Iterative Reconstruction of Micro Computed Tomography Scans Using Multiple Heterogeneous GPUs.

Graphics processing units (GPUs) facilitate massive parallelism and high-capacity storage, and thus are suitable for the iterative reconstruction of ultrahigh-resolution micro computed tomography (CT) scans by on-the-fly system matrix (OTFSM) calculation using ordered subsets expectation maximization (OSEM). We propose a finite state automaton (FSA) method that facilitates iterative reconstruction using a heterogeneous multi-GPU platform through parallelizing the matrix calculations derived from a ray tracing system of ordered subsets. The FSAs perform flow control for parallel threading of the heterogeneous GPUs, which minimizes the latency of launching ordered-subsets tasks, reduces the data transfer between the main system memory and local GPU memory, and solves the memory-bound of a single GPU. In the experiments, we compared the operation efficiency of OS-MLTR for three reconstruction environments. The heterogeneous multiple GPUs with job queues for high throughput calculation speed is up to five times faster than the single GPU environment, and that speed up is nine times faster than the heterogeneous multiple GPUs with the FIFO queues of the device scheduling control. Eventually, we proposed an event-triggered FSA method for iterative reconstruction using multiple heterogeneous GPUs that solves the memory-bound issue of a single GPU at ultrahigh resolutions, and the routines of the proposed method were successfully executed on each GPU simultaneously.

High-efficiency dual single layer graphene modulator integrated on slot waveguides.

This paper presents an experimental and theoretical investigation of a graphene-integrated electro-absorption modulator (EAM) based on a slot waveguide. Due to the enhanced light-matter interaction of graphene, the device exhibits an impressive modulation efficiency (0.038 dBµm-1V-1) and bandwidth (≈ 16 GHz). Starting from these results, we carried out an extensive design study, focusing on three crucial design parameters and exploring the associated trade-offs in insertion loss, extinction ratio and bandwidth. The simulation results offer valuable insights into the influence of each design parameter, reaffirming that our slot waveguide platform holds great promise for realizing a high-performance EAM balancing optical and electrical performance. It is important to note that the slot waveguide was defined through standard deep ultraviolet (DUV) lithography, allowing seamless integration into high-density systems.

Feasibility evaluation of middle-phase 18F-florbetaben positron emission tomography imaging using centiloid quantification and visual assessment.

Background: 18F-florbetaben (FBB) positron emission tomography (PET) scan has been widely used in research and routine clinical practice. Most studies used late-phase (scanning from 90 to 110 min after injection) FBB scans to generate beta-amyloid accumulation data. The feasibility of middle-phase scan is seldom discussed. Using the middle-phase data can shorten the patients' waiting between the injection and scan, and hospital can acquire more flexible schedule of routine scan. Methods: Paired middle-phase (60-80 min) FBB scans and standard (90-110 min) FBB scans were obtained from 27 subjects (12 neurodegenerative dementia, 8 mild cognitive impairment, 3 normal control, and 4 patients not suffering from neurodegenerative dementia). Standardized uptake value ratios (SUVRs) were calculated and converted to centiloid (CL) scale to investigate the impact on image quantification. CL pipeline validation were performed to build an equation converting the middle-phase data into equivalent standard scans. Cohen's kappa of binary interpretation and brain amyloid plaque load (BAPL) score were also used to evaluate the intrareader agreement of the FBB image from the two protocols. Results: The middle-phase FBB SUVR showed an excellent correlation, which provided a linear regression equation of SUVRFBB60-80 = 0.88 × SUVRFBB90-110 + 0.07, with R2=0.98. The slope of the equation indicated that there was bias between the middle and standard acquisition. This can be converted into the CL scale using CL = 174.68 × SUVR - 166.39. Cohen's kappa of binary interpretation and BAPL score were 1.0 (P<0.0001). Conclusions: Our findings indicate that the middle-phase FBB protocol is feasible in clinical applications for scans that are at either end of beta-amyloid spectrum, which provides comparable semiquantitative results to standard scan. Patient's waiting time between the injection and scan can be shortened.

Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer's disease transgenic mice.

Occurrence of amyloid-ß (Aß) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aß levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aß aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection.

Efficient pH-universal aqueous supercapacitors enabled by an azure C-decorated N-doped graphene aerogel.

Current aqueous supercapacitors (SCs) possess the relative low energy density, and there is therefore widespread interest in cost-effective fabrication of capacitive materials with promoted specific capacitance and/or broadened voltage window. Here, a redox-active azure C-decorated N-doped graphene aerogel (AC - NGA) is fabricated using a simple hydrothermal self-assembly method through strong noncovalent π-π interaction. AC - NGA highlights an excellent charge storage performance (a high 591F g-1 gravimetric capacitance under a current density of 1.0 A g-1 and ultrahigh voltage window of 2.3 V) under pH-universal conditions. The capacitive contribution of charge storage is 91.7%, exceeding or comparable to those of the best pseudocapacitors known. Furthermore, a symmetric AC - NGA//AC - NGA device realizes high energy and power densities (15.2-60.2 Wh kg-1 at 650-23,000 W kg-1) and excellent cycling stability in acidic, neutral, and basic aqueous solutions. This work offers a cost-effective strategy to combine redox dye molecules with heteroatom-doped graphene aerogel for building green efficient pH-universal aqueous supercapacitors.

Unveiling the molecular basis of inflamm-aging induced by advanced glycation end products (AGEs)-modified human serum albumin (AGE-HSA) in patients with different immune-mediated diseases.

Increased serum advanced glycation end products (AGEs) are commonly found in the patients with Diabetes mellitus (DM), aging-related diseases, and immune-mediated diseases. These diseases are notorious for vasculopathy, immune dysfunctions, and low-grade inflammation mimicking inflamm-aging. However, the molecular basis of inflamm-aging related to AGEs remains elucidation. In this study, we incubated human serum albumin (HSA) and glucose at 37 °C in 5% CO2 incubator for 0-180 days to generate AGE-HSA. We found the mixture gradually changing the color from transparancy to brown color and increased molecular weight during incubation. The pH value also gradually decreased from 7.2 to 5.4 irrelevant to ionic charge or [Ca2+] concentration, but dependent on gradual glycation of the alkaline amino acids, lysine and arginine. Functionally, 40 µg/mL of AGE-HSA decreased IL-2 production from human Jurkat T cell line via suppressing p-STAT3, p-STAT4, and p-STAT6 with an increased tendency of senescence-associated ß-galactosidase (SA-ßgal) expression but irrelevant to change of Th1/Th2/Treg subpopulations. In contrast, AGE-HSA enhanced CC motif chemokine ligand 5 (CCL-5), IL-8, macrophage migration inhibitor factor (MIF), and interleukin 1 receptor antagonist (IL-1Ra) but suppressed SA-ßgal expression by human macrophage-like THP-1 cells. Interestingly, AGE-HSA abrogated the HSA-induced soluble intercellular adhesion molecules 1 (sICAM-1), sE-selectin and endothelin release from human coronary artery endothelial cells (HCAEC) and enhanced SA-ßgal expression. The accelerated and increased HSA glycations by individual inflammation-related cytokine such as IL-2, IL-6, IL-17, TGF-ß, or TNF-α in the in vitro study reflect increased serum AGE levels in patients with immune-mediated diseases. In conclusion, AGE-HSA can exert immunosuppresive, inflammatory and vasculopathic effects mimicking inflamm-aging in these patients.

40.1-GHz sub-freezing 850-nm VCSEL: microwave extraction of cavity lifetimes and small-signal equivalent circuit modeling.

We present an 850-nm vertical-cavity surface-emitting laser (VCSEL) constructed for a wide operating temperature range from 25°C to -50°C sub-freezing temperature, demonstrating 40.1-GHz at -50°C. The optical spectra, junction temperature, and microwave equivalent circuit modeling of a sub-freezing 850-nm VCSEL between -50°C and 25°C are also discussed. Reduced optical losses, higher efficiencies, and shorter cavity lifetimes at sub-freezing temperatures are the leading causes of the improved laser output powers and bandwidths. The e-h recombination lifetime and the cavity photon lifetime are shortened to 113 and 4.1 ps, respectively. Could potentially supercharge VCSEL-based sub-freezing optical links for applications in frigid weather, quantum computing, sensing, aerospace, etc.

Immunoprofile of adenosquamous carcinoma in gastric cancer.

BACKGROUND: Gastric adenosquamous carcinoma (GASC) is a rare subtype of gastric cancer. Research on GASC treatment is limited, and its outcome is usually poor. We investigated the clinical features, immunoprofile of GASC, and determined the optimal treatment modality for these patients. METHODS: Patients with GASC from Taipei Veterans General Hospital were retrospectively reviewed. Clinical features and treatment outcomes were evaluated. Adequate samples were examined for surrogate biomarkers for immunotherapy by IHC staining. RESULTS: Total 14 (0.35%) GASC patients were found among 4034 gastric cancer patients. The median tumor size was 6.8 cm in 10 patients with stage III GASC, and all these patients underwent radical gastrectomy followed by adjuvant therapy. The median progression-free survival (PFS) and overall survival (OS) were 6.0 and 11.5 months, respectively. Two patients with stage IV GASC received frontline immunotherapy. Their median PFS and OS were 9.0 and 12.5 months. In immunoprofiling, 25.0% (n = 3), 75.0% (n = 9), and 33.3% (n = 4) of the samples had deficient mismatch repair (dMMR) protein, combined positive score (CPS) of ≥1, and CPS of ≥10, respectively. The univariate analysis revealed that programmed death-ligand 1 ≥5% (HR: 0.12; 95% CI: 0.01-0.97; p = 0.047) was significant associated with superior OS. One stage IV patient with CPS ≥10 and dMMR proteins received nivolumab monotherapy as frontline treatment that resulted 14-month PFS. CONCLUSION: Patients with GASC are more likely to yield positive results for CPS and dMMR. Biomarkers should be examined, and immunotherapy can be considered as frontline systemic treatment.

Case Report: A case of PLA2G6 gene-related early-onset Parkinson's disease and review of literature.

Background: Early onset Parkinson's disease (EOPD) is a neurodegenerative disease associated with the action ofto genetic factors. A mutated phospholipase A2 type VI gene (PLA2G6) is considered to be one of pathogenic genes involved in EOPD development. Although EOPD caused by a mutated PLA2G6 has been recorded in major databases, not all mutant genotypes have been reported. Here, we report a case of PLA2G6-related EOPD caused by a novel compound heterozygous mutation. Case presentation: The case was an of 26-year-old young male with a 2-year course of disease. The onset of the disease was insidious and developed gradually. The patient presented with unsteady walking, bradykinesia, unresponsiveness, and decreased facial expression. Auxiliary examination showed a compound heterozygous mutation of the PLA2G6gene with c.991G > T and c.1427 + 1G > A. Mild atrophy of the cerebrum and cerebellum was detected on brain MRI. The patient was diagnosed with EOPD. We administered treatment with Madopar, which was effective. After a two-year disease course, we observed progression to stage 5 according to the Hoehn-Yahr Scale (without medicine in the off-stage). An MDS-UPDRS III score of 62 was obtained, with characteristics of severe disease and rapid progress. The diagnosis was an EOPD phenotype caused by a combination of mutations at the c.991G > T and c.1427 + 1G > A sites of the PLA2G6gene. Conclusion: After active treatment, the disease was set under control, with no significant progression during the three-month follow-up period. Dyskinesia did not recur after reducing the Madopar dose. The freezing sign was slightly decreased and the wearing-off was delayed to 2 h.

Poly(azure C)-coated CoFe Prussian blue analogue nanocubes for high-energy asymmetric supercapacitors.

Prussian blue analogues are considered as promising supercapacitor electrode materials due to their high theoretical capacitance and low cost. Yet, they suffer from poor electronic conductivity and cycling life. Here, a redox dye polymer, poly(azure C) (PAC), is in-situ grown uniformly on CoFe Prussian blue analogue (CoFePBA). As a polymer mediator, the PAC coating on each PBA not only enhances the electronic conductivity and surface area, but also improves the structural stability and specific capacitance of PBA. As a result, the optimized CoFePBA@PAC possesses ultrahigh specific capacitance (968.67 F g-1 at 1 A g-1), superior rate performance (665.78 F g-1 at 10 A g-1), and excellent long-cycling stability (92.45% capacity retention after 2000 cycles). As an application, a fabricated CoFePBA@PAC//AC asymmetric supercapacitor (AC = activated carbon) maintains 84.7% capacitance retention in 2000 cycles at 1 A g-1 and displays a superior specific energy of 29.16 W h kg-1 at the power density of 799.78 W kg-1. These results demonstrate that redox dye polymer-coated PBAs with outstanding performance have a promising prospect in the field of energy storage.

A modified method of augmented distal clavicle fracture osteosynthesis with a Fibertape coracoclavicular cerclage.

BACKGROUND: Unstable distal clavicles experience high non-union rates, prompting surgeons to recommend surgery for more predictable outcomes. There is a lack of consensus on the optimal method of surgical fixation, with an array of techniques described in the literature. We describe an alternative method of fixation involving the use of a distal clavicular anatomical locking plate with Fibertape cerclage augmentation in our series of patients. METHODS: Nine patients (8 males and 1 female), with a mean age of 36 years, who sustained unstable fracture of the distal clavicle in our institution were treated with our described technique. Postoperative range of motion, functional and pain scores, and time to radiographic union were measured over a mean follow-up period of 10 months. Incidences of postoperative complications were also recorded. RESULTS: At the last patient consult, the mean visual analog scale score was 0.88±0.35, with a mean Disabilities of the Arm, Shoulder, and Hand (DASH) score of 1.46±0.87 and American Shoulder and Elbow Surgeons (ASES) score of 94.1±3.57. The mean range of motion achieved was forward flexion at 173°±10.6°, abduction at 173°±10.6°, and external rotation at 74.4°±10.5°. All patients achieved internal rotation at a vertebral height of at least L2 with radiographical union at a mean of 10 weeks. No removal of implants was required. CONCLUSIONS: Our described technique of augmented fixation of the distal clavicle is effective, produces good clinical outcomes, and has minimal complications.

Does minimally invasive spine surgery reduce surgical site infection rates in the trauma patient? A Southeast Asian experience.

Introduction: The trauma patient has an increased susceptibility to postoperative surgical site infection (SSI). There is a lack of studies in the literature investigating the rates of SSI in minimally invasive spine (MIS) surgery for trauma patients with associated injuries, who also require surgical intervention for thoracolumbar fractures. We aim to investigate if MIS surgery for trauma patients reduces the incidence of SSI through a less invasive approach and smaller surgical incision. Methods: A case series of 30 trauma patients who underwent MIS surgery for thoracolumbar spine fractures at our center were followed up for a year. The primary outcome measured was the presence of a postoperative SSI. Subgroup analysis was performed to determine if there were specific factors that increase the risk of developing a SSI. Results: In total, 4 (13%) patients developed postoperative SSI out of which 1 was a deep infection (3%). Subgroup analysis of both patient and surgical factors did not demonstrate statistically significant results to suggest risk factors for SSI post-MIS surgery in our patient group. Conclusion: Our series of patients did not reflect a lower incidence of SSI with MIS surgery compared to incidences in the literature. This may suggest that the increased rates of SSI in the trauma patient may not be best addressed by a minimally invasive approach alone. A multidisciplinary approach that addresses other factors - such as prolonged recumbence and a compromised immunological state may yield improved results.

Clinical Features and Immunophenotypes of Double-Hit Diffuse Large B-Cell Lymphoma.

Double-hit (DH) genetics induces a reduction in the complete remission (CR) and, consequently, in poor overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Unfortunately, DH identification is time-consuming. Here, we retrospectively reviewed 92 newly diagnosed DLBCL patients, stratified them into the DH (n = 14) and non-DH groups (n = 78), and compared their clinical features and outcomes. The results revealed that the DH group had a higher percentage of bulky disease than the non-DH group (64.3% vs. 28.2%; p = 0.013). More patients in the DH group tested positive for double expresser (DE) (50.0% vs. 21.8%; p = 0.044). The three-year OS rates of patients with and without DH were 33.3% and 52.2%, respectively (p = 0.016). Importantly, advance stage and multiple comorbidities were correlated with a high mortality rate in multivariate analysis. Furthermore, by combining DE and the bulky disease, a specificity of 89.7% for DH prediction was achieved. In summary, DH genetics, not DE immunopositivity, could be a factor for an inferior OS in DLBCL. A combination of bulky disease and a positive DE immunophenotype could facilitate DH genetics prediction in newly diagnosed DLBCL patients.

Association Between Depression and Risk of Incident Cardiovascular Diseases and Its Sex and Age Modifications: A Prospective Cohort Study in Southwest China.

To examine possible associations between depression and cardiovascular disease (CVD) incidence and whether demographic factors modified those associations in the Chinese population. This prospective cohort study comprised 7,735 adults aged 18 years or older in Guizhou, China from 2010 to 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to measure the prevalence of depression. Cox proportional hazard models were used to estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) of depression and incident CVD. We identified 215 CVD cases (including 28 acute myocardial infarction (AMI) and 197 stroke cases) during an average follow-up of 7.07 years. In the multivariable-adjusted model, baseline PHQ-9 score was associated with incident CVD, AMI, and stroke. The HR per 1-SD increase for PHQ-9 score was 1.14 (95%CI: 1.03, 1.26) for CVD, 1.26 (95%CI: 1.01, 1.57) for AMI, and 1.12 (95%CI: 1.01, 1.25) for stroke. Compared with participants without depression, those with any mild or more advanced depression had a higher risk of incident CVD (HR: 1.69, 95%CI: 1.08, 2.64) and AMI (HR: 3.36, 95%CI: 1.17, 10.56). Associations between depression with CVD and stroke were suggested to be even stronger among women and participants aged <65 years (P for interaction <0.05). The effect of depression on stroke tended to be preserved in non-smokers. Depression was associated with a higher risk of incident CVD, AMI, and stroke in adults of Southwest, China, particularly in women, participants aged <65 years, and non-smokers. These findings highlighted the importance and urgency of depression healthcare.

Molecular Basis for Paradoxical Activities of Polymorphonuclear Neutrophils in Inflammation/Anti-Inflammation, Bactericide/Autoimmunity, Pro-Cancer/Anticancer, and Antiviral Infection/SARS-CoV-II-Induced Immunothrombotic Dysregulation.

Polymorphonuclear neutrophils (PMNs) are the most abundant white blood cells in the circulation. These cells act as the fast and powerful defenders against environmental pathogenic microbes to protect the body. In addition, these innate inflammatory cells can produce a number of cytokines/chemokines/growth factors for actively participating in the immune network and immune homeostasis. Many novel biological functions including mitogen-induced cell-mediated cytotoxicity (MICC) and antibody-dependent cell-mediated cytotoxicity (ADCC), exocytosis of microvesicles (ectosomes and exosomes), trogocytosis (plasma membrane exchange) and release of neutrophil extracellular traps (NETs) have been successively discovered. Furthermore, recent investigations unveiled that PMNs act as a double-edged sword to exhibit paradoxical activities on pro-inflammation/anti-inflammation, antibacteria/autoimmunity, pro-cancer/anticancer, antiviral infection/COVID-19-induced immunothrombotic dysregulation. The NETs released from PMNs are believed to play a pivotal role in these paradoxical activities, especially in the cytokine storm and immunothrombotic dysregulation in the recent SARS-CoV-2 pandemic. In this review, we would like to discuss in detail the molecular basis for these strange activities of PMNs.

Predictors of Response to Oral Medications and Low-Histamine Diet in Patients with Chronic Urticaria.

BACKGROUND: Chronic urticaria (CU) is comprised of diverse phenotypes, and thus, a shift towards a precision medical approach is warranted in its management. METHODS: This study enrolled 78 patients with CU. Serum erythrocyte sedimentation rate, hemoglobin, hematocrit, eosinophil count, IgE, antinuclear antibody (ANA), and serum diamine oxidase (DAO) levels of the patients were measured and were compared according to the patient's response to second-generation antihistamines (sgAH), corticosteroids, leukotriene receptor antagonist (LTRA), H2 blockers, and low-histamine diet. RESULTS: Age- and sex-adjusted logistic regression analysis showed that patients with duration of CU > 3 years (adjusted odd ratio [aOR] = 4.39) and a DAO level < 10 U/mL (aOR = 3.90) were significantly associated with a good sgAH response. Age > 50 years (aOR = 0.02), duration of chronic urticaria > 3 years (aOR =0.06), and an ANA titer ≥ 1 : 80 (aOR = 0.03) were significantly and inversely associated with corticosteroid response. A low-histamine diet response was significantly associated with LTRA response (aOR = 67.29). In addition, a DAO level < 5.4 U/mL (aOR = 71.95) was significantly associated with H2 blocker response. Furthermore, concomitant angioedema (aOR = 10.56), multiple food triggers (aOR = 11.69), and a DAO level < 5.4 U/mL (aOR = 3.78) were significantly associated with a low-histamine diet response. Conversely, dermatographic urticaria and a hematocrit level < 36% were significantly and inversely associated with low-histamine diet response. CONCLUSIONS: Several promising biomarkers were identified in this study to predict the efficacy of chronic urticaria treatment. DAO could be a novel biomarker for predicting the efficacy not only of dietary intervention but also for antagonists of H1 and H2 receptors.

Multistability of a Two-Dimensional Map Arising in an Influenza Model.

In this paper, we propose and analyze a nonsmoothly two-dimensional map arising in a seasonal influenza model. Such map consists of both linear and nonlinear dynamics depending on where the map acts on its domain. The map exhibits a complicated and unpredictable dynamics such as fixed points, period points, chaotic attractors, or multistability depending on the ranges of a certain parameters. Surprisingly, bistable states include not only the coexistence of a stable fixed point and stable period three points but also that of stable period three points and a chaotic attractor. Among other things, we are able to prove rigorously the coexistence of the stable equilibrium and stable period three points for a certain range of the parameters. Our results also indicate that heterogeneity of the population drives the complication and unpredictability of the dynamics. Specifically, the most complex dynamics occur when the underlying basic reproduction number with respect to our model is an intermediate value and the large portion of the population in the same compartment changes in states the following season.