Hungarian adaptation of the cerebellar cognitive affective/Schmahmann Syndrome Scale.

Recent studies have reported that cerebellar lesions can cause cognitive, behavioral, and affective symptoms. This constellation is called the cerebellar cognitive affective syndrome (CCAS). A bedside instrument, the CCAS-Scale, has been developed to screen for this clinical presentation. The aim of this study is to adapt the CCAS-Scale to Hungarian according to international cross-cultural guidelines. In cooperation with the senior author of the original CCAS-Scale, we defined a five-step adaptation protocol (license number 6758-1/2021). Step 1: translation of the scale from English to Hungarian by two separate teams. Step 2: comparison of the two translated versions, synthesis (preliminary version). Step 3: back translation by an independent professional translator. Step 4: authorization, revision, and correction. Step 5: pre-testing the scale, measuring the test times. Following our protocol, we produced the CCAS-H and the instructions booklet. We pre-tested healthy (n = 10) and cerebellar stroke patients (n = 10) and finalized the scale. Although not significantly, but cerebellar patients reached lower raw scores compared with healthy subjects. Testing times differed significantly between the two groups. A meticulous validation protocol was outlined to assess the validity and reliability of the newly adapted test. CCAS-H is a quick and adequate scale to examine the cerebellar-cognitive affective syndrome, which will be available for Hungarian professionals. Our main challenge was to define the stimuli and cues with adequate psycholinguistic and psychometric properties. As a next step, we are gathering data for the validation with the help of six other Hungarian Neurology departments.

Aspiration Risk Screening With Tongue Pressure Measurement in Acute Stroke: A Diagnostic Accuracy Study Using STARD Guidelines.

Introduction: Dysphagia can affect more than 50% of stroke patients in the acute phase. Aspiration pneumonia is a serious complication that can be prevented with dysphagia screening and assessment. Measurement of tongue elevation pressure is suggested to be a useful tool in aspiration risk screening. Objective: This study aimed to assess the diagnostic accuracy of maximum anterior tongue elevation strength (Pmax) in acute stroke care. Method: In this prospective study, data were collected in a neurology department (stroke center) where patients formed a consecutive case series. The sample consisted of thirty stroke patients who failed an initial dysphagia screening. Patients underwent anterior tongue elevation strength measurement (index test) during bedside dysphagia assessment by a speech-language pathologist and flexible endoscopic evaluation of swallowing (reference test) by an otorhinolaryngologist on the same day. Outcome variables (index values in kPa, reference values interpreted on the penetration-aspiration scale) were used for estimating measures of diagnostic accuracy in aspiration risk screening. Results: Ten patients aspirated on instrumental evaluation. At the cut-off point of ≤ 34 kPa the analysis showed 90% sensitivity, 35% specificity, 41% positive predictive value, and 88% negative predictive value. The area under the curve (AUC) for Pmax was AUC = 0.700 (95% CI [0.500-0.900]). Conclusion: Although individuals with low anterior tongue elevation strength tend to have a higher risk of aspiration, this variable alone is not capable of screening aspiration in acute stroke. In combination with a thorough noninstrumental bedside examination, it might have the potential to reduce the number of false positive cases. Further studies in this area would be worthwhile.

Optimization of Novel α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators and the Discovery of a Preclinical Development Candidate Molecule (RGH-560).

During optimization of a previously identified lead compound, attempts were made to optimize the reactive indole structural element, the suboptimal metabolic stability, as well as the low kinetic solubility. It was concluded that the indole was important for in vitro activity. With the aim of further improvements, more thorough modifications were also carried out. As a result, a new chemotype (the azetidinespirochromone family) was identified, which proved to be 1 order of magnitude less lipophilic retaining the same high level of in vitro potency as the lead series itself, however, with improved metabolic stability and kinetic solubility. Compound 53 showed the most balanced physicochemical and pharmacological profile with significant in vivo efficacy in the scopolamine-induced amnesia test. Based on these promising results, cognitive enhancement through the positive modulation of α7 nAChRs appears to be a viable approach. Compound 53 was selected to be a preclinical development candidate (as RGH-560).

Successful thrombolytic therapy is associated with increased granulocyte CD15 expression and reduced stroke-induced immunosuppression.

OBJECTIVES: Stroke-induced immunosuppression (SIIS) increases the risk of poststroke infections. We aimed to determine whether failed versus successful thrombolytic therapy (TT) resulted in SIIS-associated changes in peripheral granulocyte markers at 1 week following the insult. METHODS: We collected peripheral blood samples from 19 patients with acute ischemic stroke undergoing TT within 6 h after the onset of their first symptoms and 7 days after the insult. Age-matched controls were sampled on one occasion. We compared the expression of CD15 and CD64 on monocytes, granulocytes, and lymphocytes using flow cytometry. RESULTS: The proportion of granulocytes and CD15+ granulocytes was comparable between controls and stroke patients at both time points. While the proportion of CD15bright granulocytes was also comparable, the mean fluorescence intensity (MFI) of CD15 on this subset was reduced in stroke patients by day 7 but was overall higher at both time points compared to controls. The MFI of CD15 on granulocytes was lower in stroke patients with failed TT than in those with successful TT 1 week after the insult. CONCLUSIONS: Our current results indicate that TT may not only acutely reduce the systemic inflammatory response following stroke but may also play a role in reversing SIIS at a later stage following the insult, as reflected by the higher expression of the CD15 marker on granulocytes following successful TT.

Hungarian adaptation of an international swallowing screening method / Egy nemzetközi nyelészavarszurési módszer hazai adaptálása

Introduction: Swallowing disorders caused by stroke can affect half of the cases in the acute phase. The guidelines for nutrition therapy for stroke patients recommend several screening methods for swallowing disorders. The Gugging Swallowing Screen (GUSS) is one of the most widely used ones but has not been available in Hungarian until now. Objective: Adaptation and validation of the GUSS to Hungarian in acute stroke patients (GUSS-H). Method: Our research design was two-phased: for the adaptation, a five-step protocol was composed according to international guidelines. The second phase was the validation of the GUSS-H. For external validity, data from patients (n = 31) were compared to the reference values of the fiberoptic endoscopic evaluation of swallowing (FEES) for both dysphagia and aspiration risk. Internal validity was obtained by comparing data from two independent evaluators (n = 20). Results: According to the FEES results, dysphagia prevalence was 45%, aspiration prevalence was 32.3% in our sample. Inter-rater reliability was strong on both GUSS-H scores and severity of dysphagia (𝜅 = 0.899, p<0.001; 𝜅 = 0.801, p<0.001). The diagnostic accuracy of the test showed great results for both the risk of dysphagia and aspiration (sensitivity: 93%, 90%; specificity: 65%, 57%; positive predictive value: 68%, 50%; negative predictive value: 92%, 92%). Discussion: Compared to the original GUSS and other bedside screenings, GUSS-H performed better than average in terms of sensitivity and negative predictive value. It could predict the risk of dysphagia and aspiration, make recommendations for instrumental evaluation and dysphagia diet. Conclusion: Swallowing screening is one of the first steps of nutritional therapy for acute stroke patients which needs an interdisciplinary setting. With our study, GUSS-H is now available to Hungarian professionals.

Medical nutrition therapy of stroke patients with dysphagia ­ 2021 / A dysphagia táplálásterápiája stroke-betegek esetében - 2021.

Összefoglaló. A neurológiai betegek körében a dysphagia elofordulása gyakori, és több oka van. Az utóbbi évek kutatásai a közvetlen neurológiai kórokok (beleértve a gyakori stroke) szerepét is részletesen feltárták. Felismerték az ún. néma aspiráció jelentoségét: ez gyakran áll az (aspirációs) pneumonia hátterében, amely sokszor halálos szövodmény lehet. Az ún. poststroke pneumonia fogalma gyökeresen más értelmezésbe helyezte a stroke-ot követo tüdogyulladások megítélését, jellegzetessége alapján egyértelmuen a stroke közvetlen cerebralis hatásaként alakul ki. Egyértelmuvé vált a nyelészavar korai felismerésének és ellátásának szükségessége. A stroke-betegek megfelelo tápláltsági állapota az eredményes rehabilitációnak, a szövodményszám csökkentésének, a rövidebb kórházi kezelésnek, az alacsonyabb mortalitásnak a záloga. A dysphagia a betegség kimenetelének független elorejelzoje lehet, különösen az elso három hónapban. A nyelészavar malnutritióval, kiszáradással és a kórházi tartózkodás hosszabb idotartamával jár együtt, emeli a gyógyszerköltségeket. A stroke-beteg ellátásának egyik elso eleme a dysphagia szurése. Táplálásterápiára akkor szorul a stroke-beteg, amikor magas a kóros tápláltsági állapot kialakulásának kockázata, és per os táplálással nem fedezheto biztonságosan a megfelelo energia-, tápanyag- és folyadékbevitel. A táplálásterápia módját, eszközeit, az energia- és tápanyagbeviteli célértékeket az orvos határozza meg, az alapbetegség súlyosságától, a társbetegségektol és a laborértékektol függoen. Az étrend minden esetben individuális és progresszív, azaz alkalmazkodik a beteg állapotához és annak változásához. A dietetikus feladata a megfelelo diéta összeállítása mellett a beteg, a hozzátartozó és a kezeloszemélyzet oktatása, az állapot követése, a beteg tápláltsági állapotának, tápanyagbeviteli értékeinek gyakori elemzése, szükség esetén tápszerek ajánlása. Orv Hetil. 2021; 162(40): 1601-1609. Summary. Among neurological patients, the incidence of dysphagia is common and has several causes. Research in recent years has explored the role of direct neurological pathogens (including frequent strokes). The frequency of 'silent aspiration', which often underlies (aspirational) pneumonia and can be a fatal complication, has been recently discovered. The concept of 'post-stroke pneumonia' has drastically changed the assessment of post-stroke pneumonia. Based on its characteristics, it clearly develops as a direct cerebral effect of stroke. The need for early detection and early care of swallowing disorder has become clear. Adequate nutritional status of stroke patients is the key to successful rehabilitation, reduction of complications, shorter hospitalization, and lower mortality. Dysphagia can be an independent predictor of disease outcome, especially in the first three months. Swallowing disorder is associated with malnutrition, dehydration and longer lengths of hospital stay, increasing drug costs. One of the first elements in the care of a stroke patient is screening for dysphagia. The stroke patient needs nutritional therapy when the risk for abnormal nutritional condition is high or if the condition is already present, or when oral nutrition does not safely cover adequate energy, nutrient and fluid intake. The method and means of nutritional therapy, the goals of energy and nutrient intake are determined by the doctor, depending on the severity of the underlying disease, comorbidities and laboratory values.The diet is individual and progressive in each case. The dietitian's task is not only to compile a proper diet, but also to educate the patients and relatives. The dietitian is responsible for monitoring the patient's nutritional status. Orv Hetil. 2021; 162(40): 1601-1609.

HTS-based discovery and optimization of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor.

HTS campaign of the corporate compound collection resulted in a novel, oxalic acid diamide scaffold of α7 nACh receptor positive allosteric modulators. During the hit expansion, several derivatives, such as 4, 11, 17 demonstrated not only high in vitro potency, but also in vivo efficacy in the mouse place recognition test. The advanced hit molecule 11 was further optimized by the elimination of the putatively mutagenic aromatic-amine building block that resulted in a novel, aminomethylindole compound family. The most balanced physico-chemical and pharmacological profile was found in case of compound 55. Docking study revealed an intersubunit binding site to be the most probable for our compounds. 55 demonstrated favorable cognitive enhancing profile not only in scopolamine-induced amnesia (place recognition test in mice) but also in natural forgetting (novel object recognition test in rats). Compound 55 was, furthermore, active in a cognitive paradigm of high translational value, namely in the rat touch screen visual discrimination test. Therefore, 55 was selected as a lead compound for further optimization. Based on the obtained favorable results, the invented aminomethylindole cluster may provide a viable approach for cognitive enhancement through positive allosteric modulation of α7 nAChRs.

Epileptic Seizure Provoked by Bone Metastasis of Chronic Lymphoid Leukemia and Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine cutaneous tumor, rarely metastasizing to the brain. Chronic lymphoid leukemia (CLL) is a disease predisposing to MCC. According to previous reports, headache and focal neurological deficits suggest disease progression to the brain. We present a patient with MCC whose seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. Case Presentation. A 62-year-old female patient had a history of CLL. A lesion with the appearance of an atheroma was removed from the right upper arm. Histology confirmed the diagnosis of MCC. She was admitted to the neurology department with her first GM seizure. The cranial MRI/MRA showed bone metastases in the right parietal and both frontal areas, compressing the brain. Flow cytometry of CSF did not reveal metastasis of MCC. CONCLUSIONS: The case history of the patient was unique even among the rare cases of MCC with neurological involvement. The seizure was not elicited by a cerebral metastasis, but by bone metastases compressing the brain. In addition to patient history, clinical presentation and radiological findings enabled a suspected diagnosis of skull metastasis of MCC compressing the brain, causing symptomatic epileptic seizures.

Arbuscular Mycorrhizal Fungus Rhizophagus irregularis Influences Artemisia annua Plant Parameters and Artemisinin Content under Different Soil Types and Cultivation Methods.

Artemisinin extracted from Artemisia annua has been used efficiently in malaria treatment since 2005. In this study, the variations in plant parameters (plant biomass, glandular trichome density, essential oil total chemical content, artemisinin production, and polyphenol oxidase (PPO) activity) were tested under different soil types (Luvisol, Gleysol, Anthrosol and sterile peat) and cultivation conditions (potted plants in semi-open field, and open field experiments) for plants inoculated with arbuscular mycorrhizal fungus (AMF) Rizophagus irregularis. Under semi-open field conditions, the AMF colonization of A. annua plant roots varied, and presented the highest percentage in Luvisol and sterile peat. The increase in the root colonization rate positively influenced some plant parameters (biomass, glandular trichome density, artemisinin concentration, essential oil quantity and composition), but no effects on PPO enzyme activity were detected. AMF fungus R. irregularis significantly increased the artemisinin content and essential oil yield of plants cultivated in Luvisol, Gleysol, Anthrosol and in peat. These soil types can offer appropriate conditions for A. annua cultivation and artemisinin production even on a smaller scale. Under open field conditions, low (about 5%) AMF colonization was observed. No differences in artemisin contents were detected, but essential oil yield significantly increased compared to control plants. AMF treatment increased beta-farnesene and germacrene D concentrations in Artemisia plants in the open field experiment.

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm.

The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo-gical examination excluded mycotic etiology of the aneu-rysm and "normal aneurysm wall" was described. The brain stem haemorrhage - Duret bleeding - was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Population-based stroke screening days in the 12th district of Budapest in 2011 and 2016 - What have and what have not changed?

BACKGROUND AND PURPOSE: Population-based screening is an option to identify persons at high risk for stroke. However it is associated with rather high expenses, necessitating the selection of effective methods that take local characteristics into account. The 12th district of Budapest has a long tradition of population-based screening for frequent and preventable diseases. The Szent János Hospital hosts an annual stroke screening day. In the present study, previously published data from the 2011 screening were compared with those obtained in 2016, looking for changes and tendencies throughout the examined period. METHODS: The screening day was conducted in a generally similar way in 2011 and 2016. Similarly to the previous event, the program was organized on a Saturday, the call for the event was spread by the local newspaper. The crew composition was the same. As regards the components of the screening (currently including general history taking, risk status assessment, blood pressure measurement, BMI assessment, cholesterol and blood glucose tests, carotid duplex ultrasonography, and ophthalmological examination), the only difference was the absence of cardiologic examination (it was conducted on an independent day). The anonymous data sheet was the same. RESULTS: The number of participants in the 2016 event was 33, to provide more comfortable conditions. The female predominance was slightly less pronounced but was still present in 2016 (60.6% vs. 72.9%). The mean age became substantially higher (71.2 y vs. 62.9 y). The ratios of participants with higher level of education (97% vs. 94%) and those who are married were still remarkable. The most frequent risk factors were the same; however the ratio of participants with hypertension, 'other heart disease', and diabetes increased, whereas that of with hyperlipidemia and obesity decreased. The incidence of atrial fibrillation was unaltered. None of the participants in 2016 admitted smoking (previously this ratio was 20.8%) or drinking heavily. The findings of the carotid ultrasonography revealed a more favorable vascular status. Ophthalmological assessments (predominantly hypertensive alterations on fundoscopy) revealed that the pathological vs. physiological ratio switched to 1:2 from 2:1. The final evaluation of the screening program likewise demonstrated an improved overall state of health of the population. CONCLUSION: We observed a more favorable stroke risk status of the population in 2016. Whether it is indeed a tendency unknown at present. The role of the local media in calling for screening is still decisive, and the cohesive power of the family is important.

[Chocolate consumption and Hungarian Nobel laureates]. / Csokoládéfogyasztás és a magyar Nobel-díjasok.

INTRODUCTION: Certain dietary items contain significant amounts of flavonoids which was shown to improve cognitive function. An earlier investigation demonstrated a strong linear correlation between chocolate consumption and the number of Nobel laureates in a given country. However, Hungary and the Hungarian Nobel laureates were not included in this analysis. AIM: In this publication, we aim to complement these data by analyzing data available for Hungary. METHOD: The number of Nobel laureates per country and the international data on chocolate consumption were based on the previously published results. The amount of chocolate consumption in Hungary was based on data from the Hungarian Central Statistical Office. GDP per capita and Research and Development Expenditure data for the investigated countries were derived from the World Bank. RESULTS: There are 11 Nobel laureates from Hungary. Based on this, Hungary ranks the 9th amongst the 24 studied countries. However, it only ranks the 19th when it comes to chocolate consumption. Correlations were found between the number of Nobel laureates and GDP per capita (r = 0.734; p = 0.001) as well as Research and Development Expenditure (r = 0.532; p = 0.01) amongst the studied countries. CONCLUSION: The achievements of Hungarian scholars do not support the earlier notion that there is a link between the number of Nobel laureates (cognitive function) and the chocolate consumption in a given country. Their biographies highlight the importance and more possibilities of research funding in wealthier countries. Orv Hetil. 2019; 160(1): 26-29.

A case report of isolated distal upper extremity weakness due to cerebral metastasis involving the hand knob area.

BACKGROUND: Unilateral weakness of an upper extremity is most frequently caused by traumatic nerve injury or compression neuropathy. In rare cases, lesion of the central nervous system may result in syndromes suggesting peripheral nerve damage by the initial examination. Pseudoperipheral hand palsy is the best known of these, most frequently caused by a small lesion in the contralateral motor cortex of the brain. The 'hand knob' area refers to a circumscribed region in the precentral gyrus of the posterior frontal lobe, the lesion of which leads to isolated weakness of the upper extremity mimicking peripheral nerve damage. The etiology of this rare syndrome is almost exclusively related to an embolic infarction. CASE PRESENTATION: We present the case of a 70-year-old male patient with isolated left sided upper extremity weakness and clumsiness without sensory disturbance suggesting a lesion of the radial nerve. Nerve conduction studies had normal results excluding peripheral nerve damage. Neuroimaging (cranial CT and MRI) detected 3 space occupying lesions, one of them in the right precentral gyrus. An irregularly shaped tumor was found by CT in the left lung with multiple associated lymph node conglomerates. The metastasis from this mucinous tubular adenocarcinoma with solid anaplastic parts to the 'hand knob' area was responsible for the first clinical sign related to the pulmonary malignancy. CONCLUSIONS: Pseudoperipheral palsy of the upper extremity is not necessarily the consequence of an embolic stroke. If nerve conduction studies have normal results, neuroimaging - preferably MRI - should be performed, as lesion in the hand-knob area of the precentral gyrus can also be caused by a malignancy.

Assessment of the Efficiency of Stroke Awareness Campaigns in Hungary.

BACKGROUND: The critical period of stroke management lies between the disease onset and the time of the emergency call, relying on stroke-related knowledge of the population. Public campaigns play a role in spreading relevant health information. Due to the substantial expenses of these campaigns, the assessment of their efficiency is reasonable. METHODS: We assessed the number of thrombolytic treatments performed in Hungary, subjected to national media coverage and in particular in Budapest, being the location of the Stroke Day campaign, in the period between 2008 and 2015. We compared the change in the daily mean number of thrombolytic treatments performed during the preceding and following day, week, and month. Data were also compared with annual means. RESULTS: No meaningful changes can be seen in the number of thrombolytic treatments on the days immediately following Stroke Days, and casual differences can be seen in the following week. The comparison of the numbers of thrombolytic treatments performed in the postcampaign months with the monthly means in the corresponding years revealed a positive effect in each year except for 2012, 2014, and 2015. Regarding the whole examined period, however, the effect is not statistically significant, neither for data obtained from Hungary nor from Budapest. CONCLUSIONS: Better outcomes were observed 1 month after a campaign than more immediately. This can be partly explained by ongoing media coverage in a given period rather than exposure of the public on a single Stroke Day.

A nationwide study of the epidemiology of relapsing polychondritis.

OBJECTIVE: Relapsing polychondritis (RP) is a rare autoimmune inflammatory disease that attacks mainly cartilaginous structures or causes serious damage in proteoglycan-rich structures (the eyes, heart, blood vessels, inner ear). This study shows results regarding the epidemiology, progression, and associations of this highly variable disease by collecting all cases from a 124-million-person-year Central European nationwide cohort. METHODS: We used the Hungarian Health Care Database to identify all persons with possible RP infection. We followed patients who had International Classification of Diseases 10th edition code M94.1 at least once in their inpatient or outpatient records between January 1, 2002 and December 31, 2013 in Hungary. We classified these patients into disease severity groups by their drug consumption patterns between January 1, 2010 and December 31, 2013. We analyzed the regional distribution of RP incidences as well. Overall maps of comorbidity are presented with network layouts. RESULTS: We identified 256 patients with RP among cumulatively 11.5 million registered inhabitants. We classified these patients into four severity classes as "extremely mild" (n=144), "mild" (n=22), "moderate" (n=41), and "severe" (n=4). Two additional groups were defined for patients without available drug data as "suspected only" (n=23) and "confirmed but unknown treatment" (n=22). The age and sex distributions of patients were similar to worldwide statistics. Indeed, the overall survival was good (95% confidence interval for 5 years was 83.6%-92.9% and for 10 years was 75.0%-88.3% which corresponds to the overall survival of the general population in Hungary), and the associations with other autoimmune disorders were high (56%) in Hungary. Almost any disease can occur with RP; however, the symptoms of chromosomal abnormalities are only incidental. Spondylosis can be a sign of the activation of RP, while Sjögren syndrome is the most frequent autoimmune association. Regional distribution of incidences suggests arsenic drinking water and sunlight exposure as possible triggering factors. CONCLUSION: The good survival rate of RP in Hungary is probably associated with the early diagnosis of the disease.

Phylogenetic analyses of eurotiomycetous endophytes reveal their close affinities to Chaetothyriales, Eurotiales, and a new order - Phaeomoniellales.

Symbiotic fungi living in plants as endophytes, and in lichens as endolichenic fungi, cause no apparent symptoms to their hosts. They are ubiquitous, ecologically important, hyperdiverse, and represent a rich source of secondary compounds for new pharmaceutical and biocontrol products. Due in part to the lack of visible reproductive structures and other distinctive phenotypic traits for many species, the diversity and phylogenetic affiliations of these cryptic fungi are often poorly known. The goal of this study was to determine the phylogenetic placement of representative endophytes within the Eurotiomycetes (Pezizomycotina, Ascomycota), one of the most diverse and evolutionarily dynamic fungal classes, and to use that information to infer processes of macroevolution in trophic modes. Sequences of a single locus marker spanning the nuclear ribosomal internal transcribed spacer region (nrITS) and 600 base pairs at the 5' end of the nuclear ribosomal large subunit (nrLSU) were obtained from previous studies of >6000 endophytic and endolichenic fungi from diverse biogeographic locations and hosts. We conducted phylum-wide phylogenetic searches using this marker to determine which fungal strains belonged to Eurotiomycetes and the results were used as the basis for a class-wide, seven-locus phylogenetic study focusing on endophytic and endolichenic Eurotiomycetes. Our cumulative supermatrix-based analyses revealed that representative endophytes within Eurotiomycetes are distributed in three main clades: Eurotiales, Chaetothyriales and Phaeomoniellales ord. nov., a clade that had not yet been described formally. This new order, described herein, is sister to the clade including Verrucariales and Chaetothyriales. It appears to consist mainly of endophytes and plant pathogens. Morphological characters of endophytic Phaeomoniellales resemble those of the pathogenic genus Phaeomoniella. This study highlights the capacity of endophytic and endolichenic fungi to expand our understanding of the ecological modes associated with particular clades, and provides a first estimation of their phylogenetic relationships in the Eurotiomycetes.

A multigene phylogenetic synthesis for the class Lecanoromycetes (Ascomycota): 1307 fungi representing 1139 infrageneric taxa, 317 genera and 66 families.

The Lecanoromycetes is the largest class of lichenized Fungi, and one of the most species-rich classes in the kingdom. Here we provide a multigene phylogenetic synthesis (using three ribosomal RNA-coding and two protein-coding genes) of the Lecanoromycetes based on 642 newly generated and 3329 publicly available sequences representing 1139 taxa, 317 genera, 66 families, 17 orders and five subclasses (four currently recognized: Acarosporomycetidae, Lecanoromycetidae, Ostropomycetidae, Umbilicariomycetidae; and one provisionarily recognized, 'Candelariomycetidae'). Maximum likelihood phylogenetic analyses on four multigene datasets assembled using a cumulative supermatrix approach with a progressively higher number of species and missing data (5-gene, 5+4-gene, 5+4+3-gene and 5+4+3+2-gene datasets) show that the current classification includes non-monophyletic taxa at various ranks, which need to be recircumscribed and require revisionary treatments based on denser taxon sampling and more loci. Two newly circumscribed orders (Arctomiales and Hymeneliales in the Ostropomycetidae) and three families (Ramboldiaceae and Psilolechiaceae in the Lecanorales, and Strangosporaceae in the Lecanoromycetes inc. sed.) are introduced. The potential resurrection of the families Eigleraceae and Lopadiaceae is considered here to alleviate phylogenetic and classification disparities. An overview of the photobionts associated with the main fungal lineages in the Lecanoromycetes based on available published records is provided. A revised schematic classification at the family level in the phylogenetic context of widely accepted and newly revealed relationships across Lecanoromycetes is included. The cumulative addition of taxa with an increasing amount of missing data (i.e., a cumulative supermatrix approach, starting with taxa for which sequences were available for all five targeted genes and ending with the addition of taxa for which only two genes have been sequenced) revealed relatively stable relationships for many families and orders. However, the increasing number of taxa without the addition of more loci also resulted in an expected substantial loss of phylogenetic resolving power and support (especially for deep phylogenetic relationships), potentially including the misplacements of several taxa. Future phylogenetic analyses should include additional single copy protein-coding markers in order to improve the tree of the Lecanoromycetes. As part of this study, a new module ("Hypha") of the freely available Mesquite software was developed to compare and display the internodal support values derived from this cumulative supermatrix approach.

Preparing an annotated gold standard corpus to share with extramural investigators for de-identification research.

OBJECTIVE: The current study aims to fill the gap in available healthcare de-identification resources by creating a new sharable dataset with realistic Protected Health Information (PHI) without reducing the value of the data for de-identification research. By releasing the annotated gold standard corpus with Data Use Agreement we would like to encourage other Computational Linguists to experiment with our data and develop new machine learning models for de-identification. This paper describes: (1) the modifications required by the Institutional Review Board before sharing the de-identification gold standard corpus; (2) our efforts to keep the PHI as realistic as possible; (3) and the tests to show the effectiveness of these efforts in preserving the value of the modified data set for machine learning model development. MATERIALS AND METHODS: In a previous study we built an original de-identification gold standard corpus annotated with true Protected Health Information (PHI) from 3503 randomly selected clinical notes for the 22 most frequent clinical note types of our institution. In the current study we modified the original gold standard corpus to make it suitable for external sharing by replacing HIPAA-specified PHI with newly generated realistic PHI. Finally, we evaluated the research value of this new dataset by comparing the performance of an existing published in-house de-identification system, when trained on the new de-identification gold standard corpus, with the performance of the same system, when trained on the original corpus. We assessed the potential benefits of using the new de-identification gold standard corpus to identify PHI in the i2b2 and PhysioNet datasets that were released by other groups for de-identification research. We also measured the effectiveness of the i2b2 and PhysioNet de-identification gold standard corpora in identifying PHI in our original clinical notes. RESULTS: Performance of the de-identification system using the new gold standard corpus as a training set was very close to training on the original corpus (92.56 vs. 93.48 overall F-measures). Best i2b2/PhysioNet/CCHMC cross-training performances were obtained when training on the new shared CCHMC gold standard corpus, although performances were still lower than corpus-specific trainings. DISCUSSION AND CONCLUSION: We successfully modified a de-identification dataset for external sharing while preserving the de-identification research value of the modified gold standard corpus with limited drop in machine learning de-identification performance.