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PURPOSE: Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity.PROCEDURES: Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters.RESULTS: In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology.CONCLUSION: [68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

Commonly, sparks emit light according to the well-known black (gray) body radiation. Recently, we reported on color‐changing sparks based on erbium powder, which switch their light emission between black body emission (surface combustion) and element‐specific emission (vapor phase combustion). Herein, we investigated the spark formation from the adjacent rare‐earth elements. The corresponding boiling points are significantly below (Yb, Sm, Tm) or above (Y, Lu) the boiling point of Er. While Yb and Sm evaporate too fast to form longer sparks, Y, Lu and Tm form color‐changing sparks with varying length of the element‐specific emission phase. The sparks were investigated by time‐resolved emission spectroscopy, long‐time exposures, and NIR/MIR imaging. The same basic pyrotechnic formulation containing one of these metal powders reveals a strongly differing burning behavior depending on the boiling point of the metal. The burning characteristics change from a green strobe (Yb) to intense colorful crackling (Tm) and finally a sparkling fountain with long‐flying sparks (Lu, Y, Er).

Molecular imaging & biology : MIB 24(2), 288-297 (2022). doi:10.1007/s11307-021-01686-x, Published by Springer Nature Switzerland, Cham

Starting from 4-nitropyrazole, eight mesoionic pyrazolium-4-aminides were prepared by a six-step reaction sequence. The deprotonation of 1,2-disubstituted 4-amido-1H-pyrazolium salts by an anion exchange resin in its hydroxide form is the final step of the synthesis. A tautomeric equilibrium between the mesoionic compounds (pyrazolium-4-aminides) and N-heterocyclic carbenes (pyrazol-3-ylidenes) can be formulated; however, the NHC tautomers were not detected by means of NMR spectroscopy in polar aprotic solvents such as DMSO-d 6 or MeCN-d 3. Apart from tautomerism, anionic N-heterocyclic carbenes can be formulated as a result of a deprotonation of the mesoionic compounds­. Trapping reactions were performed with selenium, which resulted in the formation of pyrazole-3-selenones. Methylation at the selenium atom gave the corresponding 3-(methylselanyl)-4-amido-1H-pyrazolium salts, which were deprotonated to give new mesomeric betaines, 3-(methylselanyl)-1H-pyrazolium-4-aminides as unique compounds­. DFT-calculations as well as 77Se NMR spectroscopic measurements were carried out.

A connected, locally finite graph $\Gamma $ is a Cayley–Abels graph for a totally disconnected, locally compact group G if G acts vertex-transitively on $\Gamma $ with compact, open vertex stabilizers. Define the minimal degree of G as the minimal degree of a Cayley–Abels graph of G. We relate the minimal degree in various ways to the modular function, the scale function and the structure of compact open subgroups. As an application, we prove that if $T_{d}$ denotes the d-regular tree, then the minimal degree of $\mathrm{Aut}(T_{d})$ is d for all $d\geq 2$ .

International audience; The etiopathogenesis of critical COVID-19 remains unknown. Indeed given major confounding factors (age and comorbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major comorbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 “critical” (in the ICU under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from non-critical patients, several driver genes promoted critical COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was supported in a second independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible.

Journal of experimental & clinical cancer research 40(1), 288 (2021). doi:10.1186/s13046-021-02043-0, Published by Springer, Berlin ; Heidelberg

Sydnone methides are described from which only one single example has been mentioned in the literature so far. Their deprotonation gave anions which can be formulated as π‐electron rich anionic N‐heterocyclic carbenes. Sulfur and selenium adducts were stabilized as their methyl ethers, and mercury, gold as well as rhodium complexes of the sydnone methide carbenes were prepared. Sydnone methide anions also undergo C−C coupling reactions with 1‐fluoro‐4‐iodobenzene under Pd(PPh3)4 and CuBr catalysis. 77Se NMR resonance frequencies and 1 J C4‐Se as well as 1 J C4‐H coupling constants have been determined to gain knowledge about the electronic properties of the anionic N‐heterocyclic carbenes. The carbene carbon atom of the sydnone methide anion 3 j resonates at δ=155.2 ppm in 13C NMR spectroscopy at −40 °C which is extremely shifted upfield in comparison to classical N‐heterocyclic carbenes., Except for a single example, sydnone methides have been unknown to date. Syntheses are described here, leading to 10 stable and intensely colorful, slightly fluorescent sydnone methides with Z=CN, COOMe, and SO2Me, respectively. On deprotonation, unique anionic π‐electron‐rich N‐heterocyclic carbenes are formed which react to thioethers and selenoethers, mercury, gold and rhodium complexes, and 4‐acylsydnone methide on treatment with acyl chlorides.

Zusammenfassung Ziel der Studie Die Strategie Aktiv Altern der Weltgesundheitsorganisation (WHO) umfasst die Bereiche Gesundheit, Teilhabe am sozialen Leben sowie Sicherheit im Alter. Als politischer Aktionsrahmen unterstützt die Strategie die zukünftige Alterspolitik der Kommunen. Wie kommunale Akteurinnen und Akteure selbst die WHO-Strategie beurteilen, ist Gegenstand dieser Befragung. Methodik Wir haben 5 Expertinnen und Experten aus dem Landkreis Konstanz mittels systematisierenden, leitfadengestützten Interviews befragt. Grundlage des Leitfadens bildete eine selbst konzipierte Indikatorenliste, die die 102 Handlungsempfehlungen strukturiert bündelt. Die Bekanntheit der WHO-Strategie und eine gegebenenfalls kurze Einführung in die 3 Bereiche bildeten den Intervieweinstieg, anschließend erfolgte der Abgleich kommunaler Aktivitäten mit der Indikatorenliste, die Erhebung des kommunalen Handlungsbedarfes sowie die Identifikation bislang unberücksichtigter Aspekte. Im Sinne einer Triangulation führten wir eine quantitative Befragung in weiteren Landkreisen durch. Die Auswertung erfolgte mittels qualitativer Inhaltsanalyse nach Gläser und Laudel mit dem Extraktionsprogramm MIA. Ergebnisse Keine der interviewten Personen kannte die WHO-Strategie Aktiv Altern. Nach einer kurzen Erläuterung zur WHO-Strategie und Indikatorenliste, stuften die Interviewpersonen die Strategie jedoch als praktikabel ein. Als gut umsetzbar schätzten sie v. a. Handlungsempfehlungen aus den Teilbereichen Teilhabe in der Gesellschaft (z. B. Schaffung von Seniorenbeiräten), sowie aus dem Bereich Sicherheit im öffentlichen Raum und Verkehr (z. B. Schutzmaßnahmen für ältere Fußgänger/innen) ein. In einzelnen Bereichen, wie der medizinischen Versorgung und der formellen Pflege, vermissten die Interviewpersonen Indikatoren, sodass wir die Neuaufnahme zusätzlicher Handlungsempfehlungen empfehlen. Schlussfolgerung Die Bekanntheit der WHO-Strategie Aktiv Altern sollte in Richtung der Kommunen, der eigentlichen Zielgruppe, verbessert werden. Aktiv Altern ist, unter Berücksichtigung des hier festgestellten Weiterentwicklungsbedarfes, eine praktikable Orientierungshilfe und bietet mehrere Chancen für die Alterspolitik im kommunalen Feld.

Usually, the color of a spark formed by an incandescent particle is controlled by its temperature according to gray body radiation. With the help of low boiling metals, gas phase combustion and consequently element-specific emission can be achieved. Here, we report on a detailed discussion of colored sparks in the context of models given in literature and extend the achievable colors of sparks to blue (tellurium) and bright orange (sodium on silica). To the best of our knowledge, we present the first color-changing sparks based on appropriately sized erbium powder. These sparks switch their combustion behavior between surface combustion and gas phase combustion, accompanied by a change between orange and green emission. The color of the sparks has been investigated by long-time exposure and time-resolved emission spectroscopy. Finally, a formulation for a smokeless sparkling fountain based on red-orange diamond sparks and color-changing and branching erbium sparks is presented.