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Microtubule (MT) and F-actin cytoskeletal crosstalk and organization are important aspects of axon guidance mechanisms, but how associated proteins facilitate this function remains largely unknown. While the MT-associated protein, CKAP5 (XMAP215/ch-TOG), has been best characterized as a MT polymerase, we have recently highlighted a novel role for CKAP5 in facilitating interactions between MT and F-actin in vitro and in embryonic Xenopus laevis neuronal growth cones. However, the mechanism by which it does so is unclear. Here, using in vitro reconstitution assays coupled with TIRF microscopy, we report that the TOG5 domain of CKAP5 is necessary for its ability to bind to and bundle actin filaments, as well as to crosslink MTs and F-actin in vitro. Additionally, we show that this novel MT/F-actin crosslinking function of CKAP5 is possible even in MT polymerase-incompetent mutants of CKAP5 in vivo . Indeed, CKAP5 requires both MT and F-actin binding, but not MT polymerization, to promote MT-F-actin alignment in growth cones and axon outgrowth. Taken together, our findings provide mechanistic insights into how MT populations penetrate the growth cone periphery through CKAP5-facilitated interaction with F-actin during axon outgrowth and guidance. [Media: see text] [Media: see text] [Media: see text].

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

Histone deacetylase 6 (HDAC6, Class IIb) is a promising target for anticancer drugs. So far, few nonselective HDAC inhibitors have received regulatory approval as anticancer agents. However, they are associated with cell toxicity. Thus, isoform-selective inhibitors may be desirable. Here, we conducted structure-based virtual screening of multiple libraries containing a total of 2,250,135 compounds against HDAC6. The top hits with good docking scores and potential selectivity over HDAC10 (Class IIb) were submitted to 100 ns molecular dynamics simulation to monitor their dynamic behaviors and stability in the binding pockets of these enzymes. Furthermore, the drug-likeness and ADMET properties of these hits were estimated computationally. Four diverse compounds from different sources, including NCI and ZINC databases (BDH33926500, CID667061, Cromolyn, and ZINC000103531486), show potential selectivity for HDAC6., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kemal Yelekci reports was provided by Kadir Has University. Kemal Yelekci reports financial support was provided by Health Institutes of Türkiye (TUSEB). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the highly regenerative axolotl and found that the harmonized atlas also improves cell type annotation, particularly of sparse neuronal subtypes. We observed that the transcriptomes of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The resources presented here can guide future studies in comparative transcriptomics, simplify cell-type nomenclature differences across studies, and help prioritize targets for future analgesic development.

Laboratory scale conventional single-use bioreactor was used to investigate the effect of different stirrer speeds on the Arthrospira platensis (Spirulina platensis) culture. Experiments were handled in two steps. First step was the selection of the stirring speeds, which was simulated via using CFD, and the second was the long term cultivation with the selected speed. During 10 days of batches as the first step, under identical culture conditions, stirrer speed of 230 rpm gave higher results, compared to 130 and 70 rpm, with respect to dry biomass weight, absorbance value (AB) and chlorophyll-a concentration. Volumetric productivity during the growth phase of the cultures were calculated as 0.39 ± 0.03, 0.28 ± 0.01, and 0.19 ± 0.02 g L -1  d -1 , from the fast to the slower speeds. According to the results a 17 day batch was handled with 230 rpm in order to monitor the effects on the culture. The culture reached a volumetric productivity of 0.33 ± 0.04 g L -1  d -1 . Statistical analysis showed the significance of the parameters related with the stirring speed., (© 2024 American Institute of Chemical Engineers.)

Introduction: Hyponatremia is the most common electrolyte disorder often present in peritoneal dialysis (PD) patients. The aim of this retrospective study was to investigate the effect of hyponatremia on mortality in patients undergoing PD., Methods: The health records of adult individuals with an inserted PD catheter identified via the centralized national e-health database were used., Results: The mean age of the 846 patients included in the study was 52.48 years (±14.6). The mean sodium level was 136.51 mEq/L. Sodium levels <137 mEq/L were associated with higher death risk independent of comorbidities. There was a 0.821 times less reduction in mortality for each mEq /L increase in serum sodium., Conclusion: Our study provides evidence that monitoring and adjusting serum sodium levels is crucial in managing PD patients with hyponatremia, as low serum sodium level was found to be a significant and independent predictor of mortality., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Determining and monitoring ground deformations is critical for hazard management studies, especially in megacities, and these studies might help prevent future disaster conditions and save many lives. In recent years, the Golden Horn, located in the southeast of the European part of Istanbul within a UNESCO-protected region, has experienced significant changes and regional deformations linked to rapid population growth, infrastructure work, and tramway construction. In this study, we used Interferometric Synthetic Aperture Radar (InSAR) and Global Navigation Satellite System (GNSS) techniques to investigate the ground deformations along the Golden Horn coastlines. The investigated periods are between 2015 and 2020 and 2017 and 2020 for InSAR and GNSS, respectively. For the InSAR analyses, we used sequences of multi-temporal synthetic aperture radar (SAR) images collected by the Sentinel-1 and ALOS-2 satellites. The ground displacement products (i.e., time series and velocity maps) were then cross-compared with those achievable using the Precise Point Positioning (PPP) technique for the GNSS solutions, which can provide precise positions with a single receiver. In the proposed analysis, we compared the ground displacement velocities obtained by both methods by computing the standard deviations of the difference between the relevant observations considering a weighted least square estimation procedure. Additionally, we identified five circle buffers with different radii ranging between 50 m and 250 m for selecting the most appropriate coherent points to conduct the cross-comparison analysis. Moreover, a vertical displacement rate map was produced. The comparison of the vertical ground velocities derived from PPP and InSAR demonstrates that the PPP technique is valuable. For the coherent stations, the vertical displacement rates vary between -4.86 mm/yr and -23.58 mm/yr and -9.50 and -27.77 mm/yr for InSAR and GNSS, respectively.

Purpose: To investigate the impact of missing data and imputation with the response function (RF) approach on bias and precision of disability estimates as well as reliability of scale of WHO Disability Assessment Schedule 2.0., Material and Methods: Data were collected by face-to-face interviews and self-report surveys from 284 respondents with low back pain. Hypothetical datasets were created by using person and item parameters of real data. A simulation study was devised to assess the ability parameters and reliability measures on incomplete and imputed datasets. Rasch model was used to evaluate latent trait levels. Imputation was carried out using the response function method., Results: Almost the same level of bias and MSE was reached. While the missing rate increases, the Person separation index slightly reduced, still exceeded 0.94 and Cronbach alpha values have similar mean values of 0.99 with larger variations. After deletion of four items of "work or school activities" in domain 5, reliability measures reduced the lowest., Conclusion: Construct validity is preserved. Problems regarding the compliance of the items with the target group still persist. When researchers encounter missingness in data collected with WHODAS 2.0, the response function can be usefully implemented to impute missing values to improve the reliability of disability level estimates.Implications for rehabilitationThe Turkish version of the 36-item WHODAS is reliable and valid for assessing health and disability status in patients with low back pain.A critical issue is a systematic nonresponse was highly observed in items related to "work/school life activities" which are allowed to be skipped and excluded from the scoring according to WHODAS 2.0 training manual.Imputation of missing values within four items of "work or school activities" in domain 5 using the response function approach showed satisfactory reliability for the estimation of disability in adults with low back pain.This study showed missing data imputations with response function can be implemented by a statistician as contribute to a missing data management process better tailored to clinicians' interpretations.

Background: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data., Methods: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features., Results: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003)., Conclusions: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Introduction: Hand washing and the use of gloves in accordance with the standards are among the most significant methods used in infection control., Methodology: This study is an analytical cross-sectional study. The sample of the study consisted of 132 health personnel working in the emergency department of a public hospital., Results: The mean of the hand hygiene belief scale was 85.50 ± 8.71, mean of the hand hygiene practice inventory was 67.70 ± 5.19. The participants' mean general attitude towards the use of gloves was 43.71 ± 7.57, the mean of awareness about the use of gloves was 15.17 ± 3.88, the mean attitude towards the usefulness of glove use was 19.43 ± 1.47, and their attitude towards the necessity of using gloves was 12.63 ± 3.57. It was determined that glove usefulness score has a statistically significant and increasing effect on hand hygiene belief, while glove usefulness and glove awareness scores have statistically significant and increasing effects on hand hygiene practice., Conclusions: This study determined that the hand hygiene beliefs and practices of the health personnel working in the emergency department are quite high, their attitudes towards the use of gloves are positive, the attitude towards the usefulness of glove use has a significant and increasing effect on hand hygiene belief, and glove usefulness and glove awareness attitudes have a significant and increasing effect on hand hygiene practice., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Yıldız Denat, Banu Cihan Erdogan, Zeynep Yilmaz.)

Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib., Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR's) and prognostic nutritional index (PNI's) optimum cut-off value. The relationship between OS with PNI and NLR was investigated., Results: Fifty-two patient's data were analyzed. The median age was 57 years, 22 (41.5%) of the patients were female. The optimal cut-off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95% confidence interval [CI]: 0.19-0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95% CI: 0.29-1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95% CI: 0.17-0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95% CI: 0.18-0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95% CI: 0.21-0.80 P = 0.01) were the only independent factors for longer OS., Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib., Competing Interests: None

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population., Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases., Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism., Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term., Funding: None., Competing Interests: EAV, AS, CB, RM, KH, AGS, GR, MJS, and PBR are employees of Janssen Research and Development LLC and shareholders of Johnson & Johnson (J&J) stock. Many data partners (including JMR, JMRA, MAM, MdW, LHJ, GB, PRR) on this project have received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The funding source had no role in writing the manuscript or the decision to submit it for publication. Odysseus Data Services, where SvS is employed, is a beneficiary of the mentioned IMI 2 JU project. DPA has received support from the EMA and Innovative Medicines Initiative. DPA's research group has received grant support from Amgen, Chesi-Taylor, Novartis, GSK, UCB Biopharma and J&J. DPA's department has received advisory/consultancy fees from AstraZeneca, Amgen, Astellas, J&J, and UCB Biopharma. DPA's department has received fees for speaker services from Amgen and UCB Biopharma. DPA's has other financial or non-financial interests in Janssen, on behalf of the IMI-funded EHDEN and European Medical Information Framework (EMIF) consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department that was open for external participants. TDS received financial support from the Institute de Salud Carlos Ill (ISCIII; Miguel Servet 2021: CP21/00023) which is co-funded by the European Union. The funding source had no role in writing the manuscript or the decision to submit it for publication. PRR, MdW, LHJ work for a research group who received/receives unconditional research grants from Chiesi, Amgen, UCB, J&J, European Medicines Agency (EMA), and IMI. GH provided funding for use of the CUIMC database and the OHDSI infrastructure. GH received support through a grant to Columbia University (NIH R01 LM006910). MAS receives grants from the US Department of Veterans Affairs within the scope of this work, and grants and contracts from the US National Institutes of Health, US Food & Drug Administration, and Janssen Research & Development outside the scope of this work. EPM receives salary support from the Department of Medicine at University of Calgary. EPM receives consulting fees from Janssen Research & Development for work that is outside the scope of the current study. FM's main employment is for Heliant d.o.o, an EHR provider in Serbia. JDP received salary support through the Universidad de Norte. DJD and ZC are full-time employees of CPRD, which provides contract research services for government and related healthcare authorities, and the pharmaceutical industry, including Janssen. FN holds some AstraZeneca shares and was employed there until 2019. RV, AJB, AP2, LD, and CH received partial funding for this work by the University of California Health System and its Center for Data-Driven Insights and Innovation. MGK received support for the manuscript via institutional (internal funding) only. AJB's research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor’s Office of Planning and Research, California Institute for Regenerative Medicine, L’Oréal, and Progenity. AJB receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. AJB is a co-founder and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche. AJB has received honoraria and travel reimbursement for invited talks from J&J, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, many academic institutions, medical or disease specific foundations and associations, and health systems. AJB is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, Vet24seven, and several other non-health related companies and mutual funds. DRM has grants or contracts from Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). FB has a leadership or fiduciary role as the program chair of j-ISBA., (© 2023 The Author(s).)

Oral cancer is a paradigm of Slaughter's concept of field cancerization, where tumors are thought to originate within an area of cells containing genetic alterations that predispose to cancer development. The field size is unclear but may represent a large area of tissue, and the origin of mutations is also unclear. Here, we analyzed whole exome and transcriptome features in contralateral tumor-distal tongue (i.e. distant from the tumor, not tumor-adjacent) and corresponding tumor tissues of 15 patients with squamous cell carcinoma of the oral tongue. The number of point mutations ranged from 41 to 237 in tumors and from one to 78 in tumor-distal samples. Tumor-distal samples showed mainly clock-like (associated with aging) or tobacco smoking mutational signatures. Tumors additionally showed mutations that associate with cytidine deaminase AID/APOBEC enzyme activities or a UV-like signature. Importantly, no point mutations were shared between a tumor and the matched tumor-distal sample in any patient. TP53 was the most frequently mutated gene in tumors (67%), whereas a TP53 mutation was detected in only one tumor-distal sample, and this mutation was not shared with the matched tumor. Arm-level copy number variation (CNV) was found in 12 tumors, with loss of chromosome (Chr) 8p or gain of 8q being the most frequent events. Two tumor-distal samples showed a gain of Chr8, which was associated with increased expression of Chr8-located genes in these samples, although gene ontology did not show a role for these genes in oncogenic processes. In situ hybridization revealed a mixed pattern of Chr8 gain and neutral copy number in both tumor cells and adjacent nontumor epithelium in one patient. We conclude that distant field cancerization exists but does not present as tumor-related mutational events. The data are compatible with etiologic field effects, rather than classical monoclonal field cancerization theory. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Transporter associated with antigen processing 1 (TAP1) and TAP2 serve pivotal roles in adaptive immunity. Tumor cells often show reduced antigen presentation on their surface as one mechanism to escape immune recognition. Whether downregulation of TAPs is a common mechanism of tumor immune evasion in squamous cell carcinoma of the oral tongue (SCCOT) is unclear. In the present study, samples from 78 patients with SCCOT and 17 patients with benign hyperplastic tongue lesions were analyzed for TAP1 and TAP2 expression by immunohistochemistry. The percentage of positive cells and staining intensity were scored. Associations with clinicopathological variables and survival outcome were also investigated. The results demonstrated that TAP1 and TAP2 levels were highly associated with each other in individual samples and were upregulated in SCCOT compared with benign lesions (P<0.001). The proportion of TAP1- or TAP2-positive tumor cells was >80% in all but two of the tumors, whereas 25.6 and 23.0% of the tumors showed weak intensity of TAP1 and TAP2, respectively. There were no significant associations with clinicopathological variables or survival outcomes between TAP-intermediate/strong and TAP-weak tumors. However, in patients <70 years old and with early stage SCCOT, male patients had better outcomes than female patients (log-rank P<0.05), and the best outcome was observed in male patients with intermediate/strong TAP expression. In conclusion, loss of TAP was not a frequent event in SCCOT and stronger TAP expression in male patients was associated with improved survival, providing further evidence for sex-specific immune modulation in cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Attaran et al.)

The use of unmanned aerial vehicles (UAV) in photogrammetric mapping/surveying facilities has increased recently due to the developments on photogrammetric instruments and algorithms that enhance high-quality final products (orthoimages, digital surface model-DSM, etc.) in fast, accurate, and economical way. The aim of this study was to assess the accuracy of a UAV-based post-processing kinematic (PPK) solution. To do that, two methods were implemented with PPK solution and georeferencing with ground control points (GCPs). According to the statistical results, root mean square error (RMSE) values obtained from the GCPs and PPK solutions in the horizontal component are 6.5 cm and 5.4 cm, respectively. The RMSE values in the vertical component (ellipsoidal heights) were obtained as 4.8 cm (GCPs) and 5.2 cm (PPK), respectively. The results show that UAV-PPK method can also be used to produce photogrammetric products where high accuracy (≤ 10 cm) is required without GCPs. In addition, the results obtained regarding the use of this method clearly show that it can be applied in many different fields such as agriculture, forestry, natural disasters, and geomatics., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The visual system forms the basis of visual word decoding processes. Reading is a left-lateralized function. The interaction between the two hemispheres via the corpus callosum is required for successful reading. It is known that callosal function and morphology are affected in reading disorders. This study investigated the differences in callosal transfer speed of verbal and nonverbal stimuli in healthy university students. We hypothesized that if the callosal transfer has a role in slow reading, transfer speed would differ between slow and fast readers. Moreover, if the difference was affected by the type of stimulus, this will provide information about the level of neural processing at which the difference is based/aroused. Fifty-one participants were grouped as slow (n = 15, 8 female) and fast (n = 36, 22 female) readers. Three types of stimuli (word, legal pseudoword, and non-verbal grating) were presented from the right or left visual field. Latencies of the evoked potentials (N1) were used to measure interhemispheric transfer time. We found that slow readers have a slower right-to-left transfer speed at the parietal site, which is related to the visual word decoding process. The finding was similar to previous studies examining individuals with dyslexia. This difference was not seen with grating stimuli; we suggest that the difference originates at the orthographic visual lexical level rather than at earlier basic visual processing. We did not observe any effect of lexical and sublexical routes on the callosal transfer time because of evaluated time windows., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis ( IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A) , specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide variants, 75 duplications, and 104 deletions). The most and least frequently mutated genes were IKZF1 and CREBBP , respectively. There were statistically significant differences between patients and controls for mutation distribution in eight genes ( ERG, CRLF2, CREBBP, TSLP, JAK2, ZAP70, FOXO3A, and NR3C1 ). The expression analysis revealed that JAK and ERG were significantly overexpressed in patients compared with controls (respectively, p  = 0.004 and p  = 0.003). This study combined genes and pathways previously analyzed in pediatric BCP-ALL into one dataset for a comprehensive analysis from the same samples to unravel candidate prognostic biomarkers. Novel mutations were identified in all of the studied genes., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Crescentic IgA nephropathy (IgAN) with the positivity for antineutrophilic cytoplasmic antibody (ANCA) is a novel and uncommon entity. The optimal management of this condition is not well-defined. We report a 49-years-old woman with complaints of skin rash and swelling of lower limbs. She had hematuria, proteinuria and, progressive renal impairment with positive myeloperoxidase (MPO)-ANCA test. A renal biopsy revealed MPO-ANCA-associated crescentic IgAN. Induction therapy was intravenous methylprednisolone, cyclophosphamide and, therapeutic plasma exchange (TPE). An unexpected disease flare-up was observed during induction immunosuppressive therapy which regressed after long-term TPE. The patient experienced a full renal recovery after treatment with long-term TPE, cyclophosphamide, and corticosteroids.  DOI: 10.52547/ijkd.6490.

Introduction: The incidence of chronic subdural hematoma (CSDH) is increasing. This study evaluates the etiologic causes and findings of CSDH and compared unilateral CSDH with bilateral CSDH. This study aims to draw attention to this increasingly prevalent condition., Methods: We retrospectively analysed 195 surgically treated cases of CSDH in our clinic between 2008 and 2018., Results: The average age of the patients was 65.7 ± 19.6 years. The most common symptom was headache (53.3%). The case background was the use of anticoagulant (37.9%), head trauma (34.3%). The hematomas were 28.7% right side, 44.6% left side, and 26.7% bilateral. The mean Glasgow Coma Score (GCS) was 13.4 ± 2.9, early postop 13.8 ± 2.5, and late postop was 14.6 ± 1.1. Postoperative complications included acute subdural hematoma (5.1%), cerebral infarction (1.5%), wound infection (0.5%) and others (13.3%). Re-expansion of the brain were statistically significantly less frequent and impaired consciousness, anticoagulant use, early and late postop thickness were statistically significantly more frequent in patients with bilateral CSDH., Conclusions: CSDH is seen more patients of advanced age, those who use anticoagulants, patients with hypertension and diabetes and in patients with a history of head trauma. Prognosis is worse in bilateral CSDH. We estimate that the incidence of CSDH will go up in the future., (© 2021 John Wiley & Sons Ltd.)

As early detection is crucial for improvement of cancer prognosis, we searched for biomarkers in plasma from individuals who later developed squamous cell carcinoma of the oral tongue (SCCOT) as well as in patients with an already established SCCOT. Levels of 261 proteins related to inflammation and/or tumor processes were measured using the proximity extension assay (PEA) in 179 plasma samples (42 collected before diagnosis of SCCOT with 81 matched controls; 28 collected at diagnosis of SCCOT with 28 matched controls). Statistical modeling tools principal component analysis (PCA) and orthogonal partial least square - discriminant analysis (OPLS-DA) were applied to provide insights into separations between groups. PCA models failed to achieve group separation of SCCOT patients from controls based on protein levels in samples taken prior to diagnosis or at the time of diagnosis. For pre-diagnostic samples and their controls, no significant OPLS-DA model was identified. Potentials for separating pre-diagnostic samples collected up to five years before diagnosis ( n = 15) from matched controls ( n = 28) were seen in four proteins. For diagnostic samples and controls, the OPLS-DA model indicated that 21 proteins were important for group separation. TNF receptor associated factor 2 (TRAF2), decreased in pre-diagnostic plasma (< 5 years) but increased at diagnosis, was the only protein showing altered levels before and at diagnosis of SCCOT ( p -value < 0.05). Taken together, changes in plasma protein profiles at diagnosis were evident, but not reliably detectable in pre-diagnostic samples taken before clinical signs of tumor development. Variation in protein levels during cancer development poses a challenge for the identification of biomarkers that could predict SCCOT development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gu, Coates, Wang, Erdogan, Salehi, Sgaramella, Zborayova and Nylander.)

Background: Pilonidal sinus is a common health problem. The current study aimed to compare the impact of autologous platelet-rich plasma (PRP) with that of minimally invasive techniques in terms of pain reduction, return to daily activities, quality of life, and duration of wound healing after open excision and secondary closure., Methods: Patients who were over 18 years old and had chronic PS disease between March 2018 and January 2019 were enrolled and randomly divided into three groups. Open surgery and moist dressings were applied to patients in group A. Open surgery followed by PRP application was performed on patients in group B. Group C underwent curettage of the sinus cavity followed by application of PRP. In this prospective randomized controlled study, patients completed questionnaires (including the Nottingham Health Profile (NHP), Short Form-36 (SF-36) and clinical information) before and after surgery. Demographics, preoperative characteristics, healing parameters, and quality-of-life scores were evaluated and calculated before and after surgery., Results and Conclusion: The cavity volume and wound-healing time were compared among the groups on postoperative days 0, 2, 3, 4, and 21. Each patient was followed up throughout the process of wound healing, and follow-up was continued afterward to monitor the patients for recurrence. Due to the nature of the treatment that group C received, this group achieved shorter healing times and smaller cavity volume than the other groups. In contrast, the recovery time per unit of cavity volume was significantly faster in group B than in the other groups. Overall postoperative pain scores were significantly lower for both PRP groups (open surgery, group B; minimally invasive surgery, group C) than for group A (p < 0.001) and showed different time courses among the groups. In the treatment of PS disease, PRP application improves postoperative recovery in that it speeds patients' return to daily activities, reduces their pain scores and increases their quality of life. Trial registration The current study is registered on the public website ClinicalTrials.gov (ClinicalTrials.gov identifier number: NCT04697082; date: 05/01/2021)., (© 2021. The Author(s).)

Purpose: To demonstrate whether early changes in systemic inflammatory markers are related with pazopanib treatment response in soft tissue sarcoma and renal cell carcinoma., Methods: Forty-one patients with metastatic clear cell renal carcinoma (mRCC) (n=22) and advanced stage soft tissue sarcoma (STS) (n=19) were assessed. Systemic inflammatory markers such as neutrophils, lymphocytes, c-reactive protein (CRP), mean platelet volume (MPV), lactate dehydrogenase (LDH) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at both baseline and 1-month of pazopanib treatment were obtained and their relation with the first radiological response about 3-months later after pazopanib treatment was evaluated., Results: Disease control rate (DCR) at the first initial radiological evaluation was 58.5 % for all, it was 77.3% for the RCC group and 36.8% in the STS group. Serum neutrophil, NLR and CRP levels were significantly decreased from baseline in RCC patients who had DCR with pazopanib treatment. Also, serum CRP levels after pazopanib treatment was significantly lower in RCC patients who had DCR (+) rather than those who progressed., Conclusions: Early decline in serum CRP, neutrophil and NLR levels in RCC patients who received pazopanib at the first month was significantly associated with disease control, assuming a predictive role for the first radiological assessment. However, there was no significant association between change in serum inflammatory marker levels and disease control in STS patients.

Purpose: In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer., Methods: 87 patients with metastatic colorectal cancer had been followed up with palliative care due to disease progression or ECOG performance status after receiving at least two cycles of chemotherapy. PPS was estimated as the time between the last progression date and last control or death date in patients who were followed up with palliative care., Results: 87 patients with metastatic colorectal cancer were included in the study. Evaluation with multivariate analysis of factors affecting PPS revealed a significantly longer PPS (10.8 weeks) in patients with ECOG score 0 or 1 than the PPS of patients with ECOG score 2-5 (3 weeks) (p=0.01). It was also found that PPS was 14.4 weeks in patients with CEA levels <5ng/ml,while it was 6.7 weeks in patients with CEA levels ≥5 ng/ml (p=0.001) and PPS was 13.7 weeks in patients with controlled disease after first-line chemotherapy while it was 8 weeks in patients with progression (p=0.03); both were statistically significant. No significant association was found between PPS and age, gender, tumor location, sites of metastasis, and RAS status., Conclusion: ECOG performance status score of 0-1, CEA levels below 5 ng/ml, and disease control with first-line chemotherapy are related to longer PPS in patients with metastatic colorectal cancer.

Employers have increasingly turned to virtual interviews to facilitate online, socially distanced selection processes in the face of the COVID-19 pandemic. However, there is little understanding about the experience of job candidates in these virtual interview contexts. We draw from Event System Theory (Morgeson et al., 2015) to advance and test a conceptual model that focuses on a high-stress, high-stakes setting and integrates literatures on workplace stress with literatures on applicant reactions. We predict that when applicants ruminate about COVID-19 during an interview and have higher levels of COVID-19 exhaustion, they will have higher levels of anxiety during virtual interviews, which in turn relates to reduced interview performance, lower perceptions of fairness, and reduced intentions to recommend the organization. Further, we predict that three factors capturing COVID-19 as an enduring and impactful event (COVID-19 duration, COVID-19 cases, COVID-19 deaths) will be positively related to COVID-19 exhaustion. We tested our propositions with 8,343 job applicants across 373 companies and 93 countries/regions. Consistent with predictions, we found a positive relationship between COVID-19 rumination and interview anxiety, and this relationship was stronger for applicants who experienced higher (vs. lower) levels of COVID-19 exhaustion. In turn, interview anxiety was negatively related to interview performance, fairness perceptions, and recommendation intentions. Moreover, using a relevant subset of the data (n = 6,136), we found that COVID-19 duration and deaths were positively related to COVID-19 exhaustion. This research offers several insights for understanding the virtual interview experience embedded in the pandemic and advances the literature on applicant reactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose: To evaluate early continence of patients who underwent inpatient rehabilitation after radical cystectomy (RC) and orthotopic bladder substitution (ONB)., Methods: We conducted a retrospective analysis on the data of 283 patients who underwent a three weeks inpatient rehabilitation after RC and ONB for bladder cancer between January 2016 and July 2017. All patients were treated with a special multimodal continence therapy. The continence status was evaluated by measuring urine loss by a 24-h pad test and urine volume on uroflowmetry at the beginning (T1) and at the end (T2) of inpatient rehabilitation. Multivariate linear regression analysis was performed to identify independent predictors of urine loss., Results: Median patient age was 63 years. NS was documented for 142 patients (50.2%). Median urine loss decreased significantly (p < 0.001) in the 24-h pad test, from 442 gm at T1 (median 29 days after surgery) to 88 gm at T2 (median 50 days after surgery). Urine volume increased significantly (p < 0.001) from a median of 78 ml at T1 to a median of 157 ml at T2. Age (p = 0.002), diabetes (p = 0.031), obesity (p = 0.003), and nerve sparing (p = 0.011) were identified as independent predictors for urine loss at the end of inpatient rehabilitation., Conclusion: Continence improved significantly during the three weeks of inpatient rehabilitation. Younger age, the absence of diabetes or obesity, and NS resulted in better continence in the early postoperative period after ONB., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival., Methods: The records of 125 patients with metastatic RCC admitted between January 2005 and February 2018 were retrospectively analyzed and 63 patients who received pazopanib or sunitinib were included in the study while 62 patients were excluded due to insufficient data. Clinical and histological characteristics, treatment responses, progression-free survival (PFS), and overall survival (OS) of the patients were compared., Results: Patients with metastatic RCC who received pazopanib or sunitinib as tyrosine kinase inhibitors (TKI) in first-line treatment were analyzed; 45 (71.4%) were male while 18 (28.6%) were female, and the median age was 60. 43 (68.3%) patients were treated with sunitinib and 20 (31.7%) with pazopanib. PFS ​​of pazopanib and sunitinib were 10.6 and 7.2 months, respectively. Median OS was 14.5 months in patients receiving pazopanib and 13.6 months in those receiving sunitinib. There was no statistical difference in PFS and OS between both treatments. The median OS of clear-cell RCC was 15.2 months, while of non-clear-cell RCC was 7.7months., Conclusions: High ECOG score, non-clear-cell histology, presence of liver metastasis in metastatic RCC patients were found to be associated with shorter OS and PFS. Sunitinib and pazopanib produced similar OS and PFS rates in first-line treatment of metastatic RCC.

Background and Aim: We aim to evaluate serum vitamin D levels, vitamin D receptor (VDR) expression in the intestinal epithelium, and their relation with epithelial barrier proteins and bone metabolism in children with Celiac disease (CD)., Methods: Immunostaining for VDR, Claudin-2 and E-cadherin was performed in duodenal samples of the patients with CD and controls. H-score [∑Pi(I+1)] where I is the intensity score and Pi is the corresponding percentage of stained cells was calculated for each samples. The clinic, laboratory and histopathological findings were compared between patients and controls., Results: Thirty-six patients with CD and age and sex matched 36 controls were enrolled. 25-OH vitamin D levels were significantly lower in the patient group compared to the control group. The mean bone mineral density (BMD) value was significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. H-scores for both VDR and Claudin-2 were significantly lower in patient group when compared to the control group. H-scores for VDR, Claudin-2 and E-cadherin were significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. There were positive correlations between 25-OH vitamin D level and H-scores for VDR, E-cadherin and Claudin-2 in patient group., Conclusions: Our findings showed that vitamin D deficiency is common among children with CD. Expression of VDR and epithelial barrier proteins Claudin-2 and E-cadherin which have important roles in paracellular pathway, was decreased in children with CD in correlation with histological findings of disease severity. Furthermore, deficiency of vitamin D was related to decreased expression of VDR and epithelial barrier proteins E-cadherin and Claudin-2. These findings indicate that paracellular pathway structures responsible for calcium absorption are disturbed in CD which is aggravated by vitamin D deficiency., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: We aimed to assess whether skeletal muscle loss during EGFR thyrosine kinase inhibitor therapy of advance non-small cell lung cancer patients is an independent prognostic factor for progression-free survival (PFS) and overal survival (OS)., Methods: A total of 45 patients who had computed tomography images were retrospectively evaluated at the diagnosis and during the treatment period before progression occurs., Results: During treatment 19 patients (42.2%) had skeletal muscle loss. Objective response rates in muscle loss group and muscle stable group were 36.8% and 73.0%, respectively (p<0.01). Median follow-up time was 18.9 months (14.8-32.1). Median PFS was 14.7 months (95% CI 12.1-17.3) in muscle stable group and 7.6 months (95% CI 6.7-8.5) in muscle loss group (p<0.01). Median OS was 18.3 months (95% CI 16.5-20.2) in muscle loss group while it was 30.1 months (95% CI 22.1-38.2) in muscle stable group (p<0.01). In multivariate analysis for both PFS and OS, skeletal muscle loss was an independent prognostic factor. Hazard ratios (HR) for PFS and OS were 12.2 (95% CI 4.3-34.4) and 3.51 (95% CI 1.41-8.73) respectively., Conclusion: On CT imaging skeletal muscle loss before progression is an independent prognostic factor for both PFS and OS in advance non-small cell lung cancer patients who received EGFR tyrosine kinase inhibitor therapy.

Purpose: The aim of this study was to determine the effect of the distraction cards, virtual reality and Buzzy® methods on venipuncture pain and anxiety in children aged 7-12 years., Design and Methods: This was a randomized controlled trial with parallel groups conducted between November 16, 2017 and August 14, 2018 at the pediatric venipuncture unit of a university hospital in Western Turkey. The sample consisted of 142 children who met the inclusion criteria. The experimental group consisted of 108 children divided into three groups: Distraction Cards (DC; n = 35), Virtual Reality (VR; n = 37), and Buzzy® (n = 36). The control group (n = 34) received no intervention during venipuncture. Data were collected using a descriptive characteristics form, and the Visual Analog Scale (VAS), Wong-Baker FACES, and Children's Fear Scale (CFS). The participants themselves and their parents and the researcher scored venipuncture pain and anxiety levels. The study was approved by the Ethics Committee. Permission was obtained from related institutions. Informed consent was obtained from parents. Verbal consent was obtained from children prior to participation., Results: Buzzy® group had the lowest mean VAS score (2.2 ± 2.0), followed by the VR (2.7 ± 2.8), DC (3.4 ± 2.4), and control (5.2 ± 2.8) groups (p < 0.05). According to all raters (child, parent, and researcher), the Buzzy® group had the lowest mean Wong Baker FACES score, followed by the VR, DC, and control groups (p < 0.05). According to all raters, the Buzzy® group had the lowest mean CFS score, followed by the VR, DC, and control groups (p < 0.05)., Conclusions: The DC, VR, and Buzzy® methods were effective in reducing venipuncture pain and anxiety in children., Practice Implications: Nurses can use the DC, VR, and Buzzy® methods to help reduce venipuncture pain and anxiety in children. The clinical trial registration number is NCT04421430. (https://clinicaltrials.gov/ct2/show/study/NCT04421430)., Competing Interests: Declaration of Competing Interest The author declares that there is no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy., Methods: The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above., Results: There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37)., Conclusion: The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.

The cytoskeleton is a dynamic, fundamental network that not only provides mechanical strength to maintain a cell's shape but also controls critical events like cell division, polarity, and movement. Thus, how the cytoskeleton is organized and dynamically regulated is critical to our understanding of countless processes. Live imaging of fluorophore-tagged cytoskeletal proteins allows us to monitor the dynamic nature of cytoskeleton components in embryonic cells. Here, we describe a protocol to monitor and analyze cytoskeletal dynamics in primary embryonic neuronal growth cones and neural crest cells obtained from Xenopus laevis embryos., (© 2021 Cold Spring Harbor Laboratory Press.)

This article presents the case of a 32-year-old female patient with schwannoma. The patient had swelling on the anterior aspect of her right foot for 1 year with increasing pain over the past 2 months. Moreover, a positive Tinel sign was present over the swelling. Magnetic resonance imaging revealed a large schwannoma mass in the deep peroneal nerve. Consequently, the patient?s large schwannoma was completely excised along with its capsule. Schwannomas are benign tumors of the peripheral nerves that rarely exhibit malignant transformation. Treatment is considered to be curative if complete resection is achieved.

Axon guidance is a critical process in forming the connections between a neuron and its target. The growth cone steers the growing axon toward the appropriate direction by integrating extracellular guidance cues and initiating intracellular signal transduction pathways downstream of these cues. The growth cone generates these responses by remodeling its cytoskeletal components. Regulation of microtubule dynamics within the growth cone is important for making guidance decisions. TACC3, as a microtubule plus-end binding (EB) protein, modulates microtubule dynamics during axon outgrowth and guidance. We have previously shown that Xenopus laevis embryos depleted of TACC3 displayed spinal cord axon guidance defects, while TACC3-overexpressing spinal neurons showed increased resistance to Slit2-induced growth cone collapse. Tyrosine kinases play an important role in relaying guidance signals to downstream targets during pathfinding events via inducing tyrosine phosphorylation. Here, in order to investigate the mechanism behind TACC3-mediated axon guidance, we examined whether tyrosine residues that are present in TACC3 have any role in regulating TACC3's interaction with microtubules or during axon outgrowth and guidance behaviors. We find that the phosphorylatable tyrosines within the TACC domain are important for the microtubule plus-end tracking behavior of TACC3. Moreover, TACC domain phosphorylation impacts axon outgrowth dynamics such as growth length and growth persistency. Together, our results suggest that tyrosine phosphorylation of TACC3 affects TACC3's microtubule plus-end tracking behavior as well as its ability to mediate axon growth dynamics in cultured embryonic neural tube explants., (© 2020 Wiley Periodicals LLC.)

Purpose: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting., Methods: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included., Results: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85)., Conclusion: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.

Purpose: 18F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) combined with computed tomography (CT) scan is accepted as a standard tool in the staging of oesophageal cancer (OC). Histological subtype of tumour is known to be a major determinant of prognosis and metabolic behaviour. In this study, we aimed to evaluate the effect of histological subtypes of OC on standard uptake value (SUV max ), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) obtained by PET/CT, and also to compare this effect with prognosis., Material and Methods: Images and clinical course data of 57 patients who were diagnosed with EC and treated in our hospital between 2009 and 2016 were evaluated in a retrospective manner. PET/CT images were re-analysed in terms of metabolic parameters, and observations were compared with histological subtypes., Results: No significant difference was observed between histological subtypes with SUV max , overall survival (OS), or progression-free survival (PFS). Thus, MTV was observed to be related with histological subtype; MTV values of adenocancer patients were significantly higher than those of squamous cell cancer patients., Conclusions: Metabolic tumour volume was related with histological subtype of OC, but clinical staging, TLG, and SUV max values were not related with histological subtype, which may suggest the use of MTV as a routine parameter for OC and inclusion of MTV observations in prognostic scoring., Competing Interests: The authors report no conflict of interest., (Copyright © Polish Medical Society of Radiology 2020.)

Axolotls and other salamanders have the capacity to regenerate lost tissue after an amputation or injury. Growth and morphogenesis are coordinated within cell groups in many contexts by the interplay of transcriptional networks and biophysical properties such as ion flows and voltage gradients. It is not, however, known whether regulators of a cell's ionic state are involved in limb patterning at later stages of regeneration. Here we manipulated expression and activities of ion channels and gap junctions in vivo, in axolotl limb blastema cells. Limb amputations followed by retroviral infections were performed to drive expression of a human gap junction protein Connexin 26 (Cx26), potassium (Kir2.1-Y242F and Kv1.5) and sodium (NeoNav1.5) ion channel proteins along with EGFP control. Skeletal preparation revealed that overexpressing Cx26 caused syndactyly, while overexpression of ion channel proteins resulted in digit loss and structural abnormalities compared to EGFP expressing control limbs. Additionally, we showed that exposing limbs to the gap junction inhibitor lindane during the regeneration process caused digit loss. Our data reveal that manipulating native ion channel and gap junction function in blastema cells results in patterning defects involving the number and structure of the regenerated digits. Gap junctions and ion channels have been shown to mediate ion flows that control the endogenous voltage gradients which are tightly associated with the regulation of gene expression, cell cycle progression, migration, and other cellular behaviors. Therefore, we postulate that mis-expression of these channels may have disturbed this regulation causing uncoordinated cell behavior which results in morphological defects.

Aim: To evaluate the relationship between the time from cessation of anticoagulant/antiplatelet medication to surgery and risk of postoperative acute subdural hematoma (ASDH) after burr hole drainage of chronic subdural hematoma (CSDH)., Material and Methods: A retrospective study of patients who underwent burr hole drainage of CSDH between December 2014 and December 2019 was performed. Demographic and clinical data regarding age, gender, medication (antithrombotic therapy), smoking, daily alcohol consumption, history of head trauma, presenting symptoms, and neurological examination were collected from the medical records. Patients were divided into 3 groups based on time from referral to surgery: < 24 hours, 24?72 hours, and > 72 hours., Results: One hundred seventeen patients underwent burr hole drainage of CSDH during the 5-year study period. Seventy-two patients were male (61.5%) and 45 were female (38.5%). Mean age was 70.5 ± 7.2 years. Postoperative ASDH occurred in 2 of the 32 patients (6.3%) who were not taking antithrombotic medication and 6 of the 85 patients (7.1%) who were taking antithrombotic medication. The difference was not significant (p=0.797)., Conclusion: The risk of ASDH after burr hole drainage of CSDH was not affected by antithrombotic medication. Although the literature suggests that antiplatelet and anticoagulant drugs to be discontinued between 5 and 7 days before surgery, our results showed that acute hemorrhage was not detected in any patient who underwent surgery more than 72 hours after referral.

Purpose: To assess whether regorafenib and TAS-102 treatments are associated with a change in Skeletal Muscle Area (SMA) as well as to compare Skeletal Muscle Mass (SMM) loss levels between regorafenib and TAS-102 treatments and prognostic significance in the patients with metastatic colorectal cancer (mCRC)., Methods: A total of 36 mCRC patients, who received regorafenib or TAS-102 in the third-line and subsequent settings were assessed in the analysis. SMM changes were assessed with CT scans findings, and they were categorized into two groups as SMM-loss (SMM decrease ≥2%) and SMM-stable (SMM change <2%)., Results: The SMM change after regorafenib therapy was significantly worse compared with TAS-102 therapy (p=0.001). The median overall survival (OS) was longer in SMM-stable group than in SMM-loss group (12.8 months; 95%CI:9.8-15.7) vs. 6.4 months; 95%CI:5.2-7.7, respectively;p=0.04). Cox regression analysis showed that SMM loss was independent prognostic indicator for OS (HR, 2.87; 95%CI: 1.07-7.42, p=0.03)., Conclusion: Although patients who received regorafenib had more SMM loss than those who received TAS-102, there was no difference in OS between drugs.

Objective: Spinal epidural fibrosis is commonly seen after laminectomy. There is not yet proven any agent preventing fibrosis in clinical usage. We used diclofenac sodium and diltiazem, which are fibrosis inhibitors., Methods and Materials: 40 rats were divided into four groups of equal numbers: control, diclofenac sodium, diltiazem, and diclofenac sodium + diltiazem. Laminectomies were performed at L5 and L6. After a 4 week period, the rats were decapitated and the vertebral column blocks were removed for histopathologic examination. Fibrosis percentage, spread of fibrous regions, and fibroblast numbers were evaluated in each group and compared between the groups., Results: The distribution of epidural fibrosis density, percentage of fibrosis, and distribution of fibroblasts in the diclofenac sodium + diltiazem group were significantly lower than in the other groups. The fibroblast numbers of the diltiazem, and diclofenac sodium + diltiazem groups were significantly lower than in the other groups., Conclusion: Diclofenac sodium + diltiazem used together provided better outcomes because each of them prevented fibrosis via different ways, probably through synergistic action (Tab. 5, Fig. 3, Ref. 43).

Background/objectives: The effect of pediatric psoriasis on quality of life has been demonstrated, but data regarding its influence on caregiver quality of life are scarce. The objective was to investigate how psoriasis affects quality of life of children and their caregivers., Methods: This multicenter study included 129 children with psoriasis and their caregivers, who were family members accompanying patients to the clinic. Patient quality of life was measured using the Child Dermatology Life Quality Index. Caregiver quality of life was assessed using Dermatological Family Impact Scale, a 15-item questionnaire validated for use in the Turkish language., Results: Mean Child Dermatology Life Quality Index score was 7.6, indicating a moderate effect on patient quality of life. Symptoms and feelings were the most severely impaired domains of patient quality of life, and emotions was the most severely impaired domain of caregiver quality of life. Dermatological Family Impact Scale score was significantly correlated with Child Dermatology Life Quality Index (correlation coefficient [r] = .554, P < .001) and Psoriasis Area and Severity Index (r = .350, P < .001). Caregivers of patients receiving systemic agents or phototherapy had relative impairment of multiple domains of quality of life compared to caregivers of patients receiving topical treatment only., Conclusion: Psychosocial effect of pediatric psoriasis was shown to extend beyond the individual, highlighting the importance of addressing patient and caregiver quality of life concerns in an integrated approach., (© 2018 Wiley Periodicals, Inc.)

Purpose: Efficient and adequate evaluation of therapeutic response in hepatocellular carcinoma (HCC) is an evolving field. We aimed to evaluate apparent diffusion coefficient (ADC) values in the prediction of response to sorafenib and prognosis in patients with advanced HCC., Methods: Baseline magnetic resonance (MR) imaging was performed before treatment. After sorafenib started, clinical and radiological response were evaluated at approximately 3 months later. ADC measurements were performed by a 12- year experienced radiologist who evaluated MR before and after sorafenib therapy., Results: A total of 17 patients (median age 60 years, range 51-66 and M/F ratio=3.25/1) were analyzed. A significant increase in ADC levels in responders was observed 3 months after sorafenib therapy. Baseline and post-sorafenib ADC values were not significantly associated with mortality (hazard ratio/HR baseline ADC=1.003, p=0.98) and after sorafenib (HR 0.480, p=0.48, respectively)., Conclusion: Advanced HCC patients with a favorable response to sorafenib had a significant increase in ADC value at the first radiological evaluation. The predictive and prognostic role of ADC for overall survival is still unknown and further research is needed to investigate any possible association.

Purpose: Uncontrolled pain, especially in patients with advanced cancer, affects quality of life negatively and causes negative physical and psychological conditions. The aim of this study was to explore the pain experiences of patients with advanced cancer and how they manage with pain, and to present a view of pain management approaches of nurses from the perspectives of the patients., Methods: This was a qualitative descriptive study of sixteen hospitalized patients with advanced cancer. Data were collected using semi-structured interviews with patients. Data were analysed by Colaizzi's phenomenological method., Results: This study found that patients with advanced cancer who had pain experienced anxiety, helplessness, hopelessness and many restrictions in daily life as well as inability to manage with pain. Most of the patients with advanced cancer were not satisfied with their nursing care with regard to pain management. The themes that emerged were pain perception and experiences, effects of pain on daily life, pain management and management strategies and the patients' perspectives about nursing approaches to pain., Conclusions: This study demonstrated the difficulties of patients with advanced cancer who experienced pain in their daily lives, yet lack pain management strategies. Furthermore, nurses' caring approaches to patients with advanced cancer who experienced pain was found inadequate. Oncology nurses should provide educational interventions in order to enhance knowledge and skills about pain assessment and non-pharmacologic and pharmacologic strategies used in pain management., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, we identify leader humility, characterized by being open to admitting one's limitations, shortcomings, and mistakes, and showing appreciation and giving credit to followers, as a critical leader characteristic relevant for team creativity. Integrating the literatures on creativity and leadership, we explore the relationship between leader humility and team creativity, treating team psychological safety and team information sharing as mediators. Further, we hypothesize and examine team power distance as a moderator of the relationship. We tested our hypotheses using data gathered from 72 work teams and 354 individual members from 11 information and technology firms in China using a multiple-source, time-lagged research design. We found that the positive relationship between leader humility and team information sharing was significant and positive only within teams with a low power distance value. In addition, leader humility was negatively related to team psychological safety in teams with a high power distance value, whereas the relationship was positive yet nonsignificant in teams with low power distance. Furthermore, team information sharing and psychological safety were both significantly related to team creativity. We discuss theoretical and practical implications for leadership and work teams. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: To compare the cosmetic result of the PEAK Plasma Blade with traditional scalpel in patients who had primary cesarean delivery by using POSAS (Patient and Observer Assessment Scale)., Material and Methods: Fourty women between 20 and 40 years, who were planning to have primary cesarean delivery, were randomized for skin incision with PEAK Plasma Blade (n:20) and with scalpel (n:20) were blinded to their group allocation. At six months, the cosmetic outcome of the cesarean scar was assessed using the POSAS. Subjective scar rating was performed using the patient component of the POSAS. Objective scar assessment was performed by an observer dermatologist blinded to the patient's group allocation., Results: The observer scores (p = 0,003), patient scores (p = 0,001) and the total scores (p = 0,001) of the POSAS scale were significantly lower in favor of the Peak Plasma Blade group with respect to the scalpel group., Conclusion: The PEAK Plasma Blade has superior cosmetic outcome compared to traditional scalpel skin incision at cesarean section., (Copyright © 2018. Published by Elsevier B.V.)

Background: Microtia reconstruction is a challenging procedure, especially in developing nations. The most complex part is learning how to fabricate a framework from costal cartilage. We herein propose a training regimen for ear reconstruction with the use of a plastic eraser., Materials and Methods: The texture of a plastic eraser made from polyvinyl chloride is similar to that of human costal cartilage. The first step of the training is carving out the sixth through eighth rib cartilages from a block of plastic eraser. The second step is a fabrication of the framework from plastic rib cartilages, referring to a template from the intact auricle., Results: As plastic erasers are inexpensive and universally available, inexperienced surgeons can repeatedly perform this framework training. Following several of these training sessions in developing nations, the co-authors and local surgeons successfully performed their microtia reconstructions in a reasonable operative time., Conclusions: This realistic carving model allows surgeons to gain experience before performing an actual ear reconstruction, even in resource-constrained circumstances., Competing Interests: There are no conflicts of interest.

Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α-mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration., (© 2017 Erdogan et al.)

Background and Objectives: Although the use of oral risperidone in children and adolescents has been well studied, there is little information on the intramuscular use of long-acting injectable risperidone (LAIR). The aims of this study were to investigate the effectiveness and adverse effects of LAIR in children and adolescents with conduct disorder, bipolar disorder, and schizophrenia., Methods: In total, 42 patients (age range 12-17 years) who were non-adherent to oral antipsychotic drugs, received 25 mg of LAIR intramuscularly every 2 weeks. The drug was administered at least four times and up to 66 times (median drug use: 9.50 times). The effectiveness and adverse effects of the treatment were examined., Results: There was an improvement in 13 (92.8%) of the 14 patients diagnosed with bipolar disorder, in 25 (78.1%) of 32 patients diagnosed with conduct disorder and in one (50%) of two patients diagnosed with schizophrenia. Six patients had comorbid conduct disorder and bipolar disorder. Totally, 81% of the patients improved with LAIR. Weight-gain, daytime somnolence, muscle stiffness and spasms, impaired concentration, and fatigue were the most common side effects through the whole sample. Menstrual problems were common in girls. In the study, 57.1% of the patients continued to receive their injections regularly until the end of the treatment, under physician control. A total of 16.7% discontinued the treatment due to non-adherence. The LAIR treatment was terminated in 26.2% of the patients, due to weight-gain, dystonia, and galactorrhea., Conclusions: In children and adolescents with conduct disorder, bipolar disorder and schizophrenia who show noncompliance with oral drugs, LAIR may improve treatment compliance. LAIR is a reliable treatment in terms of its effectiveness. Weight-gain, dystonia, and galactorrhea were the adverse effects that were responsible for LAIR treatment cessation.