Objective MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. Methods Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. Results Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). Conclusion MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.

The selection of sustainable suppliers (SSS) is the first step in applying a sustainable supply chain and sustainable production. Therefore, it is necessary to select the supplier that best meets the set sustainability criteria. However, the selection of suppliers cannot be done by applying symmetric information, because the company does not have complete information, so asymmetric information should be used when selecting suppliers. Since the SSS applies three main sustainability criteria, environmental, social, and economic criteria, this decision-making problem is solved by applying multi-criteria decision-making (MCDM). In order to solve the SSS for the needs of agricultural production, interval fuzzy logic was applied in this research, and six suppliers with whom agricultural pharmacies in Semberija work were taken into consideration. The application of interval fuzzy logic was performed using the methods PIPRECIA (Pivot pairwise relative criteria importance assessment) and MABAC (Multi-Attributive Border Approximation Area Comparison). Using the PIPRECIA method, the weights of criteria and sub-criteria were determined. Results of this method showed that the most significant are economic criteria, followed by the social criteria. The ecological criteria are the least important. The supplier ranking was performed using the MABAC method. The results showed that supplier A4 best meets the sustainability criteria, while supplier A6 is the worst. These results were confirmed using other MCDM methods, followed by the sensitivity analysis. According to the attained results, agricultural producers from Semberija should buy the most products from suppliers A4, in order to better apply sustainability in production. This paper showed how to decision make when there is asymmetric information about suppliers.

Giant paraclinoid aneurysm remains a treatment challenge because of their complex anatomy and surgical difficulties stems frequently from a calcified or atherosclerotic aneurysmal neck and compression of the optic pathways.1-9 To improve exposure, facilitate the dissection of the aneurysm, assure vascular control, reduce brain retraction and temporary occlusion time, and enable simultaneous treatment of possible associated aneurysms, we combined the cranio-orbital zygomatic (COZ) approach9 with endovascular balloon occlusion of the internal carotid artery (ICA) and suction decompression of the aneurysm.4 The patient is a 50-yr-old female who presented with headache and hemianopsia. MRI, CT, and 4-vessel angiography revealed a giant right ophthalmic paraclinoid partially thrombosed aneurysm. Surgery was performed via right COZ approach with removal of the anterior clinoid. Unroofing the optic canal and opening the falciform ligament and the optic sheath, allowing the dissection and mobilization of the optic nerve from the aneurysm and the origin of ophthalmic artery. The endovascular team placed a deflated, double lumen balloon catheter in the ICA 2 cm above the common carotid bifurcation. Proximal control is achieved by inflating the balloon. Distal control is then gained by temporary clipping just proximal of the origin of PcomA.4 Retrograde suction decompression through the catheter partially collapses and softens the aneurysm.1,4,6-8 Carotid occlusion was applied twice, 2:47 and 2:57 min. Intraoperative angiogram revealed the obliteration of the aneurysm and the patency of the carotid and ophthalmic artery. The patient recovered well, and visual deficit resolved and was neurologically intact. Patient consented for surgery. Illustrations in video reprinted with minimal modification from Surgical Neurology, vol 50, issue 6, Arnautović KI, Al-Mefty O, Angtuaco E, A combined microsurgical skull-base and endovascular approach to giant and large paraclinoid aneuroysms, 504-518,4 Copyright 1998, with permission from Elsevier Science Inc.

ABSTRACT Optimal vitamin D status is very important for reflecting not only bone but overall woman’s health. The aim of the study was to determine pharmacokinetic variability of 25-hydroxy vitamin D, to reveal and quantify the most significant factors that affect its variability in the population of healthy non-menopausal women using the population pharmacokinetic (PopPK) approach. The study population consisted of 74 healthy reproductive women aged from 35 to 50 years, without the use of any supplement. A population pharmacokinetics analysis was conducted using a nonlinear mixed-effects model software. A total of 35 factors were assessed: demographic, clinical, biochemical data and lifestyle factors. The average age and bodyweight of our participants were 40.11 ± 4.35 years 65.30 ± 6.80 kg, respectively. The observed mean serum concentration of 25-hydroxy vitamin D was 26.51 ± 13.49 ng/mL with a wide range of 6.97 to 59.89 ng/mL. Development final PopPK model of the clearance of 25-hydroxy vitamin D showed that only the average daily dose of vitamin D intake from food had a significant influence, with a magnitude of its effects of 0.00401. These results could help when individualizing vitamin D intake in the form of supplements, especially during the wintertime, in healthy reproductive women.

Aim: To determine the impact of the COVID-19 pandemic on the overall practice of the histopathological and cytological laboratory at the University Hospital Centre Rijeka, and on the diagnosis of the most common cancers. Methods: The numbers of histopathological and cytological reports, newly diagnosed cancers of breast, lung, colon, endometrium, and prostate, molecular tests for EGFR mutations and HPV were extracted. Two periods, from March 1 to September 30 in 2019 and 2020 were analysed and compared, as the periods before and during the COVID-19 pandemic. Results: The total number of reports was statistically significantly lower during the COVID-19 pandemic in 2020, compared to the same period in 2019 (p&lt;0.000), histopathology by 24%, non-gynecological cytology by 20%, gynecological cytology by 13%, and Pap tests by 11%. During COVID-19 compared to the same period in 2019 the number of newly diagnosed malignant tumors was significantly reduced for colon cancers (–25%, p &lt;0.0001). The decrease in the new cases of breast (–3%) and prostate cancer (–4%) was less pronounced while the increase was recorded for lung (+ 2%) and endometrial cancer (+ 53%). The number of HPV tests dropped significantly during the COVID-19 pandemic, by 40% (p &lt;0.0001). Conclusions: This study confirmed the expected significant reduction in workload during the first wave of the COVID-19 pandemic in 2020, from 11% to 40%, although the number of patients with newly diagnosed cancers, except for colon, did not fall significantly. It would be important to form a joint national registry that would collect diagnostic and also therapeutic procedures, especially for oncology patients, in order to gain a more objective insight into the problems of the health system during pandemics. These data can be used to consider measures and strategies for the most adequate care, not only for COVID-19 but also for all other patients. © 2021 Hrvatski Lijecnicki Zbor. All rights reserved.

New computing technologies inspired by the brain promise fundamentally different ways to process information with extreme energy efficiency and the ability to handle the avalanche of unstructured and noisy data that we are generating at an ever-increasing rate. To realize this promise requires a brave and coordinated plan to bring together disparate research communities and to provide them with the funding, focus and support needed. We have done this in the past with digital technologies; we are in the process of doing it with quantum technologies; can we now do it for brain-inspired computing? The benefits and future prospects of neuromorphic, or bio-inspired, computing technologies are discussed, as is the need for a global, coordinated approach to funding, research and collaboration.

The application of machine learning (ML) techniques could facilitate the identification of predictive biomarkers of somatostatin analog (SSA) efficacy in patients with neuroendocrine tumors (NETs). We collected data from 74 patients with a pancreatic or gastrointestinal NET who received SSA as first-line therapy. We developed three classification models to predict whether the patient would experience a progressive disease (PD) after 12 or 18 months based on clinic-pathological factors at the baseline. The dataset included 70 samples and 15 features. We initially developed three classification models with accuracy ranging from 55% to 70%. We then compared ten different ML algorithms. In all but one case, the performance of the Multinomial Naïve Bayes algorithm (80%) was the highest. The support vector machine classifier (SVC) had a higher performance for the recall metric of the progression-free outcome (97% vs. 94%). Overall, for the first time, we documented that the factors that mainly influenced progression-free survival (PFS) included age, the number of metastatic sites and the primary site. In addition, the following factors were also isolated as important: adverse events G3–G4, sex, Ki67, metastatic site (liver), functioning NET, the primary site and the stage. In patients with advanced NETs, ML provides a predictive model that could potentially be used to differentiate prognostic groups and to identify patients for whom SSA therapy as a single agent may not be sufficient to achieve a long-lasting PFS.

BACKGROUND The association between adverse pregnancy outcomes (APOs) and maternal apical periodontitis remains unclear as it has not been examined rigorously or reviewed systematically. OBJECTIVE To systematically review and critically evaluate the available evidence on the association of maternal apical periodontitis with several APOs. METHODS A literature search was conducted using the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Database of Systematic Reviews (CDSR), from inception to 25 February 2021, with no language restrictions. Observational studies including longitudinal clinical trials, cohort, case-control, and cross-sectional studies of prospective and retrospective design were included. Articles with duplicate or overlapping results, abstract-only papers, case reports, case series, animal studies and reviews were excluded. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The Newcastle-Ottawa Scale (NOS) and the adapted form of the NOS were used to assess the quality for case-control and cross-sectional studies, respectively. RESULTS Two case-control and one cross-sectional study were included in the current review. The included studies were published between 2015 and 2017, with a total of 1187 participating individuals with an approximate age range of 15 to 40 years. As the included studies reported different outcomes, the heterogeneity of data prevented the use of a meta-analysis. The overall quality of the evidence was "Fair" for two out of three included studies, while one study was categorised as "Good". DISCUSSION Two out of three included primary studies had a substantial number of methodological inconsistencies and flaws, and caution should be exercised in interpreting the results of this systematic review because several important covariates were not considered in the original investigations. CONCLUSION Based on a limited volume and "Fair" and "Good" quality of evidence, a positive association between maternal apical periodontitis and APOs was observed. However, more "Good" quality clinical studies are needed to confirm the results of the current review.

Introduction: Clance Impostor Phenomenon Scale (CIPS) is the most common and psychometrically sound instrument used to measure the impostor phenomenon. The aim of this study was to translate and make a cultural adaptation of the CIPS from English into Croatian. Materials and Methods: The translation process included two independent forward translations, combination of the forward translations into one single translation, back-translation, back-translation review, pre-piloting and drafting of the final translation after several revisions and minor adjustments by a professional reviewer. Results: We noticed no semantic differences when comparing the original and the back-translated versions of the CIPS. Thus, the final translation was only slightly changed in comparison with the first version. Conclusions: The version of the CIPS which was translated and culturally adapted into Croatian represents a reliable translation ready to be used in Croatia and Bosnia and Herzegovina.

With recent clinical breakthroughs, immunotherapy has become the fourth pillar of cancer treatment. Particularly, immune cell-based therapies have been envisioned as a promising treatment option with curative potential for leukemia patients. Hence, an increasing number of preclinical and clinical studies focus on various approaches of immune cell-based therapy for treatment of acute leukemia (AL). However, the use of different immune cell lineages and subsets against different types of leukemia and patient disease statuses challenge the interpretation of the clinical applicability and outcome of immune cell-based therapies. This review aims to provide an overview on recent approaches using various immune cell-based therapies against acute B-, T-, and myeloid leukemias. Further, the apparent limitations observed and potential approaches to overcome these limitations are discussed.