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.

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.

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.

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.

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.

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.

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.

In Situ Measurements of Strain Evolution in Graphene/Boron Nitride Heterostructures Using a Non-Destructive Raman Spectroscopy Approach.

The mechanical properties of engineered van der Waals (vdW) 2D materials and heterostructures are critically important for their implementation into practical applications. Using a non-destructive Raman spectroscopy approach, this study investigates the strain evolution of single-layer graphene (SLGr) and few-layered boron nitride/graphene (FLBN/SLGr) heterostructures. The prepared 2D materials are synthesized via chemical vapor deposition (CVD) method and then transferred onto flexible polyethylene terephthalate (PET) substrates for subsequent strain measurements. For this study, a custom-built mechanical device-jig is designed and manufactured in-house to be used as an insert for the 3D piezoelectric stage of the Raman system. In situ investigation of the effects of applied strain in graphene detectable via Raman spectral data in characteristic bonds within SLGr and FLBN/SLGr heterostructures is carried out. The in situ strain evolution of the FLBN/SLGr heterostructures is obtained in the range of (0-0.5%) strain. It is found that, under the same strain, SLG exhibits a higher Raman shift in the 2D band as compared with FLBN/SLGr heterostructures. This research leads to a better understanding of strain dissipation in vertical 2D heterostacks, which could help improve the design and engineering of custom interfaces and, subsequently, control lattice structure and electronic properties. Moreover, this study can provide a new systematic approach for precise in situ strain assessment and measurements of other CVD-grown 2D materials and their heterostructures on a large scale for manufacturing a variety of future micro- and nano-scale devices on flexible substrates.

Reliability and validity of the Chinese version of the kiddie-schedule for affective disorders and schizophrenia-present and lifetime version DSM-5 (K-SADS-PL-C DSM-5).

BACKGROUND: As the Diagnostic and Statistical Manual of Mental Disorders fifth version (DSM-5) was published, the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) was modified to adapt the new version (K-SADS-PL DSM-5). We translated it to Chinese (K-SADS-PL-C DSM-5) and described its reliability and validity. METHODS: A total of 154 groups of 6 to 18-year-old children and their guardians were included. Trained interviewers interviewed subjects using the K-SADS-PL-C DSM-5. Interrater reliability was assessed by audio recording. Parent-reported scales, like child behavior checklist (CBCL), the Chinese version of Swan-son Nolan and Pelham, version IV scale-parent form (SNAP-IV), social responsiveness scale (SRS-1), and children-reported scales like depression self-rating scale for children (DSRSC) and the screen for child anxiety related emotional disorders (SCARED) were used to examine the validity of depressive disorder, ADHD, ASD, and ODD. RESULTS: The K-SADS-PL-C DSM-5 had fair to excellent interrater (0.537-1.000) and test-retest (0.468-0.885) reliability of affective disorder and neurodevelopment disorder. The convergent validity of affective disorder and neurodevelopment disorder was good, and their divergent validity was acceptable. LIMITATIONS: i) Clinical questionnaires were insensitive in classifying disorders and had limitations in derived diagnoses. ii) Samples only came from clinical environment, iii) covered limited disease species, and iv) were small. CONCLUSION: The K-SADS-PL-C DSM-5 can support reliable and valid diagnoses for children with affect, neurodevelopmental, and behavioral disorders in China.

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.

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.

Outcomes of patients with different lepidic percentage and tumor size of stage I lung adenocarcinoma.

BACKGROUND: To evaluate the long-term outcomes after surgical resection for stage I lung adenocarcinoma based on the percentage of lepidic component (LC) and invasive tumor size (IS). METHODS: The clinicopathological characteristics of 1049 patients with stage I lung adenocarcinoma who underwent surgery between 2006 and 2016 were retrospectively reviewed. Tumors were categorized into groups: A (LC ≥ 50%) and B (LC < 50%). Groups A0 and A1 consisted of minimally invasive adenocarcinomas (MIA) and other lepidic-predominant invasive adenocarcinomas, respectively. Group B was categorized into B1 (IS ≤ 1 cm), B2 (1 < IS≤2 cm), and B3 (2 < IS≤3 cm) by invasive tumor size and divided into subgroups (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]) according to the presence[lep+] or absence[lep-] of LCs. Cumulative incidence of recurrence (CIR) and cancer-specific survival (CSS) were examined. RESULTS: LC decreased with increasing IS. Only 24 (8.5%) tumors in group A had an IS >1 cm. 10-year CIR and CSS were 15.2% and 86.0%. LC and IS were found to be independent predictors of CSS. Patients in group A had 1.4% 10-year CIR and 100% 10-year CSS. In group B, a significantly higher CIR and worse CSS were observed as IS increased (p < 0.001), but LC was not a predictor for CSS (p = 0.593). No significant differences in CIR or CSS were found in presence of LC or not when LC < 50% (B1[lep+]/[lep-], B2[lep+]/[lep-], and B3[lep+]/[lep-]: p = 0.36/0.48, p = 0.82/0.94, and p = 0.90/0.37, respectively). CONCLUSIONS: LC≥50% tumors demonstrated excellent prognosis regardless of IS. The outcomes of LC < 50% tumors were well predicted by IS, corresponding to the T-staging system. The predictive value of LC for prognosis became insignificant.

Chlorhexidine in the treatment of microsporidial stromal keratitis and the effect of host immunity: A case series and literature review.

Microsporidial stromal keratitis is an increasingly well-known vision-threatening disease. A large proportion of cases are initially misdiagnosed as herpes simplex keratitis and treated with topical steroids. In most of such cases, medical treatment failed, and corneal transplantation was required. This study reported the results of 0.02% topical chlorhexidine used to treat three cases of microsporidial stromal keratitis and reviewed the literature on the outcomes of microsporidial stromal keratitis treatment. In the first case, histopathology of a specimen from penetrating keratoplasty (PK) revealed severe chronic inflammation involving the entire stromal layer but no microorganism activity after the application of topical chlorhexidine for 10 months. The second case exhibited complete resolution of keratitis after topical chlorhexidine. The patient in the third case did not respond to medical treatment, and therapeutic PK was performed. Histopathological examination revealed numerous microsporidial spores that had colonized in the mid and deep stroma, where few inflammatory cells were observed. These findings explain the variable microsporidial susceptibility to chlorhexidine, suggesting the crucial role of host immunity. In cases of host immunity, topical chlorhexidine may represent a promising option for the treatment of microsporidial stromal keratitis.

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.

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.

Intraocular osseous metaplasia presenting as a solid mass in chronic retinal detachment: a case report.

BACKGROUND: Intraocular osseous metaplasia is a rare histological finding associated with benign cellular transformation. Its development requires inflammatory cytokines and the process takes many years. Previous case reports of intraocular ossification manifested as linear calcification or white plaques. In contrast, our case presented with a tumor-like solid mass, in which a long-standing chronic inflammatory stimulation may contribute to the stunning appearance. CASE PRESENTATION: This is a 48-year-old woman with past history of advanced Coat's-like retinopathy and chronic retinal detachment in the left eye for 12 years. She underwent vitreoretinal surgery to prevent phthisis bulbi. During the operation, a 9 mm solid mass was found embedded within the proliferative tissue above the retina and was removed. Pathological findings revealed bone formation in the center of the mass surrounded by fibrous metaplasia and focal gliotic changes. Layers of cohesive cells were found lining on the external side of the mass, and further immuno-histochemical study suggested them retinal pigment epithelial cells. Postoperatively, the retina was attached with stable visual acuity and normal intraocular pressure. CONCLUSION: To our knowledge, the appearance of a tumor-like mass representing intraocular osseous metaplasia in eyes with chronic inflammation or retinal detachment has not been reported in previous case reports. This case emphasizes the importance of considering osseous metaplasia as one of the differential diagnoses of an unknown intraocular mass, especially in eyes with great severity of chronic inflammation. Also, our immuno-histochemical study provided more evidence on the pathological role of retinal pigment epithelial cells in developing ossification.

Predicting Pharmacist Intention to Contribute to COVID-19 Management at the Community Level: A Cross-Sectional Survey Study.

Introduction: The role of pharmacists in public health management is expected to grow into a key player in the continuing measures of managing the COVID-19 pandemic, especially in the community setting. However, their intention to provide essential public health services for combating the pandemic and the impact of their attitude and beliefs are largely unknown. This study aimed to investigate the intention-to-practice COVID-19-related responsibilities of pharmacists based on the theory of planned behavior (TPB), identify the key factors predicting their intention, and explore the usefulness of the TPB model in predicting such an intention. Methods: A cross-sectional, self-administered questionnaire was completed by pharmacists in Macao between May and August 2020. Quantitative responses regarding intention-to-practice COVID-19-related duties, and the four TPB variables [attitude (A), subjective norms (SN), perceived behavioral control (PBC), and past behavior (PB)] were measured. Cronbach's alpha and composite reliability were used to determine the reliability and validity of the tool. In addition to descriptive statistics, Pearson's correlation was used to determine the strengths of the association, and multiple linear regression was used to predict the association between the intention and the four key variables. Results: More than half of the pharmacists practicing in Macao completed the questionnaire (296/520) giving a response rate of 56.9%. Among them, 75% were 26-40 years old and 56% were female. The majority of the participants (91.9%) demonstrated a positive intention to contribute to the COVID-19 infection management (mean = 4.19 ± 0.51). The mean scores for A, SN, PBC, and PB were 4.06 ± 0.52, 3.71 ± 0.58, 3.76 ± 0.65, and 4.03 ± 0.54, respectively. A (ß = 0.671), SN (ß = 0.608), PBC (ß = 0.563), and PB (ß = 0.829) were all positively correlated with intention (all P < 0.001). It was found that 72.5% of the variance in the intention-to-practice COVID-19-related duties could be explained by the TPB model using the four key variables with A and PB being two possible predictors. Conclusion: Pharmacists showed favorable A, SN, PBC, and intention in participating in COVID-19 management in the community setting. Specific training, enhanced stakeholder communication, and improved pharmacy management are essential to increase the willingness of pharmacists to take part in the COVID-19 pandemic and other public health emergencies alike in the future.

Bullous drug eruption after second dose of mRNA-1273 (Moderna) COVID-19 vaccine: Case report.

BACKGROUND: In December 2020, Moderna released the mRNA-1273 vaccine. The most common side effects are headache, muscle pain, redness, swelling, and tenderness at the injection site. In addition, there have been dermatological adverse events, such as hypersensitivity reactions. Although rare, various bullous eruptions have been described following vaccination. Bullous pemphigoid has been reported to occur most often after receipt of influenza and the diphtheria-tetanus-pertussis vaccine. To the best of our knowledge, there have been no reports of bullous drug eruptions resulting from mRNA vaccines. CASE SUMMARY: A 66-years-old obese Guyanese male presented with a bullous rash following receipt of a commercial COVID-19 mRNA vaccine. He received the first dose uneventfully. However, within 24 h of receiving the second dose, he developed fever, myalgias, and malaise accompanied by a painful blistering rash of his torso, arms, and legs. His fever and myalgias improved after 24 h, but his painful rash did not, and five days after the initial symptoms, he presented to the hospital. There were many violaceous, poorly demarcated patches on his trunk, arms, and thighs on examination, many of which had large flaccid bullae within, and a few areas on his buttocks, posterior shoulder, and scrotum were eroded. The exam was also significant for lower extremity muscle tenderness, stiffness with preserved strength. A skin biopsy showed epidermal necrosis and sparse perivascular dermatitis concerning Stevens-Johnson syndrome or erythema multiforme. However, in the absence of mucous membrane involvement or targetoid lesions, the diagnosis of an extensive bullous fixed drug eruption was made. CONCLUSION: This case illustrates that the bullae eruption occurred as a result of receiving the Moderna vaccination.