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In recent decades, medicinal leeches of the genus Hirudo have experienced a sharp decline throughout their distribution range due to their overexploitation for medical use and habitat alteration. Such a phenomenon is not fully understood because of the complex taxonomy of the genus, which remained unsettled until the beginning of the XXI century, when the implementation of DNA taxonomy allowed for a better understanding of the diversity of the genus and the distribution ranges of Hirudo species. Only the Mediterranean medicinal leech Hirudo verbana Carena, 1820 is currently reported to occur in Italy and its major islands, although records of other Hirudo species have been reported in the literature. In this study, we report the occurrence of the Dragon leech Hirudo troctina Johnson, 1816 in Sardinia and provide its molecular characterization. In addition, based on a review of the existing literature and museum collections, we provide an ample synopsis of the available evidence regarding the occurrence of the species on the island. Hirudo troctina proved to be widespread and abundant in Sardinia during the XIX century but became rarer and rarer in the XX and XXI centuries possibly due to its overexploitation for medicinal use and export in mainland Europe, the abandonment of traditional grazing practices, and the decline of wetland habitats and amphibian populations. Currently, the only recently validated occurrence sites of the species are the water bodies of the “Giara di Gesturi”, a basaltic plateau in central-southern Sardinia. No corroborated evidence of the possible occurrence of other Hirudo species on the island was found. A better understanding of Hirudo troctina distribution in Sardinia will allow the amelioration of its protection and management practices, also under the provisions of the European “Habitats Directive”, where the H. medicinalis species complex is listed in Annex V.

Ednan K Bajwa,1 Dawn Cislak,1 Amit Kumar,1 Dan Li,1 Eric J Messina,1 Tom Reynders,2 Jean-François Denef,2 Vasile Corcea,3 Ketan P Buch,4 Eseng Lai,1 S Aubrey Stoch1 1MRL, Merck & Co., Inc., Rahway, NJ, USA; 2Translational Medicine, MSD Belgium, Brussels, Belgium; 3PMSI Republican Clinical Hospital “T. Mosneaga”, ARENSIA EM Unit, Chisinau, Republic of Moldova; 4Department of Internal Medicine, Pulmonary and Critical Care Medicine, Lexington VA Healthcare, Lexington, KY, USACorrespondence: Ednan K Bajwa, Translational Medicine, Merck Research Laboratories Massachusetts LLC, 33 Avenue Louis Pasteur, MAILSTOP BMB-3-420, Boston, MA, 02115-5727, USA, Tel +1 617 992-3470, Email ednan.bajwa@merck.comPurpose: This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with COPD (PH-COPD).Methods: Eligible participants were 40– 80 years old with COPD (FEV1/FVC < 0.7; FEV1 > 30% predicted) and PH (mean pulmonary arterial pressure ≥ 25 mmHg). Participants were randomized 2:1 to MK-5475 or placebo via dry-powder inhaler once daily for 7 days in Part 1 (360 μg) or 28 days in Part 2 (380 μg). Safety was assessed by adverse events (AEs) and arterial blood oxygenation. Part-2 participants had pulmonary vascular resistance (PVR; primary PD endpoint) and pulmonary blood volume (PBV; secondary PD endpoint) measured at baseline and Day 28. A non-informative prior was used to calculate posterior probability (PP) that the between-group difference (MK-5475 – placebo) in mean percent reduction from baseline in PVR was less than − 15%.Results: Nine participants were randomized in Part 1, and 14 participants in Part 2. Median age of participants (86.4% male) was 68.5 years (41– 77 years); 95.5% had moderate-to-severe COPD. Incidences of AEs were comparable between MK-5475 and placebo: overall (5/14 [36%] versus 5/8 [63%]), drug-related (1/14 [7%] versus 2/8 [25%]), and serious (1/14 [7%] versus 1/8 [13%]). MK-5475 caused no meaningful changes in arterial blood oxygenation or PBV. MK-5475 versus placebo led to numerical improvements from baseline in PVR (− 21.2% [95% CI: − 35.4, − 7.0] versus − 5.4% [95% CI: − 83.7, 72.9]), with between-group difference in PVR less than − 15% and calculated PP of 51%.Conclusion: The favorable safety profile and numerical reductions in PVR observed support further clinical development of inhaled MK-5475 for PH-COPD treatment.Keywords: pulmonary hypertension, chronic obstructive pulmonary disease, MK-5475, soluble guanylate cyclase stimulator, dry powder inhaler, pulmonary vascular resistance

Owing to the “Racovitzan impediment”, the groundwater fauna of most biogeographical regions is currently inadequately known, thus hampering our understanding of subterranean biodiversity and its protection. Based on an extensive bibliographical review accompanied by fieldwork to localize occurrence sites, a checklist of crustacean taxa reported to date from Sicilian groundwater is provided, and their distribution is described. Among the 63 taxa recorded to date, 43 belong to the class Copepoda (orders Cyclopoida and Harpacticoida), 15 to the class Malacostraca (orders Amphipoda, Bathynellacea, Isopoda, and Thermosbaenacea), and 5 to the class Ostracoda (order Podocopida). Conversely, to date, no representatives of the copepod order Calanoida nor species of the class Branchiopoda have been recorded from groundwater habitats on the island. Several taxa require accurate taxonomic revision or are yet to be formally described and are thus at present left in open nomenclature. Finally, the date of publication of several copepod and amphipod taxa is amended. A high incidence of stygobites (i.e., obligate groundwater dwellers) has been observed in malacostracans, whereas nearly half of the recorded copepods were non-stygobites. This pattern is mirrored by the incidence of endemic species, which is higher in malacostracans than in copepods. The only non-stygobitic crustacean species endemic to Sicily observed in the frame of present review is the asellid isopod Proasellus montalentii. The paucity of information currently available on the Sicilian groundwater ostracods prevents us from drawing conclusions regarding this crustacean group. The origin and composition of Sicilian groundwater crustacean fauna can be explained by considering three major faunal assemblages: the presence of ancient paleoendemic taxa, likely of Miocene origin, the colonization of the groundwater of the island during late Pliocene and Pleistocene land connections with peninsular Italy, and the direct colonization of these environments from the sea; no species of African origin have been discovered to date. Based on currently available data, the groundwater of southeastern Sicily hosts the highest species richness and some of the most biogeographically interesting taxa. Unfortunately, a progressive lowering and salinization of the local aquifers possibly due to climate change and its overexploitation threats this fauna, and several taxa are disappearing even before their discovery and description.

Abstract Subterranean ecosystems (comprising terrestrial, semi-aquatic, and aquatic components) are increasingly threatened by human activities; however, the current network of surface-protected areas is inadequate to safeguard subterranean biodiversity. Establishing protected areas for subterranean ecosystems is challenging. First, there are technical obstacles in mapping three-dimensional ecosystems with uncertain boundaries. Second, the rarity and endemism of subterranean organisms, combined with a scarcity of taxonomists, delays the accumulation of essential biodiversity knowledge. Third, establishing agreements to preserve subterranean ecosystems requires collaboration among multiple actors with often competing interests. This perspective addresses the challenges of preserving subterranean biodiversity through protected areas. Even in the face of uncertainties, we suggest it is both timely and critical to assess general criteria for subterranean biodiversity protection and implement them based on precautionary principles. To this end, we examine the current status of European protected areas and discuss solutions to improve their coverage of subterranean ecosystems.

Abstract Molnupiravir is an orally administered, small‐molecule ribonucleoside prodrug of β‐D‐N4‐hydroxycytidine (NHC) that has demonstrated potent, broad‐spectrum preclinical activity against RNA viruses and has a high barrier to the development of resistance. A double‐blind, placebo‐controlled, phase I trial was conducted to evaluate the pharmacokinetics (PKs), safety, and tolerability of 10.5‐day administration of multiple doses of molnupiravir and its metabolites in healthy, adult participants. Participants were randomly assigned (3:1) to receive molnupiravir (400 mg [n = 6], 600 mg [n = 6], and 800 mg [n = 12]) or matching placebo (n = 8) every 12 h (q12h) for 10.5 days. Blood was collected to evaluate the PKs of NHC in plasma and of its active metabolite, NHC‐triphosphate (NHC‐TP), in peripheral blood mononuclear cells (PBMCs). Molnupiravir was generally well‐tolerated. All adverse events were mild or moderate in severity and none led to treatment discontinuation. No clinically meaningful dose‐related safety findings were observed. Mean time to maximal concentration was ~1.50 to 1.98 h for plasma NHC and ~4.00 to 8.06 h for PBMC NHC‐TP. Accumulation was minimal (

Understanding the thermal properties of zeolites is crucial for their industrial applications. This study explores the thermal stability and dehydration process of clinoptilolite using high-temperature X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Clinoptilolite’s thermal decomposition was monitored from 25 °C to 1200 °C, with results analyzed based on its crystal structure. Principal components analysis (PCA) of the DRIFT spectra indicated progressive water removal and dehydration upon heating, leading to the formation of hydrogen bonds. Thermogravimetric analysis (TGA) revealed a two-step endothermic weight loss: initially, physically adsorbed water was lost up to 100 °C, followed by the removal of tightly bound water and hydroxyl groups until 800 °C. Clinoptilolite remained the dominant phase up to 800 °C, after which albite and cristobalite took over. Rietveld refinement showed that the sample initially contained 70% clinoptilolite, 24% albite, and 6% cristobalite. Above 800 °C, clinoptilolite disappeared, leaving 93% albite and 7% cristobalite. FT-IR spectra changes due to water loss were evident: drying of adsorbed water occurred up to 75 °C and minimal changes were observed from 75 °C to 135 °C, followed by further dehydration until 240 °C. Complete dehydration was confirmed by the disappearance of OH stretching vibration bands by 395 °C, consistent with TGA findings.

Among the many possible applications of iron phosphate glasses, one of them is that they are promising materials in waste vitrification, particularly for radioactive waste. In vitrified form, waste elements should be permanently immobilized in a glass network as they are susceptible to harsh environmental conditions. The self-diffusion of the vitrified material species may limit the potential usefulness of the glasses. This paper presents the possibility of using molecular dynamics simulations to study this process and the substitution of SrO into an iron phosphate glass network. It was evidenced that the self-diffusion mechanism differed significantly depending on whether the glass was in a solid or liquid state. The proposed method also offered a relatively easy prediction of glass characteristic temperatures, such as transformation and flow. We also observed, and here describe, an aggregation process of the glass elements that may drive their crystallization. The obtained results are discussed in light of the experimental and theoretical structural feature literature data.

Abstract Phase I trials inform on the initial safety profile of a new molecule and impact whether further development is pursued or not. Understanding the effect of non‐pharmacological factors on the variability of routine safety parameters could improve decision making in these early clinical trials, helping to separate signals related to the new molecule from background “noise.” To understand the impact of non‐pharmacological factors on routine safety parameters, we evaluated pooled safety data from over 1000 healthy participants treated with placebo in phase I trials between 2009 and 2018. The phase I participants were predominantly men, less than or equal to 50 years, White, and non‐Hispanic; and approximately an equal proportion had body mass index in the normal and overweight/obese range. Following administration of placebo, vital signs, electrocardiogram, and laboratory parameters remained near predose baseline values. Large changes from baseline were observed for many safety parameters, but these occurred in a relatively small number of participants. At least one adverse event (AE) occurred in 49.7% of participants receiving placebo in single ascending dose (SAD) studies and in 72.4% of participants receiving placebo in multiple ascending dose (MAD) studies, with headache being the most commonly reported AE (18.7% in SAD and 28.3% in MAD studies). Overall, these analyses are consistent with non‐pharmacological factors having a small impact on routine safety parameters in a phase I trial. The provided supplemental data may be used to contextualize the magnitude and frequency of abnormal safety values and AEs observed in phase I trials.

The Scientific Committee for the Italian Fauna is managing the new checklist of the animal species of Italy. The previous checklist was published in 1993-1995 and included both protozoans and Metazoa (more than 57,000 species); the new project, which includes only Metazoa, started in 2020 and is aimed at updating the former checklist (with more than 60,000 expected species) by on-line datasets and data papers. The new checklist includes marine species recorded in the Italian seas, divided into nine marine sectors, within the Italian Economic Exclusive Zone, and terrestrial and freshwater species recorded in administrative regions, as well as in the three macro-regions (northern continental, southern peninsular and insular - Sicily and Sardinia - macro-regions). Records from geopolitical units biogeographically related to Italy (i.e., Canton Ticino, CH; Corsica, F; San Marino Republic and Vatican City) are also included. Over 180 Italian and foreign taxonomists have so far participated to the first phase of this new project, providing datasets for taxa at different hierarchical level, from phyla to subfamilies and tribes. The list is intended to be a fundamental instrument not only for the faunistic knowledge of Italy, but also for biodiversity conservation strategies in the country and in the European Union. The new Checklist of the Italian fauna will be available from the LifeWatch Italy platform, and it will be progressively updated. Furthermore, data papers for taxa at different hierarchical level could be published with continuity in a special section of the journal Biogeographia – The Journal of Integrative Biogeography.

The large branchiopod fauna of Sardinia is reviewed based both on literature and newly collected data. Based on the available evidence, 13 taxa are present on the island (8 Anostraca, 2 Notostraca, and 3 Spinicaudata). Among them, the finding of the spinicaudatan Leptestheria dahalacensis is new for Sardinia, while the spinicaudatans Cyzicus bucheti and Eulimnadia sp. were overlooked in the most recent synopses on the fauna of the island due to misidentifications. Conversely, Cyzicus tetracerus and Limnadia lenticularis, previously erroneously reported based on misidentifications, must be excluded from the fauna of Sardinia. The finding of Eulimnadia sp. is the first record in Europe and the northernmost record of the genus. The occurrence of Leptestheria dahalacensis in Sardinia is rather unexpected and probably due to its accidental introduction linked with rice cultures. At least four of the 13 Sardinian large branchiopod species are absent from the Italian mainland and Sicily, stressing the uniqueness of its fauna and its significant contribution to the Mediterranean inland water crustacean diversity.

Scarce data are currently available about the distribution of the Mediterranean medicinal leech Hirudo verbana in Italy, and most of the known occurrence localities are based on records collected in the nineteenth and the first half of the twentieth century, which were not confirmed in the last decades, mostly due to a lack of surveys. Accordingly, the available knowledge on the distribution of the species is far from being updated and representative, although a significant negative trend of H. verbana throughout the country is supposed. The lack of sound distribution data is a significant shortfall, which hinders the implementation of the monitoring of the species as required by the Article 17 of the “Habitats Directive” on the species of Union concern. To provide recent, validated distributional data for the Mediterranean medicinal leech in Italy to be used as baseline data for further surveys and monitoring, we present herein a set of unpublished observations collected in the last decades in peninsular Italy, Sicily, and Sardinia. Moreover, we report observation of H. verbana feeding on amphibians, a feeding habit to date poorly documented for the Mediterranean medicinal leech. Based on both published and novel data, H. verbana is characterised by a large but fragmented distribution in Italy. Therefore, dedicated monitoring programs and the collection of validated occasional observations are highly desirable to get a clearer picture of the real distribution of the species.

Celem artykułu jest ukazanie współczesnych wyzwań kulturoznawstwa medialnego, które staje się istotnym sektorem nauk stosowanych nakierowanych na wytwarzanie wiedzy społecznie użytecznej. Wiedza ta z kolei jest wykorzystywana do rozwiązywania konkretnych problemów użytkowników i generacji medialnych (np. pokolenia Z, młodych dorosłych), związanych z wykorzystywaniem nowych mediów, w tym mediów społecznościowych, do celów interakcji, komunikacji, edukacji. Badania w obrębie tak rozumianego kulturoznawstwa medialnego są powiązane z podejściem zorientowanym na użytkowników (user‑text oriented approach). Przyjęcie takiej optyki badania zjawisk jest wynikiem zmiany paradygmatycznej w ramach samych mediów, tzn. przejściem od mediów masowych do mediów sieciowych, oraz efektem tzw. zwrotu performatywnego, który przyczynił się do większego namysłu nad „stosowalnością wiedzy” oraz samą performatywnością w odniesieniu do sfery symbolicznej i w rozumieniu Judith Butler. Problematyka ta została zobrazowana na wybranych przykładach.

Autorka artykułu przedstawia kluczowe momenty rozwoju oraz główne założenia koncepcji edukacji medialnej, wypracowanej w Instytucie Filologii Polskiej Uniwersytetu Pedagogicznego im. Komisji Edukacji Narodowej w Krakowie. Przedstawiony rys historyczny stanowi podstawę do rozważań o możliwych strategiach rozwoju instytucjonalnego w kontekście presji dynamicznie rozwijającego się rynku pracy.

Abstract Molnupiravir (MK‐4482) is an oral prodrug of the antiviral ribonucleoside analog, N‐hydroxycytidine (NHC), which has activity against RNA viruses, including severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a phase I safety and pharmacokinetic study of molnupiravir in healthy Japanese adult participants. A sample size larger than typically used in pharmacokinetic studies was implemented to collect additional safety data in the Japanese population to support special approval for emergency use in Japan. Single doses of molnupiravir up to 1600 mg and multiple doses of 400 and 800 mg administered every 12 h (q12h) for 5.5 days were generally well‐tolerated. NHC appeared rapidly in plasma and reached maximum concentration (Cmax), with a median time to Cmax (Tmax) between 1.00 and 2.00 h. Area under the concentration versus time curve from zero to infinity (AUC0–inf), area under the concentration versus time curve from zero to 12 h (AUC0–12), and Cmax of plasma NHC increased approximately dose proportionally. With q12h dosing, the geometric mean (GM) accumulation ratios for NHC AUC0–12 and Cmax were ~1 for 400 and 800 mg. Pharmacokinetics of NHC triphosphate (NHC‐TP), the active metabolite of NHC was assessed in peripheral blood mononuclear cells and also demonstrated roughly dose proportional pharmacokinetics. The GM accumulation ratios for NHC‐TP AUC0–12 and Cmax were ~2.5 for 400 and 800 mg. Following administration with food, only a modest reduction (24%) in plasma NHC Cmax with comparable AUC0–inf was seen, supporting administration without regard to food.

Abstract Aluminum phosphates are materials with relatively wide potential applications in many industries. The vibrational features of selected compounds were established on Raman and infrared spectroscopy. The experimentally determined spectra are compared to those calculated by ab initio methods. This gives a unique possibility of a proper assignment of the experimental spectral features to specific modes of vibration. In the results, it was evidenced that the spectra are characterized by two specific intense bands in the mid- and high-frequency range due to the P–O–P and P–O bonds in [PO4] tetrahedron vibrations. The position of the high-frequency band is related to the number of bridging oxygen atoms connecting [PO4] tetrahedrons in the unit cell. Additionally, the differences in the spectra were evidenced as a result of different polymorphic forms of the selected compounds. Therefore, the results may be useful in determining the phase composition of polyphase materials or structural features of aluminum–phosphate glasses and glass–ceramic materials.

In the frame of the activities of the LIFE11 NAT/GR/1014 ForOpenForests, some water bodies occurring in the "Ethnikos Drymos Oitis” (GR2440004) and “Oros Kallidromo” (GR2440006) (Sterea Ellada) were investigated with the aim of providing a first census of the composition and diversity of their crustacean fauna. Overall, the sampling of 15 water bodies (7 of them listed as “Mediterranean temporary ponds” sensu EU “Habitats Directive”) led to the finding of 13 branchiopod, 11 copepod, and 7 ostracod taxa, including 4 species new for mainland Greece, i.e. the copepods Arctodiaptomus alpinus (Imhoff, 1885) and Diaptomus cf. serbicus, and the branchiopods Leptestheria dahalacensis (Rüppel, 1837) and Wlassicsia pannonica Daday, 1904. The comparative analysis of the observed species assemblages and richness suggests that the protection of those ponds identified as “priority habitats” according to the “Habitats Directive” is effective for the specialized and peculiar crustacean biota of these ecosystems, but it is not sufficient in order to preserve efficiently the whole diversity of temporary pond-dwelling crustaceans occurring in the study area. Therefore, the implementation of synergistic conservation measures dedicated to both “priority” and “non-priority” habitats is desirable.

This manuscript summarizes the outcomes of the 6th EuroSpeleo Protection Symposium. Special emphasis was laid on presenting and discussing monitoring activities under the umbrella of the Habitats Directive (EU Council Directive 92/43/EEC) for habitat type 8310 "Caves not open to the public" and the Emerald Network. The discussions revealed a high level of variation in the currently conducted underground monitoring activities: there is no uniform definition of what kind of underground environments the "cave" habitat should cover, how often a specific cave has to be monitored, and what parameters should be measured to evaluate the conservation status. The variation in spatial dimensions in national definitions of caves further affects the number of catalogued caves in a country and the number of caves to be monitored. Not always participants are aware of the complete national monitoring process and that data sets should be freely available or easily accessible. The discussions further showed an inherent dilemma between an anticipated uniform monitoring approach with a coherent assessment methodology and, on the contrary, the uniqueness of caves and subterranean biota to be assessed – combined with profound knowledge gaps and a lack of resources. Nevertheless, some good practices for future cave monitoring activities have been identified by the participants: (1) Cave monitoring should focus on bio- and geodiversity elements alike; (2) Local communities should be involved, and formal agreements envisaged; (3) Caves must be understood as windows into the subterranean realm; (4) Touristic caves should not be excluded ad-hoc from regular monitoring; (5) New digital tools and open FAIR data infrastructures should be implemented; (6) Cave biomonitoring should focus on a large(r) biological diversity; and (7) DNA-based tools should be integrated. Finally, the importance of the 'forgotten' Recommendation No. 36 from the Bern Convention as a guiding legal European document was highlighted.

Groundwater ecosystems host a rich and unique, but still largely unexplored and undescribed, biodiversity. Several lineages of ostracod crustaceans have subterranean representatives or are exclusively living in groundwaters. The stygobitic genus Pseudolimnocythere Klie, 1938 has a West Palearctic distribution, and includes few living and fossil species of marine origin. Through a comprehensive literature review and the description of the two new living species, Pseudolimnocythere abdita sp. nov. and Pseudolimnocythere sofiae sp. nov., from springs in the Northern Apennines, Italy, a morphological analysis was carried out with the aim of comparing the valve morphology of living and fossil species, and to discuss previous hypotheses about time and mode of colonization of inland waters. Pseudolimnocythere species show a low variability in valve morphology, with a remarkable stasis over geological times. The distribution of extant and fossil species is consistent with a scenario of multiple and independent events of colonization of continental habitats linked to sea level variations starting from Middle Miocene in the Paratethys and, later, in the Mediterranean. The most common colonization routes of inland waters have taken place through karst formations along ancient coastlines, although we cannot exclude some minor active migration through the hyporheic zone of streams. Available distribution data suggest a poor dispersal ability of Pseudolimnocythere species after they had colonized continental waters.

The unsaturated karst represents a transitional zone connecting the land surface to the water table of the underlying saturated zone through percolating water and small perched aquifers. It constitutes a significant groundwater reservoir and hosts a high biodiversity of specialized and endemic species. Whereas investigating this ecotone can shed light on the invertebrate diversity of the whole karst system, ecological studies in the unsaturated karst have been hampered by access, mapping, and sampling challenges. We studied the unsaturated zone of 52 caves in the Lessinian Massif (NE-Italy), which is dominated by carbonate rocks interspersed with spot areas composed mainly of igneous rocks. Our aim was to understand which ecological and historical factors may have shaped the distribution of the groundwater crustacean copepods at a regional spatial scale in the Lessinian unsaturated karst. We collected 33 species belonging to the orders Harpacticoida and Cyclopoida. Species richness estimators and related species accumulation curves suggest an exhaustive sampling effort. A hydrologic analysis performed in a Geographic Information System environment divided the study area in three distinct drainage basins: Eastern Lessini, Lessinian Core, and Western Lessini. Regression analyses indicated that richness of non-stygobitic copepods (i.e., surface-water species which exploit groundwater for different purposes) was mainly driven by inter-basin differences. Richness of stygobitic copepods (i.e., obligate groundwater dwellers) was instead strongly related to lithological features and responded negatively to surface thermal variability. Next, we used a kernel density estimation to spatially explore diversity patterns in the area. The highest density of stygobitic harpacticoids was identified in the Eastern Lessinian basin, which is lithologically more heterogeneous and surrounded by practically non-aquiferous igneous rocks that may limit dispersal. Conversely, the Western Lessinian basin hosted a high density of stygobitic cyclopoid species. This spatial pattern suggests different colonization pathways for the two taxa, with a strong effect of igneous rocks in hampering dispersal of most harpacticoids. Lithological barriers seemingly did not affect non-stygobitic copepods, which were found across the whole area. Altogether, these results emphasize the key role played by the interaction of hydrological features, climate, and lithology in determining different copepod biodiversity patterns in the unsaturated karst.

Celem przedstawionych w artykule badań była diagnoza kluczowych problemów, z jakimi mierzyły się w roku 2020 i 2021 krakowskie instytucje kultury. Na potrzeby artykułu w czerwcu 2021 roku przeprowadzono trzy ustrukturyzowane wywiady pogłębione z przedstawicielami krakowskich instytucji kultury. Pytania badawcze wyprowadzono z przeglądu zastanej literatury przedmiotu (szczegóły metodologiczne w artykule). Badanie miało charakter pilotażowy.

Abstract Iron phosphates are a wide group of compounds that possess versatile applications. Their properties are strongly dependent on the role and position of iron in their structure. Iron, because of its chemical character, is able to easily change its redox state and accommodate different chemical surroundings. Thus, iron-phosphate crystallography is relatively complex. In addition, the compounds possess intriguing magnetic and electric properties. In this paper, we present crystal structure properties of a newly developed iron-phosphate compound that was obtained by devitrification from iron-phosphate glass of pyrophosphate stoichiometry. Based on X-ray diffraction (XRD) studies, the new compound (Fe7P11O38) was shown to adopt the hexagonal space group P63 (No. 173) in which iron is present as Fe3+ in two inequivalent octahedral and one tetrahedral positions. The results were confirmed by Raman and Mössbauer spectroscopies, and appropriate band positions, as well as hyperfine interaction parameters, are assigned and discussed. The magnetic and electric properties of the compound were predicted by ab initio simulations. It was observed that iron magnetic moments are coupled antiferromagnetically and that the total magnetic moment of the unit cell has an integer value of 2 µB. Electronic band structure calculations showed that the material has half-metallic properties.

Niphargus enslini Karaman, 1932 was collected only once in 1905 from the Falkensteiner Höhle (Baden-Württemberg, Germany). Two years after its description, the species was synonymized with Niphargus virei and not studied any more. During recent surveys on German niphargids, further samples collected in this cave did not yield N. enslini specimens, but this species was collected in the Blätterteighöhle and in the Schwarzer Brunnen, two caves located in Baden-Württemberg and intercepting the same karstic aquifer feeding Falkensteiner Höhle. In an integrative taxonomic approach, we carefully studied the morphology of the newly collected specimens and sequenced two molecular markers (fragments of the cytochrome c oxidase subunit I (COI) and of the nuclear 28S rRNA gene) to test for possible conspecificity of N. enslini with N. virei. Morphological analysis confirmed that N. enslini is distinct from the N. virei species complex. We provide a redescription of newly collected material, together with new drawings of a more than 100 years old topotypic female. We briefly discuss the putative origin of N. enslini and the age of its split from the N. virei species complex.

Abstract Islatravir (MK‐8591) is a nucleoside analogue in development for the treatment and prevention of HIV‐1. Two phase 1 trials were conducted during initial evaluation of islatravir: rising single doses (Study 1) and rising multiple doses (Study 2) of oral islatravir in male and female participants without HIV (aged 18–60 years). Safety, tolerability, and pharmacokinetics of islatravir (plasma) and islatravir‐triphosphate (peripheral blood mononuclear cells) were assessed. In Study 1, 24 participants, assigned to 1 of 3 panels, received alternating single doses of islatravir in a fasted state from 5 mg to 400 mg, or placebo, over 3 dosing periods; a 30 mg dose was additionally assessed following a high‐fat meal. In Study 2, 8 participants per dose received 3 once‐weekly doses of 10, 30, or 100 mg islatravir or placebo in a fasted state. For each panel in both trials, 6 participants received active drug and 2 received placebo. Islatravir was generally well‐tolerated, with no serious adverse events or discontinuations due to adverse events. Islatravir was rapidly absorbed (median time to maximum plasma concentration 0.5 hours); plasma half‐life was 49–61 h; intracellular islatravir‐triphosphate half‐life was 118–171 h. Plasma exposure increased in an approximately dose‐proportional manner; there was no meaningful food effect. There was a modest degree of intracellular islatravir‐triphosphate accumulation after multiple weekly dosing. After single oral doses of islatravir greater than or equal to 5 mg, intracellular islatravir‐triphosphate levels were comparable to levels associated with efficacy in preclinical studies. These results warrant continued clinical investigation of islatravir.

Summary: Background: Vaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate. Methods: In this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo. In Part 1, younger (18–54 years) and, in Part 2, older (≥55 years) adults seronegative for SARS-CoV-2 nucleocapsid received one of four V590 dose levels (5.00 × 105; 2.40 × 106; 1.15 × 107; or 5.55 × 107 plaque-forming units [pfu]) or placebo. In Part 3, a single V590 dose level (5.55 × 10⁷ pfu) or placebo was administered to younger SARS-CoV-2 seropositive adults. Primary endpoints included adverse events (AEs) and for Parts 1 and 2 anti-SARS-CoV-2 serum neutralising antibody responses measured by 50% plaque reduction neutralisation (PRNT50) assay at Day 28. Registration NCT04569786 [P001-02]. Findings: 232 participants were randomised and 219 completed the study. In seronegative participants, anti-SARS-CoV-2 spike-specific antibody responses to V590 were low and comparable to placebo across the lower dose levels. At the highest dose level (5.55 × 107 pfu), anti-SARS-CoV-2 spike-specific PRNT50 was 2.3-fold higher than placebo. The most frequently reported AEs were injection-site pain (38.4%), headache (15.1%) and fatigue (13.4%). Interpretation: V590 was generally well-tolerated. However, Day 28 anti-SARS-Cov-2 spike-specific antibody responses in seronegative participants following a single intramuscular administration of V590 were not sufficient to warrant continued development. Funding: The study was funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

A group of four amphoras found in the anchialine cave of Vodeni Rat in the Croatian island of Sveti Klement, on a rocky ledge at 24 m water depth, indicates that a freshwater source was exploited at the bottom of this karstic pit by islanders and/or passing-by sailors from the late Roman Republican Period to the Early Medieval Period. In other words, prior to the 4th–7th century CE, Vodeni Rat was not an anchialine cave but a Pleistocene karstic pit with a freshwater pool at the bottom. Seawater started to infiltrate this cavity via newly opened fissures in the surrounding limestone after the 4th–7th century CE, as the archeometric age of the youngest intact amphora found down in the pit suggests. At present, the 29-m-deep water body is stratified, with a saline water layer at the bottom, a freshwater layer at the surface, and a transitional brackish water layer in the middle. Our study of the physical and biological characteristics of the cave water column revealed diversified and highly partitioned populations of stygobitic crustaceans including ostracods, copepods, amphipods, and thermosbaenaceans. Some species known to be exclusively endemic of highly saline habitats were collected from the bottom saline layer, whereas others known to be of freshwater origin were found in the upper water layer. This suggests that the freshwater dwellers were already present in this cave prior to the early medieval event that caused seepage of seawater into this karstic pit.

Abstract Gefapixant (MK‐7264) is a first‐in‐class, selective antagonist of the P2X3 purinergic receptor currently being investigated as a therapeutic agent for the treatment of refractory or unexplained chronic cough. In non‐clinical studies, gefapixant was eliminated primarily by renal excretion of the parent drug. The objective of this study was to assess the disposition of gefapixant in humans. The absorption, metabolism, and excretion profiles of gefapixant were assessed after oral administration of a single dose of [14C]gefapixant to six healthy adult males. Following a single‐oral [14C]gefapixant dose to healthy adult males, the mass balance was achieved, with 98.9% of the administered radioactivity recovered in urine and feces. Elimination of gefapixant occurred primarily via renal excretion of the intact drug (64%); metabolism was a minor pathway of elimination of gefapixant (12% and 2% recovered in urine and feces, respectively). Single‐dose administration of [14C]gefapixant 50 mg was generally well tolerated in healthy adult males. The fraction of the anticipated therapeutic oral dose of gefapixant absorbed is estimated to be at least 78%. Gefapixant is expected to be the major circulating drug‐related material in plasma, and the majority of the dosed drug will be excreted unchanged in urine.

Summary: Background: We report on the safety and immunogenicity of V591, a measles vector-based SARS-CoV-2 vaccine candidate. Methods: In this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial, healthy adults with no history of COVID-19 disease were assigned to intramuscular injection of V591 or placebo (4:1 ratio). In part 1, younger adults (18-55 years) received V591 median tissue culture infectious dose (TCID50)-levels of 1×105 or 1×106 or placebo, 56 days apart. In part 2, younger and older (>55 years) adults received a single dose of one of four (104/105/106/107) or one of two (105/106) V591 TCID50 levels, respectively, or placebo. Primary outcome: safety/tolerability. Secondary outcome: humoral immunogenicity. ClinicalTrials.gov: NCT04498247. Findings: From August–December 2020, 444 participants were screened and 263 randomised (210 V591; 53 placebo); 262 received at least one and 10 received two doses of V591 or placebo. Adverse events were experienced by 140/209 (67.0%) V591 dose-group participants and 37/53 (69.8%) placebo-group participants following injection 1; most frequent were fatigue (57 [27.3%] vs 20 [37.7%]), headache (57 [27.3%] vs 19 [35.8%]), myalgia (35 [16.7%] vs 10 [18.9%]), and injection-site pain (35 [16.7%] vs 4 [7.5%]). No deaths nor vaccine-related serious adverse events occurred. At Day 29, no anti-SARS-CoV-2 spike serum neutralising antibody and IgG-responses were identified in placebo or the three lower V591 dose-groups; responses were detected with V591 1×107 TCID50, although titres were lower than convalescent serum. Interpretation: V591 was generally well tolerated, but immunogenicity was insufficient to warrant continued development. Funding: Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Temporary ponds are the most peculiar and representative water bodies in the arid and semi-arid regions of the world, where they often represent diversity hotspots that greatly contribute to the regional biodiversity. Being indissolubly linked to these ecosystems, the so-called “large branchiopods” are unanimously considered flagship taxa of these habitats. Nonetheless, updated and detailed information on large branchiopod faunas is still missing in many countries or regions. Based on an extensive bibliographical review and field samplings, we provide an updated and commented checklist of large branchiopods in Tunisia, one of the less investigated countries of the Maghreb as far as inland water crustaceans are concerned. We carried out a field survey from 2004 to 2012, thereby collecting 262 crustacean samples from a total of 177 temporary water bodies scattered throughout the country. Large branchiopod crustaceans were observed in 61% of the sampled sites, leading to the identification of fifteen species. Among these, the halophilic anostracan Branchinectella media is here reported for the first time for the country; conversely, four of the species reported in literature were not found during the present survey. Based on literature and novel data, the known large branchiopod fauna of Tunisia now includes 19 species, showing a noteworthy species richness when the limited extension of the country is considered. For each species, the regional distribution is described and an annotated list of references is provided. Under a conservation perspective, the particular importance of the temporary ponds occurring in the Medjerda river alluvial plain is further stressed. In this location, several large branchiopod taxa with different ecological requirements converge and form unique and species-rich assemblages that should be preserved.

Praktyka w obszarze arteterapii wymaga namysłu nad jej fundamentami: rozumieniem zdrowia oraz rozumieniem sztuki, które uzasadnia jej miejsce w podejmowanych procesach terapeutycznych. Pojęcie zdrowia obecnie podlega dyskusji, a pojęcie sztuki jest z natury otwarte. W każdych działaniach terapeutycznych rozumianych jako towarzyszenie w procesie zdrowienia obowiązuje zasada: primum non nocere. Bezrefleksyjne angażowanie sztuki w działania terapeutyczne jest potencjalnie szkodliwe. Rozumiem zdrowie jako dynamiczny stan równowagi, który zawdzięczamy żywotności procesów homeostazy i allostazy, a zdrowienie jako skuteczny wysiłek podejmowany przez organizm w celu zarządzania tymi procesami. Zdrowie jest zarówno byciem w dobrej formie, jak i zdolnością dążenia do dobrej formy. Żywotność i efektywność procesów homeostazy łączę z ludzką zdolnością do bycia obecnym. Podobnie sztukę rozumiem jako specyficzne ludzkie doświadczenie trudnego, często bolesnego procesu dążenia do dobrej formy, jak i samą formę, którą za Robertem Plantem Armstrongiem (1971) nazywam „poruszającą obecnością”. Twórcze procesy ekspresyjne, w wyniku których takie formy powstają, widzę jako kierowane potrzebą adaptacji i transcendencji, a obecność jako warunek, który pozwala nam bezpośrednio spotkać zarówno to, co tożsame, jak i inne. Poświecenie równej uwagi procesowi i formie uważam za kluczowe w arteterapii.

Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.e., seasonal variation) are necessary. Methods: Five decades of clinical trial literature were leveraged to build a model-based meta-analysis (MBMA) describing the relationship between RSV serum neutralizing activity (SNA) and clinical endpoints. The MBMA was validated by backward translation to animal challenge experiments and forward translation to predict results of a recent RSV mAb trial. MBMA predictions were evaluated against a human trial of 70 participants who received either placebo or one of four dose-levels of MK-1654 and were challenged with RSV [NCT04086472]. The MBMA was used to perform clinical trial simulations and predict efficacy of MK-1654 in the infant target population. Findings: The MBMA established a quantitative relationship between RSV SNA and clinical endpoints. This relationship was quantitatively consistent with animal model challenge experiments and results of a recently published clinical trial. Additionally, SNA elicited by increasing doses of MK-1654 in humans reduced RSV symptomatic infection rates with a quantitative relationship that approximated the MBMA. The MBMA indicated a high probability that a single dose of ≥ 75 mg of MK-1654 will result in prophylactic efficacy (> 75% for 5 months) in infants. Interpretation: An MBMA approach can predict efficacy of neutralizing antibodies against RSV and potentially other respiratory pathogens.

Calanoids of the family Diaptomidae are the most widespread copepods in the lentic inland waters of the Palearctic region. In Italy, studies on the family date back to the end of 19th century. Since then, several papers contributed to increasing the knowledge on their presence, distribution, and ecological preferences. Nevertheless, new records for the area and the discovery of putative new species stress that the current knowledge on these inland water crustaceans is still far from being exhaustive. This paper presents an updated and annotated checklist and bibliography of the Diaptomidae of the Italian peninsula and surrounding islands, including Corsica and the Maltese islands, compiled through a critical review of the existing literature and carrying out further field research. The doubtful records reported in the literature are discussed and clarified. The updated checklist includes 30 diaptomid species and subspecies; among them, an alien species and three putative new species pending formal description are reported. About 20% of the observed species are endemic or subendemic to the study area. The faunal provinces ascribed to the Mediterranean limnofaunistic region host the highest species richness and contribute to the checklist with rare species and unique occurrences. The high species richness observed in the Mediterranean area supports the hypothesis of a long-lasting persistence of an ancient and peculiar copepod fauna.

The article is an introduction to the critical analysis of media messages in the times of post-truth politics. In the first part we can find basic informations about fake news, and their distinction into their two main types: disinformation and misinformation. In the next chapter, the Author focuses on describing the contemporary media context. We find here a reference to the work of Jean Baudrillard and his theory of replacing the truth with its simulation. The article closes recommendations for media users who want to develop their media competences.

The efficiency of the purchasing process co-decides on the success of the production organization. One of the basic tools for quality purchasing management is the selection and evaluation of suppliers. We can use a wide range of tools to evaluate suppliers, and this evaluation can be based on a large and diverse set of criteria. In the case of evaluating many potential suppliers according to a number of criteria, it is not possible to rely solely on the intuitive nature of the evaluation. Therefore, managerial tools based on the mathematical principles of multi-criteria decision-making have been increasingly important. The article deals with the analysis of the realized research focused on the use of mathematical methods in the evaluation of suppliers in an industrial enterprise. This article aims to analyse the possibility to use tools based on determining weighted order when evaluating suppliers. Data obtained from the research in a selected industrial enterprise in the Czech Republic was used for evaluation.