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Abstract Background The Csangos are an East-Central European ethnographic group living mainly in east of Transylvania in Romania. Traditionally, ethnography distinguishes three Csango subpopulations, the Moldavian, Gyimes and Burzenland Csangos. In our previous study we found that the Moldavian Csangos have East Asian/Siberian Turkic ancestry components that might be unique in the East-Central European region and might help to better understand the history of Hungarian speaking ethnic groups of the area. Since then, we obtained further Csango samples from Moldavia and from a distinct region of Gyimes, which two Csango subgroups are traditionally different since they live in a degree of isolation not only from other people but also from each other. Here we present the first genomic analysis of Gyimes Csangos, which intended to compare the genetic makeup of these two Csango subgroups using both allele-frequency and haplotype-based methods. The main goal of the study was to investigate the genetic isolation of the Csangos on a genome-wide SNP basis and to assess the isolation of Gyimes Csangos, which in contrast to the Moldavians was not yet studied. Results Our results show that these two Csango groups show slight differences from each other. We confirmed the genetic isolation of Moldavian Csangos and revealed that Gyimes Csangos have a similar, but detectably weaker isolation. In the case of Gyimes Csangos we detected also a stronger East European or presumably Asian derived ancestry. Conclusion The Gyimes Csangos show a degree of genetic isolation comparable to that of the Moldavians. The Asian ancestry that differentiates the Moldavian Csango people from the other East-Central European populations may be present in the Gyimes Csangos in an even higher degree, since Gyimes Csango individuals show a more significant share from that ancestry component.

Background: The usability of subcutaneous vedolizumab (s.c. VDZ) treatment in inflammatory bowel diseases (IBD; ulcerative colitis (UC), Crohn’s disease (CD)) has been proven via clinical trials while real-world data collection is ongoing. Objectives: Our study evaluates the effectiveness, safety, patients’ preferences, and psychological factors associated with s.c. VDZ treatment, after switching from intravenous (i.v.) formulation. Design: Prospective, multicenter cohort study including IBD patients switching from i.v. VDZ to s.c. treatment and were evaluated over 52 weeks. Methods: Serum VDZ levels and C-reactive protein (CRP) were measured at the baseline and w52. At w12, a questionnaire on the patient’s satisfaction and psychological characteristics was administered. The primary outcome was the drug persistence rate (cessation was due to loss of response (LOR), adverse events, patient request, and other causes) at w52, while the secondary outcomes were the changes in the clinical corticosteroid-free remission (CSFR) and biochemical remission (BR; CRP ⩽ 5 mg/L) rates, safety issues, serum drug levels, patients’ preferences, and psychological features. Results: In total, 70 IBD patients were evaluated (32 CD patients, 38 UC patients; male/female ratio: 41.4%; median age: 43.2 years). In the CD group, 81.3% were in CSFR and 65.6% were in BR, while in the UC group, 71.7% were in CSFR and 69.4% were in BR. Overall, 17.1% of the patients ceased s.c. VDZ treatment after a median of 26.2 (interquartile range 20–47) weeks. LOR was registered in 3/12 ceased patients. In addition, CSFR and BR rates were stable, while serum VDZ levels increased by w52 ( p

Abstract The thermal spring-fed Lake Pețea located in NW Romania southeast of the city of Oradea harbors a unique endemic warm water biota. It is the only location in Europe where thermal water endemic melanopsid Microcolpia parreyssii (Philippi, 1847) lived along with the highly endangered warm-water relict neritid Theodoxus prevostianus. Lake Petea’s evolution was mainly controlled by major climate-driven hydrological changes also seen in regional records. The hydrological changes were mainly controlled by varying input of thermal water due to recurring increased/decreased recharge of the underground karst water system. The driving factor was warming connected to the interstadial GI 1 increasing recharge by melting of regional ice sheets in the Late Glacial. Conversely, during the Younger Dryas (H0) and the Holocene increasing/decreasing moisture availability was in control. Low stands created multiple bottlenecks reducing genetic variability seen in the appearance of extreme morphologies during next rapid climate melioration. The studied gastropods responded mostly similarly to changes controlling the availability of elements in shell construction and habitat reduction leading to changes in shape, density, size. Periods of lower lake levels and reduced warm water input are characterized by the emergence of elongated tightly coiled shells while globular, compressed loosely coiled shells develop at times of warmer water provision and increased Mg availability. In size there is a contrasting trend. Namely globose Th. prevostianus shells are larger than the elongated ones. Conversely globose, compressed Microcolpia are generally smaller than their elongated spindle-shaped counterparts. In this sense the development of dwarf morphotypes in warmer water habitats is characteristic of Lake Pețea melanopsids. This type of dwarfism i.e. the reduction of shell size is lacking though in Lake Pețea neritids. Our findings also confirm the presence of various ecophenotypes of Microcolpia in the pond degrading our endemic species Mi. parreyssii to a variety of Mi. daudebartii.

This study focuses on palaeoenvironmental changes in the Bottomless Lake (Tăul fără fund) Sphagnum peat bog situated near Bǎgǎu in Romania. The central research question was how the lake has changed over time, and how environmental factors and human activities have influenced the changes. By employing previous loss-on-ignition and radiocarbon analyses in addition to new radiocarbon, grain size, magnetic susceptibility and geochemical analyses, a more precise reconstruction of the bog's regeneration and erosion phases was achieved. A multi-proxy analysis of the core sequence provided crucial insights regarding the interconnections between various elements. Notably, plant-derived elements (Na, K) exhibited correlations with organic matter, and carbonate elements (Ca, Mg) with carbonate content; while Fe and magnetic susceptibility displayed changes in relation to inorganic matter content. Remarkably, the findings reflected the global 8200 cal BP and 4200 cal BP events, along with their environmental effects, within the Transylvanian Basin. There was mediaeval lakebed cleaning around 500300 cal BP, during which the deeper of two water layers was contaminated with more recent materials. The shallower water layer is connected with the modern water circulation, which reduces the apparent age of peat samples taken from its immediate vicinity.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

This study presents a comprehensive palaeoenvironmental reconstruction of the southern part of the Danube–Tisza interfluve in the Carpathian Basin from the Late Pleistocene to Early Holocene, addressing the region’s response to global climate forcings and local environmental factors based on multi-proxy analyses of two key protected areas: the Katymár brickyard and the hay meadows and loess banks of Hajós. By integrating radiocarbon-dated malacological, macrobotanical, pollen, phytolith, geochemical, and sedimentological analyses, it was possible to provide a picture of past climate–ecosystem interactions. The Katymár North sequence provides an extended chronology from Marine Isotope Stage 3 (MIS3, ca. 36,000 cal BP) through the Last Glacial Maximum (LGM) and into the Early Holocene, while the Hajós sequence offers high-resolution data for the LGM–Holocene transition. By the late Ice Age, humidity and surface moisture superseded temperature as primary palaeoecological limiting factors, promoting ecotone-like forest–steppe environments during cooling periods.

The loess–paleosol profile of Máza brickyard in SW Hungary was investigated through multivariate analyses of malacofauna and sedimentological analyses. The aim was to reconstruct the complex developmental history of both sediment and malacofauna. Three age–depth models were calculated, and the best-fit model, the OxCal P-sequence, was chosen for further analysis. The profile overlays the MIS3 and MIS2, beginning at approximately 45,000–50,000 cal BP and ending at the Pleistocene/Holocene boundary. The accumulation rates were two periods of intensive accumulation, equal to those observed in the Bácska Loess Plateau in Hungary, and two periods of decreased accumulation. Between ~38,000 and 31,000 cal BP, a decreased accumulation period was observed in Máza and other profiles from the Bácska Loess Plateau, indicating a common weak accumulation period at the end of MIS3. Correspondence and cluster analyses provided a higher-resolution paleoecological reconstruction, revealing a more detailed picture of the evolution of the studied section. The presence of thermophilous gastropod species with a high contribution to the correspondence analysis was significant in the sections. Although Granaria frumentum, Helicopsis striata, Chondrula tridens, and Pupilla triplicata were not significant species in the Máza malacofauna as a whole, their presence was associated with warming periods and the emergence of open vegetation.

Ever since its introduction, computed tomography has come a long way. No longer is it merely a method that is used in clinical diagnostics, but it is becoming more and more popular among palaeontologists because it can be used to analyse both external and internal structures of fossil remains, such as small insects, snail shells and plant remains. The present study describes non-destructive analyses of Late Cretaceous and early Holocene charophyte gyrogonites by using the micro-CT technique, from sample preparation (embedding, fixing) to visualisation and assessment of images obtained. In addition to this non-destructive examination, we wished to test whether or not computed tomography could be used to examine the gyrogonites. Our preliminary results have made it clear that the micro-CT technique is worth employing for further research. It has proved possible to visualise the samples in 3D, rotate them, and observe them from different directions. By using the appropriate parameters, we have also been able to observe density differences between parts of characean remains and to study several important defining features of these.

Suleiman the Magnificent died during the siege of Szigetvár in 1566, close to the battlefield in Turbék Vineyard Hill site, Hungary. On the place of his death, a memorial place was established with a tomb, a mosque, a monastery, and a deep moat system north of the building complex. After its destruction, the memorial place was covered with demolished material and soil. This significant site was re-identified and excavated during the archaeological, historical, and geoarchaeological research work that started in 2015. As a result of the correlative evaluation of previously published sedimentological and chronological data, the filling of the moat accumulated during the seventeenth century. Our goal was the natural and anthropogenic vegetation reconstruction of the adjacent region of the memorial place and the plant utilization of the community living there. During the analyses, more than 30,000 plant remains were identified belonging to 77 taxa. The results gave indications for ploughed lands, vegetable and fruit cultivation, vineyards, pasture lands, forest patches, and trampled areas related to active human activity. The lithostratigraphic and geochronological results of the moat sequence coincide well with our carpological and anthracological data.

Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system.

Abstract Background German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcső-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3–6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. Results Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. Conclusion This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

The Rejtek I. Rock Shelter in the Bükk Mountains of the inner Western Carpathian region plays an important role in the Late Pleistocene and Holocene environmental historical analyses. The investigations of the cave sediment accumulated from the end of the Pleistocene and the recovered paleontological finds, together with the archaeological artefacts, provided an opportunity to develop stratigraphic classifications. In addition, by comparing archaeostratigraphic, lithostratigraphic and biostratigraphic data, it was possible to link environmental and prehistoric events. The importance of the site is shown by both the mollusc and floral cold- and warm-tolerant species that were present in the area during the Late Pleistocene. The early expansion of thermophilous species indicates the presence of a refuge already during the Late Pleistocene. Based on the documents of the excavation, the previous works, the sediment sequence, as well as the sediment samples and the filling material of the mollusc shells, together with the new chronology, we were able to clarify the relative order of the excavated layers and the description of the sediment types in the Rejtek I. Rock Shelter.

Hungary’s first national park was created in 1973 in the Hortobágy area to protect Europe’s largest contiguous steppe area and its flora and fauna. The Hortobágy National Park—the Puszta was inscribed on the UNESCO World Heritage List as a cultural landscape in 1999. The park’s outstanding importance is due to the predominantly non-arboreal steppe vegetation, home to a unique bird fauna, and alkaline and chernozem soils with a complex, mosaic-like spatial structure. In addition, the landscape of Hortobágy has a pastoral history stretching back thousands of years. Several hypotheses have been put forward that suggest that the alkaline soils and the habitats that cover them were formed as a result of human activities related to river regulation that began in the second half of the 19th century. However, paleoecological and paleobiological studies over the last 30–40 years have pointed to the natural origin of the alkaline steppes, dating back to the end of the Ice Age. For thousands of years, human activities, in particular, grazing by domestic animals, hardly influenced the natural evolution of the area. The drainage of marshy and flooded areas began in the 19th century, as well as the introduction of more and more intensive agriculture, had a significant impact on the landscape. This paper aims to describe the past natural development of this special alkaline steppe ecosystem, with particular reference to the impacts of past and present human activities, including conservation measures.

This study presents a comprehensive palaeoenvironmental reconstruction of the southern part of the Danube–Tisza interfluve in the Carpathian Basin from the Late Pleistocene to Early Holocene, addressing the region's response to global climate forcings and local environmental factors based on multi-proxy analyses of two key protected areas: the Katymár brickyard and the hay meadows and loess banks of Hajós. By integrating radiocarbon-dated malacological, macrobotanical, pollen, phytolith, geochemical, and sedimentological analyses, it was possible to provide a picture of past climate–ecosystem interactions. The Katymár North sequence provides an extended chronology from Marine Isotope Stage 3 (MIS3, ca. 36,000 cal BP) through the Last Glacial Maximum (LGM) and into the Early Holocene, while the Hajós sequence offers high-resolution data for the LGM–Holocene transition. By the late Ice Age, humidity and surface moisture superseded temperature as primary palaeoecological limiting factors, promoting ecotone-like forest–steppe environments during cooling periods. [ABSTRACT FROM AUTHOR]

The loess–paleosol profile of Máza brickyard in SW Hungary was investigated through multivariate analyses of malacofauna and sedimentological analyses. The aim was to reconstruct the complex developmental history of both sediment and malacofauna. Three age–depth models were calculated, and the best-fit model, the OxCal P-sequence, was chosen for further analysis. The profile overlays the MIS3 and MIS2, beginning at approximately 45,000–50,000 cal BP and ending at the Pleistocene/Holocene boundary. The accumulation rates were two periods of intensive accumulation, equal to those observed in the Bácska Loess Plateau in Hungary, and two periods of decreased accumulation. Between ~38,000 and 31,000 cal BP, a decreased accumulation period was observed in Máza and other profiles from the Bácska Loess Plateau, indicating a common weak accumulation period at the end of MIS3. Correspondence and cluster analyses provided a higher-resolution paleoecological reconstruction, revealing a more detailed picture of the evolution of the studied section. The presence of thermophilous gastropod species with a high contribution to the correspondence analysis was significant in the sections. Although Granaria frumentum, Helicopsis striata, Chondrula tridens, and Pupilla triplicata were not significant species in the Máza malacofauna as a whole, their presence was associated with warming periods and the emergence of open vegetation. [ABSTRACT FROM AUTHOR]

The research utilizes an interdisciplinary approach, combining geological, ecological, and historical methods. It delves into the environmental evolution of Lake Kolon over a span of 17,700 years, shedding light on the intricate interplay between geological processes and ecological changes. The historical, statistical (PCA, DCA), and palaeoecological analyses centers on a core sequence situated in the heart of the lake, building upon previous research endeavors (pollen, malacological, macrobotanical and sedimentological analyses with radiocarbon dating). Forest fires occurred at the end of the Last Glacial Maximum (LGM); the boreal forest–steppe environment changed into temperate deciduous forest at the Pleistocene–Holocene boundary; human-induced environmental change into open parkland occurred; and from medieval times, communities used the land as pasture. This type of reconstruction is crucial for understanding how ecosystems respond to climate change over time, which has broader implications for modern-day conservation efforts and managing ecosystems in the face of ongoing climate change.

UNLABELLED: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinsons disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors. LINKED ARTICLES: This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Abstract The ancient Hungarians, “Madzsars”, established their control of the Carpathian Basin in the late ninth century and founded the Hungarian Kingdom around 1000AD. The origin of the Magyars as a tribal federation has been much debated in the past. From the time of the conquest to the early fourteenth century they were ruled by descendants of the Arpad family. In order to learn more about the genetic origin of this family, we here analyzed the genome of Bela III one of the most prominent members of the early Hungarian dynasty that ruled the Hungarian Kingdom from 1172 to 1196. The Y-Chromosome of Bela III belongs to haplogroup R1a-Z2123 that is today found in highest frequency in Central Asia, supporting a Central Asian origin for the ruling lineage of the Hungarian kingdom. The autosomal DNA profile of Bela III, however, falls within the genetic variation of present-day east European populations. This is further supported through his mtDNA genome that belongs to haplogroup H, the most common European maternal lineage, but also found in Central Asia. However, we didn’t find an exact haplotype match for Bela III. The typical autosomal and maternal Central Eastern European ancestry among Bela III autosomes might be best explained by consecutive intermarriage with local European ruling families.

Lake Kolon (Hungary), situated in the middle of the Turjánvidék area between the saline lakes of the Danube valley and the Homokhátság, is one of the most significant natural aquatic habitats in the Danube–Tisza Interfluve region. The central question of this study is how the lake changed, and how environmental factors and human activities have influenced these paleoenvironmental changes in Lake Kolon. A multiproxy analysis of a core sequence (loss on ignition, grain size, magnetic susceptibility, and geochemistry) provided crucial insights. Notably, correlations are observed in the following relationships: (1) clay, organic matter, and elements derived from organic sources, such as Na, K, and Zn; (2) MS, sand, inorganic matter, and elements originating from inorganic sources, such as Fe, Al, Ti, Na, K, and P; and (3) carbonate content and elements originating from carbonate sources, such as Ca and Mg. The lake’s paleoenvironment underwent significant changes in the past 27,000 years. Late-Pleistocene wind-blown sand provided the bottom for an oligotrophic lake (17,700 BP), followed by a calcareous mesotrophic Chara-lake phase (13,800 BP). Peat accumulation, along with the eutrophic lake phase, began at the Pleistocene–Holocene boundary around 11,700 BP. From 10,300 BP, with the emergence of an extended peatland phase, the percentage of organic matter (peat) increased significantly. Anthropogenic changes occurred from around 9000–8000 BP due to the different emerging cultures in the Carpathian basin, and from 942–579 BP due to the Hungarian settlements and activity nearby, respectively.

This study covers the examination of four loess–paleosol profiles in Hungary through grain size composition, organic matter, carbonate content and magnetic susceptibility measurements. One of the profiles (with a thickness of 25.72 m) can be found in the Gödöllő hills, on the border of town Pécel, and the other three profiles (Kisdorog-West—5.60 m, Kisdorog-East—6.40 and Bonyhádvarasd—8.16 m) are located in the Tolna hills of the Transdanubia region. The sections were continuously sampled with an interval of 4 cm. The same interval was also applied to the other three profiles. During the field exploration of the Pécel profile, we were able to study the complete loess wall, which was deposited on the sediment of the nearby Rákos stream. Based on the Ostracod fauna of the clay sediment beneath, the fluvial deposit can be considered as originating from the Upper Miocene. In the case of the Transdanubian sections, a significant change can be observed in the prevailing wind direction based on the grain size analyses. In addition, the results of magnetic susceptibility measurements suggest that the development of the Pécel profile took place during MIS 9–10, while the age of the three Transdanubian sections can be assumed to be the MIS 2–4.

Understanding sedimentation processes in response to past hydrogeological and climatic changes and capturing millennial-scale variations is a key focus of lacustrine paleoenvironmental research. This study presents the first high-resolution chronology and sedimentary data for the small thermal-spring-fed Lake Pețea, NW Romania, and unravels the evolutionary history of the lake harboring a unique endemic fauna. Its small size and single source of water make it particularly sensitive to hydrological changes. In the recent past, over-exploitation of the thermal water has led to the complete drying up of the lake and the extinction of its fauna. Nevertheless, past spatio-temporal variation of environmental factors, in particular the fluctuation of lake levels and water temperature, must have had a significant impact on the survival and evolution of the endemic mollusk fauna. This fact makes this study particularly important. Based on our results, a three-stage sedimentary evolution occurred, mainly controlled by major climate-driven hydrological changes also seen in regional records, i.e., 17.5–14.5 ka shallow eutrophic lake, 14.5–5.5 ka oligotrophic carbonate-rich lake, and 5.5–0.5 ka shallow eutrophic lake. A major lowstand at 11.7–10.2 ka due to drier climate was followed by progressively rising water levels up to 5 ka followed by a drop. The main control on lake level fluctuations and sedimentary phases was the varying input of thermal water due to recurring increased/decreased recharge of the underground shallow karst water system. The driving factor of thermal water discharge was different during the Late Glacial than the Holocene. It was the warming of the climate at 14.5 ka cal BP and melting of regional ice sheets in addition to increased precipitation that created an oligotrophic lake by recharging the underground thermal water system. Conversely, during the Holocene, increasing/decreasing moisture availability driven by major climate forcings was in control of thermal water recharge, erosion, and fluctuating lake levels.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997–2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary.

Abstract Background Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene. Methods Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing. The altered protein was investigated by in vitro cloning, expression and immunohistochemistry. Results The first cases in Hungary, − two patients in one family, where the parents were fourth-degree cousins - showed the typical clinical features of WRS: early onset diabetes mellitus with hyperglycemia, growth retardation, infection-induced multiple organ failure. The genetic background of the disease was a novel alteration in the EIF2AK3 gene involving the splice site of exon 11– intron 11–12 boundary: g.53051_53062delinsTG. According to cDNA sequencing this created a new splice site and resulted in a frameshift and the development of an early termination codon at amino acid position 633 (p.Pro627AspfsTer7). Based on in vitro cloning and expression studies, the truncated protein was functionally inactive. Immunohistochemistry revealed that the intact protein was absent in the islets of pancreas, furthermore insulin expressing cells were also dramatically diminished. Elevated GRP78 and reduced CHOP protein expression were observed in the liver. Conclusions The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.

In the present work, well radiocarbon-dated Quaternary malacological and palynological analyses were implemented on 4 cm samples deriving from one of the thickest and best developed last glacial sequences of Central Europe the Madaras brickyard and the borehole of Kolon Lake in the southern part of Hungary. Using a combination of mollusc, anthracological, palynological and climatic proxies evidence preserved within loess, we demonstrate that long-term changes (e.g. the last 39,000 (28,000) years) in paleoclimatic dynamics on the northern edge of the Bácska-Titel loess plateau, on the southern part of the Great Hungarian Plain. These proxy data are reflected in the following ecological changes: a turnover from predominantly cold-tolerant mollusc fauna in a boreal type forest-steppe context under cold conditions during the last glacial then followed by a shift to a predominantly xerotheromphilous land snail fauna in a temperate forest-steppe context under a warm temperate climate in the early Holocene. Certain warm-adapted, Central and SSE European distribution mollusc species such as Caucasotachea vindobonensis and Granaria frumentum, were found to have been associated with temperate forest-steppe in both the Holocene record and the present-day ecosystem.