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Background: The number of liver transplant recipients (LTR) is worldwide increasing and, as the survival is improving as well, there is an increasing number of patients needing total hip arthroplasty (THA). There might be increased risks for this specific group of patients and due to their comorbidities costs might be higher too. Using a big national database outcome and cost of THA should be compared between liver transplant recipients and the general population. Methods: The study was performed using a collection of Medicare, Medicaid, and private insurance claims. Length of stay (LOS), 30-day readmissions, complications rates up to 5 years, and 90-day total cost of care between liver transplant recipients and matched non-transplant patients should be compared. All primary THAs from 2010 to 2019 were identified. 513 patients with a liver transplant before their THA were matched to 10,759 patients without a history of solid organ transplant at a 1:20 ratio based on age, sex, Charlson Comorbidity Index, obesity, and diabetes status. Results: LTR had a longer average LOS (4.2 vs. 3.4 days, p Conclusions: These findings suggest that complications and costs are no major point of concern in patients with liver transplant that are operated with THA.

Összefoglaló. A dohányzás jelenleg is az egyik legjelentősebb népegészségügyi probléma hazánkban. Az orvosi szakterületek többségében előkerül a dohányzásleszokás-támogatás kérdése. Ezért az orvostársadalom számára az aktuális gyógyszeres terápiás ismeretek összefoglalása hasznos lehet. A jelen közleményben a leszokástámogatás elsődlegesen választandó gyógyszeres terápiáját tekintjük át a legújabb összefoglalók és irányelvek szerint. A gyógyszeres lehetőségek közül jelenleg a vareniklin és a nikotinpótló terápia választandó elsőként, nemcsak a leszokás, hanem az ártalomcsökkentés tekintetében is. A legújabb kutatási eredmények szerint a kis dózisú vareniklin hatékonysága megközelíti a standard adagolás hatékonyságát, ugyanakkor kevesebb mellékhatás jelentkezik. A nikotinpótló kezeléssel kapcsolatban ki kell emelni, hogy egyre több tudományos evidencia áll a transdermalis és oralis készítmények kombinálása mellett, szemben a monoterápiával. A kis dózisú vareniklin, illetve a nikotinpótló terápia akkor is segítséget nyújt a naponta elszívott cigaretták mérséklésében, ha a kliens nem kíván leszokni, de a dohányzás ártalmait csökkentené. A nikotinerg rendszeren kívül más módon ható gyógyszerek szerepe is felmerült. Egyre több összefoglaló támogatja az antidepresszívumok használatát a nikotinfüggőség kezelésében. Ezek közül a bupropion használatával kapcsolatban van a legtöbb adat, amelyről tudjuk, hogy kombinálható a nikotinpótló terápiával és a vareniklinnel is. A gyógyszeres terápiát minden esetben tanácsos magatartásorvoslási módszerekkel, illetve adherenciát fokozó intervenciókkal kombinálni. Ezenkívül a szakellátási szint bevonása is javasolt, hogy a lehető legtöbb segítséget kapja meg a páciens a leszokáshoz. Orv Hetil. 2021; 162(40): 1610–1618. Summary. Smoking is still one of the most significant public health problems in Hungary. The issue of smoking cessation support comes up in most medical specialties. Therefore, a summary of the current pharmacotherapeutic knowledge may prove useful to the medical community. In this paper, we review the first-line pharmacotherapy for smoking cessation based on the latest summaries and guidelines. Regarding the smoking cessation agents, varenicline and nicotine replacement therapy are currently the primary choice, not only in terms of cessation but also in terms of harm reduction. The results of previous studies suggest that the efficacy of low dose varenicline is close to that of standard dosing, with fewer side effects. With regard to nicotine replacement therapy, it should be emphasized that there is an increasing scientific evidence for the combination of transdermal and oral formulations as opposed to monotherapy. Low dose varenicline and nicotine replacement therapy also help reduce the number of cigarettes smoked daily if the client does not want to quit but would reduce the harms of smoking. The role of medications acting in other ways than the nicotinergic system has also emerged. An increasing number of reviews support the use of antidepressants in the treatment of nicotine addiction. Of these, most data are available on the use of bupropion, which is known to be combined with nicotine replacement therapy and varenicline. In all cases, it is advisable to combine pharmacotherapy with behavioral therapy as well as interventions that increase adherence. In addition, it is also recommended to include specific therapeutic interventions in order to get as much help as possible for the patient to quit smoking. Orv Hetil. 2021; 162(40): 1610–1618.

Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications. See related commentary by McMullen et al., p. 5271

Objective This study aimed at identifying which types of social media content could achieve positive differences in Facebook users' interactions and smokers' motivational language between posts with and without motivational interviewing (MI) content. Methods We included 701 Facebook posts (N = 701) which were categorized into five different groups according to specific MI strategies. The control group comprised entertaining and informative posts. Primary outcomes were Facebook users' interactions: engagement rate, negative feedback, and fan-total reach ratio. Secondary outcomes were Facebook post comments reflecting smokers' motivational language: change talk and sustain talk. Results Facebook posts which used MI strategies were associated with significantly higher engagement rate, higher fan-total reach ratio, and more change talk compared to the control group. Of specific MI strategies, "elaborating change talk" strategies elicited considerably more change talk. "Affirming change talk" strategies obtained higher fan-total reach ratio and generated significantly more change talk. Finally, "relational MI" strategies achieved significantly higher engagement rate.. Conclusions Social media contents based on MI increased engagement and generated conversation about tobacco use cessation without relevant negative feedback. The findings suggest that MI strategies may play a promising role in creation of social media contents to support tobacco use cessation.

The rise of COVID-19 in March, 2020 led to an urgent and acute need for communication guidelines to help clinicians facing a novel disease, amidst a cacophony of voices and demands, find the words to use in the face of this public health emergency. We identified critical topics that arose at the interface of staff, patient and family to guide the structure and content of a guideline. Organized in an easy to read table, the guide was made available to a wide variety of websites, organizations and schools as a free PDF resource across the country and beyond.

Motivation Polygenic scores (PGS) aim to genetically predict complex traits at an individual level. PGS are typically trained on genome-wide association summary statistics and require an independent test dataset to tune parameters. More recent methods allow parameters to be tuned on the training data, removing the need for independent test data, but approaches are computationally intensive. Based on fine-mapping principles, we present RápidoPGS, a flexible and fast method to compute PGS requiring summary-level Genome-wide association studies (GWAS) datasets only, with little computational requirements and no test data required for parameter tuning. Results We show that RápidoPGS performs slightly less well than two out of three other widely used PGS methods (LDpred2, PRScs and SBayesR) for case–control datasets, with median r2 difference: -0.0092, -0.0042 and 0.0064, respectively, but up to 17 000-fold faster with reduced computational requirements. RápidoPGS is implemented in R and can work with user-supplied summary statistics or download them from the GWAS catalog. Availability and implementation Our method is available with a GPL license as an R package from CRAN and GitHub. Supplementary information Supplementary data are available at Bioinformatics online.

Összefoglaló. Bevezetés: Az előrehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követően, az invazív eszközös terápiák bevezetését. Célkitűzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás időtartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történő terápiát. A kezelés elfogadásához szükséges időintervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több idő az első, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált időszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb időt, míg 71 betegnél egy hónapnál több időt igényelt. A dyskinesisek átlagos időtartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése előtti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészítő terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off időtartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-időtartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az előrehaladott Parkinson-kóros betegek, akiknek hosszabb időtartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészítő gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839–847. Summary. Introduction: In advanced stages of Parkinson’s disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. Objective: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. Method: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mureş, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. Results: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off-time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. Conclusion: Device-aided therapy is adopted sooner by patients with advanced Parkinson’s disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839–847.

Background The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. Methods In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. Results Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091. Conclusion TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. Trial registration ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence and diverse functions. PACAP binds to specific PAC1 and non-specific VPAC1/2 receptors. PACAP is considered as a growth factor, as it plays important roles during development and participates in reparative processes. Highest concentrations are found in the nervous system and endocrine glands, where several functions are known, including actions in tissue growth, differentiation and tumour development. Therefore, we have investigated expression of PACAP and its receptors in different tumours, including those of endocrine glands. We showed earlier that PACAP and PAC1 receptor staining intensity decreased in pancreatic ductal adenocarcinoma. In the present study we aimed to investigate alterations of PACAP and PAC1 receptor in human insulinoma and compared the immunostaining pattern with samples from chronic pancreatitis patients. We collected perioperative and histological data of patients who underwent operation because of insulinoma or chronic pancreatitis over a five-year-long period. Histology showed chronic pancreatitis with severe scar formation in pancreatitis patients, while tumour samples evidenced Grade 1 or 2 insulinoma. PACAP and PAC1 receptor expression was studied using immunohistochemistry. Staining intensity was very strong in the Langerhans islets of normal tissue and discernible staining was also observed in the exocrine pancreas. Immunostaining intensity for both PACAP and PAC1 receptor was markedly weaker in insulinoma samples, and disappeared from chronic pancreatitis samples except for intact islets. These findings show that PAC1 receptor/PACAP signalling is altered in insulinoma and this suggests a possible involvement of this system in tumour growth or differentiation.

In electric vehicles battery life can be prolonged by using hybrid energy storage systems (HESS ), which combine high energy density batteries with supercapacitors, characterized by high power density. This paper deals with the control of electronic power converters from an active parallel HESS. The load of the HESS is the electrical motor drive of an electric vehicle. The interfaces between the DC-link and the power sources are four-phase bidirectional DC-DC converters driven in current control mode, based on the current references supplied by an active parallel HESS power distribution algorithm. We present a rule-based fuzzy energy management algorithm for a HESS powered electric vehicle and its simulation in MATLAB/Simulink® environment using the Quasi-Static Simulation (QSS ) and Fuzzy Logic toolboxes. Also, simulation results in driving and regenerative braking operation modes of the electric vehicle are presented.

A tanulmány az ingyenes házhozszállítás és a szállítási díjjal való árazás stratégiáját vizsgálja. Egy termék vásárlásakor házhozszállítás esetén felmerül a kérdés, hogy a termék árában benne kell lennie a szállítási díjnak vagy a kettőt szét kell választani, és a termék ára mellett külön meg kell jelennie annak? A probléma elemzéséhez Kelemen [2017b] modelljét alkalmazzuk, amit kiegészítünk a szállítási díjat kifogásoló fogyasztókkal. Egy olyan modellbe helyezzük az elemzést, ami a térbeliséget mélyrehatóbban veszi figyelembe a piac méretén, a szállítási díjon és az utazási költségen keresztül. A szállítási díjjal való árazás magasabb profitot eredményez, azonban ehhez a piacot jól kell ismerni. This paper studies the free shipping and partitioned pricing strategy (product price with shipping fee). If a product is ordered for delivery, it is not straightforward that the price should consist of the shipping fee or the product price and shipping fee should be separated. We extend the model of Kelemen [2017b] with shipping charge skepticism. In this framework, we can investigate the spatial properties in more detail through the size of the market, the shipping fee and the transportation cost. As a result of that, the partitioned pricing ensures higher profit, but it requires the knowledge of key characteristics of the market.

Over 140,000 people in the United States have died as a result of infection with COVID-19. These patients have varying death experiences based on their location of death, the availability and utilization of various medical technologies, the amount of strain on the local health care system, the involvement of specialist palliative care (PC) teams, and access to essential medications to alleviate symptoms at the end of life. The objective of this report is to describe the death experiences of four patients cared for in an urban academic medical center who received very different degrees of medical interventions and to examine the interventions of our interdisciplinary PC team. We conclude that PC teams must adapt to this new landscape by creating best practices for ensuring adequate symptom control, modifying approaches for withdrawal of life-sustaining medical technologies, and gaining facility with communication through teleconferencing platforms to meet the challenge of alleviating suffering for people dying from COVID-19.

A study was conducted on the current problem of developing a fuzzy model for assessing the risks of Unmanned Aerial Vehicle (UAV) flights in mountainous terrain, taking into account risk-oriented factors influencing the flight. As a result, we obtained a quantitative assessment of flight risk and a linguistic interpretation of the level of safety of UAV flight, which will allow a reasonable approach to decision support. For the first time, the study proposed fuzzification of input data using a multidimensional membership function, presented in the form of linguistic estimates of the probability of a risk event and quantitative estimates of the number of “reliability” of the ground control manager's conclusions in his conclusions. For the first time, a generalized step-by-step algorithm for obtaining a quantitative assessment of flight risk and a linguistic interpretation of the level of safety of UAV flight have been constructed. Experimental approbation and verification of the conducted research on test data of UAV flight simulation are carried out. The study will be a useful tool to support safe decisions about UAV flight in different mountainous terrain

Összefoglaló. Bevezetés és célkitűzés: A terápiarezisztens fokális epilepsziák sebészeti kezelése elterjedten használt kezelési lehetőség. Célunk az epilepsziasebészet-hatékonyság változásának vizsgálata egy évtizednyi távlatból a budapesti centrumban. Módszerek: Az Országos Klinikai Idegtudományi Intézetben reszektív epilepsziasebészeti beavatkozásokon átesett fokális epilepsziás betegek adatai kerültek feldolgozásra. A vizsgált 10 év beteganyagát két periódusra osztottuk a műtét időpontja szerint (2006–2010 és 2011–2016). Vizsgálati szempontjaink: demográfiai adatok, az epilepszia kezdete és típusa, mágnesesrezonancia-lelet, preoperatív rohamfrekvencia, műtéttípus és szövettani lelet. Az epileptológiai kimenetelt az Engel-klasszifikáció alapján értékeltük. Eredmények: Epilepsziasebészeti beavatkozás 187 betegen történt, akik közül 137-nél került sor reszekciós műtétre. A betegek 65%-ában temporalis, 18%-ában frontalis, míg 7%-ában olyan multilobaris epilepszia igazolódott, mely a temporalis vagy a frontalis lebenyt érintette. Teljes rohammentességet (Engel I/A) az 1. évben 68%-ban, a 2. évben 64%-ban, míg az 5. évben 63%-ban mértünk. A két intervallum összehasonlításakor az 1 éves rohammentesség aránya 60%-ról (temporalis: 67%, extratemporalis: 50%) 73%-ra (temporalis: 79%, extratemporalis: 62%) javult a második periódusban. Az etiológia szempontjából a hippocampalis sclerosis aránya 28%-ról 14%-ra csökkent, a fokális corticalis dysplasiák aránya 22%-ról 31%-ra növekedett. Következtetés: A sebészeti kezelés fokális epilepsziák esetén – alapos előzetes kivizsgálást követően – általában biztonságos és a legnagyobb arányban sikeres beavatkozás. A legkedvezőbb kimenetel temporalis lokalizációban érhető el. A hatékonyság az évek során egyre javuló tendenciát mutatott az egyre nehezebb sebészeti esetek ellenére. Ez magyarázható a sebészeti technikák fejlődésével, illetve a jobb, műtét előtti elektrofiziológiai és képalkotó technikákkal, amelyek bevezetésével pontosabb lokalizáció adható. Orv Hetil. 2021; 162(6): 219–226. Summary. Introduction and objective: The surgical treatment of medically intractable focal epilepsies is a well established practice. Our aim was to examine the efficacy of epilepsy surgery within a decade long period in our centre in Budapest. Methods: Data of drug-resistant patients with resective epilepsy surgery in the National Institute of Clinical Neurosciences were evaluated. The examined 10-year period was divided based on the year of the operation in two parts (2006–2010 and 2011–2016). The following data were collected: demography, beginning and type of epilepsy, magnetic resonance, preoperative seizure frequency, type of surgery and histology. Epileptological outcome was based on modified Engel’s classification. Results: Out of 187 surgeries, we identified 137 patients with resective intervention: 65% temporal lobe, 18% frontal, and 7% multilobar epilepsy. Seizure-freedom (Engel I/A) was 68% in the first postoperative year, 64% in the second, and 63% in the fifth year. In the first period, 1-year seizure freedom was 60% (temporal: 67% extratemporal: 50%), while in the second period it was 73% (temporal 79%, extratemporal 62%). Hippocampal sclerosis ratio dropped from 28% to 14%, while focal cortical dysplasia ratio increased from 22% to 31%. Conclusion: Surgical treatment in focal epilepsy – after thorough presurgical evaluation – is generally safe and successful. The most favorable outcome is in temporal localization. The efficacy tended to improve over time despite of the more challenging cases. This can be explained with the development of surgical techniques and improvement of presurgical localization. Orv Hetil. 2021; 162(6): 219–226.

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.

Recently, 3-dimensional (3D) printing technology has been used in the development of titanium metaphyseal cones to manage severe bone loss in revision total knee arthroplasty (rTKA). This study assessed (1) radiographs; (2) functional outcomes; (3) complications; and (4) 2-year implant survivorship in patients receiving 3D-printed titanium metaphyseal cones for moderate-to-severe tibial and femoral bone loss in rTKA. A single institution, retrospective chart review was performed for patients with large bone defects treated with a 3D-printed femoral or tibial titanium metaphyseal cone between 2015 and 2017 during rTKA (N=54). Paired sample t tests analyzed Knee Society Scores (KSS). Kaplan–Meier analyses determined implant survivorship when the endpoint was cone revision for aseptic loosening, cone revision for any reason, and reoperation for any reason. The authors found that 51 (98.1%) of 52 available radiographs demonstrated well-fixed components without any evidence of loosening or migration. Mean postoperative KSS scores were significantly higher when compared with preoperative scores (80.4 vs 52.0; P >.001). One patient experienced aseptic loosening of their cone. Seven additional cones were explanted as a consequence of reinfection, 1 of which was removed prior to arthrodesis. Cone survivorship was 98.5% when the endpoint was cone revision due to aseptic loosening, 88.2% when cone revision was due to any reason, and 77.9% for any reoperation. Metaphyseal cones appear to be well-suited for large bone defects during rTKA and the authors' findings suggest that cones may be a viable option for metaphyseal fixation during rTKA. Future studies should focus on their durability during a longer time period. [ Orthopedics . 2021;44(1):43–47.]

Anthropogenic activities are rapidly changing the environment, and species that do not respond face a higher risk of extinction. Species may respond to environmental changes by modifying their behaviors, shifting their distributions, or changing their morphology. Recent morphological responses are often measured by changes in body size. Changes in body size are often attributed to climate change, but may instead be due to differences in available resources associated with changes in local land-use. The effects of temperature and land-use can be uncoupled in populations of the small carpenter bee Ceratina calcarata, which have experienced changes in agricultural and urban cover independent of climate change. We studied how the morphology of this bee has changed over the past 118 years (1902-2019) in relation to climate change and the past 45 years (1974-2019) in relation to agricultural and urban cover. Over this time, summer temperatures increased. We found that male and female size decreased with increasing temperature. Male size also decreased with agricultural expansion. Female size, however, increased with agricultural expansion. These results suggest that rising temperatures correlate with a decrease in female body size, while, opposite to predicted, agricultural land-use may select for increased female body size. These opposing pressures act concurrently and may result in bee extirpation from agricultural habitats if selection for large sizes is unsustainable as temperatures continue to increase. Furthermore, this study emphasizes the need to consider multiple environmental stressors when examining the effects of climate change due to their interactions.

Objectives The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and related diseases, including morphologic mimics, focusing on recent updates and relevant findings for pathologists. Methods The workshop panel reviewed 99 cases of cutaneous and systemic mastocytosis (SM) and SM and associated hematologic neoplasms (SM-AHN). Results Despite a common theme of KIT mutation (particularly D816V), mastocytosis is a heterogeneous neoplasm with a wide variety of presentations. This spectrum, including rare subtypes and extramedullary organ involvement, is discussed and illustrated by representative cases. Conclusions In the age of targeted treatment aimed at KIT, the accurate diagnosis and classification of mastocytosis has major implications for therapy and further interventions. Understanding the clinical, pathologic, and genetic findings of mastocytosis is crucial for selecting the proper tests to perform and subsequent arrival at a correct diagnosis in this rare disease.

Funder: Funding details are provided in the Supplementary Material, Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, ���select and shrink for summary statistics��� (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28���1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08���1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30���1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p

Infectious bronchitis (IB) is a highly contagious viral disease of chickens, known to cause severe economic losses. Vaccination against IB virus (IBV) is an important control measure against the disease. The objective of the present study was to test Avishield IB GI- 13, the vaccine candidate against IBV, strain V-173/11 (GI-13 genotype), according to European Pharmacopoeia (Ph. Eur.) efficacy requirements. Laboratory study on specific- pathogen-free (SPF) chickens showed 100% protection against challenge 10 days after vaccination of 1–7 day-old chickens by three recommended routes. Duration of immunity was shown to be at least 8 weeks after vaccination. Chickens with maternally derived antibodies (MDA) were 100% protected against challenge 21 and 35 days after vaccination. Testing of the vaccine candidate in field conditions on commercial broiler and layer farms showed 80– 90% protection against homologous challenge after spray (broilers and layers) or oral (broilers) vaccine administration. Serum antibodies were monitored during the studies, and although good seroconversion was observed in MDA-positive chickens 34 days after vaccination or later, the data from SPF chickens indicate that non-humoral immunity is important in protection against challenge. Neutralizing antibodies in tears were detected, however, their level could not be fully linked with individual protection scores. A cross- protection study showed that administration of the combination of Avishield IB H120 vaccine and Avishield IB GI-13 vaccine candidate at day 1, confers good protection against heterologous QX-like challenge. Stability of the vaccine after reconstitution in 0.2% skimmed milk solution or distilled water at room temperature was confirmed over the period of 3 h. The vaccine candidate fully complied with Ph. Eur. requirements, with very good protection levels, indicating that it can be administered already at 1 day of age by spray at the hatchery or at 7 days of age by drinking water on the farm.

Absztrakt: Bevezetés: Parkinson-kórban gastrointestinalis zavarok a betegség minden stádiumában előfordulnak, gyakran évekkel a diagnózis felállítása előtt. Jelentőségük előrehaladott Parkinson-kórban nagy, mert az életminőséget tovább rontják, és korlátozhatják mind a hagyományos, mind az eszközös terápiás lehetőségeket. Célkitűzés: Előrehaladott Parkinson-kórban szenvedő betegeknél jelentkező gastrointestinalis zavarok felmérése. Módszer: Retrospektív tanulmányunkban 6 éves periódusban minden olyan, levodopára reagáló Parkinson-kóros beteg adatait elemeztük, akinél legalább napi 2 óra off állapot bizonyítható, az on állapot súlyossága a Hoehn–Yahr-skálán mérve legalább 3 pont, és legalább napi négyszer kapott levodopát különböző kombinációkban. A gastrointestinalis panaszokat a következő célzott kérdésekre adott igen-nem válaszok segítségével azonosítottuk: volt-e nyelészavar, étvágytalanság, gyomortáji diszkomfort, puffadás, korai jóllakottság, émelygés, hányás, székrekedés. Eredmények: A 286 beteget két csoportra osztottuk a gastrointestinalis panaszok jelenléte, illetve hiánya szerint. A legalább egy gastrointestinalis tünetre panaszkodó 181 beteg esetében szignifikánsan hosszabb volt a kórtartam (10,13 ± 4,03 vs. 7,4 ± 2,42 év), illetve súlyosabb a klinikai kép (hosszabb off periódusok: 4,03 ± 1,32 vs. 2,91 ± 1,02 óra, tartósabbak a dyskinesisek: 2,76 ± 0,91 vs. 1,83 ± 0,61 óra, magasabb a Hoehn–Yahr-pontszám). Ezek a betegek nagyobb levodopaadagokat kaptak nagyobb adagolási frekvenciával. A gastrointestinalis panaszok közül a székrekedés (59%) és a meteorismus (32,5%) volt a leggyakoribb. A panaszok nagy többsége szignifikánsan gyakrabban fordult elő a dyskinesises betegeknél. Következtetés: A tápcsatorna működésére vonatkozó panaszok gyakoriak előrehaladott Parkinson-kórban. Ezek felmérése a rutinvizsgálat szerves része kell, hogy legyen. Meg kellene határozni a betegek gastrointestinalis profilját, interdiszciplináris megközelítésben, a megfelelő klinikai és paraklinikai módszerekkel. A gastroparesis és a dyskinesisek közötti kapcsolat fontos láncszem lehet az előrehaladott Parkinson-kór patomechanizmusában, ennek tisztázására további vizsgálatok szükségesek. Orv Hetil. 2020; 161(39): 1681–1687.

Purpose Pancreatic fistula following pancreatic resections is still a relevant complication. The present work shows the efforts of a single institute to decrease this problem. Methods A total of 130 patients (63 men, 67 women) with a mean age of 60 (range: 23–81) years were operated on between January 2013 and March 2020. The most frequent type of pancreatic resection was a Whipple procedure with partial antrectomy. During all operations, an innovative method was used, namely a modification of the purse-string suture pancreatojejunostomy. Moreover, an early drain removal policy was applied, based on the drain amylase level on the first and subsequent postoperative days. Results Mean postoperative hospital stay was 13 days (range: 7–75). The overall morbidity rate was 43.8%; the clinically relevant (grade B/C) pancreatic fistula (CR-POPF) rate was 6.9%. Delayed gastric emptying (DGE) was observed in 4% of the patients. The ratio of operative mortality was 0.7%; the reoperation rate was 5.3%. Based on the drain amylase level on the first postoperative day, two groups could be established. In the first one, the drain was removed early, on the fourth day in average (range: 2–6). In the other group, the drain was left in situ protractedly or reinserted later on. Conclusion A single center’s experience proves that the refinement of the technique can improve the results of pancreatic surgery.

Absztrakt: Bevezetés: A korszerű onkoplasztikus emlősebészet következményeként megjelenő jelentős emlőrekonstrukciós igény számos rendszerszintű kérdést vet fel. Vizsgálatra és szabályozásra várnak az onkoterápiák hatására és az idő múlásával bekövetkező esztétikai változások, illetve hosszú távú szövődmények miatti korrekciós műtétek indikációi; meghatározandó a helyreállító beavatkozások optimális és maximális száma, az elérni kívánt esztétikai végcél és az ezekhez szükséges emlősebészeti kapacitások, valamint finanszírozás. Célkitűzés: A jelen vizsgálat célja, hogy kérdőíves vizsgálattal felmérje a magyar emlőrákos populáció korszerű emlőrekonstrukciós igényeit és véleményét. Anyag és módszer: A vizsgálatba 500, mastectomián és azonnali vagy halasztott-azonnali emlőrekonstrukción átesett nőbeteg került bevonásra. Tizenegy kérdésből álló kérdőív segítségével történt az emlő rekonstrukciójához való ismereteknek és személyes viszonyulásnak, az esztétikai végeredménnyel és az ellátás szakmai színvonalával kapcsolatos elvárásoknak, továbbá az ellátórendszerrel és a finanszírozással kapcsolatos igényeknek a felmérése, majd elvégeztük az eredmények biostatisztikai elemzését. Eredmények: A betegek medián életkora 47 év (min.–max.: 26–73) volt, döntő részük (59%; n = 294) házas volt, és 52% (n = 260) rendelkezett egyetemi végzettséggel. A betegek 70%-a (n = 348) az emlő-helyreállítás eredményeként mezítelenül is nagyjából egyforma emlőket szeretett volna. Ehhez 43%-uk (n = 217) maximum kettő, 37%-uk (n = 184) maximum három-négy műtétet vállalna. A felmérésben részt vettek 44%-a (n = 220) szerint az egészségbiztosítónak három-négy rekonstrukciós beavatkozást kellene támogatnia. A betegek 86%-a (n = 430) a daganatos emlő korszerű sebészi kezelését speciálisan képzett emlősebészre bízná. Következtetés: Az emlőrák modern onkoplasztikus sebészi ellátása összetett, rendszerszintű kérdéseket vet fel. Az emlőrákos betegek jól képzett emlősebészeket szeretnének, akik az emlőrák korszerű sebészi kezelésén túl mastectomia esetén az egészségbiztosító által támogatott formában, maximum két műtéttel képesek magas esztétikai eredménnyel az emlők helyreállítására. Orv Hetil. 2020; 161(29): 1221–1228.

The Hungarian Pediatric Oncology Network provides centralized treatment and population-based registration for cases of childhood cancer since 1973. We collected and analized data on late mortality, secondary malignancies and cardiac diseases in survivors (> 5 years) of childhood cancer to evaluate long-term risks. We extracted all solid tumour cases (3,650 followed up for 5–39.3 years, diagnosis: 1973–2008) from the database of the Hungarian Childhood Cancer Registry and checked against the Population Registry. Among the 301 patients who died after 5 years (8.2%) the most common causes of death were progression of primary cancer (52.5%), secondary malignancies (16%) and cardiovascular diseases (8%). Late mortality rates (SMR, total: 35,006 pyrs) showed highly elevated risk of death (SMR: 10.7 95% CI 9–12.4) for the second 5 years of follow up and moderately elevated risk for 10-year survivors (SMR: 3.5 95% CI 3–4.1). Marked differences were detected in the pattern of causes of death between diagnostic groups of primary cancer; with highest risks beyond 10 years for CNS tumours, Hodgkin disease, osteosarcoma and advanced stage neuroblastoma. The longstanding mortality risk for 5-year survivors underlines the need for tailored long-term follow-up and monitoring of late consequences according to the context of different primary diseases of childhood cancer.

Absztrakt: Bevezetés és célkitűzés: A szerzők a Regnault „B” típusú emlőfelvarrás sebészi technikájának módosításával végzett onkoplasztikus műtéti technikát és az új emlősebészeti módszer alkalmazásához kapcsolódó retrospektív klinikopatológiai vizsgálat eredményeit mutatják be. Módszer: 2012. április és 2018. október között, emlőrák miatt, módosított Regnault „B” technikával operált 215 nőbeteg klinikopatológiai adatait prospektíven vezetett adatbázis alapján retrospektív módon vizsgáltuk. A betegek életminőségét validált kérdőív segítségével mértük fel, míg a műtétek esztétikai eredményét a szintén validált Breast Cancer Conservative Treatment (BCCT.core) számítógépes program és az 5 pontos Likert-skála alapján értékeltük. Eredmények: A betegek átlagéletkora 53 év (szórás: 29–81 év) volt. A medián utánkövetési idő 47 hónap (szórás: 7–85 hónap) volt. Az átlag műtéti idő 47 perc (szórás: 35–85 perc) volt, míg a patológiai tumorméret átlagosan 33 mm-nek (szórás: 18–58 mm) bizonyult. Pozitív sebészi szél miatt 13 (6%) esetben irányított reexcisióra, míg 3 (1,4%) esetben mastectomiára kényszerültünk. Az összesített szövődményarány 7,4% (n = 16) volt. Az esztétikai eredmények Likert-skála szerinti átlagértéke 4,2 (szórás: 2–5), míg a BCCT.core program alapján 1,3 pont (szórás: 1–4 pont) volt. Az életminőséggel kapcsolatos kérdőívek eredményei magas betegelégedettséget igazoltak. Következtetés: A módosított Regnault „B” emlőmegtartó technika biztonságos és hatékony standard ’level II.’ onkoplasztikus emlősebészeti technika. A műtét magas betegelégedettséggel, illetve kozmetikai eredménnyel képes a közepes vagy nagyobb térfogatú emlők külső, illetve külső-felső negyedeinek T1–T3-as tumorai miatt az emlők akár 20–50%-ának eltávolítására, majd egyidejű parenchymaáthelyezéssel történő rekonstrukciójára. A módszer előnye, hogy nem igényel ellenoldali szimmetrizációs műtétet, míg hátránya, hogy az emlő bőrpalástján vezetett metszések komplettáló mastectomia esetén az azonnali rekonstrukciót nehezítik. Orv Hetil. 2020; 161(24): 1002–1011.

The article deals with subjectivity, which is a condition and a means of self-development of future specialists in the social sphere. We treat subjectivity as the source and root cause of student activity. It makes the future social worker responsible for understanding the goals and objectives of his or her future professional activity. Subjectivity includes a system of ideas about oneself as a subject of professional activity, professional self-esteem, professional ideal, awareness of the importance of professional activity. The characteristics of subjectivity are self-awareness, independence, activity, openness to self-improvement, self-development, self-regulation, self-identification, self-education, self-cultivation, which motivates the formation of pedagogical culture of future social workers. The personality of the students was manifested in the need for creative activity while studying in the higher education institutions. It is found that the level of subjectivity of students is directly dependent on their focus on forming a pedagogical culture. Subjectivity is aimed at forming value orientations and a hierarchy of motives for activity. In the context of the acmeological approach, the subjective orientation of the individual is connected with the implementation of the life plan and the improvement of the system of target programs. During the formation of subjectivity, we invite students to complete an acmeogram, purposefully work on the study of micro- and macro-acme, consider acme events and objectively analyze the reasons for their non-use. In the practical plane for the development of subjectivity, students worked actively to identify well-formed character traits that foster professional achievement and to analyze those personality traits that need to be reduced. In order to improve subjectivity, future social workers purposefully worked to develop a plan of concrete practical actions that they would initiate for personal and professional improvement. As the results of the formative stage of the experimental study showed, the improvement of subjectivity as a means of self-development of the future social worker had a positive effect on the formation of indicators of the motivational-value component of the pedagogical culture. The results of the experimental design phase using the Kolmogorov-Smirnov criterion confirmed the effectiveness of the pedagogical culture formation activity and confirmed its validity and veracity.

A Miskolci Egyetem egyik nagyszabású projektje számos lehetőséget kínál az egyetemi és ipari partnerek együttműködésére az anyagtudományok legkülönbözőbb területein. Ebben a cikkben a Gépészmérnöki és Informatikai Kar, Anyagszerkezettani és Anyagtechnológiai Intézete és a Robert Bosch Energy and Body Systems Kft. szakembereinek együttműködésében megvalósított három kutatási témában eddig elért eredményekről számolunk be. A bemutatott témakörök – Anyagkiválasztás ventilátor kerék fröccsönthetőségének javítása céljából; Vezetőképes kenőanyagok fejlesztése gördülő csapágyakhoz; Polimer alkatrészek kopásállóságának növelése aktív ernyős plazmanitridálással – ún. alapkutatásokhoz kapcsolódó témakörök. Az elért eredmények hozzájárulhatnak az autóipari fejlesztések során olyan új konstrukciók, termékek kidolgozásához és újszerű technológiák bevezetéséhez, amelyek révén az ipari partner versenyképes piaci termékekkel bővítheti választékát az autóipari alkatrészekkel szemben támasztott egyre magasabb követelmények kielégítése, az élettartam és a megbízhatóság növelése mellett.

Absztrakt: A jelenleg is zajló SARS-CoV-2 okozta pandémia miatt a betegek 6%-ában tartós gépi lélegeztetést igénylő légzési elégtelenség alakul ki. A későbbi felső légúti szűkület létrejöttének veszélye miatt „békeidőben” korai tracheotomia jönne szóba. A jelen helyzetben azonban a fokozott aeroszolképződéssel járó beavatkozások kerülendők, ezért a javallatok újragondolására van szükség. A nemzetközi ajánlások alapján alakítottuk ki saját eljárásrendünket. Orv Hetil. 2020; 161(19): 767–770.

THE AIMS OF THE PAPER Employers adjust their competence expectations to their employees in relation to the current situation in the goods andlabour market. However, defining personal attributes that contribute to company success on the market is a difficult managerial task. Thus, research into employer competence expectations involves a number of methodological problems. The aim of the present research is to assess the general competency expectations of employers in the current domestic labour market situation. However, our research experience also contributes to the further development of the related measurement methodology. METHODOLOGY In the framework of a corporate questionnaire survey (N = 100), we examined competency expectations about fresh graduates. For our expert questionnaire, the development of the measuring tool was based on the results of previous in-depth interviews (Tothne Teglas - Hledik 2018), which revealed the content-related components of employers' expectations about new graduates and their related way of thinking. Through the expert questionnaire we measured employers' (chronological) preferences for competences along a 54-item competency scale in relation to the processes of both recruitment and work commencement. Competence variables were examined using hierarchical clustering. MOST IMPORTANT RESULTS The analyses helped identify ten competency variables in the employers' system of expectations related to the selection and integration of graduates. In the sample under analysis we found that a high level of expectations at the time of entry was clearly expected by employers and this has expanded further than previously explored. Future success factors identified in labour market forecasts, such as self-study ability, the ability to cope with complex problems, creativity, and the use of new information technologies, however, do not appear as components of the entry expectations towards fresh graduates in the sample of employers under analysis, but only later in relation to their becoming experts. RECOMMENDATIONS Identifying competency expectations for new graduates can represent an important starting point for employment and development issues, in particular for labour market players. However, from a research methodological point of view, we believe that this research into expectations about fresh graduates has helped developed a measurement tool that is better tailored to the practices of employers and enables more accurate measurement.

Ferrocene-1,1 '-dithiol reacts with PCl3 and P(NMe2)(3) to give [3]ferrocenophanes with SPS-ansa-bridges comprising potentially reactive P-Cl and P-N bonds at the central bridge atom. The products were characterized by NMR data and single-crystal XRD studies. The P-chloro-derivative exists both in the solid state and in solution as a mixture of two energetically nearly degenerate conformers with different stereochemical disposition of the ansa-bridge. Activation parameters for the dynamic equilibration between both isomers in solution were determined by dynamic NMR spectroscopy. Computational studies suggest that the isomerization proceeds via a torsional motion of the bridging SPS-unit rather than via configuration inversion at the phosphorus atom.

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. Results: Out of 30, 860 articles reviewed, 328 randomized controlled trials on 35, 600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%–2%) for partial pancreatoduodenectomy and

Simple Summary The outcome of pediatric AML improved considerably worldwide during the past few decades. Hereby, we summarize the therapeutic results of pediatric AML patients registered between 2012 and 2019 in Hungary. As compared to our previous results, improvement was registered in event-free (EFS) and overall (OS) survival, which can be attributed to the application of contemporary diagnostic and therapeutic guidelines, advanced supportation, and higher efficacy of hematopoietic stem cell transplantation. Between 2016 and 2019, a statistically significant increment of 2-year EFS was confirmed over the period between 2012 and 2015. The most prominent progress was observed in acute promyelocytic leukemia (APL). Multidimensional flow cytometry made possible the prompt introduction of ATRA in two cases with M3v, who also represent the first pediatric APL patients in Hungary to be treated with arsenic-trioxide. Besides joining multinational pediatric AML treatment groups, our future aims include the introduction of centralized treatment centers and diagnostic facilities. Abstract Outcome measures of pediatric acute myeloid leukemia (AML) improved considerably between 1990 and 2011 in Hungary. Since 2012, efforts of the Hungarian Pediatric Oncology-Hematology Group (HPOG) included the reduction in the number of treatment centers, contemporary diagnostic procedures, vigorous supportation, enhanced access to hematopoietic stem cell transplantation (HSCT), and to targeted therapies. The major aim of our study was to evaluate AML treatment results of HPOG between 2012 and 2019 with 92 new patients registered (52 males, 40 females, mean age 7.28 years). Two periods were distinguished: 2012–2015 and 2016–2019 (55 and 37 patients, respectively). During these periods, 2 y OS increased from 63.6% to 71.4% (p = 0.057), and the 2 y EFS increased significantly from 56.4% to 68.9% (p = 0.02). HSCT was performed in 37 patients (5 patients received a second HSCT). We demonstrate advances in the diagnosis and treatment of acute promyelocytic leukemia (APL) in two cases. Early diagnosis and follow-up were achieved by multidimensional flow cytometry and advanced molecular methods. Both patients were successfully treated with all-trans retinoic acid and arsenic-trioxide, in addition to chemotherapy. In order to meet international standards of pediatric AML management, HPOG will further centralize treatment centers and diagnostic facilities and join efforts with international study groups.

Background When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20–65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. Methods In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. Results The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. Conclusions The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. Trial registration Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. Trial registration number: 008899/2016/OTIG. Date of registration: 08 February 2016.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan–Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81–0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36–0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

Background: Approximately fifteen percent of patients with tuberous sclerosis complex (TSC) phenotype do not have any genetic disease-causing mutations which could be responsible for the development of TSC. The lack of a proper diagnosis significantly affects the quality of life for these patients and their families. Methods: The aim of our study was to use Whole Exome Sequencing (WES) in order to identify the genes responsible for the phenotype of nine patients with clinical signs of TSC, but without confirmed tuberous sclerosis complex 1/ tuberous sclerosis complex 2 (TSC1/TSC2) mutations using routine molecular genetic diagnostic tools. Results: We found previously overlooked heterozygous nonsense mutations in TSC1, and a heterozygous intronic variant in TSC2. In one patient, two heterozygous missense variants were found in polycystic kidney and hepatic disease 1 (PKHD1), confirming polycystic kidney disease type 4. A heterozygous missense mutation in solute carrier family 12 member 5 (SLC12A5) was found in one patient, which is linked to cause susceptibility to idiopathic generalized epilepsy type 14. Heterozygous nonsense variant ring finger protein 213 (RNF213) was identified in one patient, which is associated with susceptibility to Moyamoya disease type 2. In the remaining three patients WES could not reveal any variants clinically relevant to the described phenotypes. Conclusion: Patients without appropriate diagnosis due to the lack of sensitivity of the currently used routine diagnostic methods can significantly profit from the wider application of next generation sequencing technologies in order to identify genes and variants responsible for their symptoms.

Background The aim of the study was to evaluate the current opinion and clinical decision-making process of international pancreatologists, and to systematically identify key study questions regarding the diagnosis and treatment of chronic pancreatitis (CP) for future research. Methods An online survey, including questions regarding the diagnosis and treatment of CP and several controversial clinical case vignettes, was send by e-mail to members of various international pancreatic associations: IHPBA, APA, EPC, ESGE and DPSG. Results A total of 288 pancreatologists, 56% surgeons and 44% gastroenterologists, from at least 47 countries, participated in the survey. About half (48%) of the specialists used a classification tool for the diagnosis of CP, including the Mayo Clinic (28%), Mannheim (25%), or Buchler (25%) tools. Overall, CT was the preferred imaging modality for evaluation of an enlarged pancreatic head (59%), pseudocyst (55%), calcifications (75%), and peripancreatic fat infiltration (68%). MRI was preferred for assessment of main pancreatic duct (MPD) abnormalities (60%). Total pancreatectomy with auto-islet transplantation was the preferred treatment in patients with parenchymal calcifications without MPD abnormalities and in patients with refractory pain despite maximal medical, endoscopic, and surgical treatment. In patients with an enlarged pancreatic head, 58% preferred initial surgery (PPPD) versus 42% initial endoscopy. In patients with a dilated MPD and intraductal stones 56% preferred initial endoscopic ± ESWL treatment and 29% preferred initial surgical treatment. Conclusion Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged.

Background: The identification of important proteins is critical for medical diagnosis and prognosis in common diseases. Diverse sets of computational tools were developed for omics data reductions and protein selections. However, standard statistical models with single feature selection involve the multi-testing burden of low power with the available limited samples. Furthermore, high correlations among proteins with high redundancy and moderate effects often lead to unstable selections and cause reproducibility issues. Ensemble feature selection in machine learning may identify a stable set of disease biomarkers that could improve the prediction performance of subsequent classification models, and thereby simplify their interpretability. In this study, we developed a three-stage homogeneous ensemble feature selection approach for both identifying proteins and improving prediction accuracy. This approach was implemented and applied to ovarian cancer proteogenomics data sets: 1) binary putative homologous recombination deficiency positive or negative; and 2) multiple mRNA classes (differentiated, proliferative, immunoreactive, mesenchymal, and unknown). We conducted and compared various machine learning approaches with homogeneous ensemble feature selection including random forest, support vector machine, and neural network for predicting both binary and multiple class outcomes. Various performance criteria including sensitivity, specificity, kappa statistics were used to assess the prediction consistency and accuracy. Results: With the proposed three-stage homogeneous ensemble feature selection approaches, prediction accuracy can be improved with the limited sample through continuously reducing errors and redundancy, i.e. Treebag provided 83% prediction accuracy (85% sensitivity and 81% specificity) for binary ovarian outcomes. For mRNA multi-classes classification, our approach provided even better accuracy with increased sample size. Conclusions: Despite the different prediction accuracies from various models, homogeneous ensemble feature selection proposed identified consistent sets of top ranked important markers out of 9606 proteins linked to the binary disease and multiple mRNA class outcomes.

The urgency of the work lies in the development of a fuzzy model for quantifying experts for smart city transportation and mobility, for ranking them and selecting an expert group, which integrates different models of competence of experts and reveals the subjectivity of the answers to the questions in their evaluation. The development of such a model will allow to increase the degree of validity of the decision making of the choice of experts (employees, specialists) municipality, which are best suited for the competences, qualities or psychophysiological peculiarities for the effective fulfillment of the task for smart city transportation and mobility. As a result, for the first time, a seven-step general algorithm for the expert group, for smart city transportation and mobility, assessment and selection model has been developed that integrates different expert competence models and can be applied to different areas of specialist selection. A structural framework for the evaluation and ranking of the expert group was also proposed for the first time, as well as examples of constructing membership functions for the evaluation questionnaire. Experimentally tested the general algorithm of fuzzy model of evaluation on the test example of the choice of the head of expert group among 5 experts on 3 models of competences (model of self- esteem, model of special abilities and skills, model of psychophysiological qualities of personality).

Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake state and high intra-hippocampal corticosterone on consolidation of aversive contextual memories as well as consolidation of association between simple trauma-related cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a “safe box” and then trained in fear conditioning paradigm in a distinct “shock box” with a prominent simple auditory cue serving as a phasic background cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1μl) or corticosterone (10ng in 1μl saline) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory test twenty-four hours later revealed that the saline-injected animals with sleep during consolidation had significantly stronger freezing response in the shock box compared to the safe box as well as increased freezing in response to the tone. Lack of post-learning sleep in saline injected animals led to generalization of fear response to the safe context, while association between simple cue and fear response was preserved. High intra-hippocampal corticosterone level during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to single stimulus was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable complex memories for a traumatic episode and distinct behavioral outcomes.HighlightsWe studied effect of sleep and intrahippocampal corticosterone on consolidation of memories surrounding stressful event modeled by fear conditioning in rats.Sleep following traumatic fear conditioning event is important for subsequent manifestation of fear response (freezing) specifically in the context of traumatic event but not in a neutral safe context.Lack of sleep or high intra-hippocampal corticosterone level during memory consolidation leads to generalization of fear response to both the traumatic and safe context.Increased freezing in response to a trauma-related auditory cue was observed in saline injected rats regardless of wake/sleep state during consolidation.Post-learning intra-hippocampal corticosterone injection blocked response to a trauma-related auditory cue regardless of wake/sleep state during consolidation.

Well-managed legume-based food systems are uniquely positioned to curtail theexistential challenge posed by climatechangethrough the significant contributionthat legumes can make toward limiting Green House Gas (GHG) emissions. Thispotential is enabled by the specific functional attributes offered only by legumes,which deliver multiple co-benefits through improved ecosystem functions, includingreduced farmland biodiversity loss, and better human-health and -nutrition provisioning.These three critical societal challenges are referred to collectively here as the“climate-biodiversity-nutrition nexus.” Despite the unparalleled potential of the provisionsoffered by legumes, this diverse crop group remains characterized as underutilizedthroughout Europe, and in many regions world-wide. This commentary highlightsthat integrated, diverse, legume-based, regenerative agricultural practices shouldbe allied with more-concerted action on ex-farm gate factors at appropriatebioregional scales.Also,thatthiscanbeachievedwhilstoptimizing production, safeguarding food-security, and minimizing additional land-use requirements. To helpavoid forfeiting the benefits of legume cultivation for system function, a specificand practical methodological and decision-aid framework is offered. This is basedupon the identification and management of sustainable-development indicators forlegume-based value chains, to help manage the key facilitative capacities anddependencies. Solving the wicked problems of the climate-biodiversity-nutrition nexus demands complex solutions and multiple benefits and this legume-focus must beallied with more-concerted policy action, including improved facilitation of the catalyticprovisions provided by collaborative capacity builders—to ensure that the knowledgenetworks are established, that there is unhindered information flow, and that newtransformative value-chain capacities and business models are established.

The food- and feed-value systems in the European Union are not protein self-sufficient. Despite the potential of legume-supported production systems to reduce the externalities caused by current cultivation practices (excessive use of N fertilizer) and improve the sustainability of the arable cropping systems and the quality of human diets, sufficient production of high-protein legume grains in Europe has not been achieved due to multiple barriers. Identifying the barriers to the production and consumption of legumes is the first step in realizing new pathways towards more sustainable food systems of which legumes are integral part. In this study, we engage stakeholders and decision-makers in a structured communication process, the Delphi method, to identify policy interventions leveraging barriers that hinder the production and consumption of legumes in the EU. This study is one of a kind and uses a systematic method to reach a common understanding of the policy incoherencies across sectors. Through this method we identify policy interventions that may promote the production of legumes and the creation of legume-based products in the EU. Policies that encourage reduced use of inorganic N fertilizer represent an important step toward a shift in the increased cultivation of legumes. Relatedly, investment in R&amp, D, extension services, and knowledge transfer is necessary to support a smooth transition from the heavy use of synthetic N fertilizer in conventional agriculture. These policy interventions are discussed within current EU and national plant-protein strategies.

Objective. Individuals with neurological disease or injury such as amyotrophic lateral sclerosis, spinal cord injury or stroke may become tetraplegic, unable to speak or even locked-in. For people with these conditions, current assistive technologies are often ineffective. Brain-computer interfaces are being developed to enhance independence and restore communication in the absence of physical movement. Over the past decade, individuals with tetraplegia have achieved rapid on-screen typing and point-and-click control of tablet apps using intracortical brain-computer interfaces (iBCIs) that decode intended arm and hand movements from neural signals recorded by implanted microelectrode arrays. However, cables used to convey neural signals from the brain tether participants to amplifiers and decoding computers and require expert oversight, severely limiting when and where iBCIs could be available for use. Here, we demonstrate the first human use of a wireless broadband iBCI. Methods. Based on a prototype system previously used in pre-clinical research, we replaced the external cables of a 192-electrode iBCI with wireless transmitters and achieved high-resolution recording and decoding of broadband field potentials and spiking activity from people with paralysis. Two participants in an ongoing pilot clinical trial completed on-screen item selection tasks to assess iBCI-enabled cursor control. Results: Communication bitrates were equivalent between cabled and wireless configurations. Participants also used the wireless iBCI to control a standard commercial tablet computer to browse the web and use several mobile applications. Within-day comparison of cabled and wireless interfaces evaluated bit error rate, packet loss, and the recovery of spike rates and spike waveforms from the recorded neural signals. In a representative use case, the wireless system recorded intracortical signals from two arrays in one participant continuously through a 24-hour period at home. Significance. Wireless multi-electrode recording of broadband neural signals over extended periods introduces a valuable tool for human neuroscience research and is an important step toward practical deployment of iBCI technology for independent use by individuals with paralysis. On-demand access to high-performance iBCI technology in the home promises to enhance independence and restore communication and mobility for individuals with severe motor impairment.

Simple Summary Housing and management conditions strongly influence the health, welfare and activity behaviour of horses. To improve horses’ living conditions, it is necessary to establish objective and quantifiable measures that allow for a comparison between environmental living conditions and of how horses of different ages and health statuses are influenced by these environmental conditions. Thus, the aim of the present study was to record and compare time budgets (=percentage of time spent on specific activities) of old (≥20 years) horses and of horses suffering from chronic orthopaedic disease that are living in different husbandry conditions with an automated tracking device. These horses were found to spend similar percentages of time feeding, resting and moving compared to healthy controls. Horses living on different farms and with different turn-out conditions differed in their time budgets. Horses living in open-air group housing on a paddock had less pronounced peaks in their feeding and movement activities over time compared to horses living in more restricted husbandry systems. The findings of the study can help to identify potential improvements of husbandry conditions of horses to maximise their health and welfare. Abstract Housing and management conditions strongly influence the health, welfare and behaviour of horses. Consequently, objective and quantifiable comparisons between domestic environments and their influence on different equine demographics are needed to establish evidence-based criteria to assess and optimize horse welfare. Therefore, the present study aimed to measure and compare the time budgets (=percentage of time spent on specific activities) of horses with chronic orthopaedic disease and geriatric (≥20 years) horses living in different husbandry systems using an automated tracking device. Horses spent 42% (range 38.3–44.8%) of their day eating, 39% (range 36.87–44.9%) resting, and 19% (range 17–20.4%) in movement, demonstrating that geriatric horses and horses suffering from chronic orthopaedic disease can exhibit behaviour time budgets equivalent to healthy controls. Time budget analysis revealed significant differences between farms, turn-out conditions and time of day, and could identify potential areas for improvement. Horses living in open-air group housing on a paddock had a more uniform temporal distribution of feeding and movement activities with less pronounced peaks compared to horses living in more restricted husbandry systems.

Abstract: Introduction: Hereditary spherocytosis is a genetically determined familial hemolytic anemia. Clinically it is ranged from an asymptomatic condition to severe hemolytic anemia. The major complications are aplastic or megaloblastic crisis, hemolytic crisis, cholecystitis and cholelithiasis. Aim: To shortly summarize the most characteristic symptoms of hereditary spherocytosis from the prism of our centers in order to help primary care-physicians or pediatricians in this affection recognition. Method: In our retrospective study, we processed a period of 6 years between 2012–2017, we studied the clinical signs, laboratory and imagistical findings, evolution and complications. Results: In this period, 47 cases were admitted with hereditary spherocytosis diagnosis to our departments. The most frequent symptoms were jaundice, hepato- and splenomegaly. The observed complications were: hemolytic crisis, aplastic crisis, cholecystitis and cholelithiasis. Conclusion: The main diagnostic elements are anamnesis, clinical signs, laboratory findings and anamnestic data. Early diagnosis is extremely important in order to provide substitution therapy and correct imagistic and hematologic controls. Orv Hetil. 2019; 160(45): 1798–1803.