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Using (10087±44)×106 J/ψ events collected with the BESIII detector, numerous Ξ− and Λ decay asymmetry parameters are simultaneously determined from the process J/ψ→Ξ−Ξ¯+→Λ(pπ−)π−Λ¯(n¯π0)π+ and its charge-conjugate channel. The precisions of α0 for Λ→nπ0 and α¯0 for Λ¯→n¯π0 compared to world averages are improved by factors of 4 and 1.7, respectively. The ratio of decay asymmetry parameters of Λ→nπ0 to that of Λ→pπ−, ⟨α0⟩/⟨αΛ−⟩, is determined to be 0.873±0.012+0.011−0.010, where the first and the second uncertainties are statistical and systematic, respectively. The ratio is smaller than unity more than 5σ, which signifies the existence of the ΔI=3/2 transition in Λ for the first time. Beside, we test for CP violation in Ξ−→Λπ− and in Λ→nπ0 with the best precision to date.
Using e+e− collision data, corresponding to an integrated luminosity of 892pb−1 collected at center-of-mass energies from 4.84 to 4.95\,GeV with the BESIII detector, we search for the process e+e−→K+K−ψ(3770) by reconstructing two charged kaons and one D meson from ψ(3770). No significant signal of e+e−→K+K−ψ(3770) is found and the upper limits of the Born cross sections are reported at 90\% confidence level.
Understanding how epigenetic variation in non-coding regions is involved in distal gene-expression regulation is an important problem. Regulatory regions can be associated to genes using large-scale datasets of epigenetic and expression data. However, for regions of complex epigenomic signals and enhancers that regulate many genes, it is difficult to understand these associations. We present StitchIt, an approach to dissect epigenetic variation in a gene-specific manner for the detection of regulatory elements (REMs) without relying on peak calls in individual samples. StitchIt segments epigenetic signal tracks over many samples to generate the location and the target genes of a REM simultaneously. We show that this approach leads to a more accurate and refined REM detection compared to standard methods even on heterogeneous datasets, which are challenging to model. Also, StitchIt REMs are highly enriched in experimentally determined chromatin interactions and expression quantitative trait loci. We validated several newly predicted REMs using CRISPR-Cas9 experiments, thereby demonstrating the reliability of StitchIt. StitchIt is able to dissect regulation in superenhancers and predicts thousands of putative REMs that go unnoticed using peak-based approaches suggesting that a large part of the regulome might be uncharted water.
Highlights
• Single nucleotide variants (SNVs) may affect transcription factor (TF) binding
• Fast statistical approach to assess significance of differential TF binding for SNVs
• Validate new approach on in vitro and in vivo TF binding assays
• Applications on GWAS SNVs and large eQTL studies illustrate utility
Summary
Non-coding variants located within regulatory elements may alter gene expression by modifying transcription factor (TF) binding sites, thereby leading to functional consequences. Different TF models are being used to assess the effect of DNA sequence variants, such as single nucleotide variants (SNVs). Often existing methods are slow and do not assess statistical significance of results. We investigated the distribution of absolute maximal differential TF binding scores for general computational models that affect TF binding. We find that a modified Laplace distribution can adequately approximate the empirical distributions. A benchmark on in vitro and in vivo datasets showed that our approach improves upon an existing method in terms of performance and speed. Applications on eQTLs and on a genome-wide association study illustrate the usefulness of our statistics by highlighting cell type-specific regulators and target genes. An implementation of our approach is freely available on GitHub and as bioconda package.
Human 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis, mostly expressed in leukocytes and thus a crucial component of the innate immune system.
In this study, we show that 5-LO, besides its canonical function as an arachidonic acid metabolizing enzyme, is a regulator of gene expression associated with euchromatin. By Crispr-Cas9-mediated 5-LO knockout (KO) in MonoMac6 (MM6) cells and subsequent RNA-Seq analysis, we identified 5-LO regulated genes which could be clustered to immune/defense response, cell adhesion, transcription and growth/developmental processes. Analysis of differentially expressed genes identified cyclooxygenase-2 (COX2, PTGS2) and kynureninase (KYNU) as strongly regulated 5-LO target genes. 5-LO knockout affected MM6 cell adhesion and tryptophan metabolism via inhibition of the degradation of the immunoregulator kynurenine. By subsequent FAIRE-Seq and 5-LO ChIP-Seq analyses, we found an association of 5-LO with euchromatin, with prominent 5-LO binding to promoter regions in actively transcribed genes. By enrichment analysis of the ChIP-Seq results, we identified potential 5-LO interaction partners. Furthermore, 5-LO ChIP-Seq peaks resemble patterns of H3K27ac histone marks, suggesting that 5-LO recruitment mainly takes place at acetylated histones.>
In summary, we demonstrate a noncanonical function of 5-LO as transcriptional regulator in monocytic cells.
Samples of Crustacea and Annelida (Polychaeta, Sipuncula, and Hirudinea) were collected in the Bering Sea and the northwestern Pacific Ocean during scientific cruise SO-249 BERING in 2016. Biological samples were collected from 32 locations by the team on-board RV Sonne using a chain bag dredge at depths ranging between 330–5,070 m, and preserved in 96% ethanol. Specimens were morphologically identified to the lowest taxonomic level possible using a Leica M60 stereomicroscope. The generated data here comprise taxonomic information as well as annotated bathymetric and biogeographic information from a total of 78 samples (26 Crustacea, 47 Polychaeta, 4 Sipuncula, and 1 Hirudinea). The dataset was prepared following Darwin Core Biodiversity standards for FAIR data sharing based on Ocean Biodiversity Information System (OBIS) and Global Biodiversity Facility (GBIF) guidelines. The standardised digitised data were then mobilised to both OBIS and GBIF under CC BY 4.0 licence to publicly share and adopt the data. As records of these important marine taxa from bathyal and abyssal depths are sparse, especially from the deep Bering Sea, the herein generated and digitised data aid in filling existing knowledge gaps on their diversity and distribution in that region. As part of the “Biogeography of the NW Pacific deep-sea fauna and their possible future invasions into the Arctic Ocean” (BENEFICIAL) project, this dataset thus not only increases our knowledge in re-assessing and uncovering the deep-sea diversity of these taxa, but also serves policy and management sectors by providing first-hand data for global report assessments.
The monophyly of Theraphosinae is supported by both morphological and molecular phylogenies. However, intergeneric relationships often show polytomies and branches with low support. A previous phylogenetic study proposed an intergeneric relationship for the subfamily based on molecular data and divided it into three tribes: Grammostolini, Hapalopini and Theraphosini. However, not all genera of Theraphosinae were sampled, and some relationships were inferred based on morphological similarities. Regarding the Hapalopini from Brazil, the relationships of some genera are still uncertain, such as Kochiana, Catanduba, and Munduruku. In this paper, we describe four new species of Hapalopini from Brazil: Cyriocosmus paresi sp. nov., Hapalopus akroa sp. nov., H. guidonae sp. nov., and K. fukushimae sp. nov. In addition, we propose an updated diagnosis for these three genera and for the species K. brunnipes and M. bicoloratum.
Ophioderma teres (Lyman, 1860), an ophiuroid previously believed to have a wide distribution in the eastern Pacific, has been found to have an unclear taxonomic identity. While considered a well-known species, recent studies have revealed that O. teres lacks a holotype and has vague boundaries with its congeners Ophioderma teres unicolor H.L. Clark, 1940 and Ophioderma sodipallaresi Caso, 1986, as well as with two additional new morphotypes detected in Mexico and Nicaragua, causing continuous misidentifications. This study utilized an integrative taxonomy approach based on morphologic, morphometric, and molecular evidence to clarify the taxonomic status of O. teres, O. sodipallaresi, O. teres unicolor, and the two new morphotypes. Data integration led to the following results: 1) the neotype designation and redescription of O. teres; 2) the proposal of O. sodipallaresi as a junior synonym of O. teres; 3) the status change of O. unicolor stat. nov. from subspecies to species, and 4) the description of the morphotypes as the new species Ophioderma aija sp. nov. and Ophioderma bichi sp. nov. An identification key to the eastern Pacific species of Ophioderma was also developed. This work contributes to the knowledge of Ophioderma in the region, increasing the number of described species and providing resources for their accurate identification.
In this study, we describe two new species of Mesobiotus based on morphological data collected through light and scanning electron microscopy. Descriptions include DNA sequences of four commonly used molecular markers (18S rDNA, 28S rDNA, ITS-2, and COI). Mesobiotus efa sp. nov. was discovered in North-West Russia and belongs to the group of species with smooth cuticle, harmsworthi-type OCA, typical Mesobiotus claws IV with unindented lunules, and egg chorion with reticulated processes in form of ‘sharp wide cones’ or ‘cones with long slender endings’, egg process bases with well-developed crone of dark thickenings without finger-like projections, and egg shell surface between the processes with ridges without reticulation, areolation or semi-areolation. It can be distinguished from all know species of this group by a unique combination of morphological and morphometric characters. Mesobiotus vulpinus sp. nov. was found in the Russian Far East, and is similar to Mesobiotus mauccii by having an egg chorion with polygonal relief. The new species can be distinguished from M. mauccii by having a narrower buccal tube, by details of oral cavity armature, and by longer egg chorion processes. Furthermore, we provide results of the phylogenetic analyses of the genus Mesobiotus conducted in this study.
Although semi-aquatic cockroaches have been known for a long time, these insects remain little studied and their diversity underestimated. While a few species are known from Asia or South America, only a single one is known to be associated with water in Africa. Here, we report two species of semi-aquatic cockroaches of the subfamily Epilamprinae from Cameroon. One of these species is new: Rhabdoblatta fotoi Nyame Mbia, Legendre & Biram à Ngon sp. nov. Africalolampra camerunensis (Borg, 1902) comb. nov. was also found associated to these streams and we provide an extended description of this species, as well as for Africalolampra stipata comb. nov., also known from streams in West Africa. Another species was found in Cameroonian streams and is described here, although only identified at the family level (Blattellidae). The descriptions are based on morpho-anatomic characters, including male genitalia. Because nymphs were found primarily associated with water – more than adults – we provide a description of nymphs whenever possible. We provide molecular data (12S rRNA marker) for two of these water-associated species that we compared with published and unpublished sequences of Epilamprinae in a Maximum Likelihood approach. We also illustrate all but one species from continental Africa in the genera Africalolampra and Rhabdoblatta, including R. punctipennis (Saussure, 1895) which we reinstate. We provide a map and list of localities for Africalolampra and Rhabdoblatta spp. from continental Africa and Madagascar, as well as an identification key for species of Africalolampra. We finally discuss putative adaptations of semi-aquatic cockroaches.
Discoveries of new species often depend on one or a few specimens, leading to delays as researchers wait for additional context, sometimes for decades. There is currently little professional incentive for a single expert to publish a stand-alone species description. Additionally, while many journals accept taxonomic descriptions, even specialist journals expect insights beyond the descriptive work itself. The combination of these factors exacerbates the issue that only a small fraction of marine species are known and new discoveries are described at a slow pace, while they face increasing threats from accelerating global change. To tackle this challenge, this first compilation of Ocean Species Discoveries (OSD) presents a new collaborative framework to accelerate the description and naming of marine invertebrate taxa that can be extended across all phyla. Through a mode of publication that can be speedy, taxonomy-focused and generate higher citation rates, OSD aims to create an attractive home for single species descriptions. This Senckenberg Ocean Species Alliance (SOSA) approach emphasises thorough, but compact species descriptions and diagnoses, with supporting illustrations and with molecular data when available. Even basic species descriptions carry key data for distributions and ecological interactions (e.g., host-parasite relationships) besides universally valid species names; these are essential for downstream uses, such as conservation assessments and communicating biodiversity to the broader public.This paper presents thirteen marine invertebrate taxa, comprising one new genus, eleven new species and one re-description and reinstatement, covering wide taxonomic, geographic, bathymetric and ecological ranges. The taxa addressed herein span three phyla (Mollusca, Arthropoda, Echinodermata), five classes, eight orders and twelve families. Apart from the new genus, an updated generic diagnosis is provided for four other genera. The newly-described species of the phylum Mollusca are Placiphorella methanophila Vončina, sp. nov. (Polyplacophora, Mopaliidae), Lepetodrilus marianae Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Lepetodrilidae), Shinkailepas gigas Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Phenacolepadidae) and Lyonsiella illaesa Machado & Sigwart, sp. nov. (Bivalvia, Lyonsiellidae). The new taxa of the phylum Arthropoda are all members of the subphylum Crustacea: Lepechinella naces Lörz & Engel, sp. nov. (Amphipoda, Lepechinellidae), Cuniculomaera grata Tandberg & Jażdżewska, gen. et sp. nov. (Amphipoda, Maeridae), Pseudionella pumulaensis Williams & Landschoff, sp. nov. (Isopoda, Bopyridae), Mastigoniscus minimus Wenz, Knauber & Riehl, sp. nov. (Isopoda, Haploniscidae), Macrostylis papandreas Jonannsen, Riehl & Brandt, sp. nov. (Isopoda, Macrostylidae), Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. (Isopoda, Nannoniscidae) and Apseudopsis daria Esquete & Tato, sp. nov. (Tanaidacea, Apseudidae). In the phylum Echinodermata, the reinstated species is Psychropotes buglossa E. Perrier, 1886 (Holothuroidea, Psychropotidae).The study areas span the North and Central Atlantic Ocean, the Indian Ocean and the North, East and West Pacific Ocean and depths from 5.2 m to 7081 m. Specimens of eleven free-living and one parasite species were collected from habitats ranging from an estuary to deep-sea trenches. The species were illustrated with photographs, line drawings, micro-computed tomography, confocal laser scanning microscopy and scanning electron microscopy images. Molecular data are included for nine species and four species include a molecular diagnosis in addition to their morphological diagnosis.The five new geographic and bathymetric distribution records comprise Lepechinella naces Lörz & Engel, sp. nov., Cuniculomaera grata Tandberg & Jażdżewska, sp. nov., Pseudionella pumulaensis Williams & Landschoff, sp. nov., Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. and Psychropotes buglossa E. Perrier, 1886, with the novelty spanning from the species to the family level. The new parasite record is Pseudionella pumulaensis Williams & Landschoff, sp. nov., found in association with the hermit crab Pagurus fraserorum Landschoff & Komai, 2018.
Osteocalcin (auch Bone 6 la Protein [B G P] genannt), ein 49 Aminosäuren enthaltendes Knochenmatrixprotein, wird in den Osteoblasten synthetisiert und bei gesteigertem Knochenumsatz im Serum erhöht gefunden. Osteocalcin im Serum kann mittels eines Hadioimmunoassays gemessen werden. Die Werte steigen mit dem Lebensalter an und zeigen einen zirkadianen Rhythmus. Beim primären Hyperparathyreoidismus sind die Osteocalcinwerte erhöht. Bei Patienten mit Mammacarcinom zeigt ein Osteocalcinanstieg stets eine Metastasierung im Knochen an. Die Hyperthyreose geht mit erhöhten Osteocalcinwerten einher. Über den diagnostischen Wert einer Osteocalcinbestimmung beim Plasmozytom läßt sich zur Zeit noch keine sichere Aussage machen. Patienten mit einer histomorphometrisch gesicherten „low-turnover'"Osteoporose weisen niedrige Osteocalclnspiegel auf. Die stark erhöhten Osteocalcinwerte bei der renalen Osteopathie (sekundärer Hyperparathyreoidismus, Osteomalazie) sind z.T. auch au feine verminderte renale Elimination von Osteocalcin bei eingeschränkter glomerulärer Filtrationsrate zurückzuführen. Zusammenfassend stellt die Osteocalcinbestimmung eine Bereicherung der diagnostischen Möglichkeiten zur Beurteilung des Knochenumsatzes darf sollte vorerst jedoch noch vorwiegend wissenschaftlichen Fragestellungen vorbehalten sein.
Im Zeitraum von 1991 - 1992 wurden 2000 Stuhlproben von a) Tropenreisenden (n = 600), b) Patienten mit Durch fall (n = 500) und c) Patienten mit gastrointestinalen Symptomen, jedoch ohne Durchfall (n = 900) auf Campylobacter spp. untersucht Hierfür wurden drei Kultivierungsmethoden parallel eingesetzt: 7. eine Filtermembranmethode, 2. ein blutfreies Campylobacter-Selektivmedium und 3. ein Blutmedium mit Butzler-Supplement Zusätzlich wurde der Einfluß von Transportbedingungen untersucht mittels Vergleiches zwischen Nativ-Stuhlproben versus Stühlen, die in ein Transportnährmedium (Cary-Blair-Medium) gegeben worden waren (n = 517).
Insgesamt waren 54/2000 (2,7%) Stuhlproben positiv. Die Campylobacter-Auffindungsrate in flüssigen Stühlen (Gruppe B) lag dreifach höher im Vergleich zu nicht-durchfälligen Proben (p < 0.01). In den Gruppen b) und c) waren Patienten, die älter als 40 Jahre waren, signifikant seltener mit Campylobacter infiziert als jüngere Personen, während es bei den Tropenreisenden keinen Alterseffekt gab. Unter den drei Kultivierungsmethoden war das Filtermembranverfahren dasjenige mit der besten Campylobacter-Ausbeute (p < 0.01): Methode 1 ergab 57,5%, Methode 2 50% und Methode 3 40,7% positive Isolate. Durch den Einsatz von Cary-Blair-Transportmedium konnte die Campylobacter-Isolierungsrate um 25% gesteigert werden. Die am häufigsten isolierten Spezies waren C. jejuni und C. coli.
Das neue immunoluminometrische BeriLux® PSA - ein Test für das Routinelabor. Ein Methodenvergleich
(1993)
In dieser Studie wurde der immunoluminometrische BeriLux® PSA-Test mit zwei radio-immunologischen und einem fluorometrischen Verfahren verglichen. Für den BeriLux® PSA wurden an 150 gesunden Probanden (100 Männer und 50 Frauen) die Referenzbereiche ermittelt. Bei Männern lag die 95%-Perzentile bei 3,77 ng/ml, für Frauen lag die 95%-Perzentile bei0,1 ng/ml. Der Korrelationskoeffizient zwischen der immunoluminometrischen Methode und radioimmunologischen Methode liegt bei r = 0,99, die analytische Sensitivität von BeriLux9 PSA liegt bei 0,03 ng/ml. Die Stabilität der Serumproben bei Lagerungstemperaturen zwischen 2°C und 8°C ist über einen Tag garantiert. Über diesen Zeitraum hinaussollten Serumproben bei -20° C gelagert werden.
Purpose: To assess the diagnostic precision of three different workstations for measuring thoracic aortic aneurysms (TAAs) in vivo and ex vivo using either pre-interventional computed tomography angiography scans (CTA) or a specifically designed phantom model.
Methods: This retrospective study included 23 patients with confirmed TAA on routinely performed CTAs. In addition to phantom tube diameters, one experienced blinded radiologist evaluated the dimensions of TAAs on three different workstations in two separate rounds. Precision was assessed by calculating measurement errors. In addition, correlation analysis was performed using Pearson correlation.
Results: Measurements acquired at the Siemens workstation deviated by 3.54% (range, 2.78–4.03%; p = 0.14) from the true size, those at General Electric by 4.05% (range, 1.46–7.09%; p < 0.0001), and at TeraRecon by 4.86% (range, 3.22–6.45%; p < 0.0001). Accordingly, Siemens provided the most precise workstation at simultaneously most fluctuating values (scattering of 4.46%). TeraRecon had the smallest fluctuation (scattering of 2.83%), but the largest deviation from the true size of the phantom. The workstation from General Electric showed a scattering of 2.94%. The highest overall correlation between the 1st and 2nd rounds was observed with measurements from Siemens (r = 0.898), followed by TeraRecon (r = 0.799), and General Electric (r = 0.703). Repetition of measurements reduced processing times by 40% when using General Electric, by 20% with Siemens, and by 18% with TeraRecon.
Conclusions: In conclusion, all three workstations facilitated precise assessment of dimensions in the majority of cases at simultaneously high reproducibility, ensuring accurate pre-interventional planning of thoracic endovascular aortic repair.
This study evaluates whether the short version of the German LITMUS quasi-universal nonword repetition task (LITMUS-QU-NWR) can be used as an index test for monolingual and early second language learners (eL2) of German aged 8 to 10 years. The NWR taps into quasi-universal phonological knowledge via the so-called language-independent part and into language-specific phonological knowledge via the language-dependent part. Thirty-six monolingual and thirty-three eL2 learners of German, typically developing (TD) and diagnosed as language-impaired (DLD), participated in the study. The effects of the language group (Mo vs. eL2) and the clinical status (TD vs. DLD) on repetition accuracy are investigated by a logistic mixed-model analysis. Receiver operating characteristics (ROC) and likelihood ratios are calculated to determine the diagnostic accuracy of the two parts. The group comparisons showed significant effects of the clinical status but not of the language group. The ROC analyses and the likelihood ratios reveal better diagnostic values for the language-dependent compared to the language-independent part and almost similar diagnostic values for the monolingual and the eL2 group. The results indicate that the LITMUS-QU-NWR helps to disentangle DLD and DLD in monolingual children and eL2 learners aged 8 to 10 years.
Background: Opsoclonus-myoclonus syndrome (OMS) is a rare, immune-mediated neurological disorder. In adults, the pathogenesis can be idiopathic, post-infectious or paraneoplastic, the latter etiology belonging to the ever-expanding group of defined paraneoplastic neurological syndromes (PNS). In contrast to other phenotypes of PNS, OMS cannot be ascribed to a single pathogenic autoantibody. Here, we report the first detailed case of paraneoplastic, antibody-negative OMS occurring in association with a pancreatic neuroendocrine tumor (pNET).
Case presentation: A 33-year-old female presented with a two-week history of severe ataxia of stance and gait, dysarthria, head tremor, myoclonus of the extremities and opsoclonus. Her past medical history was notable for a metastatic pancreatic neuroendocrine tumor, and she was subsequently diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. Further workup did not reveal a paraneoplastic autoantibody. She responded well to plasmapheresis, as she was refractory to the first-line therapy with corticosteroids.
Conclusions: This case expands current knowledge on tumors associated with paraneoplastic opsoclonus-myoclonus syndrome and the age group in which it can occur. It further adds evidence to the effectiveness of plasmapheresis in severe cases of opsoclonus-myoclonus syndrome with a lack of response to first-line therapy.
The ALICE Collaboration measures the production of low-mass dielectrons in pp, p-Pb and Pb-Pb collisions at the LHC. The main detectors used in the analyses are the Inner Tracking System, Time Projection Chamber and Time-Of-Flight detector, all located around mid-rapidity. The production of virtual photons relative to the inclusive yield in pp collisions is determined by analyzing the dielectron excess with respect to the expected hadronic sources. The direct photon cross section is then calculated and found to be in agreement with NLO pQCD calculations. Results from the invariant mass analysis in p-Pb collisions show an overall agreement between data and hadronic cocktail. In Pb-Pb collisions, uncorrected background-subtracted yields have been extracted in two centrality classes. A feasibility study for LHC run 3 after the ALICE upgrade indicates the possibility for a future measurement of the early effective temperature.
Structured management programs have been developed for single diseases but rarely for patients with multiple medications. We conducted a qualitative study to investigate the views of stakeholders on the development and implementation of a polypharmacy management program in Germany. Overall, we interviewed ten experts in the fields of health policy and clinical practice. Using content analysis, we identified inclusion criteria for the selection of suitable patients, the individual elements that should make up such a program, healthcare providers and stakeholders that should be involved, and factors that may support or hinder the program’s implementation. All stakeholders were well aware of polypharmacy-related risks and challenges, as well as the urgent need for change. Intervention strategies should address all levels of care and include all concerned patients, caregivers, healthcare providers and stakeholders, and involved parties should agree on a joint approach.
We investigate the thermodynamic geometry of the quark-meson model at finite temperature, T, and quark number chemical potential, μ. We extend previous works by the inclusion of fluctuations exploiting the functional renormalization group approach. We use recent developments to recast the flow equation into the form of an advection-diffusion equation. We adopt the local potential approximation for the effective average action. We focus on the thermodynamic curvature, R, in the (μ,T) plane, in proximity of the chiral crossover, up to the critical point of the phase diagram. We find that the inclusion of fluctuations results in a smoother behavior of R near the chiral crossover. Moreover, for small μ, R remains negative, signaling the fact that bosonic fluctuations reduce the capability of the system to completely overcome the fermionic statistical repulsion of the quarks. We investigate in more detail the small μ region by analyzing a system in which we artificially lower the pion mass, thus approaching the chiral limit in which the crossover is actually a second order phase transition. On the other hand, as μ is increased and the critical point is approached, we find that R is enhanced and a sign change occurs, in agreement with mean field studies. Hence, we completely support the picture that R is sensitive to a crossover and a phase transition, and provides information about the effective behavior of the system at the phase transition.