A brief bout of moderate intensity physical activity improves preadolescent children's behavioral inhibition but does not change their energy intake.

Children in rural communities consume more energy-dense foods relative to their urban peers. Identifying effective interventions for improving energy intake patterns are needed to address these geographic disparities. The primary aim of this study was to harness the benefits of physical activity on children's executive functioning to see if these improvements lead to acute changes in eating behaviors. In a randomized crossover design, 91 preadolescent (8-10y; M age = 9.48 ± 0.85; 50.5% female; 85.7% White, 9.9% Multiracial, 9.9% Hispanic) children (86% rural) completed a 20-minute physical activity condition (moderate intensity walking) and time-matched sedentary condition (reading and/or coloring) ~ 14 days apart. Immediately following each condition, participants completed a behavioral inhibition task and then eating behaviors (total energy intake, relative energy intake, snack intake) were measured during a multi-array buffet test meal. After adjusting for period and order effects, body fat (measured via DXA), and depressive symptoms, participants experienced significant small improvements in their behavioral inhibition following the physical activity versus sedentary condition (p = 0.04, Hedge's g = 0.198). Eating behaviors did not vary by condition, nor did improvements in behavioral inhibition function as a mediator (ps > 0.09). Thus, in preadolescent children, small improvements in behavioral inhibition from physical activity do not produce acute improvements in energy intake. Additional research is needed to clarify whether the duration and/or intensity of physical activity sessions would produce different results in this age group, and whether intervention approaches and corresponding mechanisms of change vary by individual factors, like age and degree of food cue responsivity.

Spectral Slope and Lempel-Ziv Complexity as Robust Markers of Brain States during Sleep and Wakefulness.

Nonoscillatory measures of brain activity such as the spectral slope and Lempel-Ziv complexity are affected by many neurological disorders and modulated by sleep. A multitude of frequency ranges, particularly a broadband (encompassing the full spectrum) and a narrowband approach, have been used especially for estimating the spectral slope. However, the effects of choosing different frequency ranges have not yet been explored in detail. Here, we evaluated the impact of sleep stage and task engagement (resting, attention, and memory) on slope and complexity in a narrowband (30-45 Hz) and broadband (1-45 Hz) frequency range in 28 healthy male human subjects (21.54 ± 1.90 years) using a within-subject design over 2 weeks with three recording nights and days per subject. We strived to determine how different brain states and frequency ranges affect slope and complexity and how the two measures perform in comparison. In the broadband range, the slope steepened, and complexity decreased continuously from wakefulness to N3 sleep. REM sleep, however, was best discriminated by the narrowband slope. Importantly, slope and complexity also differed between tasks during wakefulness. While narrowband complexity decreased with task engagement, the slope flattened in both frequency ranges. Interestingly, only the narrowband slope was positively correlated with task performance. Our results show that slope and complexity are sensitive indices of brain state variations during wakefulness and sleep. However, the spectral slope yields more information and could be used for a greater variety of research questions than Lempel-Ziv complexity, especially when a narrowband frequency range is used.

Skeletal Muscle Compliance and Echogenicity in Resistance-Trained and Nontrained Women.

ABSTRACT: Mongold, SJ, Ricci, AW, Hahn, ME, and Callahan, DM. Skeletal muscle compliance and echogenicity in resistance-trained and nontrained women. J Strength Cond Res 38(4): 671-680, 2024-Noninvasive assessment of muscle mechanical properties in clinical and performance settings tends to rely on manual palpation and emphasizes examination of musculotendinous stiffness. However, measurement standards are highly subjective. The purpose of the study was to compare musculotendinous stiffness in adult women with varying resistance training history while exploring the use of multiple tissue compliance measures. We identified relationships between tissue stiffness and morphology, and tested the hypothesis that combining objective measures of morphology and stiffness would better predict indices of contractile performance. Resistance-trained (RT) women (n = 11) and nontrained (NT) women (n = 10) participated in the study. Muscle echogenicity and morphology were measured using B-mode ultrasonography (US). Vastus lateralis (VL) and patellar tendon (PT) stiffness were measured using digital palpation and US across submaximal isometric contractions. Muscle function was evaluated during maximal voluntary isometric contraction (MVIC) of the knee extensors (KEs). Resistance trained had significantly greater PT stiffness and reduced echogenicity (p < 0.01). Resistance trained also had greater strength per body mass (p < 0.05). Muscle echogenicity was strongly associated with strength and rate of torque development (RTD). Patellar tendon passive stiffness was associated with RTD normalized to MVIC (RTDrel; r = 0.44, p < 0.05). Patellar tendon stiffness was greater in RT young women. No predictive models of muscle function incorporated both stiffness and echogenicity. Because RTDrel is a clinically relevant measure of rehabilitation in athletes and can be predicted by digital palpation, this might represent a practical and objective measure in settings where RTD may not be easy to measure directly.

Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells.

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.

A unifying theory explains seemingly contradictory biases in perceptual estimation.

Perceptual biases are widely regarded as offering a window into the neural computations underlying perception. To understand these biases, previous work has proposed a number of conceptually different, and even seemingly contradictory, explanations, including attraction to a Bayesian prior, repulsion from the prior due to efficient coding and central tendency effects on a bounded range. We present a unifying Bayesian theory of biases in perceptual estimation derived from first principles. We demonstrate theoretically an additive decomposition of perceptual biases into attraction to a prior, repulsion away from regions with high encoding precision and regression away from the boundary. The results reveal a simple and universal rule for predicting the direction of perceptual biases. Our theory accounts for, and yields, new insights regarding biases in the perception of a variety of stimulus attributes, including orientation, color and magnitude. These results provide important constraints on the neural implementations of Bayesian computations.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: calibration for reproducibility across echo times.

Background: Restriction Spectrum Imaging restriction score (RSIrs) is a quantitative biomarker for detecting clinically significant prostate cancer (csPCa). However, the quantitative value of the RSIrs is affected by imaging parameters such as echo time (TE). Purpose: The purpose of the present study is to develop a calibration method to account for differences in echo times and facilitate use of RSIrs as a quantitative biomarker for the detection of csPCa. Methods: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE∼75ms and once at TE=90ms (TEmin 1 , TEmin 2 , and TE90, respectively). A proposed calibration method, trained on patients without csPCa, estimated a linear scaling factor (f) for each of the four diffusion compartments (C) of the RSI signal model. A linear regression model was determined to match C-maps of TE90 to the reference C-maps of TEmin 1 within the interval ranging from 95 th to 99 th percentile of signal intensity within the prostate. RSIrs comparisons were made at 98 th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrs TE90corr ) and uncorrected TE90 (RSIrs TE90 ) to RSIrs from reference TEmin 1 (RSIrs TEmin1 ) and repeated TEmin 2 (RSIrs TEmin2 ). Calibration performance was evaluated with sensitivity, specificity, area under the ROC curve, positive predicted value, negative predicted value, and F1-score. Results: Scaling factors for C 1 , C 2 , C 3 , and C 4 were estimated as 1.70, 1.38, 1.03, and 1.19, respectively. In non-csPCa cases, the 98 th percentile of RSIrs TEmin2 and RSIrs TEmin1 differed by 0.27±0.86SI (mean±standard deviation), whereas RSIrs TE90 differed from RSIrs TEmin1 by 1.81±1.20SI. After calibration, this bias was reduced to -0.41±1.20SI, representing a 78% reduction in absolute error. For patients with csPCa, the difference was 0.54±1.98SI between RSIrs TEmin2 and RSIrs TEmin1 and 2.28±2.06SI between RSIrs TE90 and RSIrs TEmin1 . After calibration, the mean difference decreased to -0.86SI, a 38% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrs TEmin1 has a sensitivity of 66% and a specificity of 72%. Prior to calibration, RSIrs TE90 at the same threshold tended to over-diagnose benign cases (sensitivity 44%, specificity 88%). Post-calibration, RSIrs TE90corr performs more similarly to the reference (sensitivity 71%, specificity 62%). Conclusion: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 78% and 38% for non-csPCa and csPCa, respectively.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study.

OBJECTIVE: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery. DESIGN: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study. SETTING: Eight clinical sites in the US Pelvic Floor Disorders Network. POPULATION OR SAMPLE: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015. METHODS: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position. MAIN OUTCOME MEASURES: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest. RESULTS: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery. CONCLUSIONS: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors.

Sleep spindle maturity promotes slow oscillation-spindle coupling across child and adolescent development.

The synchronization of canonical fast sleep spindle activity (12.5-16 Hz, adult-like) precisely during the slow oscillation (0.5-1 Hz) up peak is considered an essential feature of adult non-rapid eye movement sleep. However, there is little knowledge on how this well-known coalescence between slow oscillations and sleep spindles develops. Leveraging individualized detection of single events, we first provide a detailed cross-sectional characterization of age-specific patterns of slow and fast sleep spindles, slow oscillations, and their coupling in children and adolescents aged 5-6, 8-11, and 14-18 years, and an adult sample of 20- to 26-year-olds. Critically, based on this, we then investigated how spindle and slow oscillation maturity substantiate age-related differences in their precise orchestration. While the predominant type of fast spindles was development-specific in that it was still nested in a frequency range below the canonical fast spindle range for the majority of children, the well-known slow oscillation-spindle coupling pattern was evident for sleep spindles in the adult-like canonical fast spindle range in all four age groups-but notably less precise in children. To corroborate these findings, we linked personalized measures of fast spindle maturity, which indicate the similarity between the prevailing development-specific and adult-like canonical fast spindles, and slow oscillation maturity, which reflects the extent to which slow oscillations show frontal dominance, with individual slow oscillation-spindle coupling patterns. Importantly, we found that fast spindle maturity was uniquely associated with enhanced slow oscillation-spindle coupling strength and temporal precision across the four age groups. Taken together, our results suggest that the increasing ability to generate adult-like canonical fast sleep spindles actuates precise slow oscillation-spindle coupling patterns from childhood through adolescence and into young adulthood.

Cells in the brain are wired together like an electric circuit that can relay information from one area of the brain to the next. Even when sleeping, the human brain continues to send signals to process information it has encountered during the day. This results in two patterns of electrical activity that define the sleeping brain: slowly repeating waves (or slow oscillations) and rapid bursts of activity known as sleep spindles. Although slow oscillations and sleep spindles are generated in different regions of the brain, they often happen at the same time. This syncing of activity is thought to help different parts of the brain to communicate with each other. Such communication is essential for new memories to become stable and last a long time. In children, slow oscillations and sleep spindles appear together less frequently, suggesting that these co-occurring patterns of electrical activity develop as humans grow into adults. Here, Joechner et al. set out to understand what drives slow oscillations and sleep spindles to start happening at the same time. The team used a technique called electroencephalography (or EEG for short) to study the brain activity of children, teenagers and adults as they slept. This revealed that slow oscillations and sleep spindles occur together less often in children compared to teenagers and adults. Moreover, the slow oscillations and sleep spindles observed in the children had very different physical characteristics to those observed in adults. Further analyses showed that the more similar the children's sleep spindles were to adult spindles, the more consistently they appeared at the same time as the slow oscillations. The findings of Joechner et al. suggest that as children grow up, their sleep spindles become more adult-like, causing the spindles to happen at the same time as slow oscillations more consistently. This indicates that brain circuits that generate sleep spindles may play an essential role in developing successful communication networks in the human brain. In the future, this work may ultimately provide new insights into how age-related changes to the brain contribute to cognitive development, and suggests sleep as a potential intervention target for neurodevelopmental disorders.

Restriction spectrum imaging with elastic image registration for automated evaluation of response to neoadjuvant therapy in breast cancer.

Purpose: Dynamic contrast-enhanced MRI (DCE) and apparent diffusion coefficient (ADC) are currently used to evaluate treatment response of breast cancer. The purpose of the current study was to evaluate the three-component Restriction Spectrum Imaging model (RSI3C), a recent diffusion-weighted MRI (DWI)-based tumor classification method, combined with elastic image registration, to automatically monitor breast tumor size throughout neoadjuvant therapy. Experimental design: Breast cancer patients (n=27) underwent multi-parametric 3T MRI at four time points during treatment. Elastically-registered DWI images were used to generate an automatic RSI3C response classifier, assessed against manual DCE tumor size measurements and mean ADC values. Predictions of therapy response during treatment and residual tumor post-treatment were assessed using non-pathological complete response (non-pCR) as an endpoint. Results: Ten patients experienced pCR. Prediction of non-pCR using ROC AUC (95% CI) for change in measured tumor size from pre-treatment time point to early-treatment time point was 0.65 (0.38-0.92) for the RSI3C classifier, 0.64 (0.36-0.91) for DCE, and 0.45 (0.16-0.75) for change in mean ADC. Sensitivity for detection of residual disease post-treatment was 0.71 (0.44-0.90) for the RSI3C classifier, compared to 0.88 (0.64-0.99) for DCE and 0.76 (0.50-0.93) for ADC. Specificity was 0.90 (0.56-1.00) for the RSI3C classifier, 0.70 (0.35-0.93) for DCE, and 0.50 (0.19-0.81) for ADC. Conclusion: The automatic RSI3C classifier with elastic image registration suggested prediction of response to treatment after only three weeks, and showed performance comparable to DCE for assessment of residual tumor post-therapy. RSI3C may guide clinical decision-making and enable tailored treatment regimens and cost-efficient evaluation of neoadjuvant therapy of breast cancer.

The need for an intersectionality framework in precision medicine research.

Precision medicine research has seen growing efforts to increase participation of communities that have been historically underrepresented in biomedical research. Marginalized racial and ethnic communities have received particular attention, toward the goal of improving the generalizability of scientific knowledge and promoting health equity. Against this backdrop, research has highlighted three key issues that could impede the promise of precision medicine research: issues surrounding (dis)trust and representation, challenges in translational efforts to improve health outcomes, and the need for responsive community engagement. Existing efforts to address these challenges have predominantly centered on single-dimensional demographic criteria such as race, ethnicity, or sex, while overlooking how these and additional variables, such as disability, gender identity, and socioeconomic factors, can confound and jointly impact research participation. We argue that increasing cohort diversity and the responsiveness of precision medicine research studies to community needs requires an approach that transcends conventional boundaries and embraces a more nuanced, multi-layered, and intersectional framework for data collection, analyses, and implementation. We draw attention to gaps in existing work, highlight how overlapping layers of marginalization might shape and substantiate one another and affect the precision-medicine research cycle, and put forth strategies to facilitate equitable advantages from precision-medicine research to diverse participants and internally heterogeneous communities.

The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats.

Chronic kidney disease (CKD) progression is associated with persisting oxidative stress, which impairs the NO-sGC-cGMP signaling cascade through the formation of oxidized and heme-free apo-sGC that cannot be activated by NO. Runcaciguat (BAY 1101042) is a novel, potent, and selective sGC activator that binds and activates oxidized and heme-free sGC and thereby restores NO-sGC-cGMP signaling under oxidative stress. Therefore, runcaciguat might represent a very effective treatment option for CKD/DKD. The potential kidney-protective effects of runcaciguat were investigated in ZSF1 rats as a model of CKD/DKD, characterized by hypertension, hyperglycemia, obesity, and insulin resistance. ZSF1 rats were treated daily orally for up to 12 weeks with runcaciguat (1, 3, 10 mg/kg/bid) or placebo. The study endpoints were proteinuria, kidney histopathology, plasma, urinary biomarkers of kidney damage, and gene expression profiling to gain information about relevant pathways affected by runcaciguat. Furthermore, oxidative stress was compared in the ZSF1 rat kidney with kidney samples from DKD patients. Within the duration of the 12-week treatment study, kidney function was significantly decreased in obese ZSF1 rats, indicated by a 20-fold increase in proteinuria, compared to lean ZSF1 rats. Runcaciguat dose-dependently and significantly attenuated the development of proteinuria in ZSF1 rats with reduced uPCR at the end of the study by -19%, -54%, and -70% at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo treatment. Additionally, average blood glucose levels measured as HbA1C, triglycerides, and cholesterol were increased by five times, twenty times, and four times, respectively, in obese ZSF1 compared to lean rats. In obese ZSF1 rats, runcaciguat reduced HbA1c levels by -8%, -34%, and -76%, triglycerides by -42%, -55%, and -71%, and cholesterol by -16%, -17%, and -34%, at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo. Concomitantly, runcaciguat also reduced kidney weights, morphological kidney damage, and urinary and plasma biomarkers of kidney damage. Beneficial effects were accompanied by changes in gene expression that indicate reduced fibrosis and inflammation and suggest improved endothelial stabilization. In summary, the sGC activator runcaciguat significantly prevented a decline in kidney function in a DKD rat model that mimics common comorbidities and conditions of oxidative stress of CKD patients. Thus, runcaciguat represents a promising treatment option for CKD patients, which is in line with recent phase 2 clinical study data, where runcaciguat showed promising efficacy in CKD patients (NCT04507061).

Glycome profiling and immunohistochemistry uncover changes in cell walls of Arabidopsis thaliana roots during spaceflight.

A large and diverse library of glycan-directed monoclonal antibodies (mAbs) was used to determine if plant cell walls are modified by low-gravity conditions encountered during spaceflight. This method called glycome profiling (glycomics) revealed global differences in non-cellulosic cell wall epitopes in Arabidopsis thaliana root extracts recovered from RNA purification columns between seedlings grown on the International Space Station-based Vegetable Production System and paired ground (1-g) controls. Immunohistochemistry on 11-day-old seedling primary root sections showed that ten of twenty-two mAbs that exhibited spaceflight-induced increases in binding through glycomics, labeled space-grown roots more intensely than those from the ground. The ten mAbs recognized xyloglucan, xylan, and arabinogalactan epitopes. Notably, three xylem-enriched unsubstituted xylan backbone epitopes were more intensely labeled in space-grown roots than in ground-grown roots, suggesting that the spaceflight environment accelerated root secondary cell wall formation. This study highlights the feasibility of glycomics for high-throughput evaluation of cell wall glycans using only root high alkaline extracts from RNA purification columns, and subsequent validation of these results by immunohistochemistry. This approach will benefit plant space biological studies because it extends the analyses possible from the limited amounts of samples returned from spaceflight and help uncover microgravity-induced tissue-specific changes in plant cell walls.

ReIGNITE Radiation Therapy Boost: A Prospective, International Study of Radiation Oncologists' Accuracy in Contouring Prostate Tumors for Focal Radiation Therapy Boost on Conventional Magnetic Resonance Imaging Alone or With Assistance of Restriction Spectrum Imaging.

PURPOSE: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation. METHODS AND MATERIALS: In this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without RSIrs maps. Participant volumes were compared to the consensus expert volumes. Contouring accuracy metrics included percent overlap with expert volume, Dice coefficient, conformal number, and maximum distance beyond expert volume. RESULTS: 1604 participant volumes were produced. 40 of 44 participants (91%) completely missed ≥1 expert-defined target lesion without RSIrs, compared to 13 of 44 (30%) with RSIrs maps. On conventional MRI alone, 134 of 762 contour attempts (18%) completely missed the target, compared to 18 of 842 (2%) with RSIrs maps. Use of RSIrs maps improved all contour accuracy metrics by approximately 50% or more. Mixed effects modeling confirmed that RSIrs maps were the main variable driving improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p < 0.001). CONCLUSIONS: Radiation oncologists struggle with accurately delineating visible PCa tumors on conventional MRI. RSIrs maps improve radiation oncologists' ability to target MRI-visible tumors for prostate tumor boost.

An evolutionary conserved division-of-labor between archicortical and neocortical ripples organizes information transfer during sleep.

Systems-level memory consolidation during sleep depends on the temporally precise interplay between cardinal sleep oscillations. Specifically, hippocampal ripples constitute a key substrate of the hippocampal-neocortical dialog underlying memory formation. Recently, it became evident that ripples are not unique to archicortex, but constitute a wide-spread neocortical phenomenon. To date, little is known about the morphological similarities between archi- and neocortical ripples. Moreover, it remains undetermined if neocortical ripples fulfill distinct functional roles. Leveraging intracranial recordings from the human medial temporal lobe (MTL) and neocortex during sleep, our results reveal region-specific functional specializations, albeit a near-uniform morphology. While MTL ripples synchronize the memory network to trigger directional MTL-to-neocortical information flow, neocortical ripples reduce information flow to minimize interference. At the population level, MTL ripples confined population dynamics to a low-dimensional subspace, while neocortical ripples diversified the population response; thus, constituting an effective mechanism to functionally uncouple the MTL-neocortical network. Critically, we replicated the key findings in rodents, where the same division-of-labor between archi- and neocortical ripples was evident. In sum, these results uncover an evolutionary preserved mechanism where the precisely coordinated interplay between MTL and neocortical ripples temporally segregates MTL information transfer from subsequent neocortical processing during sleep.

20-year Results of a 3D Titanium Mesh Coating Stability of 31 Artificial Cups. / 20-Jahres-Ergebnisse der Verbundfestigkeit einer aufgesinterten 3-D-Titannetzbeschichtung von 31 Hüftpfannen.

BACKGROUND: The aim of this work was to demonstrate the bony bond strength and resilience of a three-dimensional titanium mesh coating of an artificial acetabulum produced using the diffusion bonding technique. Under the extreme conditions ranging from abrasion-related osteolysis to acetabular perforation, the degree of residual bone and the integrity of the coating were determined. The remaining zones of the (still) stable bone connection are inevitably exposed to a greater load of the layer adhesion between the titanium mesh and the core shell. The investigation was intended to provide information about the stages of damage according to Paprosky in which it was still justifiable to leave the implant in place and simply change the inlay from the purely material-technical point of view of a stable coating. The bond between bone and implant was examined with regard to a possible retention of the implant for its adaptive remodeling up to 27 years. MATERIALS AND METHODS: In a retrospective study, 31 explanted human acetabular cups of the Harris-Galante II type, with an average lifetime of 19.7 years (11-27 years), were examined by means of digital area measurement to determine both the bone areas remaining on the coating and the damaged areas of the titanium mesh. Periacetabular bone loss was recorded in a modified Paprosky (PAP) damage classification. Full hemispherical sections of 4 acetabular cups with a life time of 16, 20, 22 and 27 years were examined histopathologically using the diamond cut technique. RESULTS: The periacetabular bone loss resulted in damage class PAP I in 8 cases, PAP IIa in 7 cases, PAP IIb in 2 cases, PAP IIc in 9 cases, PAP IIIa in 3 cases and PAP IIIa in 2 cases PAP IIIb. The average amount of bone that was still firmly attached to the coating after explantation was 17% (0-70%) of the total cup surface. Paprosky I accounted for 44.1%, and PAP IIa and IIb stadiums together a total of 17.1%. The average bone fraction of the implants no longer anchored in the host bed at stages IIc, IIIa and IIIb was 2%. The average coating damage was 11% (0-100%) and was exclusively attributable to the unstable implants of stages IIc, IIIa and IIIb. The histopathological findings showed adaptive bone remodeling, that was detectable for up to 27 years through the titanium mesh down to the interface with the solid acetabular core. The titanium wire mesh was mostly surrounded by lamellar, mature bone. CONCLUSION: The results show that the connection between the Tivanium cup and the previously oldest and unchanged sintered coating - in the form of a three-dimensional titanium mesh applied in point and line contact - is very load-resistant even under the extreme loads of periacetabular osteolysis and cup perforations. Since there was no damage to the coating in periacetabular damage stages Paprosky I, IIa and IIb, it is justifiable in these damage stages to leave the implant in situ and to continue to use it with sole replacement of the inlay, but leaving the socket shell. The third-generation acetabular cup (Trilogy) with unchanged three-dimensional titanium mesh coating has been implanted in over 1.2 million cases for 26 years. After a long service life, an increasing number of wear and tear conditions can be expected in today's mostly elderly and vulnerable patient clientele. In view of the results presented here, the early detection of damage would make it possible to avoid costly and stressful explantation of the entire acetabular cup in favor of replacing the sole inlay in Paprosky stages I, IIa and IIb.

Computed tomography of hyper-attenuated liver: Pictorial essay.

Demonstration of a very dense or hyper-attenuated liver on the pre-contrast CT images of the abdomen can be an unexpected finding. It may present as a diagnostic challenge if the underlying cause of it is not apparent from the provided clinical history. There are about 12 different pathologic conditions that are associated with deposition of radiopaque elements within the hepatic parenchyma, resulting in diffuse or multi-lobar hyperdense appearance of the liver on abdominal radiographs and CT. Most of them are drug-induced or iatrogenic in nature, while others are the sequelae of genetic disorders like thalassemia, Wilson's disease, and primary hemochromatosis. This pictorial essay will present the CT appearance and etiology of hyper-attenuated liver in various clinical entities.

Estimation of ground reaction force waveforms during fixed pace running outside the laboratory.

In laboratory experiments, biomechanical data collections with wearable technologies and machine learning have been promising. Despite the development of lightweight portable sensors and algorithms for the identification of gait events and estimation of kinetic waveforms, machine learning models have yet to be used to full potential. We propose the use of a Long Short Term Memory network to map inertial data to ground reaction force data gathered in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience: novice to highly trained runners (<15 min 5 km race), and ages ranging from 18 to 64 years old. Force sensing insoles were used to measure normal foot-shoe forces, providing the standard for identification of gait events and measurement of kinetic waveforms. Three inertial measurement units (IMUs) were mounted to each participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant's waistband, approximating their sacrum. Data input into the Long Short Term Memory network were from the three IMUs and output were estimated kinetic waveforms, compared against the standard of the force sensing insoles. The range of RMSE for each stance phase was from 0.189-0.288 BW, which is similar to multiple previous studies. Estimation of foot contact had an r 2 = 0.795. Estimation of kinetic variables varied, with peak force presenting the best output with an r 2 = 0.614. In conclusion, we have shown that at controlled paces over level ground a Long Short Term Memory network can estimate 4 s temporal windows of ground reaction force data across a range of running speeds.

Estimation of gait events and kinetic waveforms with wearable sensors and machine learning when running in an unconstrained environment.

Wearable sensors and machine learning algorithms are becoming a viable alternative for biomechanical analysis outside of the laboratory. The purpose of this work was to estimate gait events from inertial measurement units (IMUs) and utilize machine learning for the estimation of ground reaction force (GRF) waveforms. Sixteen healthy runners were recruited for this study, with varied running experience. Force sensing insoles were used to measure normal foot-shoe forces, providing a proxy for vertical GRF and a standard for the identification of gait events. Three IMUs were mounted on each participant, two bilaterally on the dorsal aspect of each foot and one clipped to the back of each participant's waistband, approximating their sacrum. Participants also wore a GPS watch to record elevation and velocity. A Bidirectional Long Short Term Memory Network (BD-LSTM) was used to estimate GRF waveforms from inertial waveforms. Gait event estimation from both IMU data and machine learning algorithms led to accurate estimations of contact time. The GRF magnitudes were generally underestimated by the machine learning algorithm when presented with data from a novel participant, especially at faster running speeds. This work demonstrated that estimation of GRF waveforms is feasible across a range of running velocities and at different grades in an uncontrolled environment.