Keynote - Arctic Council Update: Perspective from the Chairmanship

Retired Coast Guard Adm. Robert J. Papp Jr. became the State Department’s special representative for the Arctic in July 2014. He leads the effort to advance U.S. interests in the Arctic region, with a focus on Arctic Ocean governance, climate change, economic, environmental, and security issues in the Arctic region as a member of the Arctic Council chairmanship. Prior to this appointment, Papp served as the 24th commandant of the U.S. Coast Guard, and led the largest component of the Department of Homeland Security. As a flag officer,Papp served as commander, Coast Guard Atlantic Area; chief of staff for the Coast Guard and commanding officer of Coast Guard Headquarters; commander, Ninth Coast Guard District; and director of Reserve and Training

Keynote - Arctic Council Update: Perspective from the Chairmanship

Retired Coast Guard Adm. Robert J. Papp Jr. became the State Department’s special representative for the Arctic in July 2014. He leads the effort to advance U.S. interests in the Arctic region, with a focus on Arctic Ocean governance, climate change, economic, environmental, and security issues in the Arctic region as a member of the Arctic Council chairmanship. Prior to this appointment, Papp served as the 24th commandant of the U.S. Coast Guard, and led the largest component of the Department of Homeland Security. As a flag officer,Papp served as commander, Coast Guard Atlantic Area; chief of staff for the Coast Guard and commanding officer of Coast Guard Headquarters; commander, Ninth Coast Guard District; and director of Reserve and Training

Impaired Immunosuppressive Effect of Bronchoalveolar Mesenchymal Stem Cells in Hypersensitivity Pneumonitis: preliminary findings

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New measurements of thousand-seed weights of species in the Pannonian flora

For understanding local and regional seed dispersal and plant establishment processes and for considering the ecotypes and other forms of specific variability, hard data of locally or regionally measured traits are necessary. We provided newly measured seed weight data of 193 taxa, out of which 24 taxa had not been represented in the SID, LEDA or BiolFlor databases. Our new measurements and formerly published data of locally collected seed weight records together covers over 70% of the Pannonian flora. However, there is still a considerable lack in seed weight data of taxonomically problematic genera, even though they are represented in the Pannonian flora with a relatively high number of species and/or subspecies (e.g. Sorbus, Rosa, Rubus, Crataegus and Hieracium). Our regional database contains very sporadic data on aquatic plants (including also numerous invasive species reported from Hungary and neighbouring countries) and some rare weeds distributed in the southwestern part of the country. These facts indicate the necessity of further seed collection and measurements

Quantification of Cell Signaling Networks Using Kinase Activity Chemosensors

The ability to directly determine endogenous kinase activity in tissue homogenates provides valuable insights into signaling aberrations that underlie disease phenotypes. When activity data is collected across a panel of kinases, a unique “signaling fingerprint” is generated that allows for discrimination between diseased and normal tissue. Here we describe the use of peptide-based kinase activity sensors to fingerprint the signaling changes associated with disease states. This approach leverages the phosphorylation-sensitive sulfonamido-oxine (Sox) fluorophore to provide a direct readout of kinase enzymatic activity in unfractionated tissue homogenates from animal models or clinical samples. To demonstrate the application of this technology, we focus on a rat model of nonalcoholic fatty liver disease (NAFLD). Sox-based activity probes allow for the rapid and straightforward analysis of changes in kinase enzymatic activity associated with disease states, providing leads for further investigation using traditional biochemical approaches

The long-term efficacy and safety of new biological therapies for psoriasis

Long-term therapy is often required for psoriasis. This article reviews the most recent long-term clinical data for biological agents that have been approved or for which late-stage development data have been released for the treatment of patients with moderate to severe plaque psoriasis. Efficacy data are available for up to five 12-week courses of alefacept (approximately 60 weeks of therapy), 36 months (144 weeks) of continuous efalizumab, 48 weeks of continuous etanercept, and 50 weeks of bimonthly infliximab. Data sources include publications, product labeling, and posters presented at recent international scientific meetings. Alefacept appears to continue to be efficacious over multiple treatment courses for some responsive patients. The efficacy of efalizumab achieved during the first 12–24 weeks of therapy appears to be maintained or improved through at least 60 weeks of continuous treatment. The efficacy of etanercept appears to be maintained through at least 48 weeks of continuous treatment. Infliximab demonstrates a high response rate soon after initiation, which appears to be maintained through 24 weeks but declines modestly with therapy out to 50 weeks. After 48 weeks, approximately 60% of efalizumab-treated and 45% of etanercept-treated patients remaining on therapy achieved ≥75% improvement from baseline in Psoriasis Area and Severity Index, as did 70.5% of infliximab patients who did not miss more than two infusions. Safety data suggest that these agents may be used for long-term administration. Long-term data from psoriasis trials continue to accumulate. Recent data suggest that biological therapies have efficacy and safety profiles suitable for the long-term treatment of patients with moderate to severe psoriasis

In situ ductails emlőcarcinoma kombinált sebészi- és sugárkezelése: Multicentrikus prospektív randomizált vizsgálat = Combined surgical and radiotherapy treatment of ductal carcinoma in situ of the breast: Multicentric prospective randomized study

289 duktális in situ emlőrák (DCIS) miatt emlőmegtartó műtéttel kezelt beteget randomizáltunk a lokális recidíva szempontjából meghatározott rizikó csoportok szerinti besorolás után. Immunhisztokémiai (IHK) módszerrel vizsgáltuk a lehetséges molekuláris prognosztikai markerek (ER, PR, Her2, p53, Bcl2 és Ki-67) expresszióját. A pozitív IHK reakció a Her2 (38%), p53 (36%) és Ki-67 (47%) markereknél a nukleáris grade-del korrelált. Ezzel szemben az ER (77%), PR (67%) és Bcl2 (67%) pozitivitás szignifikáns inverz összefüggésben volt a grade-del. A klinikai eredményeket 3 éves medián követési idő után 278 betegnél elemeztük. A magas rizikójú betegcsoportban emlőmegtartó műtét és sugárkezelés után 4 (1,7%) lokális recidíva és 1 (0,4%) távoli áttét alakult ki, emlődaganatos haláleset nem volt. A helyi daganatkiújulás 3 és 5 éves valószínűsége 1,1% és 3,1% volt. Tapasztalataink alapján a DCIS egyértelmű diagnózisa esetén az őrszem nyirokcsomó biopszia rutinszerű elvégzése nem indokolt. Korai eredményeink alapján az emlő DCIS kezelésében az emlőmegtartó műtét és posztoperatív sugárkezelés alkalmazásával a helyi daganatkiújulás éves aránya 1% alatt marad. A tumorágy "boost" kezelés hatékonyságának megítélésére és a vizsgált molekuláris markerek prognosztikai/prediktív értékének elemzésére hosszabb követési idő után lesz lehetőségünk. A molekuláris prognosztikai faktorok IHK vizsgálata segítségünkre lehet a DCIS biológiai heterogenitásának feltérképezésében. | 289 patients with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery were randomised according to predetermined risk groups. Immunohistochemistry (IHC) was performed to detect the expression of potential molecular prognostic markers (ER, PR, Her2, p53, Bcl2, and Ki-67). The positive immunostaining for Her2 (38%), p53 (36%), and Ki-67 (47%) correlated with a high nuclear grade. Significant inverse correlation was found between the expression of ER (77%), PR (67%), Bcl2 (67%) and grade. Clinical results was analysed for 278 patients at a median follow-up of 36 months. In the high-risk patient group 4 (1.7%) local recurrences and 1 (0.4%) distant metastasis occurred. No patient died of breast cancer. The 3- and 5-year probability of local recurrence was 1.1% and 3.1%, respectively. Based on our experience, the definitive diagnosis of DCIS does not warrant sentinel lymph node biopsy. Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1% in patients with DCIS. Further follow-up is needed to define the clinical benefit of tumour bed boost irradiation and to analyse the prognostic/predictive value of molecular prognostic factors. IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS

Phenotypic heterogeneity promotes adaptive evolution

Genetically identical cells frequently display substantial heterogeneity in gene expression, cellular morphology and physiology. It has been suggested that by rapidly generating a subpopulation with novel phenotypic traits, phenotypic heterogeneity (or plasticity) accelerates the rate of adaptive evolution in populations facing extreme environmental challenges. This issue is important as cell-to-cell phenotypic heterogeneity may initiate key steps in microbial evolution of drug resistance and cancer progression. Here, we study how stochastic transitions between cellular states influence evolutionary adaptation to a stressful environment in yeast Saccharomyces cerevisiae. We developed inducible synthetic gene circuits that generate varying degrees of expression stochasticity of an antifungal resistance gene. We initiated laboratory evolutionary experiments with genotypes carrying different versions of the genetic circuit by exposing the corresponding populations to gradually increasing antifungal stress. Phenotypic heterogeneity altered the evolutionary dynamics by transforming the adaptive landscape that relates genotype to fitness. Specifically, it enhanced the adaptive value of beneficial mutations through synergism between cell-to-cell variability and genetic variation. Our work demonstrates that phenotypic heterogeneity is an evolving trait when populations face a chronic selection pressure. It shapes evolutionary trajectories at the genomic level and facilitates evolutionary rescue from a deteriorating environmental stress.publishe

Self-Refereeing System in Ultimate during the Joint Junior Ultimate Championship in Three Different Divisions—A Different Way to Promote Fair-Play?

In ultimate games governed by the World Flying Disc Federation (WFDF), all competitors also take on the role of referee. The players discuss disputed calls with each other during the game, and then follow rules designed for these situations to determine how the play continues. The number one rule of the sport is to respect the spirit of the game (SOTG), which encourages competitive play while preserving mutual respect and minimizing the risk of injury. The use of SOTG in ultimate in the framework of self-arbitration as a moral practice aligns well with other tools of critical pedagogy. For this study, the SOTG scores of the WFDF Joint Junior Ultimate Championship (JJUC 2022) were analyzed. A total of 1009 players from 19 countries competed in 434 self-refereed games (29 national teams in the WJUC Under-20 (U20) tournament and 20 teams in the EYUC Under-17 (U17) tournament). All the scores from the individual criteria correlated well with the overall scores, but for the most part, they did not correlate with each other. Our experience with the scoring system has highlighted the importance of participants understanding the meaning of the results and how they may lead to a constructive reflection to improve exceptions, including scores representing fouls and rules knowledge. The findings provide important information for physical education teachers, coaches, and sport consultants and may be of use to design SOTG programs that could foster the experience of sportsmanship and to facilitate the ethical conduct of athletes in either recreative or in competitive contexts

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis