Panoramic Tissue Examination That Integrates 3-Dimensional Pathology Imaging and Gene Mutation: Potential Utility in Non-Small Cell Lung Cancer.

Novel therapeutics have significantly improved the survival and quality of life of patients with malignancies in this century. Versatile precision diagnostic data were used to formulate personalized therapeutic strategies for patients. However, the cost of extensive information depends on the consumption of the specimen, raising the challenges of effective specimen utilization, particularly in small biopsies. In this study, we proposed a tissue-processing cascaded protocol that obtains 3-dimensional (3D) protein expression spatial distribution and mutation analysis from an identical specimen. In order to reuse the thick section tissue evaluated after the 3D pathology technique, we designed a novel high-flatness agarose-embedded method that could improve tissue utilization rate by 1.52 fold, whereas it reduced the tissue-processing time by 80% compared with the traditional paraffin-embedding method. In animal studies, we demonstrated that the protocol would not affect the results of DNA mutation analysis. Furthermore, we explored the utility of this approach in non-small cell lung cancer because it is a compelling application for this innovation. We used 35 cases including 7 cases of biopsy specimens of non-small cell lung cancer to simulate future clinical application. The cascaded protocol consumed 150-µm thickness of formalin-fixed, paraffin-embedded specimens, providing 3D histologic and immunohistochemical information approximately 38 times that of the current paraffin-embedding protocol, and 3 rounds of DNA mutation analysis, offering both essential guidance for routine diagnostic evaluation and advanced information for precision medicine. Our designed integrated workflow provides an alternative way for pathological examination and paves the way for multidimensional tumor tissue assessment.

Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases.

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.

Assessment of histological and immunohistochemical features of retinal tissues using a novel tissue submission procedure.

We introduce a novel tissue submission procedure without additional equipment or storage facilities for assessing the histological and immunohistochemical features of retinal tissues. In total, 150 specimens were collected from patients who underwent vitrectomy or macular surgery from January to December 2020. Ninety-eight specimens were submitted using the new procedure, and 58 specimens were submitted as flat-mount slides to compare specimen adequacy. The tissues submitted using the new procedure were subjected to paraffin-embedding and sectioning for hematoxylin & eosin staining. Additional immunohistochemical analysis was performed to assess the cellular composition in retinal tissues with diverse etiologies. The new submission procedure had an adequacy ratio of 75.51%, which was comparable to that of the flat-mount method (p = 0.1397). The new method could produce high-quality images of histological features of tissues and facilitated immunohistochemical analysis to demonstrate cell origins. More glial cells (p = 0.000) and myofibroblasts (p = 0.012) were detected in the epiretinal membranes (ERMs) than in the internal limiting membranes (ILMs). Subgroup analysis revealed that secondary ERMs contained more macrophage-like cells (p = 0.001) and retinal pigment epithelial cells (p = 0.000) than did idiopathic ERMs. Our novel tissue submission procedure can be applied to routine clinical practice. Our study provides additional histological and immunohistochemical evidence of cellular components in retinal tissues based on a large number of human tissue samples. Moreover, tissues submitted using the new method can be permanently preserved, enabling future investigation for potential prognostic or therapeutic targets.

A Novel Tactile Function Assessment Using a Miniature Tactile Stimulator.

Several methods for the measurement of tactile acuity have been devised previously, but unexpected nonspatial cues and intensive manual skill requirements compromise measurement accuracy. Therefore, we must urgently develop an automated, accurate, and noninvasive method for assessing tactile acuity. The present study develops a novel method applying a robotic tactile stimulator to automatically measure tactile acuity that comprises eye-opened, eye-closed training, and testing sessions. Healthy participants judge the orientation of a rotating grating ball presented on their index fingerpads in a two-alternative forced-choice task. A variable rotation speed of 5, 10, 40, or 160 mm/s was used for the tactile measurement at a variety of difficulties. All participants met the passing criteria for the training experiment. Performance in orientation identification, quantified by the proportion of trials with correct answers, differed across scanning directions, with the highest rotation speed (160 mm/s) having the worst performance. Accuracy did not differ between vertical and horizontal orientations. Our results demonstrated the utility of the pre-test training protocol and the functionality of the developed procedure for tactile acuity assessment. The novel protocol performed well when applied to the participants. Future studies will be conducted to apply this method to patients with impairment of light touch.

Computer-assisted three-dimensional quantitation of programmed death-ligand 1 in non-small cell lung cancer using tissue clearing technology.

Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 µm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 µm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1-49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

A Cationic Oligomer as an Organic Template for Direct Synthesis of Aluminosilicate ITH Zeolite.

There are a large number of zeolites, such as ITH, that cannot be prepared in the aluminosilicate form. Now, the successful synthesis of aluminosilicate ITH zeolite using a simple cationic oligomer as an organic template is presented. Key to the success is that the cationic oligomer has a strong complexation ability with aluminum species combined with a structural directing ability for the ITH structure similar to that of the conventional organic template. The aluminosilicate ITH zeolite has very high crystallinity, nanosheet-like crystal morphology, large surface area, fully four-coordinated Al species, and abundant acidic sites. Methanol-to-propylene (MTP) tests reveal that the Al-ITH zeolite shows much higher selectivity for propylene and longer lifetime than commercial ZSM-5. FCC tests show that Al-ITH zeolite is a good candidate as a shape-selective FCC additive for enhancing propylene and butylene selectivity.

Direct Synthesis of Aluminosilicate IWR Zeolite from a Strong Interaction between Zeolite Framework and Organic Template.

A large amount of zeolite structures are still not synthetically available or not available in the form of aluminosilicate currently. Despite significant progress in the development of predictive concepts for zeolite synthesis, accessing some of these new materials is still challenging. One example is the IWR structure as well. Despite successful synthesis of Ge-based IWR zeolites, direct synthesis of aluminosilicate IWR zeolite is still not successful. In this report we show how a suitable organic structure directing agent (OSDA), through modeling of an OSDA/zeolite cage interaction, could access directly the aluminum-containing IWR structure (denoted as COE-6), which might allow access to new classes of materials and thus open opportunities in valuable chemical applications. The experimental results reveal that the COE-6 zeolites with a SiO2/Al2O3 ratio as low as 30 could be obtained. Very interestingly, the COE-6 zeolite has much higher hydrothermal and thermal stabilities than those of the conventional Ge-Al-IWR zeolite. In methanol-to-propylene (MTP) reaction, the COE-6 zeolite exhibits excellent selectivity for propylene, offering a potential catalyst for MTP reaction in the future.

Large Scale Two-Dimensional Flux-Closure Domain Arrays in Oxide Multilayers and Their Controlled Growth.

Ferroelectric flux-closures are very promising in high-density storage and other nanoscale electronic devices. To make the data bits addressable, the nanoscale flux-closures are required to be periodic via a controlled growth. Although flux-closure quadrant arrays with 180° domain walls perpendicular to the interfaces (V-closure) have been observed in strained ferroelectric PbTiO3 films, the flux-closure quadrants therein are rather asymmetric. In this work, we report not only a periodic array of the symmetric flux-closure quadrants with 180° domain walls parallel to the interfaces (H-closure) but also a large scale alternative stacking of the V- and H-closure arrays in PbTiO3/SrTiO3 multilayers. On the basis of a combination of aberration-corrected scanning transmission electron microscopic imaging and phase field modeling, we establish the phase diagram in the layer-by-layer two-dimensional arrays versus the thickness ratio of adjacent PbTiO3 films, in which energy competitions play dominant roles. The manipulation of these flux-closures may stimulate the design and development of novel nanoscale ferroelectric devices with exotic properties.

Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft.

PURPOSE: The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690 nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma. METHODS: For phase 1, a total of six pigmented rabbits were treated with the indirect laser delivery system. The laser source was provided by the Lumenis Opal 690 nm laser unit, delivered through a 810 nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0 mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86 mg/kg, and two rabbits did not receive verteporfin (controls). A second phase of the study involved eight rabbits using a retinoblastoma xenograft to determine the effect of indirect PDT on subretinal tumors. RESULTS: For phase 1, a total of 20 laser treatments were performed in the right eyes of six rabbits. Laser power levels ranged between 40 and 150 mW/cm2 and treatment duration ranged between 1 and 3 min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40 mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75 mW/cm2 and higher power levels. Histopathology showed focal retino-choroidal scars at the site of PDT treatment, without evidence of generalized ocular damage. Using the retinoblastoma xenograft, the indirect PDT system was shown to cause areas of tumor necrosis on histopathology. CONCLUSIONS: The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690 nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40-50 mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75 mW/cm2 and higher power levels. Fundoscopic and histopathologic examination of treated areas showed circumscribed areas of retinal damage and a lack of generalized ocular toxicity, suggesting that this modality may represent a safe and localized method for treating intraocular retinoblastoma.

Utility-oriented placement of actuator nodes with a collaborative serving scheme for facilitated business and working environments.

Places to be served by cyber-physical systems (CPS) are usually distributed unevenly over the area. Thus, different areas usually have different importance and values of serving. In other words, serving power can be excessive or insufficient in practice. Therefore, actuator nodes (ANs) in CPS should be focused on serving around points of interest (POIs) with considerations of "service utility." In this paper, a utility-oriented AN placement framework with a collaborative serving scheme is proposed. Through spreading serving duties among correctly located ANs, deployment cost can be reduced, utility of ANs can be fully utilized, and the system longevity can be improved. The problem has been converted into a binary integer linear programming optimization problem. Service fading, 3D placements, multiscenario placements, and fault-tolerant placements have been modeled in the framework. An imitated example of a CPS deployment in a smart laboratory has been used for evaluations.

Design and characterization of a variable-stiffness ankle-foot orthosis.

BACKGROUND: Ankle-foot orthoses (AFOs) are a type of assistive device that can improve the walking ability of individuals with neurological disorders. Adjusting stiffness is a common way to customize settings according to individuals' impairment. OBJECTIVE: This study aims to design a variable-stiffness AFO by stiffness module and characterize the AFO stiffness range to provide subject-specific settings for the users. METHODS: We modeled AFO using bending beams with varying fulcrum positions to adjust the stiffness. To characterize the stiffness range and profile, we used the superposition method to generate the theoretical model to analyze the AFO numerically. The intrinsic deformation of the bending beam in the AFO is considered a combination of 2 bending deformations to replicate actual bending conditions. The corresponding experiments in different fulcrum positions were performed to compare with and optimize the theoretical model. The curve fitting method was applied to tune the theoretical model by adding a fulcrum position-related coefficient. RESULTS: The AFO stiffness increased as the fulcrum moved to the proximal position. The maximum stiffness obtained was 1.77 Nm/° at a 6-cm fulcrum position, and the minimum stiffness was 0.82 Nm/° at a 0.5-cm fulcrum position with a 0.43-cm thick fiberglass beam. The corresponding theoretical model had maximum and minimum stiffness of 1.71 and 0.80 Nm/°, respectively. The theoretical model had a 4.08% difference compared with experimental values. CONCLUSIONS: The stiffness module can provide adjustable stiffness with the fulcrum position and different kinds of fiberglass bars, especially the thickness and material of the beam. The theoretical model with different fulcrum positions can be used to profile the real-time stiffness of the AFO in a dynamic motion and to determine the appropriate dimensions of the bending beam.

Mechanical properties of freestanding few-layer graphene/boron nitride/polymer heterostacks investigated with local and non-local techniques.

van der Waals two-dimensional materials and heterostructures combined with polymer films continue to attract research attention to elucidate their functionality and potential applications. This study presents the fabrication and mechanical testing of 2D material heterostacks, consisting of few-layer boron nitride and graphene heterostructures synthesized via chemical vapor deposition, capped with a polymethyl methacrylate layer and suspended across ∼200 µm wide trenches using a combined wet-dry transfer method. The mechanical characterization of the heterostacks was performed using two independent approaches: (a) non-local testing with a custom-built tensile testing platform and (b) local load-displacement testing employing atomic force microscopy probes, complemented by finite element simulations. Both approaches provided new results, which are in good agreement with each other. Overall, our findings offer new insights into a combined load capacity in complex multi-material two-dimensional systems, and can contribute to advancing micro and nano-scale device designs and implementations.

The association of EGFR amplification with aberrant exon 20 insertion report using the cobas EGFR Mutation Test v2.

Determining the exact type of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation in lung cancer has become important. We found that not all ex20ins mutations reported by cobas EGFR test v2 could be validated by Sanger sequencing even using surgical specimens with high tumor contents. This study aimed to validate the ex20ins results reported by the cobas test and to determine whether there were clinicopathological factors associated with aberrant cobas ex20ins report. In total, 123 cobas-reported cases with ex20ins were retrospectively collected and validated by Sanger sequencing and Idylla assay. Clinicopathological features between ex20ins cobas+/Sanger+ group (n = 71) and cobas+/Sanger- group (n = 52) were compared. The Idylla assay detected ex20ins in 82.6% of cobas+/Sanger+ cases but only in 4.9% of cobas+/Sanger- cases. The cobas+/Sanger- group was significantly associated with higher tumor contents, poorly differentiated patterns, tumor necrosis, and a lower internal control cycle threshold value reported by the Idylla which suggesting the presence of increased EGFR gene copy numbers. EGFR fluorescence in situ hybridization (FISH) revealed the majority of cobas+/Sanger- group had EGFR high copy number gain (16%) or amplification (76%) according to the Colorado criteria. Among cases reported to have concomitant classic EGFR and ex20ins mutations by the cobas, the classic EGFR mutations were all detected by Sanger sequencing and Idylla, while the ex20ins mutations were undetected by Sanger sequencing (0%) or rarely reported by Idylla assay (3%). FISH revealed high EGFR copy number gain (17.9%) and amplification (79.5%) in cases reported having concomitant classic EGFR and ex20ins mutations by the cobas. This study demonstrated an unusually high frequency of EGFR amplification in cases with aberrant cobas ex20ins report which could not be validated by Sanger sequencing or Idylla assay. Ex20ins reported by the cobas test should be validated using other methods especially those reported having concomitant ex20ins and classic EGFR mutations.

The role of extensive lymph node dissection in the new grading system for lung adenocarcinoma.

OBJECTIVES: This study evaluates the prognostic impact of the new grading system for lung adenocarcinoma, stratified by lymphadenectomy extent. MATERIALS AND METHODS: We analyzed 1258 lung adenocarcinoma patients who underwent curative resections between 2006 and 2017. We analyzed overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) across tumor grades and lymphadenectomy extent, categorized as IASLC-R0 (complete resection) or R(un) (uncertain resection). RESULTS: The median age of cohort was 63 and 41.9 % were male. The majority had undergone lobectomy. The distribution of tumors was 274 grade 1, 558 grade 2, and 426 grade 3 cases. After a median follow-up time of 102 months, the 10-year OS/CSS/RFS rates worsened significantly across grade 1-3: 92.4/99.3/92.3 %, 77.8/87.5/71.7 %, and 63.6/70.2/52.0 %, respectively (p < 0.001). Multivariate Cox regression analysis identified grade 3, R(un) lymphadenectomy, higher Charlson Comorbidity Index, smoking history, thoracotomy, higher pathology stage, and angiolymphatic invasion as independent prognostic factors for lower OS, CSS, and RFS. Furthermore, grade 3 patients benefited significantly from IASLC-R0 lymphadenectomy, showing significantly better OS and RFS than those who underwent R(un) lymphadenectomy (p = 0.007 for OS, p = 0.001 for RFS, post-propensity score matching). Among grade 3 tumors underwent R0 or R(un) resections found the incidence rates of local, distant, and simultaneous local and distant recurrence were 8.5 % vs 13.7 %, 11.0 % vs 12.2 %, and 11.0 % vs 20.6 %, respectively. CONCLUSION: Surgical outcomes for lung adenocarcinoma have declined across grades 1-3. IASLC-R(un) treatment worsens OS and RFS in grade 3. Intensive monitoring and adjuvant therapy should be considered when patients with grade 3 lung adenocarcinoma undergo R(un) lymphadenectomy.

Mechanically Robust Interface at Metal/Muscovite Quasi van der Waals Epitaxy.

Quasi van der Waals epitaxy is an approach to constructing the combination of 2D and 3D materials. Here, we quantify and discuss the 2D/3D interface structure and the corresponding features in metal/muscovite systems. High-resolution scanning transmission electron microscopy reveals the atomic arrangement at the interface. The theoretical results explain the formation mechanism and predict the mechanical robustness of these metal/muscovite quasi van der Waals epitaxies. The evidence of superior interface quality is delivered according to the outstanding performance of the designed systems in both retention (>105 s) and cycling tests (>105 cycles) through electromechanical measurements. With high-temperature X-ray reciprocal space mapping, the unique anisotropy of thermal expansion is discovered and predicted to sustain the thermal stress with a sizable thermal actuation. A maximum bending curvature of 264 m-1 at 243 °C can be obtained in the silver/muscovite heteroepitaxy. The electrothermal and photothermal methods show a fast response to thermal stress and demonstrate the interface robustness.

Characteristics, treatment patterns, and clinical outcomes in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions.

PURPOSE: Epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) are associated with poor prognosis and resistance to traditional therapies in patients with non-small cell lung cancer (NSCLC). We aimed to elucidate the characteristics and treatment patterns to improve outcomes among this population in Taiwan. METHODS: Patients with advanced or recurrent NSCLC harboring EGFR ex20ins from 2011 to 2021 were reviewed. The treatment groups were classified as platinum-based chemotherapy (PtC), EGFR tyrosine kinase inhibitor (TKI), and others. The response to therapy, objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and factors associated with survival were analyzed. RESULTS: Among the 71 patients, most were never-smoking males with stage IVB adenocarcinoma. The most common first-line (1L) regimen was PtC, followed by TKI. The most common second-line (2L) regimen was TKI. The median PFS of 1L treatment was 5.03 months, and the median OS was 18.43 months. Compared with that of TKI, 1L PtC use was associated with a higher ORR (26.3% vs. 9.1%) and DCR (60.5% vs. 18.2%) and a longer PFS (5.37 vs. 3.13 months, p = 0.044). PFS was also significantly longer in the 2L PtC group than in the 2L TKI group (4.73 vs. 2.25 months, p = 0.047). No patients receiving an immune checkpoint inhibitor-based regimen exhibited a therapeutic response. CONCLUSION: This study demonstrated the heterogeneous clinical characteristics and treatment pattern of NSCLC patients with EGFR ex20ins, underscoring the need for more effective therapies for this distinct molecular subtype.

3D finite-element modeling of air-cell-based cushions and buttock tissues during prolonged sitting.

INTRODUCTION: Prolonged sitting can lead to serious health issues. Patients with spinal cord injuries may even develop pressure ulcers as stress accumulates on the ischial tuberosity. Air-cell-based (ACB) cushions have been shown to reduce tissue stress and help mitigate the effects of chronic sitting. Meanwhile, finite-element simulations have been implemented for different patient conditions. However, existing models are mostly two-dimensional with unrealistic simplifications. METHODS: A realistic three-dimensional multi-physics model with fewer artificial assumptions is presented. A commercial ACB cushion and an emulational buttock consisting of an actual hip bone and soft tissue (muscle, fat, and skin layers) were considered. Computational Fluid Dynamics and Transient Structural Analysis using ANSYS were utilized to simulate the ACB cushion during expansion and buttock tissue during sitting. RESULTS: Profile of airflow and pressure distributions caused by the airflow within the ACB cushion were computed when the air was pumped into the cells. Expansion of the ACB cushion was simulated, and an optimal inner pressure range (100-500 Pa) was determined. The human buttock sitting on the cushion was then simulated and visualized. CONCLUSIONS: The realistic three-dimensional model can accurately capture deformation and stress profiles pertinent to sitting on an ACB cushion. The model allows us to optimize the ACB cushions and operating conditions missing in previous studies. The model has also resolved several weaknesses in former models, such as the artificial air layers between air cells and unrealistically imposed internal pressure.

Blast-Related Traumatic Brain Injuries Secondary to Thermobaric Explosives: Implications for the War in Ukraine.

Blast-related traumatic brain injury (bTBI) is a significant cause of wartime morbidity and mortality. In recent decades, thermobaric explosives have emerged as particularly devastating weapons associated with bTBI. With recent documentation of the use of these weapons in the war in Ukraine, clinicians and laypersons alike could benefit from an improved understanding behind the dynamic interplay between explosive weaponry, its potential for bTBI, and the subsequent long-term consequences of these injuries. Therefore, we provide a general overview of the history and mechanism of action of thermobaric weapons and their potential to cause bTBI. In addition, we highlight the long-term cognitive and neuropsychiatric sequelae following bTBI and discuss diagnostic, therapeutic, and rehabilitation strategies, with the aim of helping to guide mitigation strategies and humanitarian relief in Ukraine. Thermobaric weapons produce a powerful blast wave capable of causing bTBIs, which can be further classified from primary to quaternary injuries. When modeling the hypothetical use of thermobaric weapons in Odessa, Ukraine, we estimate that the detonation of a salvo of thermobaric rockets has the potential to affect approximately 272 persons with bTBIs. In addition to the short-term damage, patients with bTBIs can present with long-term symptoms (e.g., post-traumatic stress disorder), which incur substantial financial costs and social consequences. Although these results are jarring, history has seen radical advancements in the understanding, diagnosis, and management of bTBI. Moving forward, a better understanding of the mechanism and long-term sequelae of bTBIs could help guide humanitarian relief to those affected by the war in Ukraine.