bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of extended defects on photoluminescence of gallium oxide and aluminum gallium oxide epitaxial films
Authors: Cooke Jacqueline , Ranga Praneeth , Jesenovec Jani , McCloy John S. , Krishnamoorthy Sriram , Scarpulla Michael A. , Sensale-Rodriguez Berardi
Published: February 2022

In this work, a systematic photoluminescence (PL) study on three series of gallium oxide/aluminum gallium oxide films and bulk single crystals is performed including comparing doping, epitaxial substrates, and aluminum concentration. It is observed that blue/green emission intensity strongly correlates with extended structural defects rather than the point defects frequently assumed. Bulk crystals or Si-doped films homoepitaxially grown on (010) β-Ga2O3 yield an intense dominant UV emission, while samples with extended structural defects, such as gallium oxide films grown on either (-201) β-Ga2O3 or sapphire, as well as thick aluminum gallium oxide films grown on either (010) β-Ga2O3 or sapphire, all show a very broad PL spectrum with intense dominant blue/green emission. PL differences between samples and the possible causes of these differences are analyzed. This work expands previous reports that have so far attributed blue and green emissions to point defects and shows that in the case of thin films, extended defects might have a prominent role in emission properties.
Dapagliflozin plus exenatide on patients with type 2 diabetes awaiting bariatric surgery in the DEXBASU study
Authors: López-Cano Carolina , Santos Maria Dolores , Sánchez Enric , Martí Raquel , Bueno Marta , Gutiérrez-Carrasquilla Liliana , Lecube Albert
Published: February 2022

The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m2. A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m2 or a BMI ≤ 40.0 kg/m2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: − 11.0 to − 5.2) and 3.3 kg/m2 (95%IC: − 4.5 to − 2.2), respectively (p < 0.001 for both in comparison with Group B). A higher percentage of participants in Group A reached a BMI < 35 kg/m2 (45.8 vs 12.0%) and lost > 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes.
Sex-dependent relationship of C-reactive protein levels with HDL-cholesterol and HDL-phospholipid concentrations in children
Authors: Vales-Villamarín Claudia , de Dios Olaya , Pérez-Nadador Iris , Gavela-Pérez Teresa , Soriano-Guillén Leandro , Garcés Carmen
Published: February 2022

Obesity has been consistently associated with inflammation but the influence of HDL on this association remains under study. Our study analyzes the influence of obesity-related parameters in the relationship of high-sensitivity C-reactive protein (hs-CRP) with HDL-cholesterol and HDL-phospholipid in male and female adolescents. The study sample population comprised 350 males and 401 females aged 12 to 16 years. Information regarding anthropometric parameters, HDL-cholesterol, HDL-phospholipid, adiponectin, leptin, insulin, and hs-CRP concentrations was available. hs-CRP levels were inversely related to HDL-cholesterol and HDL-phospholipid in males but not in females, and were positively related to leptin concentrations in both sexes but were not related to adiponectin levels. In regression analyses, HDL-phospholipid and leptin appeared significantly associated to hs-CRP in males in a model explaining 14.3% of hs-CRP variation. In females, only leptin appeared related to hs-CRP concentrations. After adjusting by leptin and adiponectin, males in the highest hs-CRP tertile showed significantly lower levels of HDL-cholesterol and HDL-phospholipid than those in tertiles 1 and 2, while no significant differences in HDL-cholesterol and HDL-phospholipid concentrations by hs-CRP tertile were observed in females. In summary, high hs-CRP levels were associated with lower plasma HDL-cholesterol and HDL-phospholipid concentrations in male adolescents irrespective of adipokines, while in females, HDL-related parameters are not associated with hs-CRP concentrations.
Anomalous valley Hall effect in antiferromagnetic monolayers
Authors: Du Wenhui , Peng Rui , He Zhonglin , Dai Ying , Huang Baibiao , Ma Yandong
Published: February 2022

Anomalous valley Hall (AVH) effect is a fundamental transport phenomenon in the field of condensed-matter physics. Usually, the research on AVH effect is mainly focused on 2D lattices with ferromagnetic order. Here, by means of model analysis, we present a general design principle for realizing AVH effect in antiferromagnetic monolayers, which involves the introduction of nonuniform potentials to break of PT symmetry. Using first-principles calculations, we further demonstrate this design principle by stacking antiferromagnetic monolayer MnPSe3 on ferroelectric monolayer Sc2CO2 and achieve the AVH effect. The AVH effect can be well controlled by modulating the stacking pattern. In addition, by reversing the ferroelectric polarization of Sc2CO2 via electric field, the AVH effect in monolayer MnPSe3 can be readily switched on or off. The underlying physics are revealed in detail. Our findings open up a new direction of research on exploring AVH effect.
Enhanced Arctic warming amplification revealed in a low-emission scenario
Authors: Ono Jun , Watanabe Masahiro , Komuro Yoshiki , Tatebe Hiroaki , Abe Manabu
Published: February 2022

The Arctic region has warmed faster than the global mean in past decades. Future climate change projections also suggest this Arctic warming amplification will continue. Here, using 50-member historical and future scenario simulations by a single climate model, we find that Arctic warming amplification is stronger in a low-emission scenario, compared to a high-emission scenario, after the mid-2040s. This is because in the low-emission scenario, sea ice continues to exist beyond 2040 and the ice-albedo feedback therefore maintains Arctic warming, unlike other latitudes. By contrast, in the high-emission scenario summer sea ice melts away by about 2050. Multi-model analyses show that the strength of Arctic amplification in the low-emission scenario is highly correlated with the amount of sea-ice reduction, whereas this relationship weakens in the high-emission scenario. Our results indicate that climate change mitigation may have a side effect because Arctic warming persists even if the global warming is stabilized.
High performance low dielectric polybenzocyclobutene nanocomposites with organic–inorganic hybrid silicon nanoparticles
Authors: Peng Qiu-Xia , Hu Huan , Ma Jia-Jun , Yang Jun-Xiao
Published: February 2022

BCBNPs containing BCB group were synthesized by sol–gel method. Without affecting other properties of DVSBCB oligomer, the addition of BCBNPs can reduce its dielectric constant.
Unimolecular and water reactions of oxygenated and unsaturated Criegee intermediates under atmospheric conditions
Authors: Vereecken L. , Novelli A. , Kiendler-Scharr A. , Wahner A.
Published: February 2022

Theoretical kinetic data is used to update structure–activity relationships for Criegee intermediates, including fast reactions for intramolecular insertion in oxygenated SCI.
Field-induced mononuclear cobalt(ii) single-molecule magnet (SMM) based on a benzothiadiazole-ortho-vanillin ligand
Authors: Plyuta Nataliya , Petrusenko Svitlana , Kokozay Vladimir N. , Cauchy Thomas , Lloret Francesc , Julve Miguel , Cano Joan , Avarvari Narcis
Published: February 2022

A mononuclear octahedral cobalt(ii) complex based on a unique benzothiadiazole-ortho-vanillin ligand shows slow relaxation of the magnetization under applied dc magnetic fields.
Protective effect of food derived nutrients on cisplatin nephrotoxicity and its mechanism
Authors: Liu Chaofan , Zhou Sajin , Bai Weibin , Shi Lei , Li Xiaoling
Published: February 2022

Platinum-based metal complexes, especially cisplatin (cis-diamminedichloroplatinum II, CDDP), possess strong anticancer properties and a broad anticancer spectrum.
Hydrogen-bonded organic frameworks: design, applications, and prospects
Authors: Chen Lifang , Zhang Boying , Chen Liling , Liu Haining , Hu Yongqi , Qiao Shanlin
Published: February 2022

Hydrogen-bonded organic frameworks (HOFs) are crystalline porous polymers which are formed by the interaction of hydrogen bonding among building blocks. Unique advantages of HOFs, enabling new platforms for exploring multifunctional applications.
On the colossal barocaloric effect in higher n-alkanes
Authors: Miliante Caio M. , Christmann A. M. , Soares R. P. , Bocca J. R. , Alves C. S. , Carvalho A. M. G. , Muniz A. R.
Published: February 2022

Long-chain n-alkanes exhibit a remarkable barocaloric effect in a wide range of temperatures, enhanced by the onset of a liquid–solid pressure-induced phase transition, and are promising candidates for the development of solid-state cooling systems.
Hydrogels for 3D embedded bioprinting: a focused review on bioinks and support baths
Authors: Zhou Ke , Sun Yadong , Yang Jiquan , Mao Hongli , Gu Zhongwei
Published: February 2022

This review discusses the challenges faced by traditional 3D bioprinting of soft or low-viscosity bioinks and embedded bioprinting as an emerging solution. We highlight the challenges involved in this process and look forward to the prospects of this technology.
Multi-resistive pulse sensor microfluidic device
Authors: Pollard Marcus , Maugi Rushabh , Platt Mark
Published: February 2022

A dual tuneable flow resistive pulse sensor which utilises additively manufactured parts. The sensor allows parts to be easily changed, washed and cleaned, its simplicity and versatility allow components from existing nanopore techniques to be integrated into a single device.
Construction of coral-like architectures of boron-containing compounds: coral-like boric acid and its application performances
Authors: Bi Shengnan , Zhu Peihan , Tian Peng , Zhong Jianchu , Ye Junwei , Ning Guiling
Published: February 2022

Coral-like structures have been widely investigated for practical applications owing to their special porous architectures and surface activity. Here we report a simple strategy for the preparation of coral-like architectures of boric acid.
Synthesis and characterization of ZIF-8-based PVDF mixed matrix membranes and application to treat pulp and paper industry wastewater using a membrane bioreactor
Authors: Sonawane Amol Vijay , Murthy Z. V. P.
Published: February 2022

The metal–organic framework (MOF) zinc imidazolate framework-8 (ZIF-8) is synthesized by a solvothermal method and added into a polyvinylidene fluoride (PVDF) membrane to study its pollutant removal performance using pulp and paper industry wastewater.
Diffusion-controlled on-surface synthesis of graphene nanoribbon heterojunctions
Authors: Dobner Christoph , Li Gang , Sarker Mamun , Sinitskii Alexander , Enders Axel
Published: February 2022

We report a diffusion-controlled process for the on-surface synthesis of graphene nanoribbon heterojunctions. Differences in the diffusion kinetics of the precursor molecules were exploited to control the GNR architecture.
Phase transition model of FA cation ordering in FAPbX3 (X = Br, I) hybrid perovskites
Authors: Šimėnas Mantas , Balčiūnas Sergejus , Mączka Mirosław , Banys Jūras
Published: February 2022

We propose and solve a phase transition model describing ordering of the FA cations in FAPbX3 hybrid perovskites.
Image fusion algorithm of circular colour correction based on vehicle vision sensors
Authors: Li Yuansheng , Lei Kong , Lin Qiang , Zhao Hongfei , He Xi , Zhang Fei , Wang Yuanyuan , Hao Xu
Published: February 2022

In order to solve the problems of different visual angles, such as large brightness and colour difference, and obvious image splicing trace, an algorithm of ring image fusion based on colour correction is proposed in this paper. According to the algorithm in this paper, a Matlab toolbox was made for image fusion simulation experiment. Structural similarity (SSIM) was used to evaluate the effectiveness of this method in reducing illumination and contrast difference and the mean value of SSIM was 0.8166. The algorithm is measured in the development board and accelerated by graphic processing unit to achieve the computing efficiency of 18 ms per frame and meet the real‐time requirements of the system.
New simulations of accreting DA white dwarfs: Inferring accretion rates from the surface contamination
Authors: Wachlin F. C. , Vauclair G. , Vauclair S. , Althaus L. G.
Published: February 2022

Context.A non-negligible fraction of white dwarf stars show the presence of heavy elements in their atmospheres. The most accepted explanation for this contamination is the accretion of material coming from tidally disrupted planetesimals, which forms a debris disk around the star.

Aims.We provide a grid of models for hydrogen-rich white dwarfs accreting heavy material. We sweep a 3D parameter space that has different effective temperatures, envelope hydrogen contents, and accretion rates. The grid is appropriate for determining accretion rates in white dwarfs that show the presence of heavy elements.

Methods.Full evolutionary calculations of accreting white dwarfs were computed including all relevant physical processes, particularly the fingering (thermohaline) convection, a process neglected in most previous works, which has to be considered to obtain realistic estimations. Accretion is treated as a continuous process, and bulk-Earth composition is assumed for the accreted material.

Results.We obtain final (stationary or near-stationary) and reliable abundances for a grid of models that represent hydrogen-rich white dwarfs of different effective temperatures and hydrogen contents, which we apply to various accretion rates.

Conclusions.Our results provide estimates of accretion rates, accounting for thermohaline mixing, to be used for further studies on evolved planetary systems.
Therapiespektrum älterer Menschen mit rheumatoider Arthritis
Authors: Albrecht Katinka , Thiele Katja , Späthling Susanna , Ochs Wolfgang , Krause Andreas , Callhoff Johanna
Published: February 2022

Hintergrund Angesichts der Zunahme des Anteils älterer Menschen mit rheumatoider Arthritis (RA) gewinnen die spezifischen Anforderungen an ihre medikamentöse Versorgung an Bedeutung.

Methodik Mit Daten aus der Kerndokumentation stellen wir altersbezogene Unterschiede in den Krankheitsparametern und im Spektrum der verwendeten Medikamente vor. Diese umfassen nichtsteroidale Antirheumatika (NSAR), selektive Cox-2-Hemmer, Opioide, andere Analgetika, Glukokortikoide, konventionell synthetische Basisterapeutika (csDMARDs), Biologika (bDMARDs) und targeted synthetic (ts) DMARDs.

Ergebnisse Mehr als die Hälfte der Patienten mit RA sind über 60 Jahre alt. Ältere Patienten unterscheiden sich von Jüngeren durch längere Krankheitsdauer, häufige Komorbiditäten und reduzierte Funktionsfähigkeit. Sie geben häufiger Schmerzen, Erschöpfung und Schlafstörungen an. Ältere Patienten erhalten häufiger Glukokortikoide, Analgetika und Opioide, aber seltener DMARDs, insbesondere bDMARDs und tsDMARDs.

Schlussfolgerung Der Bedarf an Glukokortikoiden und (opioidhaltigen) Analgetika spricht bei häufigen Schmerzen und bleibend geschwollenen Gelenken dafür, dass auch bei älteren Patienten eine ausreichend krankheitsmodifizierende Therapie unter Einbeziehung der bDMARDs notwendig ist.
Aktuelle gentherapeutische Behandlungsansätze bei Hämoglobinopathien
Authors: Meisel Roland
Published: February 2022

Die Erfolge des Gentransfers in hämatopoetische Stammzellen bei Säuglingen mit schweren Immundefekten haben das Interesse geweckt, dieses Behandlungskonzept auch bei Patienten mit Hämoglobinopathien anzuwenden. In klinischen Studien wurde gezeigt, dass durch lentiviralen Transfer eines modifizierten β-Globingens in autologe hämatopoetische Stammzellen bei der Mehrzahl der β-Thalassämie-Patienten eine Transfusionsunabhängigkeit erreichbar ist und Sichelzellpatienten keine vasookklusiven Krisen mehr erleiden. Das Auftreten von zwei Leukämiefällen bei Sichelzellpatienten nach dieser Form der lentiviralen Gentherapie hat verdeutlicht, dass Weiterentwicklungen sinnvoll sind, um das Risiko von Integrationsereignissen und hämatopoetischen Neoplasien zu minimieren. Mit der neuartigen, im Jahr 2020 mit dem Nobelpreis ausgezeichneten Technologie der zielgerichteten CRISPR/Cas9-basierten Geneditierung hat ein solches Therapieverfahren kürzlich Einzug in die Klinik gehalten. In proof-of-concept-Studien konnte gezeigt werden, dass die CRISPR/Cas9-vermittelte Ausschaltung des erythrozytären Transkriptionsfaktors BCL11A in autologen hämatopoetischen Stammzellen die Expression fetalen Hämoglobins (HbF) reaktiviert und dass durch die stabile Produktion von HbF bedeutsame therapeutische Effekte bei Patienten mit Thalassämie und Sichelzellerkrankung erzielt werden.
Gibt es statisch-strukturelle Biomarker bei den Glaukomen mit der OCT?
Authors: Mardin Christian Yahya
Published: February 2022

Glaukome stellen in ihrer Endstrecke eine spezifische, sich schleichend entwickelnde Neuropathie mit später fortschreitenden Gesichtsfelddefekten dar. Die Frühdiagnose ist herausfordernd,
aber notwendig, da der Schaden irreparabel ist. Biomarker der strukturellen optischen Kohärenztomografie (OCT) können auf das Vorliegen einer neuronalen Atrophie hinweisen, sind jedoch in
der Differenzialdiagnose zu anderen Atrophieformen nicht spezifisch. Die Kombination der OCT-Parameter miteinander und mit anderen klinischen Parametern kann die Glaukomdiagnose erleichtern.
Die Anwendung von künstlicher Intelligenz (KI) auf OCT-Bilder könnte spezifischer und damit in Zukunft der reinen Schichtdickenmessung mit der OCT als Biomarker überlegen sein.
Spezifische Biomarker im Kammerwasser von Glaukompatienten
Authors: Reinehr Sabrina , Mueller-Buehl Ana M. , Tsai Teresa , Joachim Stephanie C.
Published: February 2022

Das Glaukom, eine multifaktorielle neurodegenerative Erkrankung, ist die zweithäufigste Ursache für Erblindungen. Da eine Früherkennung die rechtzeitige Behandlung ermöglicht, ist es notwendig, entsprechende Marker zu finden. Für eine Früherkennung oder auch eine Kontrolle im Behandlungsverlauf. könnten sog. Biomarker in Zukunft von Nutzen sein. Beim Glaukom könnten diese Messwerte im Kammerwasser bestimmt werden. So wurden bereits veränderte Antikörper-, Protein-, microRNA- (miRNA), oder Spurenelementlevel nachgewiesen. Dieser Übersichtsartikel gibt einen Einblick in mögliche Veränderungen im Kammerwasser von Patienten mit primären Offenwinkelglaukom (POWG), Normaldruckglaukom (NDG) oder Pseudoexfoliationsglaukom (PEXG). Untersuchungen zu Antikörperveränderungen konnten bei POWG-Patienten eine Hochregulation von Antikörpern detektieren, die mit dem Immunsystem assoziiert sind, wie z. B. das Hitzeschockprotein (HSP) 27. Das HSP27 lag auch bei PEXG-Patienten hoch-, beim NDG hingegen herunterreguliert vor. In POWG- und PEXG-Proben konnten erhöhte Werte bestimmter Proteine, u. a. Interleukine und Endothelin-1, gemessen werden. Endothelin-1 ist ein Vasokonstriktor und spielt möglicherweise eine Rolle bei der Regulation des Augeninnendrucks. Proteine, die bei der Antwort gegen oxidativen Stress eine Rolle spielen, wurden hingegen in verringerter Konzentration vorgefunden. Beim NDG waren Proteine, die für die Beseitigung von toxischen Nebenprodukten der Atmungskette zuständig sind, herunterreguliert. Es konnten außerdem verschiedene miRNAs im Kammerwasser von POWG- und PEXG-Patienten identifiziert werden, die im Zusammenhang mit der Entwicklung von Geweben, neurologischen Erkrankungen und zellulärer Organisation stehen. Weitere beim Glaukom regulierte miRNAs spielen eine Rolle bei der Remodellierung der extrazellulären Matrix und könnten so einen Einfluss auf den Abflusswiderstand im Trabekelmaschenwerk haben. Interessanterweise konnten auch veränderte Level von Spurenelementen, wie Zink oder Selen, im Kammerwasser von Glaukompatienten detektiert werden. Die erhöhten Zinkwerte könnten am Ungleichgewicht der Matrixmetalloproteinasen im Auge beteiligt und somit für einen erhöhten Augeninnendruck verantwortlich sein. All diese Studien zeigen die komplexen Kammerwasserveränderungen beim Glaukom auf. Möglicherweise kann ein Teil dieser Biomarker zukünftig zur Früherkennung der Erkrankung herangezogen werden.
Die Rolle von genetischer Prädisposition bei Krebserkrankungen im Kindesalter
Authors: Brozou Triantafyllia , Wagener Rabea
Published: February 2022

Obwohl maligne Erkrankungen im Kindesalter seltener als bei Erwachsenen auftreten, sind sie die zweithäufigste Todesursache (nach tödlichen Unfällen) bei Kindern bis zum 15. Lebensjahr. Laut dem letzten Bericht des Deutschen Kinderkrebsregisters wurden im Jahr 2018 insgesamt 2255 Kinder mit einer bösartigen Tumorerkrankung diagnostiziert. Basierend auf diesen Zahlen entwickelt eines von 337 Neugeborenen bis zum 18. Lebensjahr eine maligne Erkrankung. Verschiedene Risikofaktoren, wie Ernährung, Tabak- und Alkoholkonsum, Alter, Exposition am Arbeitsplatz sowie chronische Infektionen, die die Tumorentstehung bei Erwachsenen begünstigen, sind im Kindesalter nicht vorhanden. Vielmehr spielen vererbte oder de novo erworbene Keimbahnmutationen im Sinne einer genetischen Krebsprädisposition bei einem signifikanten Prozentsatz der Kinder eine wichtige Rolle. Diese genetische Krebsprädisposition kann klinisch unauffällig sein oder mit anderen phänotypischen Auffälligkeiten als Teil einer syndromalen Erkrankung vorkommen. Die frühzeitige Erkennung von Kindern mit genetischem Tumorprädispositionssyndrom ist für die Therapieplanung und die Nachsorge der betroffenen Patient*innen von großer Bedeutung.
Imaging Biomarkers in Thoracic Oncology: Current Advances in the Use of Radiomics in Lung Cancer Patients and its Potential Use for Therapy Response Prediction and Monitoring
Authors: Kroschke Jonas , von Stackelberg Oyunbileg , Heußel Claus Peter , Wielpütz Mark Oliver , Kauczor Hans-Ulrich
Published: February 2022

Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. The development of therapies targeting molecular alterations has significantly improved the treatment of NSCLC patients. To identify these targets, tumor phenotyping is required, with tissue biopsies and molecular pathology being the gold standard. Some patients do not respond to targeted therapies and many patients suffer from tumor recurrence, which can in part be explained by tumor heterogeneity. This points out the need for new biomarkers allowing for better tumor phenotyping and monitoring during treatment to assess patient outcome.

Method The contents of this review are based on a literature search conducted using the PubMed database in March 2021 and the authors’ experience.

Results and Conclusion The use of radiomics and artificial intelligence-based approaches allows for the identification of imaging biomarkers in NSCLC patients for tumor phenotyping. Several studies show promising results for models predicting molecular alterations, with the best results being achieved by combining structural and functional imaging. Radiomics could help solve the pressing clinical need for assessing and predicting therapy response. To reach this goal, advanced tumor phenotyping, considering tumor heterogeneity, is required. This could be achieved by integrating structural and functional imaging biomarkers with clinical data sources, such as liquid biopsy results. However, to allow for radiomics-based approaches to be introduced into clinical practice, further standardization using large, multi-center datasets is required.

Key points: 

Citation Format
ALK-positive Bronchialkarzinome
Authors: Krome Susanne
Published: February 2022

Seit der bahnbrechenden Zulassung des Tyrosinkinase-Inhibitors (TKI) Crizotinib für nicht kleinzellige Bronchialkarzinome (NSCLC) mit rearrangierter anaplastischer Lymphomkinase (ALK) hat sich die therapeutische Landschaft in erstaunlichen Schritten weiterentwickelt. So bescheinigt Prof. Ibiayi Dagogo-Jack, Boston, in seinem Kommentar in JAMA Oncology den Vertretern der 2. ALK-TKI-Generation Ceritinib, Alectinib, Brigatinib und Lorlatinib einen deutlichen Fortschritt im Hinblick auf die Penetration der Blut-Hirn-Schranke ins ZNS sowie ihrer Wirkstärke. Dies resultiert in einem signifikanten Überlebensvorteil von Patienten mit ALK-positivem NSCLC. Und die Entwicklungspipeline ist weiterhin gefüllt.
Tränenfilmspezifische Biomarker bei Glaukompatienten
Authors: Fomo Kristian Nzogang , Schmelter Carsten , Pfeiffer Norbert , Grus Franz H.
Published: February 2022

Das Glaukom bezeichnet eine Gruppe chronischer Augenkrankheiten, die zu einer Degeneration der retinalen Ganglienzellen (RGZ) und ihrer Axone führen, gefolgt von einem irreversiblen Verlust
des Sehvermögens des Patienten. Das Glaukom ist eine Krankheit, die sich zunächst asymptomatisch entwickelt, wobei die ersten Symptome erst in einem fortgeschrittenen Stadium dieser
Augenkrankheit auftreten. Aus diesem Grund ist es stets notwendig, modernste Technologien und Methoden zur Identifizierung und Charakterisierung neuer, spezifischer Biomarker für die
Frühdiagnose des Glaukoms zu entwickeln. Daher stellt die Analyse biologischer Flüssigkeiten, wie in diesem Fall der Tränenflüssigkeit von Patienten, eine attraktive Quelle für die
Identifizierung neuer spezifischer sowie sensitiver Biomarker bei Glaukom dar. Diese Biomarker könnten an den pathophysiologischen Prozessen des Glaukoms beteiligt sein oder möglicherweise
zur diagnostischen Differenzierung verschiedener Glaukomtypen dienen.
Biologisch-chemische Wirkungen von Vulkanit-Fango
Authors: Lukanov Julian , Beer André-Michael
Published: February 2022

Hintergrund Vulkanischer Fango wird in der Literatur bislang als rein
anorganisches Peloid klassifiziert und wird seit vielen Jahren wegen seiner
physikalisch-thermischen Wirkungen in der Medizin eingesetzt. In der Literatur
findet man Abhandlungen über die Wirkungen und den Wirkmechanismus von
biologische aktiven Substanzen aus Torf und Torfpräparaten. Ziel dieser
Untersuchungen ist die Aufklärung, ob auch vulkanischer Fango
über biologisch aktive Substanzen verfügt.

Material und Methoden In Organbädern wurde die Wirkung von
wässerigem Fangoextrakt unter Beteiligung von verschiedenen
Rezeptorenblockern auf die spontane kontraktile Aktivität (SKA) der
glatten Muskelstreifen untersucht.

Ergebnisse Die Ergebnisse zeigen, dass die anregenden Effekte von
wässerigem Fangoextrakt auf die SKA der glatten Muskelstreifen nur bei
gleichzeitiger Blockierung von α2 Adreno- und D2 Dopaminrezeptoren zu
unterdrücken sind. Die selbsthemmende Effekte der anregenden Wirkung von
wässrigem Fangoextrakt auf die SKA der glatten Muskulatur stehen mit
einer Blockierung von α2 Adreno und D2 Dopaminrezeptoren im
unmittelbaren Zusammenhang.

Schlussfolgerung Wässriger vulkanischer Fangoextrakt
enthält biologisch aktive Substanzen, die eine agonistische Wirkung auf
die α2 Adreno- und D2 Dopaminrezeptoren der glatten Muskulatur haben.
Den Ergebnissen entsprechend ist von pharmakologischen Wirkungen auszugehen, wie
sie von den genannten Rezeptoren bekannt sind. Die klinische Wirksamkeit muss in
klinischen Studien festgestellt werden. Damit kann der hier untersuchte
vulkanische Fango als organisch/anorganisch wirkendes Peloid eingestuft
werden.
Effects of Trampoline Exercises in Children with Developmental
Coordination Disorder: A Randomized Controlled Trial
Authors: Sulaiman Maryam , Baig Mirza Obaid , Memon Sajjan Iqbal , Ashraf Naveed , Butt Poshmal , Afzal Kiran , Iqbal Rabia
Published: February 2022

Background & Objectives Developmental Coordination Disorder is a
condition that affects motor performance and causes difficulty in learning, and
activities of daily living. This condition is very prevalent in children who
suffer from poor balance and motor impairments. The Objectives of this study are
to determine the effects of trampoline exercises on motor performance and to
assess the balance and quality of life in children.

Methodology This randomized, placebo treatment-control trial was conducted
at Federal Government Polyclinic Hospital in Islamabad Pakistan. Sample of 26
children, diagnosed with developmental coordination disorder consecutively aged
5–12 years meeting inclusion criteria were isolated into two groups;
control and experimental using purposive sampling. The Participants in the
control group performed conventional physical therapy and the experimental group
received trampoline jumping exercise interventions 3x times a week for one hour
and 1 hour 15 mins for experimental (trampoline group) for eight
weeks with conventional physical therapy sessions. We used three validated
questionnaires; Developmental Coordination Disorder (DCDQ), Paediatric Balance
Scale (PBS), and Paediatric Quality of life (PQL). The data were analyzed using
SPSS 21. A p-value<0.05 was considered statistically significant.

Results Out of 26 participants, the mean age and S.D were 8.8±1.0.
About 43% were males and 58%, were females. In the experimental
group, the motor performance showed a significant difference between the two
groups in the 8th-week p<0.007, and non-significant results for balance
improvement p>0.05. The quality of life showed significant results at
the 4th week with a p<0.03 and a non-significant difference between a
group at the 8th week with p>0.05 and both groups estimated a
p<0.001.

Conclusion Although physical therapy is commonly utilized for treating
children with developmental disorders, incorporating trampoline exercises into
the program has been associated with improved motor performance.
Construction of Substituted [4]Acene Frameworks Based on Double Cationic Cyclizations of Fluoroalkenes
Authors: Fuchibe Kohei , Ichikawa Junji , Takao Go , Hakozaki Tomohiro , Miura Keisuke , Urushibara Yusuke
Published: February 2022

In this study, 5-substituted and 5,6-disubstituted [4]acenes were synthesized by the double cationic cyclization of fluoroalkenes. (a) After being treated with Me2AlCl (1.2 equiv), 2-trifluoromethyl-1-alkenes bearing two aryl groups underwent domino Friedel–Crafts-type cyclization (two-ring construction) followed by dehydrogenation to generate 5-fluorinated [4]acenes. The same (trifluoromethyl)alkenes were treated with both Me2AlCl (1.2 equiv) and Me3Al (1.0 equiv), resulting in selective one-ring construction and the creation of bicyclic 1,1-difluoro-1-alkenes. (b) When treated with triflic acid, the bicyclic difluoroalkenes underwent regioselective protonation to generate CF2 cations; Friedel–Crafts-type cyclization of these cations provided tetracyclic ketones. The obtained ketones act as an appropriate platform for the introduction of substituents at the 5-position of [4]acenes. (c) When treated with DDQ/H+, the bicyclic difluoroalkenes underwent oxidative generation of allylic CF2 cations; Friedel–Crafts-type cyclization of these cations produced tetracyclic enones. The enones were subjected to double addition of carbanions to facilitate the introduction of two substituents at the 5- and 6-positions of dihydro[4]acenes.
Adrenal Androgen Predictive Effects on Clinical and Metabolic Abnormalities of Polycystic Ovary Syndrome
Authors: Medeiros Sebastião Freitas de , Barbosa Bruna Barcelo , Medeiros Matheus Antônio Souto de , Yamamoto Ana Karine Lin Winck , Yamamoto Márcia Marly Winck
Published: February 2022

Objective To examine the possible effects of adrenal prohormones in the prediction of clinical and metabolic abnormalities in women with polycystic ovary syndrome (PCOS).

Methods The present study enrolled 299 normal cycling non-PCOS, 156 normoandrogenemic, and 474 hyperandrogenemic women with PCOS. Baseline characteristics were compared using a chi-squared test or analysis of variance (ANOVA) as appropriate. The roles of adrenal prohormones and their ratios with total testosterone in predicting co-occurring morbidities in women PCOS were evaluated using univariate and multivariate logistic regression analyses.

Results Adrenal hyperandrogenism per dehydroepiandrosterone sulfate (DHEAS) levels were found in 32% of women with PCOS. In non-PCOS women, dehydroepiandrosterone (DHEA) and its sulfate had no predictive role concerning clinical, anthropometric, and metabolic parameters. In PCOS women, mainly in the hyperandrogenemic group, DHEA showed to be a significant predictor against most anthropometric-metabolic index abnormalities (odds ratio [OR] = 0.36–0.97; p < 0.05), and an increase in triglycerides (TG) levels (OR = 0.76; p = 0.006). Dehydroepiandrosterone sulfate presented a few predictive effects regarding PCOS-associated disorders. In controls, DHEAS predicted against the increase in estimated average glucose (OR= 0.38; p = 0.036). In the normoandrogenic group, it predicted against elevation in the waist/hip ratio (WHR) (OR= 0.59; p = 0.042), and in hyperandrogenemic PCOS women, it predicted against abnormality in the conicity index (CI) (OR = 0.31; p = 0.028).

Conclusion Dehydroepiandrosterone was shown to be a better predictor of abnormal anthropometric and biochemical parameters in women with PCOS than DHEAS. Thus, regarding adrenal prohormones, DHEA measurement, instead of DHEAS, should be preferred in PCOS management. The effects of androgen prohormones on the prediction of PCOS abnormalities are weak.
Deficiency and Insufficiency of Vitamin D in Women of Childbearing Age: A Systematic Review and Meta-analysis
Authors: Lucchetta Rosa Camila , Lemos Isabele Held , Gini Ana Luísa Rodriguez , Cavicchioli Sophia de Andrade , Forgerini Marcela , Varallo Fabiana Rossi , de Nadai Mariane Nunes , Fernandez-Llimos Fernando , Mastroianni Patricia de Carvalho
Published: February 2022

Objective To estimate the prevalence of inadequate vitamin D level and its associated factors for women of childbearing age in Brazil.

Methods A systematic review was conducted (last updated May 2020). Meta-analyses were performed using the inverse-variance for fixed models with summary proportion calculation by Freeman-Tukey double arcsine. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies.

Results Our review identified 31 studies, comprising 4,006 participants. All the studies had at least one weakness, mainly due to the use of convenience sampling and small sample size. The overall prevalence of vitamin D deficiency, insufficiency, and both deficiency and insufficiency were 35% (confidence interval, 95%CI: 34–37%), 42% (95%CI: 41–44%), and 72% (95%CI: 71–74%), respectively.

Conclusion Although the magnitude of the prevalence of inadequate levels of vitamin D is uncertain, the evidence suggests that presence of vitamin D deficiency or insufficiency in women of reproductive age can cause moderate to severe problems.
Prevalence of Depression in Pregnant Women with Bariatric Surgery History and Associated Factors
Authors: da Rocha Andréa Christina Nowak , da Cunha Ana Cristina Barros , da Silva Jaqueline Ferreira
Published: February 2022

Objective To analyze the prevalence and factors associated with depressive symptoms among Brazilian pregnant women with history of bariatric surgery (BS).

Methods This is a cohort study with 247 women who got pregnant after BS. Based on data collection via Google Form, the recruitment of participants occurred in Facebook groups for 13 months. All of them answered a form with Informed Consent, a general data protocol and the Brazilian version of the Depression, Anxiety and Stress Scale-21. Descriptive and inferential analysis were performed, and a binary logistic regression model was tested to predict the factors associated with depressive symptoms.

Results The prevalence of depressive symptoms was 32.8%, noted as being higher in the first (40.6%) and third (34.3%) gestational trimesters. Significative associations were found between depression and marital status (p = 0.000), planned pregnancy (p = 0.001), desired pregnancy (p = 0.004) and psychiatric history (p = 0.000). Women who were not married (odds ratio, OR = 3,38; p = 0.002) and had a psychiatric history (OR = 2.70; p = 0.102) had higher chances of showing depression symptoms; while planned and desired pregnancy showed as protective factors to the symptoms of depression.

Conclusion These findings highlight the importance of psychological assistance for pregnant women with history of BS, to prevent development of mental disorders and their outcomes for maternal-child health.
Imaging in Asthma Management
Authors: Niedbalski Peter J. , Choi Jiwoong , Hall Chase S. , Castro Mario
Published: February 2022

Asthma is a heterogeneous disease characterized by chronic airway inflammation that affects more than 300 million people worldwide. Clinically, asthma has a widely variable presentation and is defined based on a history of respiratory symptoms alongside airflow limitation. Imaging is not needed to confirm a diagnosis of asthma, and thus the use of imaging in asthma has historically been limited to excluding alternative diagnoses. However, significant advances continue to be made in novel imaging methodologies, which have been increasingly used to better understand respiratory impairment in asthma. As a disease primarily impacting the airways, asthma is best understood by imaging methods with the ability to elucidate airway impairment. Techniques such as computed tomography, magnetic resonance imaging with gaseous contrast agents, and positron emission tomography enable assessment of the small airways. Others, such as optical coherence tomography and endobronchial ultrasound enable high-resolution imaging of the large airways accessible to bronchoscopy. These imaging techniques are providing new insights in the pathophysiology and treatments of asthma and are poised to impact the clinical management of asthma.
Activated relaxation in supercooled monodisperse atomic and polymeric WCA fluids: Simulation and ECNLE theory
Authors: Zhou Yuxing , Mei Baicheng , Schweizer Kenneth S.
Published: February 2022

We combine simulation and Elastically Collective Nonlinear Langevin Equation (ECNLE) theory to study the activated relaxation in monodisperse atomic and polymeric Weeks–Chandler–Andersen (WCA) liquids over a wide range of temperatures and densities in the supercooled regime under isochoric conditions. By employing novel crystal-avoiding simulations, metastable equilibrium dynamics is probed in the absence of complications associated with size polydispersity. Based on a highly accurate structural input from integral equation theory, ECNLE theory is found to describe well the simulated density and temperature dependences of the alpha relaxation time of atomic fluids using a single system-specific parameter, ac, that reflects the nonuniversal relative importance of local cage and collective elastic barriers. For polymer fluids, the explicit dynamical effect of local chain connectivity is modeled at the fundamental dynamic free energy trajectory level based on a different parameter, Nc, that quantifies the degree of intramolecular correlation of bonded segment activated barrier hopping. For the flexible chain model studied, a physically intuitive value of Nc ≈ 2 results in good agreement between simulation and theory. A direct comparison between atomic and polymeric systems reveals that chain connectivity can speed up activated segmental relaxation due to weakening of equilibrium packing correlations but can slow down relaxation due to local bonding constraints. The empirical thermodynamic scaling idea for the alpha time is found to work well at high densities or temperatures but fails when both density and temperature are low. The rich and subtle behaviors revealed from simulation for atomic and polymeric WCA fluids are all well captured by ECNLE theory.
Magnesium force fields for OPC water with accurate solvation, ion-binding, and water-exchange properties: Successful transfer from SPC/E
Authors: Grotz Kara K. , Schwierz Nadine
Published: February 2022

Magnesium plays a vital role in a large variety of biological processes. To model such processes by molecular dynamics simulations, researchers rely on accurate force field parameters for Mg2+ and water. OPC is one of the most promising water models yielding an improved description of biomolecules in water. The aim of this work is to provide force field parameters for Mg2+ that lead to accurate simulation results in combination with OPC water. Using 12 different Mg2+ parameter sets that were previously optimized with different water models, we systematically assess the transferability to OPC based on a large variety of experimental properties. The results show that the Mg2+ parameters for SPC/E are transferable to OPC and closely reproduce the experimental solvation free energy, radius of the first hydration shell, coordination number, activity derivative, and binding affinity toward the phosphate oxygens on RNA. Two optimal parameter sets are presented: MicroMg yields water exchange in OPC on the microsecond timescale in agreement with experiments. NanoMg yields accelerated exchange on the nanosecond timescale and facilitates the direct observation of ion binding events for enhanced sampling purposes.
[3,3]-Sigmatropic rearrangements: a variety of methods and recent advances
Authors: Dyachenko V. D. , Baryshev B. N. , Nenajdenko V. G.
Published: February 2022

The systematic review integrates and analyzes data on [3,3]-sigmatropic rearrangements published in the past decade. The main types of [3,3]-sigmatropic rearrangements are highlighted, optimal catalytic systems for various types of transformations and for various classes of compounds are considered. Examples are given for the use of such reactions in the synthesis of structurally complex, biologically active, natural and practically valuable compounds. For a number of processes, general mechanistic features of their behaviour, the geometry of transition states and the structures of inermediates are discussed.
 The bibliography includes 533 references. .
Facile synthesis and structures of silver formamidinates and pyrazolates
Authors: Guo Zhifang , Wang Nicole , Blair Victoria L. , Izgorodina Ekaterina I. , Deacon Glen B. , Junk Peter C.
Published: February 2022

Dinuclear silver formamidinates, [Ag2(DFForm)2(py)2] (1) (DFForm, N,N′-bis(2,6-difluorophenyl)formamidinate, py = pyridine), [Ag2(mHForm)2(py)3] (2) and [Ag2(mHForm)2(CH3CN)2] (2a) (mHForm, N,N′-bis(2,3,4,6-tetrafluorophenyl)formamidinate), [Ag2(pHForm)2(py)3] (3) (pHForm, N,N′-bis(2,3,5,6-tetrafluorophenyl)formamidinate), [Ag2(PFForm)2(py)3] (4) (PFForm, N,N′-bis(2,3,4,5,6-pentafluorophenyl)formamidinate) and [Ag2(DippForm)2]·1.25CH2Cl2 (5) (DippForm, N,N′-bis(2,6-diisopropylphenyl)formamidinate), and polynuclear, mainly trinuclear, silver pyrazolates, [Ag3(Ph2pz)3]2 (6) (Ph2pz, 3,5-diphenylpyrazolate), [Ag(tBu2pz)]4 (7) (tBu2pz, 3,5-di-tert-butylpyrazolate), [Ag3(PhMepz)3] (8) (PhMepz, 3-methyl-5-phenylpyrazolate), [Ag3(Phtpz)3] (9) (Phtpz, 3-phenyl-5-(2-thienyl)pyrazolate), [Ag3(ttfpz)3] (10) (ttfpz, 3-(2-thienyl)-5-trifluoromethylpyrazolate) and [Ag2(Me2pz)(PPh3)4Cl] (11) (Me2pz, 3,5-dimethylpyrazolate) were successfully synthesized in good yield by treating silver(i) oxide with the corresponding formamidines (FormH) or pyrazoles (pzH) either in pyridine or acetonitrile. These rapid, easily handled and economical reactions are readily monitored by consumption of black silver oxide. All compounds are potential precursors in redox transmetallation reactions in the synthesis of lanthanoid and alkaline earth pyrazolate and formamidinate complexes.
PaNAC089 is a membrane-tethered transcription factor (MTTF) that modulates flowering, chlorophyll breakdown and trichome initiation
Authors: Shao Changsheng , Cai Fangfang , Bao Zhiru , Zhang Yanping , Shi Gehui , Zhou Zheng , Chen Xiyan , Li Yangyang , Bao Manzhu , Zhang Jiaqi
Published: February 2022

Flowering and senescence are essential developmental stages of green plants, which are governed by complex molecular regulatory networks. However, the connection between flowering regulation and senescence regulation in London plane tree (Platanus acerifolia) remains unknown. In this study, we identified a gene PaNAC089 from London plane tree, which encodes a membrane-tethered transcription factor (MTTF) belonging to the NAC (NAM, ATAF1/2, CUC2) transcription factor family. We investigated the functions of PaNAC089 in the regulation of flowering and senescence through the analysis of expression profiles and transgenic phenotypes. Heterologous overexpression of ΔPaNAC089 delayed flowering and inhibited chlorophyll breakdown to produce dark green rosette leaves in Arabidopsis. In addition, the trichome density of rosette leaves was decreased in transgenic lines. In ΔPaNAC089 overexpression plants, a series of functional genes with inhibited expression were identified by quantitative real-time polymerase chain reaction (qRT-PCR), including genes that regulate flowering, chlorophyll decomposition, and trichome initiation. Furthermore, ΔPaNAC089 directly binds to the promoter of CONSTANS (CO) and NON-YELLOWING2 (NYE2) in the yeast one-hybrid assay. Consistent with this, luciferase (LUC) transient expression assays also showed that ΔPaNAC089 could inhibit the activity of NYE2. To summarise, our data suggests that PaNAC089 is an MTTF that modulates flowering, chlorophyll breakdown and trichome initiation.
Constraining nitrogen sources to a seagrass-dominated coastal embayment by using an isotope mass balance approach
Authors: Russell Douglas G. , Kessler Adam J. , Wong Wei Wen , Van Oevelen Dick , Cook Perran L. M.
Published: February 2022

Nitrogen (N) is often the key nutrient limiting primary production in coastal waters. Quantifying sources and sinks of N is therefore critical to understanding the factors that underpin the productivity of coastal ecosystems. Constraining nitrogen inputs can be difficult for some terms such as N fixation and marine exchange as a consequence of uncertainties associated with scaling and stochasticity. To help overcome these issues, we undertook a N budget incorporating an isotope and mass balance to constrain N sources in a large oligotrophic coastal embayment (Western Port, Australia). The total N input to Western Port was calculated to be 1400 Mg N year−1, which is remarkably consistent with previous estimates of sedimentation rates within the system. Catchment inputs, N fixation, marine sources and atmospheric deposition comprised 44, 28, 28 and 13% of N inputs respectively. Retention of marine-derived N equated to ~3 and ~10% of total N and NOx flushed through the system from the marine end-member. The relatively high contribution of N fixation compared with previous studies was most likely to be due to the high proportion of nutrient-limited intertidal sediments where N is mediated by seagrasses and sediment cyanobacteria.