Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

Assessing silver nanoparticle and antimicrobial combinations for antibacterial activity and biofilm prevention on surgical sutures.

AIMS: To evaluate the effect of silver nanoparticles alone and in combination with Triclosan, and trans-cinnamaldehyde against Staphylococcus aureus and Escherichia coli biofilms on sutures to improve patients' outcomes. METHODS AND RESULTS: Silver nanoparticles were prepared by chemical method and characterized by UV-visible spectrophotometer and dynamic light scattering. The minimum inhibitory concentration was assessed by the Microdilution assay. The antibiofilm activity was determined using crystal violet assay. A checkerboard assay using the fractional inhibitory concentration index and time-kill curve was used to investigate the synergistic effect of silver nanoparticle combinations. The hemolytic activity was determined using an erythrocyte hemolytic assay. Our results revealed that silver nanoparticles, Triclosan, and trans-cinnamaldehyde (TCA) inhibited S.aureus and E.coli biofilms. Silver nanoparticles with TCA showed a synergistic effect (FICI values 0.35 and 0.45 against S. aureus and E. coli biofilms, respectively), and silver nanoparticles with Triclosan showed complete inhibition of S. aureus biofilm. The hemolytic activity was <2.50% for the combinations.

Identifying modifiable factors associated with COVID-19 vaccine hesitancy and acceptance among cancer patients in Jordan.

Introduction: Vaccines stand amongst the most effective medical interventions for the management of infectious diseases, and are pivotal tools for public health. The acceptance of vaccines is heavily influenced by perceptions of efficacy, safety and other modifiable factors. Purpose: This cross-sectional study sought to identify and examine the modifiable factors that can help address COVID-19 vaccine hesitancy and acceptance among cancer patients. Methods: The study was conducted between February and April 2021 using an online survey questionnaire comprising of four domains. The survey was administered to cancer patients in Jordan. Results: Among the 1,029 cancer patients who completed the online questionnaire (response rate= 73%), 58% (n=597) expressed willingness (intent) to take the vaccine. Notably, 72.5% (n=433) of those intending to take the vaccine were currently undergoing treatment. Knowledge and awareness played a significant role, with 54.3% considering them essential for vaccine acceptance. Fear of infection significantly influenced vaccine acceptance (p<0.001), with 66.8% expressing concern about potential infections. Peer encouragement was also a crucial factor, as 82.4% regarded it as an important driver for influencing vaccine acceptance (p<0.001). Conclusion: Peer encouragement, awareness, and fear emerged as the primary modifiable factors associated with greater vaccine acceptance by patients with active malignancies. Study results suggest that providing personalized and tailored information about vaccinations, focusing on safety and potential interactions with cancer and its treatment, are potentially excellent strategies for improving vaccine acceptance among cancer patients.

Comparing fracture resistance on bovine incisors restored by tooth fragment reattachment versus direct composite restoration techniques.

BACKGROUND/AIM: Anterior teeth are prone to traumatic dental injuries (TDIs). Although a number of techniques ranging from original tooth fragment reattachment (TFR) to direct composite restoration (DCR) can be used to restore uncomplicated crown fractures, there is no consensus on which method is best. The purpose of this study was to investigate the fracture resistance of bovine incisors restored by two different techniques (TFR and DCR) in three different fracture models. MATERIALS AND METHODS: Sixty extracted bovine lower incisors were randomly divided into three groups (n = 20). Angle, oblique, or transverse sections of all the teeth in a group were prepared by using a disk. The cut surfaces were scanned, and the cross-sectional areas (CSA) of the enamel and dentin were measured. Half the teeth in each group were restored by DCR (n = 10) and the other half by TFR (n = 10). The forces required to fracture the restored teeth were then measured using a Universal testing machine, and the fracture modes were analyzed (cohesive, adhesive, or mixed). RESULTS: No statistically significant differences between the TFR and DCR restorations were detected for total and enamel CSAs in any of the restoration shapes (p > .067). The fracture forces required to break DCR angle and transverse restorations were significantly greater than for the corresponding shapes restored with TFR (p < .033). However, the difference in the forces needed to fracture oblique section restorations by DCR or TFR was not statistically significant (p = .239), despite a similar trend (143.4 ± 51 N and 120.9 ± 25 N, respectively). CONCLUSION: This study revealed that a greater force is required to fracture teeth restored by the DCR than by the TFR technique, especially for a transverse section. This demonstrates that restoring a fractured tooth provides a superior outcome compared to reattaching the fractured fragment.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Expanding the genetic toolbox for Cutaneotrichosporon oleaginosus employing newly identified promoters and a novel antibiotic resistance marker.

BACKGROUND: Cutaneotrichosporon oleaginosus is an oleaginous yeast that can produce up to 80% lipid per dry weight. Its high capacity for the biosynthesis of single cell oil makes it highly interesting for the production of engineered lipids or oleochemicals for industrial applications. However, the genetic toolbox for metabolic engineering of this non-conventional yeast has not yet been systematically expanded. Only three long endogenous promoter sequences have been used for heterologous gene expression, further three dominant and one auxotrophic marker have been established. RESULTS: In this study, the structure of putative endogenous promoter sequences was analyzed based on more than 280 highly expressed genes. The identified motifs of regulatory elements and translational initiation sites were used to annotate the four endogenous putative promoter sequences D9FADp, UBIp, PPIp, and 60Sp. The promoter sequences were tested in a construct regulating the known dominant marker hygromycin B phosphotransferase. The four newly described promoters and the previously established GAPDHp successfully initiated expression of the resistance gene and PPIp was selected for further marker development. The geneticin G418 resistance (aminoglycoside 3'-phosphotransferase, APH) and the nourseothricin resistance gene N-acetyl transferase (NAT) were tested for applicability in C. oleaginosus. Both markers showed high transformation efficiency, positive rate, and were compatible for combined use in a successive and simultaneous manner. CONCLUSIONS: The implementation of four endogenous promoters and one novel dominant resistance markers for C. oleaginosus opens up new opportunities for genetic engineering and strain development. In combination with recently developed methods for targeted genomic integration, the established toolbox allows a wide spectrum of new strategies for genetic and metabolic engineering of the industrially highly relevant yeast.

Value-Added Squalene in Single-Cell Oil Produced with Cutaneotrichosporon oleaginosus for Food Applications.

Single-cell oil (SCO) produced by oleaginous microorganisms is potentially a more land-efficient and sustainable alternative to vegetable oil. The cost of SCO production can be reduced by value-added co-products like squalene, a highly relevant compound for the food, cosmetic, and pharmaceutical industry. For the first time, squalene in the oleaginous yeast Cutaneotrichosporon oleaginosus was analyzed, reaching 172.95 ± 61.31 mg/100 g oil in a lab-scale bioreactor. Using the squalene monooxygenase inhibitor terbinafine, cellular squalene was significantly increased to 2169 ± 262 mg/100 g SCO, while the yeast remained highly oleaginous. Further, SCO from a 1000 L scale production was chemically refined. The squalene content in the deodorizer distillate (DD) was found to be higher than that in DD from typical vegetable oils. Overall, this study demonstrates squalene as a value-added compound in SCO from C. oleaginosus for application in food and cosmetics without the use of genetic modifications.

The Effect of Chewing Sugar-Free Gum to Improve Bowel Movement After Colorectal Surgeries in Patients With Colorectal Cancer.

Introduction: Colorectal cancer is classified as the second most prevalent type of cancer among males and females in Jordan; approximately 1260 (10.9%) out of 11559 cases were diagnosed with colorectal cancer in 2020. According to American statistics, colorectal cancer is the third leading cause of cancer-related deaths among both males and females, as well as the second leading cause when combining both numbers . Objective: The current study aimed to assess the effectiveness of chewing gum in reducing postoperative ileus in patients with cancer after colorectal surgeries and evaluate the length of hospital stay (LOS) after colorectal resection, complications, and costs. Methods: One-hundred twenty-nine patients who underwent colorectal surgeries at a specialized cancer center in Jordan from April 2019 to May 2020 were recruited. After colorectal surgeries, patients were randomized into two groups. The control group (69 patients) received conventional postoperative care; the experimental group (60 patients) was asked to chew free sugar gum over one hour in the morning, noon, and evening until the first flatus. Result: The passage of the first flatus was significantly shorter in the experimental group (mean 48.02 h) than in the control group (116.45); p = .001. Also, there was a significant difference between both groups according to gender and age. Conclusion: Chewing free sugar gum after colorectal surgeries can significantly improve the recovery of bowel motion by accelerating the time to first auscultation to bowel sounds, the first passage of flatus, and reduction in the LOS, which went in agreement with many studies. However, chewing gum is considered a safe, cheap, and practical method to reduce ileus.

Assessing pharmacists and other healthcare providers' knowledge of hand sanitization during COVID-19 pandemic in Jordan: A comparative study.

BACKGROUND: Health care providers including pharmacists are often on the first line when dealing with COVID -19; they can be under threat of contracting and spreading the disease. We aimed to assess and compare their knowledge of hand sanitization during COVID-19 pandemic to improve quality of care. METHODS: A cross-sectional study was conducted in Jordan, on healthcare providers in different settings from 27 October till 3 December 2020, using a pre-validated electronic questionnaire. Participants (n = 523) were healthcare providers practicing in different settings. Descriptive and association statistical analyses were produced on the data using SPSS 26. Chi square was used for the categorical variables, and One way ANOVA was used on the continuous and categorical variables. RESULTS: A significant difference was recorded in total knowledge mean according to gender (59.78 vs 61.79 p = 0.030) in favor of men, and between pharmacists and other healthcare providers in favor of the latter (59.22 vs 61.45, p = 0.02). No significant difference was generally noticed between those who attended hand hygiene training and those who did not. CONCLUSION: Healthcare providers' knowledge of hand hygiene was generally good among participants, regardless of training and it was possibly increased because of fear of COVID-19 infection. Physicians were the most knowledgeable in regard of hand hygiene while pharmacists were the least among healthcare providers. Thus, structured, more frequent, and tailored training on hand sanitization in addition to new educational strategies are recommended for healthcare providers, in particular, pharmacists for better quality of care especially in pandemics.

Inverted appendix in a patient with colon cancer: a case report and long-term follow-up.

Appendiceal inversion is a rare entity that can potentially mimic serious pathology and provide diagnostic uncertainty. They are mostly diagnosed intraoperatively or during endoscopies and scans for other reasons. We report a case of an asymptomatic patient treated for colon cancer without previous history of appendectomy. We provide long-term follow-up and aim to review the relevant literature.

Effect of Different Etching Times on Pit-and-Fissure Sealant Micro-Shear Bond Strength to the Enamel of Primary Teeth.

Successful clinical use of pit-and-fissure sealants relies on the sufficient etching of the enamel, field isolation and sealant retention. The etching time changes the physical and mechanical surface properties of the etched tooth tissues; therefore, it impacts both etching depth and the bond strength of sealants to the enamel. We examined if reducing the recommended 15 s etching time of primary teeth enamel affects the micro-shear bond strength (µSBS) of pit-and-fissure sealants. The cusps of forty non-carious, extracted human primary molars were separately etched for 8, 15 or 30 s. Then, a pit-and-fissure sealant was placed and light-cured. The µSBS values were evaluated and compared among the three groups. The mean µSBS values ± standard deviations were 34.68 ± 16.93, 34.19 ± 17.35 and 36.56 ± 16.57 MPa in the cusps etched for 8, 15 and 30 s, respectively. No statistically significant differences in µSBS were observed among the three test groups. In this study, we showed for the first time that the recommended etching time of primary teeth enamel may be reduced from 15 to 8 s without compromising the µSBS of the sealant. Further evaluations in a clinical setting are warranted.

Mastering targeted genome engineering of GC-rich oleaginous yeast for tailored plant oil alternatives for the food and chemical sector.

BACKGROUND: Sustainable production of triglycerides for various applications is a major focus of microbial factories. Oleaginous yeast species have been targeted for commercial production of microbial oils. Among all the oleaginous yeasts examined in a previous comparative study, Cutaneotrichosporon oleaginosus showed the highest lipid productivity. Moreover, a new lipid production process for C. oleaginosus with minimal waste generation and energy consumption resulted in the highest lipid productivity in the history of oleaginous yeasts. However, productivity and product diversity are restricted because of the genetic intractability of this yeast. To date, successful targeted genetic engineering of C. oleaginosus has not yet been reported. RESULTS: The targeted gene editing was successfully carried out in C. oleaginosus using CRISPR/Cas system. A tailored enzyme system isolated to degrade the C. oleaginosus cell wall enabled the isolation of viable spheroplasts that are amenable to in-cell delivery of nucleic acids and proteins. The employment of both Cas9 protein and Cas mRNA was effective in obtaining strains with URA5 knockout that did not exhibit growth in the absence of uracil. Subsequently, we successfully created several strains with enhanced lipid yield (54% increase compared to that in wild type) or modified fatty acid profiles comparable with those of cocoa butter or sunflower oil compositions. CONCLUSION: This study establishes the first targeted engineering technique for C. oleaginosus using the CRISPR/Cas system. The current study creates the foundation for flexible and targeted strain optimizations towards building a robust platform for sustainable microbial lipid production. Moreover, the genetic transformation of eukaryotic microbial cells using Cas9 mRNA was successfully achieved.

Dietary Modulation of the Human Gut Microbiota and Metabolome with Flaxseed Preparations.

Flaxseeds are typically consumed either as whole flaxseed, ground flaxseed, flaxseed oil, partially defatted flaxseed meal, or as a milk alternative. They are considered a rich source of vitamins, minerals, proteins and peptides, lipids, carbohydrates, lignans, and dietary fiber, which have shown hypolipidemic, antiatherogenic, anticholesterolemic, and anti-inflammatory property activity. Here, an in vitro batch culture model was used to investigate the influence of whole milled flaxseed and partially defatted milled flaxseed press cake on the gut microbiota and the liberation of flaxseed bioactives. Microbial communities were profiled using 16S rRNA gene-based high-throughput sequencing with targeted mass spectrometry measuring lignan, cyclolinopeptide, and bile acid content and HPLC for short-chain fatty acid profiles. Flaxseed supplementation decreased gut microbiota richness with Firmicutes, Proteobacteria, and Bacteroidetes becoming the predominant phyla. Secoisolariciresinol, enterodiol, and enterolactone were rapidly produced with acetic acid, butyric acid, and propionic acid being the predominant acids after 24 h of fermentation. The flaxseed press cake and whole flaxseed were equivalent in microbiota changes and functionality. However, press cake may be superior as a functional additive in a variety of foods in terms of consumer acceptance as it would be more resistant to oxidative changes.

Insight about the characteristics and surgical resectability of adult pilocytic astrocytoma: tertiary center experience.

Aim: Adult pilocytic astrocytoma is a rare tumor. We aim to contribute to understanding its clinical course and prognosis. Patients & methods: We searched our database for patients older than 18 years with pathology-proven pilocytic astrocytoma. Patients' clinical data were analyzed. Results: Fifteen patients were identified. The median age at diagnosis was 25 years (range: 18-56). Tumors were supratentorial in 47%. Gross-total and near-total resections were achieved in 40%, and sub-total resection in 47%. One (7%) recurrence and no mortality were encountered during a median follow-up of 11 months (range: 1-76). Conclusion: Pilocytic astrocytoma behaves differently in adults compared with pediatrics. It tends to arise in surgically challenging areas where the extent of resection may be limited. Total resection should be the main therapy whenever feasible. The survival rates are good, and recurrence is low.

Pilocytic astrocytoma is a benign brain tumor that most commonly arises in children. Rarely, this tumor may also arise in adults. Surgical removal of the tumor is the main treatment. In children, the tumor most commonly arises in the cerebellum, a part of the brain where surgical accessibility is good, and complete removal of the tumor significantly decreases the possibility of it recurring. In adults, the tumor is more likely to arise in critical areas of the brain or in areas of limited surgical accessibility, thus, making surgery especially challenging, and preventing complete removal. Moreover, studies found that the probability of the tumor recurring in adults is higher than in children. Studies discussing the properties of pilocytic astrocytoma in adults reported varying results. This is mainly due to the small number of patients studied. The rarity of this tumor makes it hard for large primary studies to be conducted. In this article, we report the characteristics and outcomes of 15 adult patients treated in a single center in Jordan. In our patients, the mean age was 25 years (range: 18­56), and the tumor was located above the tentorium in 47%. Complete and near-complete removal was possible in 40%. The mean duration of follow-up after surgery was 11 months (range: 1­76). The tumor recurred in only one patient. We aim to provide more data on this rare disease and contribute further to understanding its properties.

The Accuracy of Open-Tray vs. Snap on Impression Techniques in A 6-Implant Model: An In Vitro 3D Study.

To compare the three-dimensional accuracy of an open-tray and two snap on impression techniques (with and without connecting the plastic caps of the snap on impression transfers) in a full arch 6-implant model, a reference acrylic resin model of the maxilla with six implants was fabricated. Prominent geometrical triangles, in the palate area, served as reference points for a digital overlap between scans. Three impression transfer techniques were evaluated and compared: open-tray direct impression (DI), snap on impression (SpO), and connected snap on impression (SpOC). Polyether impression material was used to make 30 impressions (n = 10), and the master model and all casts were digitally scanned with a laboratory optical scanner. The obtained 3D data were converted and recorded as STL files, which were imported to a 3D inspection software program. Angular deviations (buccal, occlusal and interproximal planes) between the study casts and the reference model were measured. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey post hoc test, with 0.05 used as the level of significance. The 3D angular deviations from the master model revealed no significant differences between the DI and SpO impression groups, but there were significant differences in the SpOC impression group, particularly in the buccal and occlusal planes. In all groups, the 3D angular deviation between the most distal scan abutments on each side of the model was significantly different from all other areas when compared to the master model. Within the limits of this study, it is possible to conclude that the indirect closed tray snap on impression technique with unconnected plastic caps exhibited the same three-dimensional accuracies as the direct open tray technique. The indirect closed tray snap on impression technique with connected plastic caps was less accurate than either the indirect closed tray snap on impression technique with unconnected plastic caps or the direct open tray technique. In the case of full arch implant supported prostheses, inaccuracies may be expected in the most distal implants for all the three impression techniques evaluated in this study. Further in vitro and in vivo research is required.

Mucormycosis: The hidden and forgotten disease.

Mucormycosis is a rare but serious fungal infection caused by a group of moulds called mucormycetes. More attention has recently been paid to it due to its association with coronavirus disease 2019 (COVID-19). Thus, it is important to review the progress of studies on mucormycosis and highlight the important findings in relation to epidemiology, clinical manifestation, major risk factors, diagnostic strategies and management. An electronic literature search was performed in PubMed using the keywords: Rhizopus, Mucorales, mucormycosis, zygomycosis, zygomycetes, COVID-19, the drugs (azoles, posaconazole, isavuconazole, amphotericin B pharmaceutical preparations and caspofungin), combination therapy, diagnosis and clinical manifestations. Studies written in the English language from January 1960 to 2021 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. The review emphasized the fact that the diagnosis of mucormycosis is difficult, it is necessary to have a high index of suspicion to identify it, surgical debridement should be done prior to the dissemination of infection to improve clinical outcomes and identifying underlying risk factors is important for proper treatment. Moreover, antifungal therapeutic options are few with polyenes and their combinations should be appropriate for empirical therapy while posaconazole and isavuconazole are best reserved for de-escalation, refractory cases or patients intolerant to amphotericin B.

Factors Affecting Jordanian Women's Surgical Treatment Decisions for Early-Stage Breast Cancer.

OBJECTIVE: This study aimed to assess factors influencing surgical treatment decisions for early-stage breast cancer among Jordanian women. METHODS: A descriptive correlational survey design was utilized to meet the study objective. A total of 180 Jordanian women diagnosed with unilateral early-stage breast cancer (Stages I-II) were recruited from the radiotherapy departments and outpatient surgical and breast cancer clinics at King Hussein Cancer Center (KHCC). Participants completed a structured questionnaire consisting of the Arabic version of the Depression Anxiety Stress Scale, Breast Surgery Beliefs and Expectations Scale, and the Arabic version of the Control Preference Scale. RESULTS: The majority of the participants underwent mastectomy as a definitive surgical treatment (i.e. 67%). Only stage at diagnosis and having a second opinion about surgical treatment options were significantly associated with the type of surgical procedure women opted for. The overwhelming majority of the participants in both groups cited the items of "Minimize the chance of breast cancer coming back" and "Minimize the chance of dying of breast cancer" as very important in their decisions for surgical treatment of unilateral early-stage breast cancer. Women who cited the item "remove breast for peace of mind" as important/very important were more likely to opt for mastectomy than women who cited the item as not important. CONCLUSIONS: Mastectomy is the preferred surgical treatment option for the majority of Jordanian women diagnosed with unilateral early-stage breast cancer at KHCC.

BRAF V600E mutation in papillary thyroid carcinoma: it's relation to clinical features and oncologic outcomes in a single cancer centre experience.

PURPOSE: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. METHODS: Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected. RESULTS: A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0-168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3-142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0-228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3-157)) (P = 0.941, HR = 0.940). CONCLUSION: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Identifying carbohydrate-active enzymes of Cutaneotrichosporon oleaginosus using systems biology.

BACKGROUND: The oleaginous yeast Cutaneotrichosporon oleaginosus represents one of the most promising microbial platforms for resource-efficient and scalable lipid production, with the capacity to accept a wide range of carbohydrates encapsulated in complex biomass waste or lignocellulosic hydrolysates. Currently, data related to molecular aspects of the metabolic utilisation of oligomeric carbohydrates are sparse. In addition, comprehensive proteomic information for C. oleaginosus focusing on carbohydrate metabolism is not available. RESULTS: In this study, we conducted a systematic analysis of carbohydrate intake and utilisation by C. oleaginosus and investigated the influence of different di- and trisaccharide as carbon sources. Changes in the cellular growth and morphology could be observed, depending on the selected carbon source. The greatest changes in morphology were observed in media containing trehalose. A comprehensive proteomic analysis of secreted, cell wall-associated, and cytoplasmatic proteins was performed, which highlighted differences in the composition and quantity of secreted proteins, when grown on different disaccharides. Based on the proteomic data, we performed a relative quantitative analysis of the identified proteins (using glucose as the reference carbon source) and observed carbohydrate-specific protein distributions. When using cellobiose or lactose as the carbon source, we detected three- and five-fold higher diversity in terms of the respective hydrolases released. Furthermore, the analysis of the secreted enzymes enabled identification of the motif with the consensus sequence LALL[LA]L[LA][LA]AAAAAAA as a potential signal peptide. CONCLUSIONS: Relative quantification of spectral intensities from crude proteomic datasets enabled the identification of new enzymes and provided new insights into protein secretion, as well as the molecular mechanisms of carbo-hydrolases involved in the cleavage of the selected carbon oligomers. These insights can help unlock new substrate sources for C. oleaginosus, such as low-cost by-products containing difficult to utilize carbohydrates. In addition, information regarding the carbo-hydrolytic potential of C. oleaginosus facilitates a more precise engineering approach when using targeted genetic approaches. This information could be used to find new and more cost-effective carbon sources for microbial lipid production by the oleaginous yeast C. oleaginosus.

A Newly Designed Automatically Controlled, Sterilizable Flat Panel Photobioreactor for Axenic Algae Culture.

In context of the global climate change, microalgae processes are gaining momentum as a biotechnological tool for direct fixation and valorization of greenhouse gases. Algae have the metabolic capacity to photosynthetically convert CO2 into high value products, such as food additives, under economic boundary conditions. High cost, commercial flat panel gas-lift bioreactors for microalgae cultivation at laboratory scale provide either small volumes or no sterile operation, which limits academic research. This brief report presents initial data for a new type of sterile operating flat panel gas-lift bioreactor with a unique asymmetrical U-shape. It utilizes automatable process control technologies that adhere to industrial standards to enhance data reproducibility and aid industrial scale up. The practicability was demonstrated using a Chlorella sorokiniana cultivation, which showed the typical growth behavior. Due to the sophisticated implemented control engineering technology, pivotal parameters as pH and temperature can be determined within a range of ±0.1 units, which was confirmed experimentally. The new flat panel gas-lift photobioreactor presented in this brief report fills the technology gap at laboratory scale with an autoclavable volume of 7.2 L. Moreover, it is easy to rebuild by means of the hereby provided blueprint, while exhibiting a six-fold cost reduction compared to commercially available flat panel photobioreactors.