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Thi Phuong Thao Hoang,1 Philipp Schindler,2 Nikolaus Börner,3 Max Masthoff,2 Mirjam Gerwing,2 Philippa von Beauvais,2 Enrico N De Toni,4 Christian M Lange,4 Jonel Trebicka,5 Haluk Morgül,6 Max Seidensticker,1 Jens Ricke,1 Andreas Pascher,6 Markus Guba,3 Michael Ingrisch,1 Moritz Wildgruber,1,* Osman Öcal1,* 1Department of Radiology, University Hospital, LMU Munich, Munich, Germany; 2Clinic for Radiology, University Hospital Muenster, Muenster, Germany; 3Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany; 4Department for Internal Medicine II, University Hospital, LMU Munich, Munich, Germany; 5Department for Internal Medicine B, Universitätsklinikum Münster, Münster, Germany; 6Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany*These authors contributed equally to this workCorrespondence: Osman Öcal, Department of Radiology, University Hospital – LMU Munich, Marchioninistrasse 15, D-81377, München, Germany, Email osman.oecal@med.uni-muenchen.dePurpose: To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model.Patients and Methods: This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan–Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years.Results: The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively.Conclusion: Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation.Keywords: hepatocellular carcinoma, transplantation, imaging, recurrence

Aim: To investigate the choroidal thickness and the microvascular network changes around the macula in thyroid eye disease (TED) patients at different stages and the relationship of those changes with risk factors, serum antibodies and the severity of TED., Methods: A total of 85 participants were enrolled. All participants underwent ophthalmology and endocrinology examinations. Subfoveal choroidal thickness (SFCT), superficial (s) and deep (d) foveal avascular zone (FAZ) area, mean (m) and central (c) superficial vascular density (SVD), deep vascular density (DVD) measurements of the enrolled cases were performed with Topcon swept source optical coherence tomography (OCT)/OCT angiography (OCTA) DRI OCT Triton. Multiple linear regression analysis was used to explore the associations between SFCT, FAZ area, SVD, DVD and the relevant factors of TED., Results: Those with active TED patients had higher c-DVD and m-DVD levels ( P <0.05), however there is no statistically significant difference in SFCT between active and stable TED patients. Among the serum antibodies, it was observed that s-FAZ and d-FAZ increased, c-SVD and m-SVD decreased in patients with high thyroid stimulating hormone-receptor autoantibodies (TRAB) level, whereas SFCT thickened in patients with high levels of both TRAB and human thyroglobulin (hTG). There was no significant difference in SFCT, FAZ, SVD and DVD measurement at gender, between hyperthyroid and euthyroid patients and among those with or without thyroid papillary carcinoma., Conclusion: The results show that both disease activation and serum antibodies differentially affect both superficial and deep retinal vascular density. It has also been shown that high serum antibody levels affect choroidal thickness independent of clinical activity., (International Journal of Ophthalmology Press.)

Spectral domain OCT imaging of the lower punctum in cases with silicone tube implantation OBJECTIVE: To record the structural changes in the lower punctum by performing spectral domain anterior segment OCT imaging of dacryocystorhinostomy cases who underwent bicanalicular silicone tube implantation., Methods: Thirty eyes of 30 patients who underwent bicanalicular Crawford silicone tube implantation with dacryocystorhinostomy were included in the study. The mean age of the cases was 53 ± 13.96 (24-72). Of the cases, 19 were female and 11 were male, 18 of them were operated on the right eye and 12 on the left eye. The lower punctum images of the cases were recorded with spectral domain anterior segment OCT preoperatively and at the 1st day, 1st month and 6th month after explantation of the silicone tube. In the lower punctum, external punctal width(EPW) and canaliculi depth (CD) were measured., Results: The mean EPW and CD measurements of the cases in the preoperative period, respectively; 544.90±144.11 µm and 451.70±197.45 µm. First day after silicone tube explantation, EPW was 818.00±186.83 µm and CD was 735.35±337.15 µm, at 1st month EPW was 665.95±142.12 µm and CD was 619.30±212.11 µm and at 6th months EPW was 530±150.29 µm and CD was 558.45±254.37 µm, respectively. Mean EPW values were found to be higher on the first day after extubation than before surgery (p = 0.001). There was no significant difference in the mean EPW values at the first and sixth months after extubation compared to pre-implantation (p>0.05). The mean CD values were higher at the 1st day, 1st month and 6th month after tube explantation than preoperative CD values, they were not statistically significant., Conclusions: According to the lower punctum OCT imaging data, silicone tube implantations applied to the canalicular system do not create a structurally significant difference in the lower punctum. The punctal opening gradually decreases after extubation. The decrease in EPW values is more pronounced than the decrease in CD values. Silicone tube implantation was more effective in maintaining canaliculi depth compared to external punctal diameter., Competing Interests: Declaration of Competing Interest There are no financial conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Periorbital fat atrophy is a known side effect of topical prostaglandin analogs (PA). This side effect may have implications in the treatment of diseases like thyroid orbitopathy. In this in vivo study we aimed to evaluate the effects of retrobulbar injection of three different PAs on orbital fat., Methods: Eighteen adult male Wistar-albino rats were divided into three groups of six animals. 0.1 ml of 0.03% bimatoprost, 0.005% latanoprost, or 0.005% travoprost was injected into the right orbits and saline was injected into the left orbits, as controls. Both orbits were exenterated after 3 weeks. Histological cross-sections were analyzed using ImageJ image analysis software. Intraconal adipocyte density was calculated., Results: There was no significant difference in the adipocyte density between the PA injected orbits and the control side in each of the three groups. When calculations from all three groups were analyzed together, again the difference in the adipocyte density between the PA injected orbits and the control side was not significant., Conclusion: No significant fat atrophy was noted in this rat model three weeks after retrobulbar injection of PAs. To evaluate retrobulbar injection of PA as a potential therapy for orbital diseases with fat proliferation, in vivo studies in different animal models, higher concentrations of PA, or longer follow-up duration are required., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Energy poverty is a critical global issue that affects millions of people worldwide. The lack of access to reliable and affordable energy services has significant economic and social impacts, including limited opportunities for education, personal development, and economic growth. This paper examines the relationship between energy poverty and economic development in selected countries using the panel quantile methodology. The findings emphasize the importance of addressing energy poverty in order to foster economic growth in the selected country group. In addition, CO 2 emissions have a positive effect on economic growth, but policies to reduce fossil fuel consumption can both boost economic growth and mitigate negative environmental impacts. Inflation has a negative effect on economic growth, so policymakers should prioritize measures to control it. Employment has a positive effect on economic growth, so job creation policies should be promoted. The study found that improving access to clean energy can increase economic growth and improve the well-being of citizens in Eastern European countries. Therefore, efforts to reduce energy poverty should be a priority to promote economic development and improve the quality of life., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cerebral vein thrombosis is a unique and rare type of cerebrovascular disease. The main challenge in identifying cerebral vein thrombosis is the presence of vague signs and symptoms that can resemble a variety of other intracranial pathologies. Our goal is to present the unique case of a young patient whose MRI scan revealed an abnormally enhancing tumor-like brain lesion that was heterogeneous in intensity and whose intraoperative view and histopathological findings were consistent with the vein of Labbe thrombosis, with ipsilateral transverse and sigmoid sinus involvement., Competing Interests: Conflicts of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: The COVID-19 (coronavirus disease 2019) pandemic is a global health emergency that is straining health care resources. Identifying patients likely to experience severe illness would allow more targeted use of resources. This study aimed to investigate the association between the thymus index (TI) on thorax computed tomography (CT) and prognosis in patients with COVID-19., Methods: A multicenter, cross-sectional, retrospective study was conducted between March 17 and June 30, 2020, in patients with confirmed COVID-19. The patients' clinical history and laboratory data were collected after receiving a signed consent form. Four experienced radiologists who were blinded to each other and patient data performed image evaluation. The appearance of the thymus was assessed in each patient using 2 published systems, including the TI and thymic morphology. Exclusion criteria were lack of initial diagnostic thoracic CT, previous sternotomy, pregnancy, and inappropriate images for thymic evaluation. A total of 2588 patients with confirmed COVID-19 and 1231 of these with appropriate thoracic CT imaging were included. Multivariable analysis was performed to predict the risk of severe disease and mortality., Results: The median age was 45 (interquartile range, 33-58) years; 52.2% were male. Two hundred forty-nine (20.2%) patients had severe disease, and 60 (4.9%) patients died. Thymus index was significantly associated with mortality and severe disease (odds ratios, 0.289 [95% confidence interval, 0.141-0.588; P = 0.001]; and 0.266 [95% confidence interval, 0.075-0.932; P = 0.038]), respectively. Perithymic lymphadenopathy on CT imaging had a significantly strong association with grades of TI in patients with severe disease and death ( V = 0.413 P = 0.017; and V = 0.261 P = 0.002, respectively). A morphologically assessable thymus increased the probability of survival by 17-fold and the absence of severe disease by 12-fold., Conclusion: Assessment of the thymus in patients with COVID-19 may provide useful prognostic data for both disease severity and mortality., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To investigate the predictive role of thiol/ disulfide homeostasis and Ischemia-modified albumin (IMA) levels for NTDs., Material and Methods: A total of 71 pregnant women (31 with NTD and 42 healthy controls) were enrolled in this study. This prospective case-control study included pregnant women with NTDs as the study group and randomly selected age-matched pregnant women with healthy fetuses as the control group. The two groups were compared on the basis of thiol/disulfide and IMA levels in the maternal and fetal samples., Results: No statistically significant difference in native thiol, total thiol, disulfide, and calculated ratios was observed between the groups. However, maternal IMA values were significantly higher in the study group. The IMA was proven to be a predictor with a sensitivity of 77.4% and specificity of 100% for NTDs at a cut-off value of 1.32., Conclusion: The examination of the maternal levels of IMA may be useful in the detection of NTDs.

Objective: To contrast the accuracy of C2 navigation template-assisted versus freehand pedicle and/or pars screw fixation in high-risk cases where a high-riding vertebral artery (VA) or narrow pedicle and complex deformities were associated., Methods: In our hospital, computed tomography (CT) data of 30 patients with pathology on C 0-1-2 , who had risk factors for VA injury, that were complex cervical deformities, atlantoaxial instabilities with narrow C2 pedicle and/or HRVA variations were retrospectively reviewed. Using computer-aided design software and desktop printer we printed 3 sets of high cervical models per case. We divided them into 3 groups using 3 different C2 screw fixation techniques: the freehand pars screw fixation group, the freehand pedicle screw fixation group, and the navigation template-assisted pedicle screw fixation group. After 180 screw placements were finished, the parts underwent a CT scan. Then the breach rates on postoperative scans were measured., Results: Our results showed that the accurate placement rate is not noticeably different between navigation template-assisted and freehand pedicle screws, where the high-riding vertebral artery and narrow pedicles were associated, but was better in the navigational template group with complex deformities. Pars screws were found to be superior in terms of accuracy., Conclusions: The current study suggests that navigational template-assisted pedicle screws are risky for high-risk individuals with abnormal anatomy, such as those with a high-riding vertebral artery, a narrow pedicle, and complex abnormalities, and alternative C2 pars screws may be a reliable option for such individuals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the magnetic resonance elastography (MRE)-derived liver stiffness measurement (LSM), T1 and T2 relaxation times, and hepatobiliary phase images in patients, who developed sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy., Methods: Thirty-four patients (M/F:22/12) who underwent liver MRI-MRE and received oxaliplatin for colorectal, gastric, and pancreas cancer were included in the study. SOS was diagnosed by Gd-EOB-DTPA-enhanced MRI in 18 patients. MRE-LSM and T1-T2 maps were evaluated. Patients with SOS were grouped according to the amount of reticular hypointensity on the hepatobiliary phase images., Results: The mean MRE-LSM in the patients with SOS was 3.14 ± 0.45 kPa, and the control group was 2.6 ± 0.5 kPa (p = 0.01). The mean-corrected T1 (cT1) relaxation time was 1181 ± 151 ms in the SOS group and 1032 ± 129 ms in the control group (p = 0.005). The mean T2 relaxation time was 50.29 ± 3.6 ms in the SOS group and 44 ± 3.9 ms in the control group (p = 0.01). Parenchymal stiffness values were 2.8 ± 0.22 kPa, 3 ± 0.33 kPa, and 3.65 ± 0.28 kPa in patients with mild, moderate, and advanced SOS findings, respectively (p = 0.002). Although cT1 and T2 relaxation times increased with increasing SOS severity, no statistical significance was found., Conclusions: We observed increased MRE-LSM in patients with SOS after chemotherapy compared to control group. T1 and T2 relaxation times were also useful in diagnosing SOS but were found inadequate in determining SOS severity. MRE is effective in diagnosing SOS and determining SOS severity in patients who cannot receive contrast agents, and it may be useful in the follow-up evaluation of these patients., (© 2022. The Author(s).)

In this technical report, we discuss the design and production of polymethyl methacrylate (PMMA) implants, which we successfully applied in two patients using silicone molds, and a retrospective review of these patients at 1- and 6-month intervals. By using open-source computer-assisted design software, three-dimensional printers, and the patient's thin-sliced computed tomography data, we designed and produced the implant template and used it to make silicone rubber mоlds for intraoperative PMMA casting with good results. As a negative of the implant, we created a silicon mold, which can be autoclaved. Two patients underwent PMMA cranioplasty using this method. Both implants were fitted into the defect without manipulation and good aesthetic аppеаrance of all patients was achieved. At follow-up 1 and 6 months after the operation, no complication was noted and the patients tolerated the cranioplasty platе wеll., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: C1/2 cervical pedicle screw fixation is a well-known procedure for treating severely damaged and unstable C1/2 fractures. On the other hand, C1/C2 screw fixation is not safe and can lead to potentially disastrous consequences. The importance of personalized 3-dimensional (3D) printed navigational guides in avoiding these consequences cannot be overstated., Methods: We retrospectively reviewed the neuroimaging data of 16 patients who had undergone fixation for treatment of C1/2 diseases. We created patient-specific C1/2 models and drill guide models using open-source 3D editing software and a desktop 3D printer. The drill guides were then placed over the respective vertebrae models and fixated with 3.5-mm screws. Following fixation, the parts were scanned with a thin-slice (01 mm) computed tomography scan, and the screw trajectories in the transverse and sagittal planes were measured at each level., Results: Of the total of 62 screws, 58 were type I (93.54%), 4 were type II (6.45%), and no screws were type III. The results showed that there was no significant deviation in the screw trajectories and the accuracy of the drill guides was 93.54%. In our study, type I and type II screws were deemed acceptable, and the acceptable rates of C1/2 screw fixation were 100%., Conclusions: In this preclinical study, we demonstrated that it is possible to create patient-specific pedicle drill guides using open-source editing software and a commercially available desktop polylactic acid printer, resulting in high accuracy rates in pedicle screw placement in C1/2 patient models., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study is to examine the impact of foreign direct investments, economic growth, and energy consumption on carbon dioxide subcomponents in the case of the USA. Dynamic ARDL (DARDL) econometric method is used covering the period 1972-2020. In addition to the total CO2 emission, the subcomponents of CO2 emission are examined separately within the framework of the EKC hypothesis in the USA by avoiding aggregation bias for the first time. The CO2 emission subcomponents used in the study are as follows; CO2 emissions from liquid fuel consumption, residential buildings, and commercial and public services; electricity and heat production; and other sectors, excluding residential buildings and commercial and public services, and CO2 emissions from transportation. Each CO2 emission component is used as a dependent variable and 6 different models were created. Foreign direct investments, trade, and energy consumption are used as control variables. No results supporting the EKC hypothesis are determined in any model, except for model 1, where total CO2 emission is the dependent variable. In addition, the trade variable has been determined as an important factor in reducing CO2 emissions in the short and long term. Trade and GDP per capita increasing and energy consumption reducing will show positive results in order to increase the environmental quality in the USA. Moreover, the study in which this EKC hypothesis is tested with CO2 emission and its subcomponents is an important study in terms of providing the opportunity to analyze the environmental quality from different angles at the same time and to take various measures together in the US economy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite recent advances in high-throughput combinatorial mutagenesis assays, the number of labeled sequences available to predict molecular functions has remained small for the vastness of the sequence space combined with the ruggedness of many fitness functions. While deep neural networks (DNNs) can capture high-order epistatic interactions among the mutational sites, they tend to overfit to the small number of labeled sequences available for training. Here, we developed Epistatic Net (EN), a method for spectral regularization of DNNs that exploits evidence that epistatic interactions in many fitness functions are sparse. We built a scalable extension of EN, usable for larger sequences, which enables spectral regularization using fast sparse recovery algorithms informed by coding theory. Results on several biological landscapes show that EN consistently improves the prediction accuracy of DNNs and enables them to outperform competing models which assume other priors. EN estimates the higher-order epistatic interactions of DNNs trained on massive sequence spaces-a computational problem that otherwise takes years to solve., (© 2021. The Author(s).)

The facilities that energy delivers to social life and economic activities render it indispensable. Hence, it is equally critical that the energy cycle must have a sustainable structure. Therefore, it is an indisputable fact that developing and performing correct and consistent energy policies is vitally necessary. Energy consumption planning includes a continuous process to reassess existing and potential alternative energy approaches and strategies. The public and private decision-makers in charge of planning and managing energy consumption policies must adapt their strategies to novel and superior alternative resources according to sustainability and efficiency criteria. In this paper, the fuzzy EDAS method is used to address the best renewable energy consumption by taking political, economic, social, technological, legal, and environmental (PESTLE) dimensions into account. The analysis of the paper indicates the most efficient renewable energy consumption is sourced by geothermal, solar, wind, hydroelectricity, and biomass, respectively. By further investigation, it is concluded that the most optimum renewable energy consumption alternatives based on PESTLE dimensions are geothermal and solar energies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

PDA is a major cause of US cancer-related deaths. Oncogenic Kras presents in 90% of human PDAs. Kras mutations occur early in pre-neoplastic lesions but are insufficient to cause PDA. Other contributing factors early in disease progression include chronic pancreatitis, alterations in epigenetic regulators, and tumor suppressor gene mutation. GPCRs activate heterotrimeric G-proteins that stimulate intracellular calcium and oncogenic Kras signaling, thereby promoting pancreatitis and progression to PDA. By contrast, Rgs proteins inhibit Gi/q-coupled GPCRs to negatively regulate PDA progression. Rgs16::GFP is expressed in response to caerulein-induced acinar cell dedifferentiation, early neoplasia, and throughout PDA progression. In genetically engineered mouse models of PDA, Rgs16::GFP is useful for pre-clinical rapid in vivo validation of novel chemotherapeutics targeting early lesions in patients following successful resection or at high risk for progressing to PDA. Cultured primary PDA cells express Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo. Here we establish the use of Rgs16::GFP expression for testing drug combinations in cell culture and validation of best candidates in our rapid in vivo screen.

Background: Following flow diverter placement, approximately 20% of intracranial aneurysms remain as residual aneurysms at 1 year. Device malapposition is a cause of residual aneurysms after flow diversion. We present a new and straightforward technique (exchange-free technique [EFT]) to enhance apposition of the surpass flow diverter (SFD), the only over-the-wire flow diverter currently available., Materials and Methods: We deployed laser-cut mini stents through the inner deployment catheter of the SFD. This maneuver was performed simply by withdrawing the micro-guidewire from its lumen and replacing it with a mini-stent (stents deliverable through microcatheters with inner diameter of 0.0165 inches), without a need to re-cross the deployed SFD or an exchange maneuver. All aneurysms in which this technique was utilized were retrospectively reviewed., Results: Twenty-eight patients (20 females) with 30 treated aneurysms were identified. The mean aneurysm diameter was 10.2 ± 6.6 mm. Technical success rate was 96.6% (29/30 aneurysms). There was no mortality or permanent morbidity related to the procedures. Except for the patient treated for an iatrogenic, surgery-related internal carotid artery pseudoaneurysm who died secondary to consequences of multiple surgeries, no cases of mortality or permanent morbidity were noted. Complete aneurysm occlusion rates were 78.2%, 82.1%, and 95.2% at 0-3, 3-6, and 9-12 months, respectively. None of the patients were re-treated., Conclusion: EFT is a simple and fast technique which was not associated with adverse effects in our series. The higher aneurysm obliteration rate obtained with EFT is probably the result of better wall apposition of the SFD., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Asian Journal of Neurosurgery.)

Summary: We propose a new spectral framework for reliable training, scalable inference and interpretable explanation of the DNA repair outcome following a Cas9 cutting. Our framework, dubbed CRISPRL and, relies on an unexploited observation about the nature of the repair process: the landscape of the DNA repair is highly sparse in the (Walsh-Hadamard) spectral domain. This observation enables our framework to address key shortcomings that limit the interpretability and scaling of current deep-learning-based DNA repair models. In particular, CRISPRL and reduces the time to compute the full DNA repair landscape from a striking 5230 years to 1 week and the sampling complexity from 1012 to 3 million guide RNAs with only a small loss in accuracy (R2R2 ∼ 0.9). Our proposed framework is based on a divide-and-conquer strategy that uses a fast peeling algorithm to learn the DNA repair models. CRISPRL and captures lower-degree features around the cut site, which enrich for short insertions and deletions as well as higher-degree microhomology patterns that enrich for longer deletions., Availability and Implementation: The CRISPRL and software is publicly available at https://github.com/UCBASiCS/CRISPRLand., (© The Author(s) 2020. Published by Oxford University Press.)

Background and Purpose: Placement of a stent within a flow diverter has been described previously but its consequences have not been analyzed. We evaluated the clinical and angiographic results of stent placement within a flow diverter during the same treatment session., Materials and Methods: All patients treated with a Surpass flow diverter were retrospectively evaluated. Patients with previously deployed stents and procedures in which scaffolding stents, a second flow diverter, or intrasaccular devices were used were excluded. Patient and aneurysm characteristics and clinical and imaging follow-up results were compared between stented and nonstented Surpass flow-diverter groups and stent assisted coiling., Results: Thirty-five patients (41 aneurysms) were treated with a Surpass flow diverter only (monotherapy group), and in 33 patients (35 aneurysms), a stent was placed within the Surpass flow diverter (stented group). Stents were placed inside the Surpass flow diverter for a variety of reasons at the operator's discretion. No statistical difference was noted between the 2 groups in age, body weight, sex, history of thromboembolic events, smoking, platelet inhibition levels, hypertension, hyperlipidemia, diabetes mellitus, malignancy, and aneurysm location. Aneurysms in the stented group were larger than those in the monotherapy group (14.8 versus 9.1 mm, P < .001). The rate of clinically significant adverse events and complete aneurysm occlusion rates at 0-3 and 3-6 months (73.3% versus 61.3%, P = .31, and 84.8% versus 70.2%, P = .14) were similar. At 9-12 months, a significantly higher proportion of aneurysms in the stented group achieved complete occlusion (93.9% versus 73.2%, P = .019). There was a trend toward a higher obliteration rate on final follow-up in the stented group (93.9% versus 82.9%, P = .14)., Conclusions: Placement of a stent within a flow diverter increases the rate of aneurysm occlusion. We propose that these results are from improved flow-diverter apposition due to the higher radial force of intracranial stents., (© 2019 by American Journal of Neuroradiology.)

Objective: To describe the rate and characteristics of air bubble retention (ABR) within cerebral aneurysms treated by flow diversion., Methods: Procedural flat detector CT (FDCT) studies were scrutinized for the presence of air bubbles (density < - 200 HU) in patients treated by flow diversion. Patients with intrasaccular treatment or previous clipping were excluded. Clinical outcomes, procedural angiograms, aneurysm characteristics and imaging features of air within the aneurysm were evaluated., Results: Bubbles were noted in 17.1% of 105 aneurysms in 85 FDCTs. Aneurysms with ABR were significantly larger (mean diameter: 18.9 versus 7.5 mm, P < 0.0001). There was a trend for the use of multiple devices during the treatment of these aneurysms (72.2% vs 49.4%, P = 0.071). All of the bubbles were located rostrally in the aneurysm sac and were smaller than 6 mm (mean diameter: 2.1 ± 1.3 mm). None of the patients had post-procedural neurological deterioration. The air had spontaneously disappeared on follow-up CT images (available in 12 patients) obtained at a mean follow-up duration of 48 h., Conclusions: ABR is not infrequent in cerebral flow diversion procedures. It is a clinically silent and self-limited technical complication. We propose air entrapment or filtration through the flow diverter as causative factors.

The seminal vesicles are paired organs of the male reproductive tract, which produce and secrete seminal fluid. Although congenital anomalies of seminal vesicles are usually asymptomatic, they may lead to various urogenital symptoms, including infertility. Due to their embryologic relationship with other urogenital organs, congenital anomalies of seminal vesicles may accompany other urinary or genital anomalies. Congenital anomalies of seminal vesicles include agenesis, hypoplasia, duplication, fusion, and cyst. These anomalies can be diagnosed with various imaging techniques. The main purpose of this article is to summarise imaging findings and clinical importance of congenital anomalies of seminal vesicles with images of some rare and previously unreported anomalies., Competing Interests: The authors report no conflict of interest.

Large-cell calcifying Sertoli cell tumor is a very rare neoplasm of the testis with less than 100 reported cases. It is associated with some genetic syndromes, and it has some features that help to distinguish benign and malign cases. An 11-year-old boy presented with testicular lesions in both testicles. He underwent right radical orchiectomy in another institution and was referred to our hospital for further treatment. The lesions were reported as large-cell calcifying Sertoli cell tumors in our institution. There were multiple hyperechoic lesions with calcifications in the left testis and lesions showed vascularization on Doppler. Sonographic features of these lesions were also suggestive of benign large-cell calcifying Sertoli cell tumor. The lesions were stabile during follow-up. The ultrasonographic appearance of large-cell calcifying Sertoli cell tumor is descriptive and, together with clinical findings, allows differential diagnosis. It can direct patient management, with a more conservative approach. We report a child with large-cell calcifying Sertoli cell tumor who could have been saved from extensive surgery, such as radical orchiectomy, if the tumor had been diagnosed correctly with sonography., Large-cell calcifying Sertoli cell tumor is a very rare neoplasm of the testis with less than 100 reported cases. It is associated with some genetic syndromes, and it has some features that help to distinguish benign and malign cases. An 11-year-old boy presented with testicular lesions in both testicles. He underwent right radical orchiectomy in another institution and was referred to our hospital for further treatment. The lesions were reported as large-cell calcifying Sertoli cell tumors in our institution. There were multiple hyperechoic lesions with calcifications in the left testis and lesions showed vascularization on Doppler. Sonographic features of these lesions were also suggestive of benign large-cell calcifying Sertoli cell tumor. The lesions were stabile during follow-up. The ultrasonographic appearance of large-cell calcifying Sertoli cell tumor is descriptive and, together with clinical findings, allows differential diagnosis. It can direct patient management, with a more conservative approach. We report a child with large-cell calcifying Sertoli cell tumor who could have been saved from extensive surgery, such as radical orchiectomy, if the tumor had been diagnosed correctly with sonography.

Aim: To determine the neuroprotective functions of quercetin and compare them with methylprednisolone in an experimental spinal cord injury model in rats., Material and Methods: Thirty male, Wistar rats were assigned to five experimental groups: sham (n=6), trauma (n=6), methylprednisolone (n=6), single dose quercetin (n=6), and multiple doses of quercetin (n=6). An aneurysm clip compression method was used to produce spinal cord injury at level T7-9 after performing a laminectomy. In the sham group, only a laminectomy was performed. Clip compression was performed to the spinal cord after laminectomy in the trauma group. For Group 3, a single dose of intraperitoneal (ip) methylprednisolone (30mg/kg) was administered after laminectomy and trauma. A single dose of ip quercet in (100mg/kg) was administered after laminectomy and trauma in Group 4. For Group 5, multiple doses of ip quercetin (100 mg/kg) were administered on the first, second, and third days after laminectomy and trauma. Spinal cord and serum samples were obtained to measure the levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant levels (TAL) at the 72nd hour. Neurofunctional examinations of all the rats according to Drummond and Moore criteria and inclined-plane tests to evaluate functional healing were performed. All rats were sacrificed via intracardiac blood depletion after the procedure., Results: Quercetin and methylprednisolone both increased plasma and tissue levels of NO and MDA, and decreased TAL, with a statistically significant difference (p < 0.05). NO and MDA levels in plasma and tissue were significantly higher in the trauma group (Group 2) when compared to the sham group (Group 1), and TAL levels were significantly lower (p < 0.05). There was a statistically significant increase in the treatment group's inclined-plane test (p < 0.05), while there was no difference in motor examination evaluations., Conclusion: The results of this experimental study suggest that quercetin can be thought as an option of treatment in spinal cord injury.

Aneurysms of the extracranial internal carotid artery (ICA) in pediatric patients are rare and mostly treated surgically. The authors present the case of a child with a giant extracranial ICA aneurysm presenting with gradual airway compression. A plan was made to explore the aneurysm surgically and straighten the associated carotid artery kinks during the operation to enable further endovascular treatment if primary reconstruction of the carotid artery proved not to be possible. Finally, the aneurysm was successfully treated with staged hybrid intervention, which consisted of surgical correction of parent artery kinks followed by endovascular implantation of stent grafts. The child tolerated the procedure well without adverse events. A craniocervical CT angiogram at 5 months showed patency of the stent construct and relief of airway compression. However, a follow-up CT angiogram at 14 months showed total occlusion of the ipsilateral carotid artery without clinical sequelae and complete cessation of airway compression. The management of this was unique since the patient is the first reported case of clopidogrel hyporesponsiveness in a child undergoing neurovascular intervention with prasugrel monotherapy. Point-of-care testing-based adjustment of prasugrel necessitated education of the patient's family regarding the loss of effect of the prasugrel tablets upon crushing and contact with air.

Background: Stereotactic radiosurgery (SRS) is widely used to treat brain pathologies alone or in concert with other treatment modalities. However, there are some side effects, such as radiation injury characterized by edema and necrosis in peripheral tissues, that must be managed. A new treatment agent against this side effect is bevacizumab, which targets increased vascular endothelial growth factor (VEGF) as a prominent etiologic factor in radiation injury. In this study, we created a rat experimental model to describe the effects of both radiation and the anti-VEGF monoclonal antibody bevacizumab following high-dose SRS, and to compare the effects of prophylactic and delayed-onset bevacizumab treatment., Methods: Fifty-four adult male Wistar rats were allocated into 9 groups based on differing Gamma-knife surgery (GKS) doses and bevacizumab treatment protocols. After 12 weeks, the rats' right frontal lobes were examined with hematoxylin and eosin staining and immunohistochemistry analysis via VEGF and CD31 antibodies., Results: Radiation necrosis occurred to varying degrees in all irradiated animals between 3 and 10 weeks post-SRS. Higher GKS dose (50% isodose of 100 Gy) led earlier necrosis and prophylaxis of bevacizumab at this dose was associated with delayed onset of necrosis. Moreover, prophylactic bevacizumab mitigated the effects of radiation necrosis following GKS at both doses, whereas this effect was not prominent with late initiation of bevacizumab (treatment protocol)., Conclusions: Our findings show that the onset and degree of radiation injury are affected by the GKS dose and protocol of bevacizumab administration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that resists efforts to identify better chemotherapeutics. PDA is associated with chronic pancreatitis and acinar cell dedifferentiation. This reduces enzyme production by the exocrine pancreas, resulting in digestive insufficiencies. Malabsorption of partially digested food causes bloating, overfilled intestines, abdominal pain, excessive feces, steatorrhea, and malnutrition. These maladies affect quality of life and restrict treatment options for pancreatitis and PDA. Here, we characterize health benefits and risks of dietary pancreatic enzymes in three mouse models of PDA-KC, KCR8-16, and KIC. KC expresses oncogenic Kras G12D in pancreatic tissue whereas KCR8-16 also has deletions of the Rgs8 and Rgs16 genes. Rgs proteins inhibit the release of digestive enzymes evoked by G-protein-coupled-receptor agonists. KC and KCR8-16 mice developed dedifferentiated exocrine pancreata within 2 months of age and became malnourished, underweight, hypoglycemic, and hypothermic. KC mice adapted but KCR8-16 mice rapidly transitioned to starvation after mild metabolic challenges. Dietary pancreatic enzyme supplements reversed these symptoms in KC and KCR8-16 animals, and extended survival. Therefore, we tested the benefits of pancreatic enzymes in an aggressive mouse model of PDA (KIC). Median survival improved with dietary pancreatic enzyme supplements and was extended further when combined with warfarin and gemcitabine chemotherapy. However, dietary pancreatic enzymes stimulated tumor growth in the terminal stages of disease progression in KIC mice., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Rhabdomyolysis is a clinical and biochemical syndrome caused by skeletal muscle injury. Our aim was to contribute to the existing data on rhabdomyolysis in our country by evaluating the etiologic, demographic, and clinical features of rhabdomyolysis patients who applied to a tertiary hospital emergency department., Methods: We retrospectively evaluated the data of patients who applied to the tertiary hospital emergency department from January 2015 to January 2016. The study population comprised patients admitted to the emergency department of our hospital with creatinine kinase levels above 5000 U/L at admission. The data of all cases that were included in the study were scanned by the researchers using the hospital's computer-based data recording system. Age, sex, creatine kinase levels, complaints, etiology, whether or not acute renal failure developed, hospitalization and discharge status, and clinic of hospitalization were screened for all patients., Results: The creatine kinase levels of the patients at admission ranged from 5052 to 59140 U/L [median 7882 U/L (IQR: 7840)]. The most frequent (23.5%) cause of admission was extremity pain. The most common reason (19.6%) in the etiology was exercise. Twenty-one patients (41.1%) were admitted to clinics, and 1 patient (1.9%) died. Acute renal failure was observed in 4 patients (8.8%)., Conclusion: Rhabdomyolysis is a clinical syndrome that can be life-threatening owing to muscle destruction. Although it is suspected after a traumatic injury, it should also be considered when other potential symptoms are observed. All clinicians should be aware of its common causes, diagnosis, and treatment options., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Iatrogenic arteriovenous fistula (AVF) is an unusual and potentially fatal complication of lumbar spinal surgery. The presentation of these injuries is usually late, with symptoms such as leg swelling or cardiac failure. It is crucial to suspect AVF in the patient which presents to emergency with lumbar spinal surgery history. The diagnosis is often based on imaging studies such as computed tomography (CT) or magnetic resonance (MR) angiography. Surgery was the first choice of treatment, but with recent advances in stent technology endovascular approach has become widely popular. We present two cases of AVF secondary to lumbar spinal surgery, one of them presenting with overt heart failure and the other one with leg swelling.

Acute non-traumatic liver disorders can originate from abnormalities of the hepatic artery, portal vein and hepatic veins. Ultrasonography and computed tomography can be used in non-traumatic acute vascular liver disorders according to patient status, indication and appropriateness of imaging modality. Awareness of the imaging findings, in the appropriate clinical context, is crucial for prompt and correct diagnosis, as delay may cause severe consequences with significant morbidity and mortality. This review article will discuss imaging algorithms, and multimodality imaging findings for suspected acute vascular disorders of the liver.

Kernohan-Woltman notch phenomenon (KWNP) is an ipsilateral motor weakness due to compression of the contralateral cerebral peduncle. Most of the KWNP cases reported have been due to subdural hematomas, intracranial space-occupying lesions, and spontaneous bleeding of vascular malformations. In this study, we present the first pediatric case of KWNP caused by a traumatic epidural hematoma. Although subdural hematomas are the most frequent reason for KWNP, epidural hematomas may cause paradoxical ipsilateral signs not only in adults but also in pediatric patients., (© 2017 S. Karger AG, Basel.)

Matrix metalloproteinase (MMP)-3 and MMP-9 polymorphisms are characterized by plaque stability in coronary arteries. The aim of the current study was to investigate the 5A/6A polymorphism in the MMP-3 gene and C/T polymorphism in the MMP-9 gene in patients with coronary artery disease (CAD). The study population consisted of 400 patients who underwent coronary angiography. There were two groups consisting of 200 consecutive patients with CAD, presenting with stable angina pectoris, and 200 consecutive patients exhibiting normal coronary arteries. Two single nucleotide polymorphisms in the MMP gene, MMP-3 and MMP-9 , were detected using a polymerase chain reaction-restriction fragment length polymorphism assay. Mean age, gender distribution, smoking status, presence of diabetes mellitus and hypercholesterolemia were identified to be similar between the groups. One hundred and twenty seven (63.5%) patients had hypertension in the CAD group, whereas only 55 (27.5%) patients had hypertension in the control group (P<0.001). No significant difference in frequency of alleles and genotypes of MMP-9 C→T between the CAD and control groups was identified. The 5A allele frequency of MMP-3 in the CAD group was significantly higher when compared with the control group (P<0.001; odds ratio=2.18). The genotype frequency of MMP-3 5A/5A in the CAD group was significantly higher when compared with the controls (P=0.005). When compared with the homozygous wild-type ( 6A/6A ) genotype of the MMP-3 gene, the cumulative frequency of heterozygote and homozygote genotypes of the MMP-3 gene was significantly higher in the CAD compared with the control group (P<0.001). Thus, the present study demonstrated that the 5A/5A and 6A/5A + 5A/5A genotypes of the MMP-3 gene were associated with an increased risk of CAD.

Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types. It has an unusually high safety margin and lacks neurotoxicity in rats at effective plasma concentrations. DZ-2384 binds the vinca domain of tubulin in a distinct way, imparting structurally and functionally different effects on microtubule dynamics compared to other vinca-binding compounds. X-ray crystallography and electron microscopy studies demonstrate that DZ-2384 causes straightening of curved protofilaments, an effect proposed to favor polymerization of tubulin. Both DZ-2384 and the vinca alkaloid vinorelbine inhibit microtubule growth rate; however, DZ-2384 increases the rescue frequency and preserves the microtubule network in nonmitotic cells and in primary neurons. This differential modulation of tubulin results in a potent MTA therapeutic with enhanced safety., Competing Interests: Diazon Pharmaceuticals Inc. holds the rights to the Patent Cooperation Treaty publication no. WO2009/134938 that covers DZ-2384. None of the authors of this manuscript are named inventors on this patent. G.C.S., A.R., and P.H. are founders and shareholders in Diazon Pharmaceuticals Inc. R.A.B. and T.M.W. are founders of Tuevol Therapeutics Inc. and are inventors on patent applications (62/067,304; 62/067,276; 62/232,901; and 62/232,922) held or submitted by the UT Southwestern Medical Center that cover the use of the GEMM rapid in vivo assay (Rgs16∷GFP;KIC model) for screening therapeutics for pancreatic ductal adenocarcinoma., (Copyright © 2016, American Association for the Advancement of Science.)

Background: The perioperative use of antithrombotic therapy is associated with increased bleeding risk after cardiac implantable electronic device (CIED) implantation. Topical application of tranexamic acid (TXA) is effective in reducing bleeding complications after various surgical operations. However, there is no information regarding local TXA application during CIED procedures. The purpose of our study was to evaluate bleeding complications rates during CIED implantation with and without topical TXA use in patients receiving antithrombotic treatment., Methods: We conducted a retrospective analysis of consecutive patients undergoing CIED implantation while receiving warfarin or dual antiplatelet (DAPT) or warfarin plus DAPT treatment. Study population was classified in two groups according to presence or absence of topical TXA use during CIED implantation. Pocket hematoma (PH), major bleeding complications (MBC) and thromboembolic events occuring within 90 days were compared., Results: A total of 135 consecutive patients were identified and included in the analysis. The mean age was 60 ± 11 years old. Topical TXA application during implantation was reported in 52 patients (TXA group). The remaining 83 patients were assigned to the control group. PH occurred in 7.7 % patients in the TXA group and 26.5 % patients in the control group (P = 0.013). The MBC was reported in 5.8 % patients in the TXA and 20.5 % patients in control group (P = 0.024). Univariate logistic regression analysis identified age, history of recent stent implantation, periprocedural spironolactone use, periprocedural warfarin use, perioperative warfarin plus DAPT use, cardiac resynchronization therapy, and topical TXA application during CIED implantation as predicting factors of PH. Multivariate analysis showed that perioperative warfarin plus DAPT use (OR = 10.874, 95 % CI: 2.496-47.365, P = 0.001) and topical TXA application during CIED procedure (OR = 0.059, 95 % CI: 0.012-0.300, P = 0.001) were independent predictors of PH. Perioperative warfarin plus DAPT use and topical TXA application were also found to be independent predictors of MBC in multivariate analyses. No thromboembolic complications was recorded in the study group., Conclusion: The present study demonstrated that the topical TXA application during CIED implantation is associated with reduced PH and MBC in patients with high bleeding risk.

Endovascular stent graft implantation is a favorable method for complex aortic coarctation accompanied by patent ductus arteriosus. Herein, an 18-year-old woman with complex aortic coarctation and patent ductus arteriosus was successfully treated by endovascular thoracic stent graft via retroperitoneal approach. The reason for retroperitoneal iliac approach was small sized common femoral arteries which were not suitable for stent graft passage. This case is the first aortic coarctation plus patent ductus arteriosus case described in the literature which is treated by endovascular thoracic stent graft via retroperitoneal approach.

The aim of this study was to evaluate whether there is a difference in the return of spontaneous circulation (ROSC) and survival with sequel-free recovery rates between the patients who underwent cardiopulmonary resuscitation (CPR) according to 2005 and 2010 guidelines. This study was conducted in the Bakırköy Dr. Sadi Konuk and Kartal Lütfi Kırdar Training and Research Hospital between dates of October 2010 and 28 February 2011 after approval of Ethics Committee. In the first months of the study, CPR was performed according to AHA 2005 ACLS guidelines (Group-1), while CPR was performed according to AHA 2010 ACLS guidelines after November 2010 (Group-2). Patients were assessed for neurological deficit with Cerebral Performance Categories Scale. Mean age was found as 69.01±13.05 (minimum: 21, maximum: 92) in 86 patients included. Of the 33 patients underwent CPR in the Group 1, ROSC was achieved in 51.5%; and 6.1% of these patients were discharged. Of the 53 patients underwent CPR in the Group 2, ROSC was achieved in 37.7%; and 9.4% of these patients were discharged. Although the number of living patients in Group 2 was higher than Group 1, the difference was not found statistically significant (5 versus 2), (P>0.05). But, neurological outcomes were found better with 2010 compared to 2005 guidelines (3/7 versus 0/2 good cerebral performance). It was found that the 2005 CPR guidelines practices in ED were more successful than the 2010 CPR guidelines practices in ROSC, but less successful in the rate of discharge from hospital and neurological sequel-free discharge rate.

Context and Objective: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism., Design and Setting: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey., Methods: 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located), and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9); second group (thrombus in main pulmonary artery branches; n = 71); third group (thrombus in pulmonary artery segmental branches; n = 34); and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8)., Results: Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009) and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033) remained independently associated with proximally localized thrombus in pulmonary artery., Conclusions: The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.