Tractography with T1-weighted MRI and associated anatomical constraints on clinical quality diffusion MRI.

Diffusion MRI (dMRI) streamline tractography, the gold-standard for in vivo estimation of white matter (WM) pathways in the brain, has long been considered as a product of WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn to propagate streamlines directly from T1 and anatomical context. Training for this network has previously relied on high resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical scans. We define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. We show that under this metric T1 tractography generated by CoRNN reproduces diffusion tractography with approximately three millimeters of error.

Characterizing Low-cost Registration for Photographic Images to Computed Tomography.

Mapping information from photographic images to volumetric medical imaging scans is essential for linking spaces with physical environments, such as in image-guided surgery. Current methods of accurate photographic image to computed tomography (CT) image mapping can be computationally intensive and/or require specialized hardware. For general purpose 3-D mapping of bulk specimens in histological processing, a cost-effective solution is necessary. Here, we compare the integration of a commercial 3-D camera and cell phone imaging with a surface registration pipeline. Using surgical implants and chuck-eye steak as phantom tests, we obtain 3-D CT reconstruction and sets of photographic images from two sources: Canfield Imaging's H1 camera and an iPhone 14 Pro. We perform surface reconstruction from the photographic images using commercial tools and open-source code for Neural Radiance Fields (NeRF) respectively. We complete surface registration of the reconstructed surfaces with the iterative closest point (ICP) method. Manually placed landmarks were identified at three locations on each of the surfaces. Registration of the Canfield surfaces for three objects yields landmark distance errors of 1.747, 3.932, and 1.692 mm, while registration of the respective iPhone camera surfaces yields errors of 1.222, 2.061, and 5.155 mm. Photographic imaging of an organ sample prior to tissue sectioning provides a low-cost alternative to establish correspondence between histological samples and 3-D anatomical samples.

Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.

Increased risk of cardiac arrhythmia in Hailey-Hailey disease patients.

BACKGROUND: Hailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease. OBJECTIVE: To investigate the association between HHD and common heart disease in a Swedish, population-based cohort. METHODS: We conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers. RESULTS: Compared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0-2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6-1.7) or heart failure (RR 1.0, CI 0.6-1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset. CONCLUSION: This study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease.

The Clonal Hematopoiesis-associated Gene Srcap Plays an Essential Role in Hematopoiesis.

Somatic mutations arising in hematopoietic stem cells (HSCs) may provide the latter with a fitness advantage, allowing the mutant HSC to clonally expand. Such mutations have been recurrently identified in the chromatin modifier, SRCAP, in both non-malignant and leukemic clones, suggesting that this gene plays a significant role in hematopoiesis. We generated a conditional Srcap loss of function murine model and determined the consequences of hematopoietic-specific loss of this gene. We show that Srcap is essential for normal fetal liver erythropoiesis and monocytopoiesis. In Srcap deficient fetal livers, the number of phenotypic HSCs is similar to that of controls, but these HSCs exhibit a profound repopulating defect. Likewise, conditional deletion of Srcap during adult hematopoiesis results in a rapid loss of HSCs. Loss of Srcap is associated with evidence of increased DNA damage in HSCs and lineage-restricted progenitors as assessed by y-H2AX expression. Consistent with this finding, we observed strong transcriptional upregulation of the p53 pathway in Srcap deficient erythroid precursors. Collectively our data highlight the importance of Srcap in maintaining HSC function and supporting hematopoietic differentiation and suggests that it plays an essential role in maintaining genomic integrity.

Vestibular perceptual learning improves self-motion perception, posture, and gait in older adults.

Vestibular motion perception declines with age, increasing the risk of falling substantially. We performed a two-week perceptual learning intervention using a self-motion direction discrimination task (2800 training trials per person) on a 6 degrees of freedom motion platform in healthy older adults (n = 40, aged 70-88 yr). Linear inter-aural and angular roll tilt vestibular thresholds improved with training (95% credible interval for pre/post difference), suggesting altered sensitivity post-training. Moreover, improved perceptual abilities transfer to actual posture (reduced sway) and gait parameters. Passive self-motion discrimination training provides a new and promising way to counteract age-related sensory decline. It can reduce the risk of falling, and thereby maintain individual autonomy and quality of life.

Interface Nucleus Complementarity: An Iterative Process for the Discovery of Modular Intermetallics Guided by Chemical Pressure.

We present an iterative process for the discovery of modular intermetallic structures based on a recently developed interface nucleus approach. The process begins with the proposal of a suitable geometric motif that may serve as an interface nucleus. We then screen crystallographic databases for structures containing this motif as potential intergrowth partners. The extent to which pairs of these structures are likely to combine into more complicated assembles is then assessed with a new chemical pressure-based metric, interface nucleus complementarity (INC). Promising combinations of structures are translated into systems for synthesis, with new compounds providing either support for the importance of the original interface nucleus or new geometrical motifs for the next round of analysis. We demonstrate this process using a fragment derived from the σ-phase structure as a starting point, leading to the synthesis of PrMg4.13Zn10.20 and a new motif to seed the next cycle.

Parental Engagement With Children Around Firearms and Unsecure Storage.

This cross-sectional study analyzed the association between parents' engagement with their children regarding responsible and safe firearm use and the security of firearm storage in their homes.

Meditation-Based Therapies for Chronic Neuropathy: A Systematic Review and Meta-Analysis.

Mind-body therapies have been found to be effective in a variety of pathologies. The purpose of this study was to evaluate the efficacy of meditation-based therapies in relieving the symptoms severity, quality of life, stress and other associated mood conditions, in individuals with chronic neuropathy of various etiologies. A systematic review of randomized controlled trials, involving adult patients with persistent peripheral neuropathy, was performed. Seven article databases were searched. A meta-analysis was conducted to assess the benefits of meditation-based therapy on symptomatology, quality of life, anxiety, depression, perceived stress, sleep quality and mindfulness score. Ten of the 1133 reviewed papers were selected for quantitative review. The meditation group had a lower standardized mean difference (SMD) score (-0.47 (95% CI: -0.97 to 0.02), p=0.062) for neuropathic pain severity score; lower anxiety scores (-2.5 (95% CI: -3.68 to -1.32), p=<0.001); lower depression scores (-1.53 (95% CI: -2.12 to -0.93), p=<0.001); lower perceived stress (-1.06 (95% CI: -3.15 to 1.04), p=0.323); higher quality of life scores (2.19 (95% CI: -0.65 to 5.03), p=0.13); lower sleep quality scores (-1.27 (95% CI: -4.22 to 1.67), p=0.397); higher mindfulness scores (6.71 (95% CI: 4.09 to 9.33), p=<0.001); and lower pain severity at 1 to 1.5 follow up (-1.75 (95% CI: -2.98 to -0.51), p=0.006). Some of the results were characterized by a substantial, statistically significant heterogeneity. Nevertheless, a major part of the results pointed in the same direction, improving symptomatology with meditation-based therapy. The studies had a risk of bias mostly regarding the measurement of the outcome, randomization process and selection of the reported result. The current study discovered that the meditation group had significantly lower pain (at 1 to 1.5 months follow-up) anxiety, and depression scores and higher mindfulness scores at the end of the interventions.

Evaluation of epilepsy lesion visualisation enhancement in low-field MRI using image quality transfer: a preliminary investigation of clinical potential for applications in developing countries.

PURPOSE: Low-field (LF) MRI scanners are common in many Low- and middle-Income countries, but they provide images with worse spatial resolution and contrast than high-field (HF) scanners. Image Quality Transfer (IQT) is a machine learning framework to enhance images based on high-quality references that has recently adapted to LF MRI. In this study we aim to assess if it can improve lesion visualisation compared to LF MRI scans in children with epilepsy. METHODS: T1-weighted, T2-weighted and FLAIR were acquired from 12 patients (5 to 18 years old, 7 males) with clinical diagnosis of intractable epilepsy on a 0.36T (LF) and a 1.5T scanner (HF). LF images were enhanced with IQT. Seven radiologists blindly evaluated the differentiation between normal grey matter (GM) and white matter (WM) and the extension and definition of epileptogenic lesions in LF, HF and IQT-enhanced images. RESULTS: When images were evaluated independently, GM-WM differentiation scores of IQT outputs were 26% higher, 17% higher and 12% lower than LF for T1, T2 and FLAIR. Lesion definition scores were 8-34% lower than LF, but became 3% higher than LF for FLAIR and T1 when images were seen side by side. Radiologists with expertise at HF scored IQT images higher than those with expertise at LF. CONCLUSION: IQT generally improved the image quality assessments. Evaluation of pathology on IQT-enhanced images was affected by familiarity with HF/IQT image appearance. These preliminary results show that IQT could have an important impact on neuroradiology practice where HF MRI is not available.

TYPE III COLLAGEN REGULATES MATRIX ARCHITECTURE AND MECHANOSENSING DURING WOUND HEALING.

Post-natal cutaneous wound healing is characterized by development of collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. Herein, we demonstrate type III collagen (Col3) as a critical regulator of re-epithelialization and scar formation during healing of Col3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3B6/B6 mice), and Col3-deficient, scar-promoting (Col3F/F, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically-aligned collagen fibers that is dose-dependently suppressed by Col3. Further, loss of Col3 alters how cells interpret their microenvironment - their mechanoperception - such that Col3-deficient cells display mechanically-active phenotypes in the absence of increased microenvironmental stiffness via upregulation and engagement of the profibrotic integrin α11. Further understanding Col3's role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness pro-regenerative mechanisms.

Induction and maintenance of mucosal healing in Crohn's disease with ustekinumab in clinical practice across all care levels in Germany (MUCUS).

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials.

National Case Volumes and Gender Disparities in Emergency Department Utilization for Psychiatric Emergencies: A Population-Based Claims Data Analysis.

Introduction The utilization of emergency departments (EDs) for managing psychiatric emergencies has significantly increased in the United States because of the increasing prevalence of mental health disorders. This study examined national case volumes and sex disparities in ED visits for psychiatric emergencies using data from the Nationwide Emergency Department Sample (NEDS). Methods This retrospective analysis included adult ED visits for psychiatric emergencies identified using relevant International Classification of Diseases, 10th Revision (ICD-10) codes. Primary endpoints included national case volumes by sex. Hospitalizations with age < 18 years and those with missing data on sex were excluded. Secondary endpoints included inpatient mortality, ED and inpatient costs, admission rates, discharge disposition, length of stay (LOS), and number of procedures. Results In 2021, there were approximately 143.5 million ED visits in the United States, with 7,978,490 of these being for psychiatric emergencies. The most common presentations were substance abuse and intoxication (5,119,086 (64.2%)), severe bipolar disorder (1,912,670 (24%)), and anxiety or panic attacks (1,015,486 (12.7%)). Approximately 3,997,223 (50.1%) were women, and 3,981,267 (49.9%) were men. Men were older (mean age: 45 versus 43 years; P<0.001), were more likely to be uninsured (712,647 (17.9%) versus 497,658 (12.5%); P<0.001), and had a higher Charlson Comorbidity Index (CCI) (CCI ≥ 2: 792,272 (19.9%) versus 643,552 (16.1%); P<0.001). More men than women presented to the ED with acute substance abuse or intoxication (3,196,945 (80.3%) versus 1,922,142 (48.1%)), bipolar disorder with or without psychosis (958,275 (24.1%) versus 954,395 (23.9%); P<0.001), and suicidal ideation (267,638 (6.7%) versus 208,989 (5.2%); P<0.001). More women than men presented with severe depression (455,683 (11.4%) versus 441,921 (11.1%)), anxiety and panic attacks (615,572 (15.4%) versus 402,108 (10.1%)), acute stress reaction (35,975 (0.9%) versus 23,888 (0.6%)), eating disorders (3,997 (0.1%) versus 27,869 (0.07%)), and a history of abuse (21,164 (0.53%) versus 19,569 (0.49%); P<0.001). Women had lower mortality rates (27,980 (0.7%) versus 63,956 (1.6%); P<0.001), lower mean ED costs (adjusted mean difference (AMD): $1,189; P<0.001), fewer in-hospital admissions (1,211,158 (30.3%) versus 1,453,162 (36.5%); P<0.001), and a higher number of prolonged hospitalizations (1,442,998 (36.1%) versus 1,194,380 (30%); P<0.001) compared with men. Conclusion This study highlights significant sex disparities in ED utilization for psychiatric emergencies. Men more frequently present with substance abuse and severe comorbidities, leading to higher healthcare costs and inpatient admissions. Women, while more likely to present with anxiety and depressive disorders, incur lower costs and have better overall outcomes.

Concurrent ependymal and ganglionic differentiation in a subset of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement.

Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.

Differences in reasons for secure and unsecure firearm storage: Results from a representative cross-sectional study of nine states.

Objectives: To examine factors that differentiate firearm owners who endorse specific reasons for secure and unsecure firearm storage. Methods: A subsample of firearm-owning adults (n = 3,119) drawn from a representative sample of adults (n = 7,785) residing in nine US states participated in an online survey. Results: The most common reason for not always using a gun safe was concerns that they render firearms too slow to access during an emergency (60.2%). The most common reasons for current firearm storage were ensuring ready access in case of emergency (59.7%) and preventing access by children and adolescents (44.6%). Firearm owners varied on their reasons based upon current storage habits, reasons for ownership, and the presence of firearms in the home. Conclusions: Firearm owners with children in the home are more likely to select storage methods they feel will prevent access by vulnerable individuals, whereas those who own for defensive purposes and those who store firearms loaded and unlocked are more likely to endorse storing their firearms for quick home defense and convenience and to see gun safes as unnecessary obstacles.

The Impact of Double Pelvic Osteotomy on Dorsolateral Subluxation in 24 Dogs.

OBJECTIVE: The aim of this study was to determine the effect of double pelvic osteotomy (DPO) on dorsolateral subluxation (DLS) of the femoral head in a weight-bearing position. STUDY DESIGN: Retrospective observational study with treatment effect analysis. Twenty-four client-owned dogs that underwent DPO due to hip dysplasia. METHODS: Computed tomography (CT) studies were performed on 24 dogs that underwent a DPO between 2015 and 2021. The patients were positioned with the femora in a weight-bearing position. The DLS score was measured pre-DPO, immediately post-DPO, and at follow-up to determine if DPO resulted in an increase in the DLS score. RESULTS: A total of 21 dogs underwent single-stage bilateral DPO and 3 dogs underwent unilateral DPO resulting in 45 hip joints available for analysis. Follow-up CT was available for 29 of these at a median of 51 days (range: 35-482 days). The mean DLS score was 36.1% ± 14.6 preoperatively, 71.4% ± 12.5 post-DPO, and 70.0% ± 15.3 at follow-up. The increase between the pre- and postoperative measurement was significant (p < 0.001). CONCLUSION: DPO results in reduced subluxation of the femoral head in a weight-bearing position. CLINICAL SIGNIFICANCE: The in vivo results suggest that DPO will result in reduced femoral subluxation during weight-bearing.