An arginine-rich nuclear localization signal (ArgiNLS) strategy for streamlined image segmentation of single cells.

High-throughput volumetric fluorescent microscopy pipelines can spatially integrate whole-brain structure and function at the foundational level of single cells. However, conventional fluorescent protein (FP) modifications used to discriminate single cells possess limited efficacy or are detrimental to cellular health. Here, we introduce a synthetic and nondeleterious nuclear localization signal (NLS) tag strategy, called "Arginine-rich NLS" (ArgiNLS), that optimizes genetic labeling and downstream image segmentation of single cells by restricting FP localization near-exclusively in the nucleus through a poly-arginine mechanism. A single N-terminal ArgiNLS tag provides modular nuclear restriction consistently across spectrally separate FP variants. ArgiNLS performance in vivo displays functional conservation across major cortical cell classes and in response to both local and systemic brain-wide AAV administration. Crucially, the high signal-to-noise ratio afforded by ArgiNLS enhances machine learning-automated segmentation of single cells due to rapid classifier training and enrichment of labeled cell detection within 2D brain sections or 3D volumetric whole-brain image datasets, derived from both staining-amplified and native signal. This genetic strategy provides a simple and flexible basis for precise image segmentation of genetically labeled single cells at scale and paired with behavioral procedures.

HoloTile light engine: new digital holographic modalities and applications.

HoloTile is a patented computer generated holography approach with the aim of reducing the speckle noise caused by the overlap of the non-trivial physical extent of the point spread function in Fourier holographic systems from adjacent frequency components. By combining tiling of phase-only of rapidly generated sub-holograms with a PSF-shaping phase profile, each frequency component-or output 'pixel'- in the Fourier domain is shaped to a desired non-overlapping profile. In this paper, we show the high-resolution, speckle-reduced reconstructions that can be achieved with HoloTile, as well as present new HoloTile modalities, including an expanded list of PSF options with new key properties. In addition, we discuss numerous applications for which HoloTile, its rapid hologram generation, and the new PSF options may be an ideal fit, including optical trapping and manipulation of particles, volumetric additive printing, information transfer and quantum communication.

4D dynamic spatial brain networks at rest linked to cognition show atypical variability and coupling in schizophrenia.

Despite increasing interest in the dynamics of functional brain networks, most studies focus on the changing relationships over time between spatially static networks or regions. Here we propose an approach to study dynamic spatial brain networks in human resting state functional magnetic resonance imaging (rsfMRI) data and evaluate the temporal changes in the volumes of these 4D networks. Our results show significant volumetric coupling (i.e., synchronized shrinkage and growth) between networks during the scan, that we refer to as dynamic spatial network connectivity (dSNC). We find that several features of such dynamic spatial brain networks are associated with cognition, with higher dynamic variability in these networks and higher volumetric coupling between network pairs positively associated with cognitive performance. We show that these networks are modulated differently in individuals with schizophrenia versus typical controls, resulting in network growth or shrinkage, as well as altered focus of activity within a network. Schizophrenia also shows lower spatial dynamical variability in several networks, and lower volumetric coupling between pairs of networks, thus upholding the role of dynamic spatial brain networks in cognitive impairment seen in schizophrenia. Our data show evidence for the importance of studying the typically overlooked voxel-wise changes within and between brain networks.

Multiprotein collagen/keratin hydrogel promoted myogenesis and angiogenesis of injured skeletal muscles in a mouse model.

Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p < 0.05). In the C2C12 myoblast-laden Col/Keratin group, a low number of CD31+ cells with minimum inflammatory cells was evident. Western blotting indicated the promotion of MyoD in mice that received cell-laden Col/Keratin hydrogel compared to the other groups (p < 0.05). Despite the increase of the myosin cell-laden Col/Keratin hydrogel group, no significant differences were obtained related to other groups (p > 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.

Volumetric Additive Manufacturing of SiOC by Xolography.

Additive manufacturing (AM) of ceramics has significantly contributed to advancements in ceramic fabrication, solving some of the difficulties of conventional ceramic processing and providing additional possibilities for the structure and function of components. However, defects induced by the layer-by-layer approach on which traditional AM techniques are based still constitute a challenge to address. This study presents the volumetric AM of a SiOC ceramic from a preceramic polymer using xolography, a linear volumetric AM process that allows to avoid the staircase effect typical of other vat photopolymerization techniques. Besides optimizing the trade-off between preceramic polymer content and transmittance, a pore generator is introduced to create transient channels for gas release before decomposition of the organic constituents and moieties, resulting in crack-free solid ceramic structures even at low ceramic yield. Formulation optimization alleviated sinking of printed parts during printing and prevented shape distortion. Complex solid and porous ceramic structures with a smooth surface and sharp features are fabricated under the optimized parameters. This work provides a new method for the AM of ceramics at µm/mm scale with high surface quality and large geometry variety in an efficient way, opening the possibility for applications in fields such as micromechanical systems and microelectronic components.

Activating Ion Channels in Collapsed Hydrogel Derived Densified MXene Films with Cellulose Nanofibers to Overcome the Areal Versus Volumetric Capacitance Trade-Off.

Concomitant achievement of all three performance pillars of a supercapacitor device, namely gravimetric, areal, and volumetric capacitance is a grand challenge. Nevertheless, its fulfilment is indispensable for commercial usage. Although, high compactness is the fundamental requirement to achieve high volumetric performance, it severely affects ion transportation in thick electrodes. Such trade-off makes it extremely challenging to realize very high areal and volumetric performance simultaneously. Here, a collapsed hydrogel strategy is introduced to develop MXene/cellulose nanofiber (CNF) based densified electrodes that offer excellent ion transportation despite a massive increase in areal mass loading (>70 mg cm-2). Quasi-oriented MXene/CNF (MXCF) hydrogels are produced through an electric field-guided co-assembly technique. Ambient dehydration of these hydrogels incorporates numerous pores in the resultant compact electrodes due to crumpling of the MXene sheets, while CNF ensures connectivity among the locally blocked pores in different length scales. The resultant collapsed MXCF densified electrode shows a remarkably high areal capacitance of 16 F cm-2 while simultaneously displaying a high volumetric capacitance of 849.8 F cm-3 at an ultrahigh mass loading of up to 73.4 mg cm-2. The universality of strategy, including the co-assembly of hydrogel and its collapse, is further demonstrated to develop high-performance asymmetric and wearable devices.

Cellular Patterning Alone Using Bioprinting Regenerates Articular Cartilage Through Native-Like Cartilagenesis.

Few studies have proved that bioprinting itself helps recapitulate native tissue functions mainly because the bioprinted macro shape can rarely, if ever, influence cell function. This can be more problematic in bioprinting cartilage, generally considered more challenging to engineer. Here a new method is shown to micro-pattern chondrocytes within bioprinted sub-millimeter micro tissues, denoted as patterned micro-articular-cartilages tissues (PA-MCTs). Under the sole influence of bioprinted cellular patterns. A pattern scoring system is developed after over 600 bioprinted cellular patterns are analyzed. The top-scored pattern mimics that of the isogenous group in native articular cartilage. Under the sole influence of this pattern during PA-MCTs bio-assembling into macro-cartilage and repairing cartilage defects, chondrogenic cell phenotype is preserved, and cartilagenesis is initiated and maintained. Neocartilage tissues from individual and assembled PA-MCTs are comparable to native articular cartilage and superior to cartilage bioprinted with homogeneously distributed cells in morphology, biochemical components, cartilage-specific protein and gene expression, mechanical properties, integration with host tissues, zonation forming and stem cell chondrogenesis. PA-MCTs can also be used as osteoarthritic and healthy cartilage models for therapeutic drug screening and cartilage development studies. This cellular patterning technique can pave a new way for bioprinting to recapitulate native tissue functions via tissue genesis.

A volumetric asymmetry study of gray matter in individuals with and without dyslexia.

Brain imaging work aimed at increased classification of dyslexia has underscored an important relationship between anterior (i.e., the inferior frontal gyrus; IFG) and posterior (i.e., superior temporal gyrus and supramarginal gyrus) brain regions. The extent to which the three components of the inferior frontal gyrus, namely the pars orbitalis, triangularis, and opercularis, are differentially related to the posterior regions, namely the superior temporal gyrus and supramarginal gyrus, needs further elucidation. Information about the nature of the anterior-posterior connections would facilitate our understanding of the neural underpinnings associated with dyslexia. Adult participants (N = 38; 16 with dyslexia) took part in an MRI study, whereby high-resolution structural scans were obtained. Volumetric asymmetry of the three regions of the IFG, the superior temporal gyrus, and the supramarginal gyrus was extracted. Significant differences were found for each of the three IFG regions, such that skilled readers had a greater leftward asymmetry of the orbitalis and triangularis, and greater rightward asymmetry of the opercularis, when compared to individuals with dyslexia. Furthermore, the pars triangularis was significantly associated with leftward asymmetry of the superior temporal gyrus for skilled but not dyslexic participants. For individuals with dyslexia, the cortical asymmetry of the IFG, and the corresponding connections with other reading-related brain regions, is inherently different from skilled readers. We discuss our findings in the context of the print-to-speech framework to further our understanding of the neural underpinnings associated with dyslexia.

Structural analysis of the female reptile reproductive system by micro-computed tomography and optical coherence tomography†.

Volumetric data provide unprecedented structural insight to the reproductive tract and add vital anatomical context to the relationships between organs. The morphology of the female reproductive tract in non-avian reptiles varies between species, corresponding to a broad range of reproductive modes and providing valuable insight to comparative investigations of reproductive anatomy. However, reproductive studies in reptilian models, such as the brown anole studied here, have historically relied on histological methods to understand the anatomy. While these methods are highly effective for characterizing the cell types present in each organ, histological methods lose the 3D relationships between images and leave the architecture of the organ system poorly understood. We present the first comprehensive volumetric analyses of the female brown anole reproductive tract using two non-invasive, non-destructive imaging modalities: micro-computed tomography (microCT) and optical coherence tomography (OCT). Both are specialized imaging technologies that facilitate high-throughput imaging and preserve three-dimensional information. This study represents the first time that microCT has been used to study all reproductive organs in this species and the very first time that OCT has been applied to this species. We show how the non-destructive volumetric imaging provided by each modality reveals anatomical context including orientation and relationships between reproductive organs of the anole lizard. In addition to broad patterns of morphology, both imaging modalities provide the high resolution necessary to capture details and key anatomical features of each organ. We demonstrate that classic histological features can be appreciated within whole-organ architecture in volumetric imaging using microCT and OCT, providing the complementary information necessary to understand the relationships between tissues and organs in the reproductive system. This side-by-side imaging analysis using microCT and OCT allows us to evaluate the specific advantages and limitations of these two methods for the female reptile reproductive system.

Volumetric analysis in primary and residual type B aortic dissection treated with stented-assisted balloon-induced intimal disruption and relamination technique can predict aortic reintervention.

OBJECTIVE: The aim of this study was to investigate the mid-term results of stented-assisted balloon-induced intimal disruption and relamination (STABILISE) in patients with aortic dissection with the implementation of volumetric analysis. METHODS: This was a single-center retrospective analysis of prospectively collected data. From May 2017 to September 2022, 42 patients underwent STABILISE for acute complicated or subacute high-risk aortic dissection. STABILISE was completed with distal extended endovascular aortic repair in 24 patients. A computed tomography scan was performed at baseline, before hospital discharge, and at 1, 3, and 5 years. Perfused total aortic, true lumen, and false lumen volumes were assessed for thoracic, visceral, and aorto-iliac segment. The ratio between false lumen and total volume was named perfusion dissection index (PDI). Complete remodeling was defined as PDI = 0, and positive remodeling as PDI ≤0.1. RESULTS: Technical success was 97.6%. No 30-day deaths, spinal cord injuries, or retrograde dissections were observed. Mean follow-up was 44 ± 19.4 months. Thoracic diameter was lower at last available computed tomography scan (36.7 vs 33.0 mm; P = .01). Aortic growth >5 mm was observed in 9.5% of the patients. Thoracic and visceral aortic complete remodeling were 92.8% and 83.3%, respectively, with no difference between acute and subacute group. Distal extended endovascular aortic repair significantly increased complete remodeling in the aorto-iliac segment, compared with STABILISE alone (69.6% vs 21.4%; P < .001). Freedom from vascular reinterventions at 3 years was 83.1% (95% confidence interval, 71.5%-96.6%). Total PDI ≤0.1 at first postoperative control was a predictor of vascular reinterventions (P < .0001). CONCLUSIONS: STABILISE is a safe and feasible technique associated with high mid-term rates of complete remodeling in the thoracic and visceral aorta. Volumetric analysis allows the quantification of aortic remodeling and represents a predictor of aortic reinterventions.

Proton therapy reduces the effective dose to immune cells in breast cancer patients.

BACKGROUND: The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC). MATERIALS AND METHODS: Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included. Mean dose to the heart (MHD), lungs (MLD), and liver (MlD), as well as the integral dose to the body (ITD), were retrieved, and we calculated EDIC as 0.12â€¯× MLD + 0.08â€¯× MHD + 0.15â€¯× 0.85â€¯× âˆš(n/45)â€¯× MlD + (0.45 + 0.35â€¯× 0.85â€¯× âˆš(n/45))â€¯× ITD/(62â€¯× 103), where n is the number of fractions. EDIC was compared between VMAT and IMPT plans. RESULTS: Median EDIC was reduced from 3.37 Gy (range: 2.53-5.99) with VMAT to 2.13 Gy (1.31-3.77) with IMPT (p < 0.01). For left-sided BC patients, EDIC was reduced from 3.15 Gy (2.53-3.78) with VMAT to 1.65 Gy (1.31-3.77) with IMPT (p < 0.01). For right-sided BC patients, EDIC was reduced from 5.60 Gy (5.06-5.99) with VMAT to 3.38 Gy (3.10-3.77) with IMPT (p < 0.01). Right-sided BC patients had a higher EDIC irrespective of the technique. Integral dose reduction was the main driver of EDIC reduction with IMPT and was associated with lung sparing for left-sided BC patients or liver sparing for right-sided BC patients. CONCLUSION: IMPT significantly reduced EDIC in BC patients undergoing locoregional adjuvant radiotherapy. Integral total dose reduction, associated with improved lung sparing in left-sided BC patients or liver sparing in right-sided BC patients, mainly drove EDIC reduction with IMPT. The emergence of dynamic models taking into account the circulatory kinetics of immune cells may improve the accuracy of the estimate of the dose received by the immune system compared to calculation of the EDIC, which is based solely on static dosimetric data.

Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Associations of Vitamins and Related Cofactor Metabolites with Mammographic Breast Density in Premenopausal Women.

BACKGROUND: Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There are, however, very limited data on the associations of dietary biomarkers and MBD. OBJECTIVE: We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women. METHODS: We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level. RESULTS: Participants' mean VPD was 10.5%. Two vitamin A metabolites (ß-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (γ-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of ß-cryptoxanthin (Q1 = 7.2%, Q2 = 7.7%, Q3 = 8.4%%, Q4 = 9.2%; P-trend = 1.77E-05, FDR P value = 1.18E-03). There was a decrease in the mean VPD across quartiles of γ-tocopherol (Q1 = 9.4%, Q2 = 8.1%, Q3 = 8.0%, Q4 = 7.8%; P -trend = 4.01E-03, FDR P value = 0.04). Seven metabolites were associated with NDV: 3 vitamin E (γ-CEHC glucuronide, δ-CEHC, and γ-tocopherol) and 1 vitamin C (gulonate) were positively associated, whereas 2 vitamin A (carotene diol 2 and ß-cryptoxanthin) and 1 vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV. CONCLUSION: We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.

Two is better than one: longitudinal detection and volumetric evaluation of brain metastases after Stereotactic Radiosurgery with a deep learning pipeline.

PURPOSE: Close MRI surveillance of patients with brain metastases following Stereotactic Radiosurgery (SRS) treatment is essential for assessing treatment response and the current disease status in the brain. This follow-up necessitates the comparison of target lesion sizes in pre- (prior) and post-SRS treatment (current) T1W-Gad MRI scans. Our aim was to evaluate SimU-Net, a novel deep-learning model for the detection and volumetric analysis of brain metastases and their temporal changes in paired prior and current scans. METHODS: SimU-Net is a simultaneous multi-channel 3D U-Net model trained on pairs of registered prior and current scans of a patient. We evaluated its performance on 271 pairs of T1W-Gad MRI scans from 226 patients who underwent SRS. An expert oncological neurosurgeon manually delineated 1,889 brain metastases in all the MRI scans (1,368 with diameters > 5 mm, 834 > 10 mm). The SimU-Net model was trained/validated on 205 pairs from 169 patients (1,360 metastases) and tested on 66 pairs from 57 patients (529 metastases). The results were then compared to the ground truth delineations. RESULTS: SimU-Net yielded a mean (std) detection precision and recall of 1.00±0.00 and 0.99±0.06 for metastases > 10 mm, 0.90±0.22 and 0.97±0.12 for metastases > 5 mm of, and 0.76±0.27 and 0.94±0.16 for metastases of all sizes. It improves lesion detection precision by 8% for all metastases sizes and by 12.5% for metastases < 10 mm with respect to standalone 3D U-Net. The segmentation Dice scores were 0.90±0.10, 0.89±0.10 and 0.89±0.10 for the above metastases sizes, all above the observer variability of 0.80±0.13. CONCLUSION: Automated detection and volumetric quantification of brain metastases following SRS have the potential to enhance the assessment of treatment response and alleviate the clinician workload.

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis.

BACKGROUND AND PURPOSE: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment. METHODS: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3 years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation-based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test, Timed 25-Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed-effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status. RESULTS: One hundred seventy patients had ≥1 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median = 27 vs. 22, p = 0.007). Among the new lesions (median = 2 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (ß = -0.04, 95% confidence interval [CI] = -0.07 to -0.01, p = 0.015; ß = -0.36, 95% CI = -0.67 to -0.06, p = 0.019, respectively). CONCLUSIONS: Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number.

Clinical validation of two volumetric absorptive microsampling devices to support home-based therapeutic drug monitoring of immunosuppression.

AIMS: Dried blood volumetric absorptive microsamples (VAMS) may facilitate home-based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography-tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso-M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated. METHODS: Clinical validation was performed for tacrolimus and mycophenolic acid by comparison of paired VAMS and venipuncture samples using Passing-Bablok regression and Bland-Altman analysis. Conversion of mycophenolic acid VAMS to serum concentrations was evaluated using haematocrit-dependent formulas and fixed correction factors defined a priori. Patients' perspectives, including useability, acceptability and feasibility, were also investigated using established questionnaires. RESULTS: Paired samples (n = 50) were collected from 25 kidney transplant recipients. Differences for tacrolimus whole-blood concentration were within ±20% for 86 and 88% of samples from the upper arm and fingerstick, respectively. Using correction factors of 1.3 for the upper-arm and 1.47 for finger-prick samples, 84 and 76% of the paired samples, respectively, were within ±20% for mycophenolic acid serum concentration. Patient experience surveys demonstrated limited pain and acceptable useability of the upper-arm device. CONCLUSIONS: Tacrolimus and mycophenolic acid can be measured using 2 common VAMS devices with similar analytical performance. Patients are supportive of home-based monitoring with a preference for the Tasso-M20 device.

Factors affecting peripheral neuropathy induced by nanoparticle albumin-bound paclitaxel in patients with pancreatic cancer.

AIM: Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity limiting the use of nab-paclitaxel (Nab-P) in treating patients with pancreatic cancer. The aim of this study was to identify the factors affecting CIPN using patient-reported outcome measures and the minimally invasive volumetric absorptive microsampling (VAMS) technique. METHODS: The maximum concentrations of paclitaxel (Cmax) were measured from 81 VAMS samples collected from 44 participants with pancreatic cancer. The association between CIPN development and demographic, clinical and pharmacokinetic factors was determined using univariable and multivariable logistic regression. The association between CIPN severity and the factors was evaluated using Spearman's rank correlation. The impact of Cmax and the number of treatment cycles on the severity was assessed using multivariable linear regression. RESULTS: The development of CIPN was significantly associated with cumulative dose (odds ratio 1.005, 95% confidence interval [CI] 1.003-1.007), treatment cycles (3.47, 2.25-5.85), alkaline phosphate (0.992, 0.985-0.998) and age (1.092, 1.020-1.179), with an area under the receiver operating characteristic curve of 0.89 (95% CI 0.83-0.95). The severity of CIPN significantly worsened with increasing cumulative dose (coefficient 0.58, 95% CI 0.44-0.69), treatment cycles (0.57, 0.44-0.68) and age (0.18, 0.00-0.35). The severity of CIPN was predictable from treatment cycles (P = .0002) and Cmax (P = .01). CONCLUSION: The higher the cumulative dose of Nab-P, treatment cycles and age, the more frequently and severely do the patients experience CIPN. In predicting the severity of CIPN using Cmax, minimally invasive VAMS is a feasible alternative to venous blood sampling.

Microporous tungsten oxide spheres coupled with Ti3C2Txnanosheets for high-volumetric capacitance supercapacitors.

In the contemporary landscape of technological advancements, the burgeoning demand for portable electronics and flexible wearable devices has necessitated the development of energy storage systems with superior volumetric performance. Tungsten oxide (WO3), known for its high density and theoretical capacitance, is a promising electrode material for supercapacitors. However, low conductivity and poor cycling stability are still the key bottlenecks for its application. Herein, a novel composite comprising hollow porous WO3 spheres (HPWS) derived by template method was electrostatic self-assembled on the surface of the Ti3C2Tx nanosheets. The resulting electrodes exhibited ultra-high volumetric capacitance of 1930 F cm-3 at 1 A g-1 and rate capability of 46% at 50 A g-1, attributed to enhanced ion accessibility from microporous structure and electron transport from conductive network of Ti3C2Tx even at a high packing density of 3.86 g cm-3. Utilizing HPWS/Ti3C2Tx as the negative electrode and porous carbon as the positive electrode, the assembled asymmetric supercapacitor achieved an energy density of 31 Wh kg-1 at a power density of 650 W kg-1 with over 107% capacitance retention after 5000 cycles. This work provides a promising approach for developing next-generation supercapacitors with ultra-high volumetric capacitance.

Factors to predict recurrence after epidural blood patch in patients with spontaneous intracranial hypotension.

OBJECTIVES: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). BACKGROUND: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. METHODS: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. RESULTS: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). CONCLUSION: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.

Advancing Global Health Surveillance of Mycotoxin Exposures using Minimally Invasive Sampling Techniques: A State-of-the-Science Review.

Mycotoxins are a heterogeneous group of toxins produced by fungi that can grow in staple crops (e.g., maize, cereals), resulting in health risks due to widespread exposure from human consumption and inhalation. Dried blood spot (DBS), dried serum spot (DSS), and volumetric tip microsampling (VTS) assays were developed and validated for several important mycotoxins. This review summarizes studies that have developed these assays to monitor mycotoxin exposures in human biological samples and highlights future directions to facilitate minimally invasive sampling techniques as global public health tools. A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted. Key assay performance metrics were extracted to provide a critical review of the available methods. This search identified 11 published reports related to measuring mycotoxins (ochratoxins, aflatoxins, and fumonisins) using DBS/DSS and VTS assays. Multimycotoxin assays adapted for DBS/DSS and VTS have undergone sufficient laboratory validation for applications in large-scale population health and human biomonitoring studies. Future work should expand the number of mycotoxins that can be measured in multimycotoxin assays, continue to improve multimycotoxin assay sensitivities of several biomarkers with low detection rates, and validate multimycotoxin assays across diverse populations with varying exposure levels. Validated low-cost and ultrasensitive minimally invasive sampling methods should be deployed in human biomonitoring and public health surveillance studies to guide policy interventions to reduce inequities in global mycotoxin exposures.