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Assistive technology is a collective term that refers to assistive devices and services for people withdisabilities. The use of assistive technology in working with people with disabilities facilitates their learning and performance of activities of daily living. The knowledge and experience of experts is necessary for the selection, purchase, and use of assistive technology. For the purpose of this work, an online survey was conducted among experts in Bosnia and Herzegovina who had the opportunity to use and apply assistive technology through their work. The research participants (N=23) were educational rehabilitators, speech therapists, teachers, pedagogues, physiotherapists, and nurses. The online questionnaire consisted of 33 open and closed-ended questions. The data obtained were processed using quantitative and qualitative data processing methods. The aim of the research was to ask experts in Bosnia and Herzegovina about their experience with the use of assistive technology, their knowledge and attitudes, and the challenges they face in their work. The results show that assistive technology has not beenused for long in Bosnia and Herzegovina and that experts encounter many challenges in their work, such as financial problems, lack of technical support, and difficulties in working with parents. They also emphasize the need for more training in assistive technology

Women who undergo breast cancer surgery often have an indication for gynaecological procedure. The aim of our study was to compare infectious complications rate after mastectomy with implant-based reconstruction in patients with and without concurrent gynaecological procedure.

Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients’ treatment from Slovenian national CM register to leading international clinical guidelines.

The aim of our study was to evaluate the quality of surgery of Slovenian breast cancer screening program (DORA) using the requested EU standards. Furthermore, we investigated whether regular quality control over the 3-year period improved the quality of surgical management.

Most data related to cutaneous melanoma survivors’ health behaviour comes from epidemiological studies and is predominantly concerned with safe-sun behaviour and self-examination. Data regarding other changes of health behaviour are scarce and so are qualitative studies in this realm. The aim of our research is to acquire insight into the experiences of patients with cutaneous melanoma in Slovenia. How did they react to the diagnosis, which changes did they introduce in their health behaviour and how do they assess the role of family doctors?

Introduction. Actinomycosis is an uncommon chronic granulomatous infection first described by Bollinger in 1877. The infection is caused by actinomyces species and it is characterized by slow contiguous spread and suppurative inflammation, formation of multiple abscesses and sinus tracts with possible drainage of “sulfur granules”. Case Outline. We report an unusual case of actinomycosis of the cheek that occurred 6 years after buccal odontogenic abscess. A 56-year-old male was referred to the Department of Oral Surgery because of a painless swelling of the left cheek, which initiated three weeks prior to the referral. The diagnosis of actinomycosis was confirmed by histopathologic examination. In accordance with the diagnosis oral penicillin was prescribed for four months with complete resolution. Conclusion. This case of actinomycosis is presented as a rarity. For proper diagnosis, careful examination and a high degree of clinical suspicion are necessary.

Introduction. Metastases to the oral cavity are uncommon, accounting for only 1% of all oral malignant tumors. When they occur they mostly originate from primary tumors of the lungs, kidney, breast and prostate. Oral metastases from the primary colorectal carcinoma are much more infrequent. Case Outline. We present an unusual case of a 78-year-old man with a soft tissue oral metastasis originating from the primary colorectal carcinoma. The patient was referred to the Department of Otorhinolaryngology, Head and Neck Surgery with an intraoral mass on the right side of the maxilla. The diagnosis was confirmed by histopathologic examination and immunohistochemical analysis. Conclusion. Oral metastases occur rarely and often can mimic much more common benign lesions, therefore they should be considered as a possibility in a differential diagnosis.

Abstract Background Increased level of serum S100B can serve as a marker of metastatic spread in patients with cutaneous melanoma (CM). In patients with elevated S100 B and/or clinical signs of disease progression PET-CT scan is a valuable tool for discovering metastases and planning treatment. The aims of this study were to determine whether regular measurements of serum S100B are a useful tool for discovering patients with CM metastases and to evaluate the diagnostic value of PET-CT during the follow-up. Methods From September 2007 to February 2010, 115 CM patients included in regular follow up at the Institute of Oncology Ljubljana were appointed to PET-CT. There were 82 (71.3%) patients with clinical signs of disease progression and 33 (28.7%) asymptomatic patients with two subsequent elevated values of S100B. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) of S100B and PET-CT were calculated using standard procedures. Results Disease progression was confirmed in 81.7% of patients (in 86.5% of patients with clinical signs of disease progression and in 69.7% of asymptomatic patients with elevated S100B). Sensitivity, specificity, PPV and NPV of S100B was 33.8%, 90.9%, 96.0% and 17.5% in patients with clinical signs of disease progression. In 20.0% of patients increased serum S100B was the only sign of disease progression. Sensitivity and PPV of S100 in this group of patients were 100.0% and 69.7%. With PET-CT disease progression was diagnosed in 84.2% of symptomatic patients and in 72.7% of asymptomatic patients with elevated S100B. The sensitivity, specificity, PPV and NPV of PET-CT for symptomatic patients was 98.5%, 90.9%, 98.5% and 90.9% and 100%, 90.0%, 95.8% and 100% for asymptomatic patients with elevated S100. Conclusions Measurements of serum S100B during regular follow-up of patients with CM are a useful tool for discovering disease progression in asymptomatic patients. The value of its use increases if measurements are followed by extended whole body PET-CT.

Abstract Background Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease. The aims of our study were: to determine the prevalence of germline CDKN2A mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible CDK4 mutations, and to determine the frequency of variations in the MC1R gene. Methods From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing. Results Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the CDK4 gene were found. Most frequently found variants of the MC1R gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant. Conclusion The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or CDK4 mutations.

This publication describes monodentate phosphine and oxazoline ligands attached to an amino acid ester and the application of their supramolecularly assembled rhodium(I) or iridium(I) complexes in asymmetric catalysis. The major feature of these complexes is the transmission of chirality from distant hydrogen bonded amino acids to the prochiral catalytic metal center ("backdoor induction"). The in situ generated homoleptic and heteroleptic rhodium(I) or iridium(I) precatalysts were studied by NMR, UV-VIS and CD spectroscopy as well as X-ray single crystal diffraction. In asymmetric hydrogenation of methyl α-acetamidocinnamate, rhodium(I) and iridium(I) complexes afforded complete conversions with enantioselectivities up to 85%, while iridium complexes proved to be more sensitive to the variation of reaction conditions, including catalyst loading, metal to ligand ratio and temperature. The hydrogenation of four other dehydroamino acid substrates resulted in similar conversion and selectivity as obtained with methyl α-acetamidocinnamate. The influence of the phosphine/oxazoline heteroleptic mixtures in catalysis was studied using both rhodium(I) and iridium(I) complexes. Finally, a homoleptic phosphine rhodium(I) complex was successfully applied in asymmetric hydroformylation of styrene and 1-octene with complete conversions and selectivity up to 40% ee for the branched styrene product.

Novel 6-substituted 2-(trifluoromethyl)quinoline 5a-5e and coumarin 6a-6d ligands with aldoxime ether linked pyridine moiety were synthesized by O-alkylation of quinoline and coumarin with (E)-picolinaldehyde oxime and subsequently with [Re(CO) 5 Cl] gave rhenium(I) tricarbonyl complexes 5a Re -5e Re and 6a Re -6d Re that were fully characterized by NMR, single-crystal X-ray diffraction, IR and UV-Vis spectroscopy. The results of antiproliferative evaluation of quinoline and coumarin ligands and their rhenium(I) tricarbonyl complexes on various human tumor cell lines, including acute lymphoblastic leukemia (CCRF-CEM), acute monocytic leukemia (THP1), cervical adenocarcinoma (HeLa), colon adenocarcinoma (CaCo-2), T-cell lymphoma (HuT78), and non-tumor human fibroblasts (BJ) showed that the quinoline complexes 5a Re -5e Re had higher inhibitory activity than coumarin complexes 6a Re -6d Re , particularly against T-cell lymphoma (HuT78) cells. 6-Methoxy-2-(trifluoromethyl)quinoline 5e and 6-methylcoumarin 6d, and their rhenium(I) tricarbonyl complexes 5e Re and 6d Re were found to arrest the cell cycle of HuT78 cells by causing a significant accumulation of cells in the G0/G1 phase and a marked decrease in the number of cells in the G2/M phase. These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (5e Re ) and 45 % (6d Re ) compared to untreated cells and cells treated with 5e and 6d. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO 4 . The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO 4 (2a Ru ) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2c Ru induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines., Purpose: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice., Methods: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries., Results: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak., Conclusions: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients., Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb., Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4., Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment., (© 2024 John Wiley & Sons Ltd.)

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

(1) Background: The objective of this study was to assess which digitization method produces the biggest deviation in the 3D images of tooth size from plaster models made using alginate impressions, which are considered the gold standard in orthodontics. (2) Methods: The sample used in this study included 30 subjects (10 males and 20 females). Measurements were made on four types of models: (1) digital models obtained through intraoral scanning and digitized models of plaster cast made from (2) alginate impressions, (3) silicone impressions, and (4) conventional plaster models. Mesio-distal (MD) and buccal/labial-lingual/palatal (BL) dimensions were measured on the reference teeth of the right side of the jaw (central incisor, canine, first premolar, and first molar). Comparisons of tooth size between the methods were conducted using a repeated measurement analysis of variance and the Friedman test, while the intraclass correlation coefficient was used to determine agreement between the different methods. (3) Results: The results showed a similar level of agreement between the conventional and digital models in both jaws and the anterior, middle, and posterior segments. Better agreement was found for the MD measurements (r = 0.337-0.798; p ≤ 0.05) compared to the BL measurements (r = 0.016-0.542), with a smaller mean difference for MD (0.001-0.50 mm) compared to BL (0.02-1.48 mm) and a smaller measurement error for MD (0.20-0.39) compared to BL (0.38-0.89). There was more frequently a better level of agreement between 3D images than measurements made using a digital caliper on the plaster models with 3D images. (4) Conclusions: The differences in measurements between the digital models and conventional plaster models were small and clinically acceptable.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors., Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita)., Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01)., Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study., Competing Interests: LH, PP, EP, EN received consultancy fees from IBSA Biochimique SA. The remaining 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. The reviewer PM declared a shared affiliation with the author TB to the handling editor at the time of review., (Copyright © 2023 Žarković, Attanasio, Nagy, Negro, Papini, Perros, Cohen, Akarsu, Alevizaki, Ayvaz, Bednarczuk, Berta, Bodor, Borissova, Boyanov, Buffet, Burlacu, Ćirić, Díez, Dobnig, Fadeyev, Field, Fliers, Frølich, Führer, Galofré, Hakala, Jiskra, Kopp, Krebs, Kršek, Kužma, Lantz, Lazúrová, Leenhardt, Luchytskiy, McGowan, Melo, Metso, Moran, Morgunova, Mykola, Beleslin, Niculescu, Perić, Planck, Poiana, Puga, Robenshtok, Rosselet, Ruchala, Riis, Shepelkevich, Unuane, Vardarli, Visser, Vrionidou, Younes, Yurenya and Hegedüs.)

Bioorganometallic complexes have attracted considerable interest and have shown promise for potential application in the treatment and diagnosis of cancer, as well as bioimaging agents, some acting as theranostic agents. The series of novel ferrocene, benzimidazo[1,2- a ]quinoline and fluorescein derivatives with bidentate pyridyl-1,2,3-triazole and 2,2'-dipyridylamine and their tricarbonylrhenium(I) complexes was prepared and fully characterised by NMR, single-crystal X-ray diffraction, UV-Vis and fluorescence spectroscopy in biorelevant conditions. The fluorescein and benzimidazo[1,2- a ]quinoline ligands and their complexes with Re(I) showed interactions with ds-DNA/RNA and HSA, characterised by thermal denaturation measurements, fluorimetric and circular dichroism titrations. The binding constants revealed that addition of Re(I) increases the affinity of fluorescein but decreases the affinity of benzimidazo[1,2- a ]quinoline. The complexation of Re(I) had the opposite effect on fluorescein and benzimidazo[1,2- a ]quinoline ligands' fluorimetric sensitivity upon biomacromolecule binding, Re(I) fluorescein complex emission being strongly quenched by DNA/RNA or HSA, while emission of Re(I) benzimidazo[1,2- a ]quinolone complex was enhanced, particularly for HSA, making it a promising fluorescent probe. Some mono- and heterobimetallic complexes showed considerable antiproliferative activity on colon cancer cells (CT26 and HT29), with ferrocene dipyridylamine complexes exhibiting the best inhibitory activity, comparable to cisplatin. The correlation of the cytotoxicity data with the linker type between the ferrocene and the 1,2,3-triazole ring suggests that direct binding of the metallocene to the 1,2,3-triazole is favourable for antitumor activity. The Re(I) benzimidazo[1,2- a ]quinolone complex showed moderate antiproliferative activity, in contrast to the Re(I) fluorescein complex, which exhibited weak activity on CT26 cells and no activity on HT29 cells. The accumulation of the Re(I) benzimidazo[1,2- a ]quinolone complex in the lysosomes of CT26 cells indicates the site of its bioactivity, thus making this complex a potential theranostic agent.

Megalin (LRP2) is a rapidly recycling multiligand endocytic receptor primarily expressed in polarized epithelial cells. Although megalin might be involved in tumor growth and invasiveness through several mechanisms, its role has been understudied in the field of molecular oncology so far. The present study aimed to evaluate the impact of megalin expression in oral squamous cell carcinoma (OSCC) on disease progression. Megalin expression was evaluated immunohistochemically in 63 OSCC specimens. Data obtained were retrospectively compared with patient clinicopathological features and their survival. The proportion of megalin-expressing cells in the primary OSCC tissue was significantly associated with metastatic spreading to lymph nodes, vascular invasion and lower overall survival rate. Results obtained by the study suggest that megalin can be considered as a novel molecule involved in OSCC pathogenesis, but also useful as a potential biomarker for cancer progression.

Seven bis(2-picolyl)amine (bpa) and five iminodiacetamide (imda) ligands were prepared with different modifications in their side chain structure. The coordination properties of the ligands (L) were influenced by changes in the aliphatic linker length (C1, C2, or C3), amide group isomers and type of chiral terminal group. Complexation with Cu(II) afforded two polymorphs of a ML complex which features tetradentate coordination of a ligand with C2 linkers, while crystal structures of three trans - fac ML 2 complexes with Cu(II) and Ni(II) show tridentate coordination of ligands with a C3 linker. The stoichiometry and stereochemistry of Zn(II) and Cu(II) complexes was further studied in solution by NMR and UV-Vis spectroscopy. DFT calculations gave an insight into the relative stability of isomers, as well as potential hydrogen bonding between two ligands in a ML 2 complex. Furthermore, ML complexes of Cu(II) exhibited DNA cleavage activity.

BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline BAP1 likely pathogenic variant (c.898&#95;899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in BAP1 (partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer., (© 2022. The Author(s).)

Ever since their initiation 60 years ago, the harmonized European Business and Consumer Surveys (BCS) have risen to the challenge of performing as a solid data pillar for quantifying leading indicators of economic activity. However, mainstream research mainly focuses on publicly available composite BCS confidence indicators and inspects their predictive accuracy. We depart from this stance by considering a battery of novel techniques for quantifying BCS-based leading indicators with the particular aim to evaluate their predictive characteristics compared to conventional BCS leading indicators. We build upon the recently established weighted balance method, forecast disagreement, and surprise index. Additionally, we differ from the standpoint of rational expectations by introducing indicators of irrational sentiment and adaptive expectations, which have not previously been used in BCS studies of this sort. Our analysis in industry, consumer, and retail trade sectors of 28 European economies reveals that most of these novel techniques (especially irrational sentiment and adaptive expectations) produce more accurate predictions of economic activity than standard BCS benchmarks. These results are robust to several panel estimation procedures (heterogeneous panel Granger causality test and panel vector autoregressions, in particular)., Supplementary Information: The online version contains supplementary material available at 10.1007/s11135-021-01306-4., Competing Interests: Conflict of interestThe authors declare that they donot have any conflict of interest to declare., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

The crystal structure of tris[dimethyl 5-({1-[(pyridin-2-yl-κN)carbamoyl-κO]ethyl}carbamoyl)benzene-1,3-dicarboxylate]zinc(II) dinitrate acetonitrile trisolvate, [Zn(C 19 H 19 N 3 O 6 ) 3 ](NO 3 ) 2 ·3CH 3 CN or [Zn(L) 3 ](NO 3 ) 2 ·3CH 3 CN, (1), has been determined by single-crystal X-ray diffraction. The neutral ligand L coordinates to the Zn 2+ cation in a bidentate fashion via the pyridine N atom and an amide O atom, forming a six-membered chelate ring. The Λ-helical chirality of the Zn 2+ coordination sphere is induced by pendant L-alanine residues through stacking interactions between the arene groups of two coordinated ligands, assisted by a hydrogen bond between amide groups bonded to the stacked arene rings. The third ligand is coordinated to the Zn 2+ cation by the same six-membered chelate ring, but in the opposite direction with respect to the analogous chelate rings of the first two coordinated ligands. Besides ionic interactions between [ZnL 3 ] 2+ complexes and NO 3 - anions, several types of hydrogen bonds and intermolecular stacking interactions contribute to the stability of the solid-state phase.

Heme and nonheme-type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [Fe II (CDA-BPA*)] 2+ ( 6 ) [CDA-BPA = N , N , N ', N '- tetrakis -(2-pyridylmethyl)-cyclohexanediamine], [Fe II (CDA-BQA*)] 2+ ( 5 ) [CDA-BQA = N , N , N ', N '- tetrakis -(2-quinolilmethyl)-cyclohexanediamine], [Fe II (Bn-TPEN)(CH 3 CN)] 2+ ( 3 ) [Bn-TPEN = N -benzyl- N , N ', N '-tris(2-pyridylmethyl)-1,2-diaminoethane], [Fe IV (O)(Bn-TPEN)] 2+ ( 9 ), and manganese, [Mn II (N4Py*)(CH 3 CN)] 2+ ( 2 ) [N4Py* = N , N -bis(2-pyridylmethyl)-1,2-di(2-pyridyl)ethylamine)], [Mn II (Bn-TPEN)(CH 3 CN)] 2+ ( 4 ) complexes as catalysts, where the possible reactive intermediates, high-valent Fe IV (O) and Mn IV (O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [Fe IV (O)(Bn-TPEN)] 2+ ( 9 ) and [Mn IV (O)(Bn-TPEN)] 2+ ( 10 ) towards flavanone under the same conditions, a 3.5-fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [Fe IV (O)(N2Py2Q*)] 2+ [ N , N -bis(2-quinolylmethyl)-1,2-di(2-pyridyl)ethylamine] species.

Aim: To determine the frequency and type of RET mutation in Slovenian medullary thyroid cancer (MTC) patients and estimate the crude annual incidence of MTC in Slovenia., Methods: This referral-center retrospective analysis involved 186 MTC patients diagnosed between 1995 and 2015 and their relatives who underwent genetic counseling and testing. The crude incidence rate of MTC was estimated with the joinpoint regression analysis. Genomic DNA was isolated, and exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene were amplified with polymerase chain reaction. Point mutations of the RET gene were detected by single-strand conformation analysis and DNA sequencing. Detected mutations were confirmed by restriction enzymes., Results: The average crude annual incidence rate of MTC in Slovenia was 0.34/100,000. A germline mutation in the RET proto-oncogene was identified in 25.9% of MTC patients. The most frequently altered codons were codons 634 and 618, followed by codon 790, codon 804, and codon 918., Conclusions: Annual incidence increase and nation-specific frequency of RET mutations justify the future use of genetic counseling and testing of MTC patients in Slovenia.