Comparison of treatment outcomes and complications of coil embolization in elderly and very elderly patients with cerebral aneurysms: a propensity score matching analysis.

PURPOSE: This single center study aims to compare the treatment outcomes and procedure-related complications of coil embolization in elderly patients (60-79 years) and very elderly patients (aged 80 years or older) with cerebral aneurysms. METHODS: Data was collected from 504 elderly patients aged 60 years or older who underwent coil embolization for intracranial aneurysms from 2018 to 2021. The study evaluated patient-related and anatomical factors and assessed various outcomes, comparing results between groups using statistical analysis and propensity score matching. RESULTS: A total of 503 cerebral aneurysms were analyzed from individuals aged 60-79 years (n = 472) and those aged 80 years or older (n = 31). The majority of the aneurysms were unruptured with an average size of 3.5 mm in height and 3.4 mm in width. The patients were compared using 1:1 propensity score matching, and no significant differences were found in factors other than age and aortic elongation. Logistic analysis revealed that being over 80 years old and having a severe aortic arch elongation were identified as risk factors for procedure-related events in both total and unruptured cases. CONCLUSIONS: The study compared coil embolization treatment for cerebral aneurysms in patients aged 60-79 and over 80, finding no significant difference in treatment outcomes except for procedure-related events. Procedure-related events were associated with severe aortic arch elongation and being over 80 years old. Coil embolization can be considered safe and effective for patients over 80, but further trials are needed for accurate conclusions.

106.25-Gbps PAM-4 bidirectional optical sub-assembly module with in-line arrangement of optical and electrical interfaces.

We successfully demonstrate a 106.25-Gbps PAM-4 bidirectional optical sub-assembly for optical access networks, including a driver amplifier and an electro-absorption modulated laser for a transmitter, a photodiode and transimpedance amplifier for a receiver, and an optical filter block. For its implementation, we propose design strategies providing an in-line arrangement of optical and electrical interfaces while ensuring optical alignment tolerance for easy assembly and reducing electrical crosstalk between the transmitter and receiver. Measured receiver sensitivity was <-11.4 dBm for the KP4 forward error correction limit during transmitter operation, and measured power penalty of 10-km single-mode fiber transmission was <0.9 dB.

53 GBd PAM-4 fully-integrated silicon photonics transmitter with a hybrid flip-chip bonded laser.

We present a fully-integrated single-lane 53 GBd PAM-4 silicon photonics (SiPh) transmitter (Tx) with a flip-chip bonded laser diode (LD). The LD is butt-coupled to a Si edge coupler including a SiO2 suspended spot-size converter. The coupled power exceeds 10 dBm with a 1 dB allowable misalignment of 2.3 µm. The RF and eye performances of the Tx are evaluated. Extinction ratio >5 dB is obtained at 3.5 Vppd voltage swing. Aided by silicon capacitors, the Tx decouples parasitic inductances leading to remarkable improvements in the eye openings and transmitter dispersion eye closure quaternary by 1.16 dB. By implementing the fully-integrated Tx with driver packaging, we successfully demonstrate 106 Gb/s real-time operation satisfying KP4-FEC threshold at -5 dBm receiver sensitivity.

Design of a discrete flexure for a SiC deformable mirror with PMN stacked-actuators.

In the present work, a discrete flexure for silicon carbide (SiC) deformable mirror (DM) with Lead-Magnesium-Niobate (PMN) stacked-actuators is designed using topology and size optimizations. In order to fulfill the designated surface strokes of the SiC mirror without adhesive failure, discrete flexures are adopted between the mirror faceplate and the actuators. As the same design process for the flexure of the final DM model, which has a 140 mm diameter mirror faceplate and 489 channels of piezoelectric PMN-30PT single crystal multilayer actuators, the topology and the sizes of the flexure for the 5×5 engineering DM model are optimized. The topology and the size optimizations are conducted by GTAM and DesignXplorer in ANSYS based on finite element method (FEM). The prototype of the designed model is built and the test results show appropriate mirror deformations comparing with the simulated results without adhesive failure.

Verification of hybrid-integrated 400-Gb/s (4 × 100 Gb/s) CWDM4 ROSA using a bandwidth-improved multilayer board.

We have successfully demonstrated a hybrid-integrated 400-Gb/s (4 × 100 Gb/s) CWDM4 PAM-4 receiver optical sub-assembly (ROSA) with a bandwidth-improved multilayer evaluation board. The proposed ROSA offers packaging simplification through passive optical alignment assembly of main components. In addition, we have proposed a structure to mitigate the bandwidth limitation issue caused by the typical edge connector mounting on the multilayer board, when needed bandwidth exceeds ∼20 GHz. With the bandwidth-improved multilayer board, the 3-dB bandwidth of the ROSA was observed to be >35.7 GHz and its receiver sensitivity was successfully measured to be <-10 dBm at FEC limit, bit error rate of 2.4e-4, for all channels.

Low-cost and miniaturized 100-Gb/s (2 × 50 Gb/s) PAM-4 TO-packaged ROSA for data center networks.

We design and implement a cost-effective and compact 100-Gb/s (2 × 50 Gb/s) PAM-4 receiver optical sub-assembly (ROSA) by using a TO-can package instead of an expensive box-type package. It consists of an optical demultiplexer, two PIN-PDs and a 2-channel linear transimpedance amplifier. The components are passively aligned and assembled using alignment marks engraved on each part. With a real-time PAM-4 DSP chip, we measured the back-to-back receiver sensitivities of the 100-Gb/s ROSA based on TO-56 to be less than -13.2 dBm for both channels at a bit error rate of 2.4e-4. The crosstalk penalty due to the adjacent channel interference was observed around 0.1 dB.

Highly alignment tolerant and high-sensitivity 100Gb/s (4 × 25Gb/s) APD-ROSA with a thin-film filter-based de-multiplexer.

We investigate and demonstrate a 100-Gb/s (4x25-Gb/s) receiver optical sub-assembly (ROSA) based on avalanche photodiodes and a thin-film filter-based de-multiplexer. The overall alignment tolerances of the ROSA are relaxed to have larger than ± 25 µm by improving optical coupling structure. The receiver sensitivity of each lane is also measured to be less than -22.2 dBm, a record minimum to our knowledge, at the bit error ratio of 10-12 for 25.78-Gb/s NRZ signal.

The Accuracy of Ultrasonography on the Location of Lipomas in the Forehead.

BACKGROUND: Preoperative recognition of tumor plane is important to avoid surgical complications in surgeries involving the scalp. Ultrasonography is a useful diagnostic tool to detect the depth of tumor noninvasively. However, some findings are not always in accordance with the actual locations of lipomas, especially in the forehead. OBJECTS: To evaluate the accuracy of preoperative ultrasonographic findings for the location of lipomas in the forehead. MATERIALS AND METHODS: The study included 14 patients with lipomas in the forehead who all underwent preoperative ultrasonography and surgical excision of the lesions. The authors compared the diagnostic location of tumors by ultrasonography with the actual location in the surgical field. RESULTS: On ultrasonography, 10 of 14 cases were diagnosed as frontalis-associated lipomas. However, 13 cases were confirmed as frontalis-associated lipomas intraoperatively, and only 1 case as superficial lipoma, which did not correspond with the ultrasonographic finding. The ultrasonographic findings were accurate in 9 of 14 cases (64.3%). CONCLUSION: The accuracy of ultrasonography on the location of lipomas in the forehead is not as high as expected. Therefore, the surgeon must consider the possibility of deep lipoma even if a forehead lipoma is superficial in location on ultrasonography.

Analysis of dimensional tolerance for an optical demultiplexer of a highly alignment tolerant 4 × 25 Gb/s ROSA module.

We have developed a 4 × 25 Gb/s ROSA (receiver optical sub-assembly) module for 100G Ethernet optical transceiver. This ROSA module has very large alignment tolerance of more than ± 250 µm between the optical DMUX (demultiplexer) and four photodiodes, for the reason it has the advantage of being easily assembled. The large alignment tolerance can be attributed to the dimensional tolerant optical DMUX, which is composed of four thin film filters attached to a parallelogram-shaped optic block. Since it is important to define the fabrication specifications for the dimension of the optic block, we analyze dimensional tolerance for the optic block using three-dimensional simulation. This parallelogram-shaped optical DMUX permits length tolerance of ± 300 µm and angular tolerance of ± 0.1°. The fabricated optical DMUX is estimated to have the angular error of less than 0.09°.

De novo steroidogenesis in tumor cells drives bone metastasis and osteoclastogenesis.

Osteoclasts play a central role in cancer-cell-induced osteolysis, but the molecular mechanisms of osteoclast activation during bone metastasis formation are incompletely understood. By performing RNA sequencing on a mouse breast carcinoma cell line with higher bone-metastatic potential, here we identify the enzyme CYP11A1 strongly upregulated in osteotropic tumor cells. Genetic deletion of Cyp11a1 in tumor cells leads to a decreased number of bone metastases but does not alter primary tumor growth and lung metastasis formation in mice. The product of CYP11A1 activity, pregnenolone, increases the number and function of mouse and human osteoclasts in vitro but does not alter osteoclast-specific gene expression. Instead, tumor-derived pregnenolone strongly enhances the fusion of pre-osteoclasts via prolyl 4-hydroxylase subunit beta (P4HB), identified as a potential interaction partner of pregnenolone. Taken together, our results demonstrate that Cyp11a1-expressing tumor cells produce pregnenolone, which is capable of promoting bone metastasis formation and osteoclast development via P4HB.

Analysis of Factors Affecting Good Neovascularization After Indirect Bypass Surgery: A Two-center Retrospective Study.

OBJECTIVE: The purpose of this study was to analyze factors affecting good neovascularization after indirect bypass surgery. METHODS: From August 2000 to July 2020, postoperative image results and medical records of 132 patients (159 hemispheres) who underwent EDAS of indirect bypass surgery at two institutions were reviewed retrospectively. Based on DSA results, angiogenesis after indirect bypass was divided into "good" or "poor" according to the Matsushima criteria. STA flap length affecting GPN were analyzed in the entire group (n = 159) and a MMD group (n = 134). RESULTS: In the entire group, GPN after EDAS was observed in 94 (59.1%) hemispheres. Age, MMD, hypertension, and bone flap size were identified as significant factors in univariate analysis. Also, in the MMD group, 86 (64.2%) hemispheres showed GPN. Hypertension and bone flap size were significant factors in both univariate and multivariate analyses. Cutoff values of bone flap size and GPN were 47.91 cm2 in the entire group and the MMD group. CONCLUSIONS: In all patients who received EDAS, good postoperative neovascularization was significant in those with a young age, MMD, without hypertension, and large bone flap size. No hypertension and large bone flap size were meaningful factors in the MMD group. AUROC showed that an appropriate bone flap size was 47.91 cm2. However, a further controlled prospective study is needed.

A Comparison of Clinical and Radiological Outcomes Between Target 360 Nano and Microplex Hypersoft 3D Used as Finishing Coil.

AIM: To compare the clinical outcomes of Target 360 nano (TG) and Microplex hypersoft 3D (MH) used as a finishing coil (FC). MATERIAL AND METHODS: From January 2018 to December 2020, we retrospectively reviewed 243 coil embolization procedures performed using TG (n=152) and MH (n=91) coils of 1mm x 2 cm the same size as FC. Further, the clinical and radiographic results were compared by matching the propensity score between the two groups. RESULTS: There were no statistically significant differences in the clinical and angiographic results of the two coils after the propensity score matching. Successful occlusion was 89% and 86.8% and FC insertion failure was 20.9% and 28.6%. There were no differences in procedure-related complications and recurrence between the groups during the eight months follow-up period (3.3% versus 4.4% and 4.4% versus 3.3%, respectively). We also compared two subgroups of failed FC insertion (19 of TG and 26 of MH). The number of angled catheters was significantly higher in the failed TG group than in the failed MH group. CONCLUSION: There was no statistically significant difference between the clinical and radiological outcomes of TG and MH used as FC. However, in the FC insertion failure subgroups, the number of angled catheters was significantly higher in the TG failed group than in the MH failed. It was experimentally confirmed that the angle change of microcatheter tip with a large angle was large; however, further studies are required.

Prediction of Antibody Viscosity from Dilute Solution Measurements.

The high antibody doses required to achieve a therapeutic effect often necessitate high-concentration products that can lead to challenging viscosity issues in production and delivery. Predicting antibody viscosity in early development can play a pivotal role in reducing late-stage development costs. In recent years, numerous efforts have been made to predict antibody viscosity through dilute solution measurements. A key finding is that the entanglement of long, flexible complexes contributes to the sharp rise in antibody viscosity at the required dosing. This entanglement model establishes a connection between the two-body binding affinity and the many-body viscosity. Exploiting this insight, this study connects dilute solution measurements of self-association to high-concentration viscosity profiles to quantify the relationship between these regimes. The resulting model has exhibited success in predicting viscosity at high concentrations (around 150 mg/mL) from dilute solution measurements, with only a few outliers remaining. Our physics-based approach provides an understanding of fundamental physics, interpretable connections to experimental data, the potential to extrapolate beyond training conditions, and the capacity to effectively explain the physical mechanics behind these outliers. Conducting hypothesis-driven experiments that specifically target the viscosity and relaxation mechanisms of outlier molecules may allow us to unravel the intricacies of their behavior and, in turn, enhance the performance of our model.

Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies.

Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, and convenient administration to patients. The ability to use computational methods to predict biophysical properties from protein sequence, potentially in combination with high throughput assays, could decrease timelines and increase the success rates for therapeutic developability engineering by eliminating lengthy and expensive cycles of recombinant protein production and testing. To support development of high-quality predictive models for antibody developability, we designed a sequence-diverse panel of 83 effector functionless IgG1 antibodies displaying a range of biophysical properties, produced and formulated each protein under standard platform conditions, and collected a comprehensive package of analytical data, including in vitro assays and in vivo mouse pharmacokinetics. We used this robust training data set to build machine learning classifier models that can predict complex protein behavior from these data and features derived from predicted and/or experimental structures. Our models predict with 87% accuracy whether viscosity at 150 mg/mL is above or below a threshold of 15 centipoise (cP) and with 75% accuracy whether the area under the plasma drug concentration-time curve (AUC0-672 h) in normal mouse is above or below a threshold of 3.9 × 106 h x ng/mL.

Is a small coil more effective as a finishing coil for the embolization of intracranial aneurysms? Outcomes using GALAXY G3™ MINI micro-coils as finishing coils in a single center.

OBJECTIVE: The purpose of this study was to compare the outcomes of coil embolization using a 0.009 inches primary outer diameter coil as finishing coil (FC) to that of 0.01 inches. METHODS: From February and August 2020, 131 aneurysms that performed coil embolization using FC with a second loop diameter of 1 mm, were reviewed retrospectively, conducting propensity score matching and logistic regression analysis. Angiographic results such as, occlusion grade, packing density, failure and event were compared between 0.009 inches coil of GALAXY G3™ MINI microcoil (n = 54) and 0.01 inches coils (n = 77). RESULTS: There were no statistically significant differences between two groups, but more events occurred in the 0.009 group. (Odds ratio, 3.65; 95% CI, 1.06-12.55; P = 0.031) In the results of coil embolization, successful occlusion occlusion (complete occlusion and residual neck) was identified more in the 0.01 group. After propensity score matching, the variables in each group were similar, but the successful occlusion was higher in the 0.01 group as in the total population. Events tended to occur more frequently in the 0.009 inch group, and logistic regression analysis showed slightly higher events in the angled microcatheter. (48.3% versus 76.9%., P = 0.075), Also, the 0.009 inch FC is an independent risk factor. (Odds ratio, 3.84; 95% CI, 1.07-13.80; P = 0.039). CONCLUSIONS: Using 0.01 inches coils as FC increased the packing density after the procedure, and showed more successful occlusion than using a 0.009 inches coil. The probability of unexpected events was observed more than three times in the 0.009 inch group.

Co-expression as a convenient method for the production and purification of core histones in bacteria.

Co-expression offers an important strategy for producing multiprotein complexes for biochemical and biophysical studies. We have found that co-expression of histones H2A and H2B (from yeast, chicken or Drosophila) leads to production of soluble heterodimeric H2AH2B complexes. Drosophila histones H3 and H4 can also be produced as a soluble (H3H4)(2) heterotetrameric complex if they are co-expressed with the histone chaperone Asf1. The soluble H2AH2B and (H3H4)(2) can be purified by simple chromatographic techniques and have similar properties to endogenous histones. Our methods should facilitate histone production for studies of chromatin structure and regulatory proteins that interact with histones. We describe a simple strategy for constructing co-expression plasmids, based on the T7 RNA polymerase system, which is applicable to other systems. It offers several advantages for quickly creating plasmids to express two or more proteins and for testing different combinations of proteins for optimal complex production, solubility or activity.

Perfusion CHO cell culture applied to lower aggregation and increase volumetric productivity for a bispecific recombinant protein.

Secreted recombinant proteins can aggregate during cell culture. We studied a poorly-behaved bispecific scaffold that increasingly aggregated (up to 62% high molecular weight species, HMW) as a function of culture time in a fed-batch and intensified cell culture processes. We identified that protein aggregates increased with accumulated protein concentration inside the bioreactor. Furthermore, results indicated that a maximum product concentration was reached beyond which no additional soluble protein accumulated in culture even when doubling the integrated viable cell density with the intensified process, suggesting additional secreted protein was precipitating. To overcome this limitation and maintain the cell-specific productivity (qp) in culture, we explored a perfusion process where recombinant protein was continuously removed from the bioreactor to maintain low product concentration and consequently, minimize protein aggregation. We studied different viable cell densities (VCDs) inside the bioreactor (one to five-fold) and found a corresponding two-fold modulation of monomer levels. In all VCD conditions, qp was maintained. On the contrary, the previous intensified process showed an "apparent" 2.5-fold decrease in qp at the end of culture because of the presumed limited protein solubility at higher concentrations. The combination of lower aggregate levels and constant qp resulted in up to four to five-fold increase in recoverable product (i.e., monomer) with the improved perfusion process.

Brain activation areas of sexual arousal with olfactory stimulation in men: a preliminary study using functional MRI.

INTRODUCTION: There have been extensive studies evaluating the functional neuroanatomy of the brain during visual sexual stimulation. However, little data exist concerning the role of olfactory stimulation in human sexuality. AIM: This preliminary study intended to elucidate the brain areas responding to an olfactory sexual stimulus using functional magnetic resonance imaging (fMRI). METHODS: Eight healthy right-handed heterosexual male volunteers (20-35 years of age), having normal olfaction and no brain diseases, were recruited. During fMRI, a women's perfume was given as an olfactory sexual stimulant in an alternating block design with a 30-second stimulation period followed by a 30-second rest. After the fMRI sessions, the participants provided ratings for both the odorant's intensity and perceived arousal. MAIN OUTCOME MEASURES: The study subjects rated the odorant stimulation and perceived sexual arousal response by Likert-type rating scales. Brain activation maps were made by blood oxygenation level-dependent (BOLD)-based fMRI with an echo-planar imaging pulse sequence. RESULTS: Two out of eight subjects experienced "strong" sexual arousal, and three subjects experienced "moderate" arousal during olfactory stimulation, resulting in a mean score of 2.25 on a 4-point scale. The common brain areas activated in response to the odor stimulus in all eight subjects included the insula, the inferior and middle frontal gyrus, and the hypothalamus. The median cingulate gyrus, thalamus, angular gyrus, lingual gyrus, and cerebellar cortex were activated in subjects who had moderate or strong sexual arousal response. CONCLUSION: Olfactory stimulation with women's perfume produces the activation of specific brain areas in men. The brain areas activated differed according to the degree of perceived sexual arousal response. Further studies are needed to elucidate brain activation response according to the different kinds and intensities of olfactory stimulation.

Compare the Intracranial Pressure Trend after the Decompressive Craniectomy between Massive Intracerebral Hemorrhagic and Major Ischemic Stroke Patients.

OBJECTIVE: Massive intracerebral hemorrhage (ICH) and major infarction (MI) are devastating cerebral vascular diseases. Decompression craniectomy (DC) is a common treatment approach for these diseases and acceptable clinical results have been reported. Author experienced the postoperative intracranaial pressure (ICP) trend is somewhat different between the ICH and MI patients. In this study, we compare the ICP trend following DC and evaluate the clinical significance. METHODS: One hundred forty-three patients who underwent DC following massive ICH (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was 56.3±14.3 (median=57, male : female=89 : 54). DC was applied using consistent criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8 and a midline shift more than 6 mm on brain computed tomography. In all patients, ventricular puncture was done before the DC and ICP trends were monitored during and after the surgery. Outcome comparisons included the ictus to operation time (OP-time), postoperative ICP trend, favorable outcomes and mortality. RESULTS: Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly and maintained within physiological range if greater than 80% of the hematoma was removed. While in MI patients, the postoperative ICP were not drop rapidly and maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007). CONCLUSION: The results of this study suggest that if greater than 80% of the hematoma was removed in ICH patients, the postoperative ICP rarely over the physiologic range. But in MI patients, the postoperative ICP was above the physiologic range for several days after the DC. Authors propose that DC is no need for the massive ICH patient if a significant portion of their hematoma is removed. But DC might be essential to improve the MI patients' outcome and timely treatment decision.

Determining the Lower Limit of Cerebral Perfusion Pressure in Patients Undergoing Decompressive Craniectomy Following Traumatic Brain Injury.

BACKGROUND: In patients with severe traumatic brain injury (TBI), maintaining systolic blood pressure >90 mm Hg, intracranial pressure (ICP) <20 mm Hg and cerebral perfusion pressure (CPP) >60-70 mm Hg is recommended to improve clinical outcomes. A recommended CPP value for patients treated with decompressive craniectomy (DC) has not been clearly studied. We aimed to determine whether the targeted CPP can be lowered in patients treated with DC. METHODS: This retrospective analysis included 191 patients who underwent DC for TBI. All patients were monitored for ICP and blood pressure during and after DC. CPP was calculated every 2 hours after DC. Patient outcomes were evaluated 6 months after initial treatment. RESULTS: Mean patient age was 50.8 years (median 52 years), and 79.1% of patients were male. Initial Glasgow Coma Scale score was 6.2 (median 6). Comparing clinical outcome based on postoperative ICP >25 mm Hg and <25 mm Hg, Extended Glasgow Outcome Scale score was 1.4 (>25 mm Hg) and 4.9 (<25 mm Hg) (P = 0.000). In patients maintained at ICP <25 mm Hg, mortality was increased significantly with CPP between 35 mmHg and 30 mm Hg (χ2, P = 0.029 vs. P = 0.062). CONCLUSIONS: Patients with TBI who underwent DC with postoperative ICP maintained <25 mm Hg and CPP >35 mm Hg may have similar mortality as patients with CPP >60-70 mm Hg who did not undergo DC. For patients with TBI who undergo DC, targeted CPP might be lowered to 35 mm Hg if ICP is maintained <25 mm Hg.