40) were likely pathogenic, and 24% (n = 51) were variants of unknown significance. No explanatory genetic variants were found in patients with plasminogen activator inhibitor type 1 deficiency or hyperfibrinolysis. A correlation existed between factor activity levels and the presence of a genetic variant in the corresponding gene in patients with rare coagulation factor deficiencies and alpha-2-antiplasmin deficiency. Co-occurrence of multiple genetic variants was present in a quarter of patients, but effect on phenotype remains unclear. Conclusion: Targeted exome analysis may offer advantages over single-gene analysis, emphasized by a number of combined deficiencies in this study. Further studies are required to determine the role of co-occurring hemostasis gene variants on the bleeding phenotype in RBDs.

Objectives: Distal radius malunion can result in pain and functional complaints. One of the functional problems that can affect daily life is impaired forearm rotation. The primary aim of this study was to investigate the effect of corrective osteotomy for distal radius malunion on forearm rotation at 12 months after surgery. We secondarily studied the effect on grip strength, radiological measurements, and patient-reported outcome measurements (PROMs). Patients and methods: This cohort study analysed prospectively collected data of adult patients with symptomatic distal radius malunion. All patients underwent corrective osteotomy for malunion and were followed for 1 year. We measured forearm rotation (pronation and supination) and grip strength and analysed radiographs. PROMs consisted of the Patient-Rated Hand/Wrist Evaluation (PRWHE) questionnaire, Visual Analogue Scale for pain, and satisfaction with hand function. Results: Preoperative total forearm rotation was 112° (SD: 34°), of which supination of 49° (SD: 25°) was more impaired than pronation of 63° (SD: 17°). Twelve months after surgery, an unpaired Student's t-test showed a significant improvement of total forearm rotation to 142° (SD: 17°) (p

Introduction Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.Trial registration number NCT06087952.

ObjectiveThis study explores the feasibility of ex-vivo high-field magnetic resonance (MR) imaging to create digital a three-dimensional (3D) representations of tongue cancer specimens, referred to as the “MR-based digital specimen” (MR-DS). The aim was to create a method to assist surgeons in identifying and localizing inadequate resection margins during surgery, a critical factor in achieving locoregional control.MethodsFresh resection specimens of nine tongue cancer patients were imaged in a 7 Tesla small-bore MR, using a high-resolution multislice and 3D T2-weighted Turbo Spin Echo. Two independent radiologists (R1 and R2) outlined the tumor and mucosa on the MR-images whereafter the outlines were configured to an MR-DS. A color map was projected on the MR-DS, mapping the inadequate margins according to R1 and R2. We compared the hematoxylin-eosin-based digital specimen (HE-DS), which is a histopathological 3D representation derived from HE stained sections, with its corresponding MR-images. In line with conventional histopathological assessment, all digital specimens were divided into five anatomical regions (anterior, posterior, craniomedial, caudolateral and deep central). Over- and underestimation 95th-percentile Hausdorff-distances were calculated between the radiologist- and histopathologist-determined tumor outlines. The MR-DS’ diagnostic accuracy for inadequate margin detection (i.e. sensitivity and specificity) was determined in two ways: with conventional histopathology and HE-DS as reference.ResultsUsing conventional histopathology as a reference, R1 achieved 77% sensitivity and 50% specificity, while R2 achieved 65% sensitivity and 57% specificity. When referencing to the HE-DS, R1 achieved 94% sensitivity and 61% specificity, while R2 achieved 88% sensitivity and 71% specificity. Range of over- and underestimation 95HD was 0.9 mm - 11.8 mm and 0.0 mm - 5.3 mm, respectively.ConclusionThis proof of concept for volumetric assessment of resection margins using MR-DSs, demonstrates promising potential for further development. Overall, sensitivity is higher than specificity for inadequate margin detection, because of the radiologist’s tendency to overestimate tumor size.

Background: MRI-guidance may aid better discrimination between Organs at Risk (OARs) and target volumes in proximity of the mediastinum. We report the first clinical experiences with Stereotactic Body Radiotherapy (SBRT) of (ultra)central lung tumours on a 1.5 T MR-linac. Materials and Methods: Patients with an (ultra)central lung tumour were selected for MR-linac based SBRT treatment. A T2-weighted 3D sequence MRI acquired during free breathing was used for daily plan adaption. Prior to each fraction, contours of Internal Target Volume (ITV) and OARs were deformably propagated and amended by a radiation oncologist. Inter-fractional changes in volumes and coverage of target volumes as well as doses in OARs were evaluated in offline and online treatment plans. Results: Ten patients were treated and completed 60 Gy in 8 or 12 fractions. In total 104 fractions were delivered. The median time in the treatment room was 41 min with a median beam-on time of 8.9 min. No grade ≥3 acute toxicity was observed. In two patients, the ITV significantly decreased during treatment (58 % and 37 %, respectively) due to tumour shrinkage. In the other patients, 81 % of online ITVs were within ±15 % of the volume of fraction 1. Comparison with the pre-treatment plan showed that ITV coverage of the online plan was similar in 52 % and improved in 34 % of cases. Adaptation to meet OAR constraints, led to decreased ITV coverage in 14 %. Conclusions: We describe the workflow for MR-guided Radiotherapy and the feasibility of using 1.5 T MR-linac for SBRT of (ultra) central lung tumours.

Background. Pulmonary endarterectomy (PEA) is the only definitive and potentially curative therapy for chronic thromboembolic pulmonary hypertension (CTEPH), associated with impressive improvements in symptoms and haemodynamics. However, it is only offered at a few centres in South Africa. The characteristics and outcomes of patients undergoing PEA in Cape Town have not been reported previously. Objectives. To assess the difference in World Health Organization functional class (WHO-FC) before and at least 6 weeks after surgery. Methods. We interrogated the adult cardiothoracic surgery database at the University of Cape Town between December 2005 and April 2021 for patients undergoing PEA at Groote Schuur Hospital and a private hospital. Results. A total of 32 patients underwent PEA, of whom 8 were excluded from the final analysis owing to incomplete data or a histological diagnosis other than CTEPH. The work-up of these patients for surgery was variable: all had a computed tomography pulmonary angiogram, 7 (29%) had a ventilation/perfusion scan, 5 (21%) underwent right heart catheterisation, and none had a pulmonary angiogram. The perioperative mortality was 4/24 (17%): 1 patient (4%) had a cardiac arrest on induction of anaesthesia, 2 patients (8%) died of postoperative pulmonary haemorrhage, and 1 patient (4%) died of septic complications in the intensive care unit. Among the survivors, the median (interquartile range) improvement in WHO-FC was 2 (1 - 3) classes (p=0.0004); 10/16 patients (63%) returned to a normal baseline (WHO-FC I). Conclusion. Even in a low-volume centre, PEA is associated with significant improvements in WHO-FC and a return to a normal baseline in survivors.

Abstract Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.

Background and aimsThrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients.MethodsLp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis.ResultsLp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61-5.81; p