bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliativversorgung und hospizliche Begleitung in der
stationären Pflege zwischen theoretischem Konzept und
Praxisalltag
Authors: Bußmann Anna , Pomorin Natalie
Published: October 2022

Ziel Trotz gesetzlicher Rahmenbedingungen befindet sich die palliative
Versorgung und hospizliche Begleitung in Pflegeeinrichtungen auf
unterschiedlichem Niveau. Zwar verfügen die meisten Einrichtungen
inzwischen über Palliative Care-Konzepte, die Integration in den
Praxisalltag erfolgt jedoch kaum. Ziel ist es, Versorgungsunterschiede im
Praxisalltag darzustellen und zu ermitteln, wodurch Abweichungen zu theoretisch
angelegten Konzepten in der Praxis bedingt sind.

Methodik Im Rahmen des Modellprojekts „Hospizliche Begleitung und
palliative Versorgung in der stationären Pflege“ werden
Struktur- und Prozessanalysen in zwei stationären Piloteinrichtungen im
städtischen und ländlichen Raum in Nordrhein-Westfalen
durchgeführt. Zusätzlich werden drei Einrichtungen eines
erweiterten Trägerkreises sowie ein fachkundiger Expertenbeirat mit
eingebunden, um (träger-) spezifische Merkmale geringzuhalten und
Erkenntnisse zu erweitern.

Ergebnisse Obwohl der Anteil palliativer Bewohner*innen ebenso wie
ihr Durchschnittsalter vergleichbar ist, bestehen zwischen den Einrichtungen
deutliche Unterschiede hinsichtlich der palliativen Verweildauer (213,2 Tage vs.
88,6 Tage) sowie der Sterberate palliativer Bewohner*innen an der
Gesamtzahl verstorbener Bewohner*innen (26% vs. 63,6%).
Die Prozessabläufe weichen trotz ähnlicher Konzepte und
Verfahrensanweisungen enorm voneinander ab. Dies hat zur Folge, dass die
Palliativversorgung in Einrichtung X zumindest formell zu einem früheren
Zeitpunkt einsetzt, zu dem bereits Vorbereitungen in Bezug auf die
Lebensendphase stattfinden. Die Identifikation palliativer
Versorgungssituationen basiert in beiden Einrichtungen, ebenso wie
Kommunikationsstrukturen, organisatorische Abläufe und der Einbezug von
Kooperationspartnern, ohne feste Strukturen auf der subjektiven Handhabung von
Mitarbeitenden.

Schlussfolgerung Es stellt sich als komplexe und herausfordernde Aufgabe
für die Pflegeeinrichtungen heraus, unter den Rahmenbedingungen ein
einheitliches und dennoch der Individualität des Menschen angepasstes
Konzept in der Praxis umzusetzen. Neben der Integration von praxistauglichen
Leitfäden und Assessments, definierten Verantwortungsbereichen sowie
Organisations- und Koordinationshilfen bedarf es ferner der Entwicklung
geeigneter Finanzierungskonzepte auf gesundheitspolitischer Ebene, um
theoretisch angelegte Palliative Care-Bedingungen in die Praxis
überführen zu können.
Current Biologics in Asthma Treatment
Authors: Imanirad Donya , Tabatabaian Farnaz
Published: October 2022

Uncontrolled asthma and/or severe asthma causes significant impairments in quality of life and is often a huge health care burden. Monoclonal antibodies have been an important addition to the therapeutic management of patients with moderate to severe asthma who do not respond to conventional asthma management. Currently the majority of Food and Drug Administration (FDA) approved biologics target T2 high inflammation. However, with the expanding knowledge of asthma pathogenesis, novel therapeutics targeting T2 low inflammation are in development. In this article we will focus on the current understanding of T2 inflammation and approved biologics for moderate to severe asthma.
Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations
Authors: Friedman Sarah A. , Masters-Israilov Alina , Robbins Matthew S.
Published: October 2022

Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of “red,” “orange,” and “green” flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.
Tomographic and centroid reconstructions of plasma emission on C-2W via enhanced 300-channel bolometry system
Authors: Bondarenko A. S. , Aviles J. , Alexander A. , Korepanov A. , Mendoza R. ,   TAE Team
Published: October 2022

The C-2W experimental device at TAE Technologies utilizes neutral beam injection and edge biasing to sustain long-lived, stable field reversed configuration (FRC) plasma. An ongoing effort is under way to optimize the electrode biasing system, which provides boundary control to stabilize the FRC. To this end, tomography offers a powerful and non-invasive technique as tomographic reconstruction of the FRC emission profile provides an important assessment of global stability. Recently, a new signal acquisition system was implemented on a bolometer array dedicated to tomography on C-2W, significantly enhancing the signal-to-noise of the collected data. The array consists of 300 simultaneously digitized photodiode channels that respond to a broad range of wavelengths, from soft x-ray to near-infrared, as well as energetic particles, yielding 180 unique lines of sight that intersect a toroidal plane of the FRC near the mid-plane. Utilizing the collected photo-signals from a set of plasma discharges in which the electrode biasing was intentionally terminated mid-shot, time-resolved reconstruction of the plasma emissivity is achieved via pixel-based 1D and 2D tomographic algorithms, revealing sharply annular profiles with a clear magnetohydrodynamic (MHD) mode structure. In addition, reconstruction of the plasma center-of-emission trajectories via a centroid algorithm applied to the same set of discharges demonstrates a cyclical plasma wobble. Crucially, both the tomography reconstruction and centroid reconstruction indicate an n = 1 toroidal mode that reverses from the electron diamagnetic direction to the ion diamagnetic direction and grows in amplitude after bias termination, qualitatively consistent with the expected stabilizing effect of electrodes.
Anti-tuberculosis drugs used in a directly observed treatment short course (DOTS) schedule alter endocrine patterns and reduce the ovarian reserve and oocyte quality in the mouse
Authors: Rao Arpitha , Nayak Guruprasad , Ananda Hanumappa , Kumari Sandhya , Dutta Rahul , Kalthur Sneha Guruprasad , Mutalik Srinivas , Thomas Sneha Ann , Pasricha Renu , Raghu Shamprasad Varija , Adiga Satish Kumar , Kalthur Guruprasad
Published: October 2022

Context Tuberculosis is one of the major infectious diseases, with people of reproductive age group having a high risk of infection. Aims The present study was designed to understand the consequences of anti-tuberculosis drugs (ATDs) used in DOTS (directly observed treatment short course) schedule on ovarian function. Methods Adult female Swiss albino mice were orally administered with combinations of ATDs used in the DOTS schedule every day for 4 weeks. At 2 weeks after the cessation of ATDs administration, the endocrine changes and ovarian function were assessed in mice. Key results Administration of ATDs to mice resulted in a prolonged estrous cycle, reduced ovarian follicle reserve, alteration in FSH, LH, and progesterone level, and decreased the number of ovulated oocytes. Further, the degree of fragmentation, degeneration, abnormal distribution of cytoplasmic organelles, abnormal spindle organisation, and chromosomal misalignment were higher in oocytes that were ovulated following superovulation. Blastocysts derived from ATDs treated mice had significantly lower total cell numbers and greater DNA damage. A marginal increase in the number of resorbed fetuses was observed in all the ATDs treated groups except in the multidrug resistance treatment group. Male progeny of ATDs treated mice had decreased sperm count and lower progressive motility, while female progeny exhibited a non-significant reduction in the number of oocytes ovulated. Conclusions The results of this study suggest that ATDs can have significant adverse effects on the ovarian reserve, cytoplasmic organisation of oocytes, and can potentially cause transgenerational changes. Implications The findings of the present study indicate ovarian toxicity of ATDs and warrant further research in the direction of identifying alternate drugs with minimal toxicity, and strategies to mitigate the ovarian toxicity induced by these drugs.
Statistics of biased tracers in variance-suppressed simulations
Authors: Maion Francisco , Angulo Raul E. , Zennaro Matteo
Published: October 2022

Cosmological simulations play an increasingly important role in analysing the
observed large-scale structure of the Universe. Recently, they have been
particularly important in building hybrid models that combine a perturbative
bias expansion with displacement fields extracted from N-body
simulations to describe the clustering of biased tracers. Here, we show that simulations that employ a technique referred
to as “Fixing-and-pairing” (F&P) can dramatically improve the statistical
precision of such hybrid models. Specifically, by numerical and analytical
means, we show that F&P simulations provide unbiased estimates for all
statistics employed by hybrid models while reducing, by up to two orders of
magnitude, their uncertainty on large scales. This roughly implies that an
EUCLID-like survey could be analysed using simulations of 2 Gpc a side — a 20%
of the survey volume. Our work establishes the robustness of F&P for current
hybrid theoretical models for galaxy clustering, an important step towards
achieving an optimal exploitation of large-scale structure measurements.
APPLESOSS: A Producer of ProfiLEs for SOSS. Application to the NIRISS SOSS Mode
Authors: Radica Michael , Albert Loïc , Taylor Jake , Lafrenière David , Coulombe Louis-Philippe , Darveau-Bernier Antoine , Doyon René , Cook Neil , Cowan Nicolas , Espinoza Néstor , Johnstone Doug , Kaltenegger Lisa , Piaulet Caroline , Roy Arpita , Talens Geert Jan
Published: October 2022

The SOSS mode of the Near Infrared Imager and Slitless Spectrograph instrument is poised to be one of the workhorse modes for exoplanet atmosphere observations with the newly launched James Webb Space Telescope (JWST). One of the challenges of the SOSS mode, however, is the physical overlap of the first two diffraction orders of the G700XD grism on the detector. Recently, the ATOCA algorithm was developed and implemented as an option in the official JWST pipeline, as a method to extract SOSS spectra by decontaminating the detector—that is, separating the first and second orders. Here, we present A Producer of ProfiLEs for SOSS (APPLESOSS), which generates the spatial profiles for each diffraction order upon which ATOCA relies. We validate APPLESOSS using simulated SOSS time series observations of WASP-52 b, and compare it to ATOCA extractions using two other spatial profiles (a best and worst case scenario on-sky), as well as a simple box extraction performed without taking into account the order contamination. We demonstrate that APPLESOSS profiles retain a high degree of fidelity to the true underlying spatial profiles, and therefore yield accurate extracted spectra. We further confirm that the effects of the order contamination for relative measurements (e.g., exoplanet transmission or emission observations) is small—the transmission spectrum obtained from each of our four tests, including the contaminated box extraction, is consistent at the ∼1σ level with the atmosphere model input into our noiseless simulations. We further confirm via a retrieval analysis that the atmosphere parameters (metallicity and C/O) obtained from each transmission spectrum are consistent with the true underlying values.
Saturable absorption performance of large area monolayer MoS2 coated planarized optical waveguide
Authors: Chew Jing Wen , Chong Wu Yi , Yap Yuen Kiat , Ng Kok Bin , Gan Soon Xin , Ahmad Harith
Published: October 2022

The development of compact waveguide-based pulsed lasers has been of great interest in the past two decades. This is supported by the rapid development of two-dimensional (2D) materials saturable absorbers (SAs). In this paper, we integrate a large area monolayer molybdenum disulphide (MoS2) on a planarized silica optical waveguide and studied its performance as an SA. A single layer MoS2 film on polydimethylsiloxane substrate is mechanically transferred to the planarized optical waveguide. The single layer MoS2 can interact with the evanescent field of the waveguide core mode, thus achieving SA. The MoS2-coated waveguide is then integrated into an erbium-doped fibre laser cavity that operates in the telecommunication wavelength region. Q-switching is achieved with a repetition rate, pulse duration and maximum pulse energy of 22.5 kHz, 5.24 µs and 4.1 nJ, respectively at a pump power of 122.8 mW. The results show that 2D material thin films can be integrated onto a planarized optical waveguide to act as SAs. These findings show the potential of using 2D materials in developing compact, integrated waveguide pulsed laser sources.
Computational Fluid Dynamics (CFD) Modelling of ZnO-SiO2 Composite Through a Consecutive Electrospray and Spray Drying Method
Authors: Qomariyah L , Puri N R , Grady E , Nurtono T , Widiyastuti  , Kusdianto  , Madhania S , Winardi S
Published: October 2022

Modelling of the droplet formation and drying process in the synthesis of Zinc Oxide-Silicon Dioxide (ZnO-SiO2) composite have been conducted through a CFD modelling. In general, modelling of spray drying only focused on exploring the drying chamber section. The phenomenon builds in a consecutive electrospray and spray drying method has been successfully studied in this paper. The influence of carrier gas flow rate (2 to 10 L/min), precursor flow rate (1 to 10 ml/h), drying chamber temperature and applied voltage (12 to 14 kV) were investigated systematically. Numerical modelling was conducted to describe the mechanism of the composite droplet formation through the jet shape of the electrospray. Evaporation of the initial composite droplet was considered in the modelling, accounting for its size evolution. Simultaneous mass transfer modelling due to the composite evaporation was solved in combination with a general dynamic equation solution. The modelling results show that the applied voltage and the precursor flow rate effectively affected the composite droplet size. While the carrier gas flow rate and the drying chamber temperature, influenced the effectiveness of the composite particle formation in the spray drying synthesis.
Chemical properties and microstructure analysis of yellow corn and okara-based composite flour
Authors: Praseptiangga D , Widyaastuti D , Sarifah R F A , Ishartani D
Published: October 2022

Composite flour is derived from mixing flour rich in starch, protein, and other ingredients. Corn and okara have great potentials of being used as raw materials for the manufacturing of this composite flour, due to their high nutritional quality and affordability. Therefore, this study was aimed to analyze the chemical characteristics and microstructure of yellow corn and okara-based composite flours. The composite flour was produced in five different formulations of yellow corn flour and dried okara. The data obtained were statistically analyzed using the One-way ANOVA with a significance level of 95% and the difference between the mean values of the data was further analyzed with DMRT. Results showed that the amount of okara flour added to that of the composite flours significantly (p<0.05) decreased moisture and carbohydrate contents, and then increased the ash, fat, protein, total dietary fiber, and resistant starch contents. While its microstructure analysis has confirmed the interaction between yellow corn starch granules and okara fiber. Furthermore, higher addition of okara flour has improved the composite flours properties. Thus, yellow corn and okara-based composite flours showed great potentials as functional food ingredients for food products diversification, due to their high protein and dietary fiber contents.
Thermo-mechanical design for ALPIDE pixel sensor chip in a high-energy particle detector space module
Authors: Coli S. , Angeletti M. , Gargiulo C. , Iuppa R. , Serra E.
Published: October 2022

The Limadou collaboration includes all Italian scientists working on the project CSES (China Seismo-Electromagnetic Satellite), a constellation of satellites equipped with the most advanced technologies for correlating ionosphere perturbations with the occurrence of seismic events [2]. For the launch of CSES-02, scheduled for mid-2022, the collaboration is realizing the high-energy particle detector [1], aimed at detecting electrons and protons trapped in Earth’s magnetosphere, with energies 5 MeV–100 MeV and 30 MeV–300 MeV respectively. This payload consists of a particle tracker, a trigger system and a calorimeter, which work in time-coincidence to accurately identify particles and measure their energy and trajectory. The tracker is based on monolithic active pixel sensors ALPIDE [4], an innovative platform with superior performances in the field of pixel detectors, developed for the upgrade of the ALICE experiment [5] at the LHC, at CERN. The challenge in the construction of the tracker has been to adapt the ALPIDE technology to the space environment and to the specifications of the space register. Lightness and stiffness, essential features for structures in a tracker module, needed to balance with the need for withstanding structural and vibrational stress in the extended range of temperature occurring in the launch phase. Proper material choice with high thermal conductivity for the heat dissipation, innovative design of thermal paths and structural test results guided the project of mechanics. The modular particle tracker consists of 5 turrets, each one made of 3 stacked staves, with 150 pixel sensors in total. For readout and control purposes, ALPIDE sensors are wire-bonded to flexible printed circuits, which enhances the fragility of the system and makes handling critical. Sensor supports in carbon fiber reinforced plastic and an external aluminum frame preserve the mechanical integrity and provide the essential thermal bridges for heat dissipation. We provide results from the intense campaign of structural, thermal and vibrational qualification tests that have been performed in compliance with the procedures required by the space register. It regards structure, module and turret elements. The envisaged solution is a novelty in the field of space applications and paves the way for important developments for particle and astroparticle physics experiments.
Application of force-compensating spring modules on mechanical frame of undulators
Authors: Chuang Ping-Shun , Chiang Hsiao-Wei , Huang Jui-Che , Kitamura Hideo , Wang Pei-Jen
Published: October 2022

A small RMS phase error and long-term stability of the
gap-drive system are important criteria for realizing high
performance undulators. The use of force compensating spring modules
of self-contained type move toward the goals. Since magnetic forces
from girders are vanished entirely at the spring module, so not only
the small systematic phase error derived from deformation of the
girders but also the small dynamic loadings on the mechanical frame
and gap-drive system. Moreover, spring modules provide a
supplemental mechanism to correct magnetic field errors at varied
gaps. Such mechanism is particular benefit for the cryogenic
permanent magnet undulators because the field errors of undulator
shall correct in both cryogenic mode and room temperature mode.
In vitro application of drug-loaded hydrogel combined with 3D-printed porous scaffolds
Authors: Huang Haokun , Wu Zhenhuan , Yang Zhuofan , Fan Xiaoxi , Bai Siqi , Luo Junsi , Chen Minmin , Xie Xiaoli
Published: October 2022

Titanium mesh and three-dimensional titanium alloy scaffolds play a key role in addressing oral and maxillofacial bone defects, which can provide a specific environment and structure for bone growth and development. The two main causes of implant surgery failure are aseptic loosening and bacterial-induced implant-associated infections. To make bone defect implants effective for a long time, the ideal scaffold should take into account the two functions of osseointegration and anti-infection. Therefore, on the basis of the low-elastic-modulus Ti-10Ta-2Nb-2Zr (TTNZ) alloys developed by the research group in the early stage, this study intends to combine the vancomycin-loaded hydrogel with the 3D-printed through-hole porous titanium alloy scaffold to endow 3D-printed TTNZ scaffolds with antibacterial properties. The antibacterial properties of the complex were investigated by the zone of inhibition test and the adhesion/free antibacterial test. The effects of the composite system on osseointegration were investigated from the aspects of cell adhesion, cell proliferation and osteogenesis-related gene expression. The results showed that loading 2.5 wt.% and 5 wt.% vancomycin did not affect the structure of chitosan–hyaluronic acid hydrogel. The properties of the hydrogels were examined by scanning electron microscopy, Fourier-transform infrared, degradation experiment in vitro and vancomycin release experiment in vitro. When combined with porous scaffolds, the drug-loaded hydrogels exhibited slower drug release rates and longer release times. In addition, in vitro studies found that the TTNZ scaffolds loaded with 5 wt.% vancomycin had a certain effect on the expression of osteogenesis-related genes in cells, but the antibacterial effect was the best. The porous scaffolds loaded with 2.5 wt.% vancomycin hydrogel TTNZ scaffolds did not inhibit cell proliferation, adhesion, alkaline phosphatase activity, and osteogenesis-related gene ex-pression, but the antibacterial effect on free bacteria was not as good as that of TTNZ scaffolds loaded with 5 wt.% vancomycin. This study, complementing the advantages of the two and controlling the local release rate of vancomycin, provides a new idea for future 3D printing of titanium alloy stents for anti-infection.
Hydrogen justice
Authors: Müller Franziska , Tunn Johanna , Kalt Tobias
Published: October 2022

For a rapid energy transition to renewable energy, green hydrogen is increasingly considered a solution to a myriad of challenges: climate neutrality, clean energy supply, and decoupling of growth and carbon emissions. However, whether the global hydrogen transition will indeed be a just transition is far from certain. This paper introduces the concept of hydrogen justice as an analytical toolkit to help examining justice challenges of the global hydrogen transition. Placing hydrogen justice at the nexus of energy, water and climate justice, and incorporating crucial insights from political ecology and decolonial studies we highlight potential hydrogen injustices and suggest a six-dimensional concept of hydrogen justice: procedural, distributive, restorative, relational, recognitional and epistemological justice. Our research explores socio-ecological, political and economic conditions in hydrogen target countries and examines emerging hydrogen projects and partnerships. Hydrogen injustices may manifest around issues of energy access in countries with high rates of energy poverty, water access in arid regions, as well as forced displacements, impairments of Indigenous livelihoods and the strengthening of authoritarian rule. We conclude that hydrogen injustices result from the interplay of global hydrogen governance and local conditions in producing countries. We illustrate this with examples from transnational hydrogen projects situated in Morocco and Namibia. Finally, we suggest strategies for redressing hydrogen injustices by integrating justice principles at all scales of hydrogen governance.
Mapping urban–rural differences in the worldwide achievement of sustainable development goals: land-energy-air nexus
Authors: Tian Yunyu , Tsendbazar Nandin-Erdene , van Leeuwen Eveline , Herold Martin
Published: October 2022

Land use efficiency (LUE), energy efficiency (EE), and air quality are key indicators when assessing urban-related Sustainable Development Goals, yet recent trends and trade-offs in and around urban areas worldwide remain largely unknown. We use an Earth Observation approach to map the land-energy-air sustainability nexus and highlight distinct urban–rural gradients worldwide (2000–2015). In the Global South, urban areas perform relatively better in land-energy-air sustainability trends than rural areas, which are the least sustainable in our global comparative analysis. Comparatively, urban areas in the Global North tend to be less sustainable than surrounding rural regions. Trade-offs among land-energy-air change directions are mostly related to EE versus air quality in urban areas, while spatial and temporal trade-offs between LUE and EE are more pronounced in suburban and rural areas. Integrating satellite data is crucial for tracking the progress of the land-energy-air nexus and can guide context-specific strategies to account for urban–rural differences in achieving sustainability and creating more livable environments.
How robust are modern graph neural network potentials in long and hot molecular dynamics simulations?
Authors: Stocker Sina , Gasteiger Johannes , Becker Florian , Günnemann Stephan , Margraf Johannes T
Published: October 2022

Graph neural networks (GNNs) have emerged as a powerful machine learning approach for the prediction of molecular properties. In particular, recently proposed advanced GNN models promise quantum chemical accuracy at a fraction of the computational cost. While the capabilities of such advanced GNNs have been extensively demonstrated on benchmark datasets, there have been few applications in real atomistic simulations. Here, we therefore put the robustness of GNN interatomic potentials to the test, using the recently proposed GemNet architecture as a testbed. Models are trained on the QM7-x database of organic molecules and used to perform extensive molecular dynamics simulations. We find that low test set errors are not sufficient for obtaining stable dynamics and that severe pathologies sometimes only become apparent after hundreds of ps of dynamics. Nonetheless, highly stable and transferable GemNet potentials can be obtained with sufficiently large training sets.
Optimizing ion implantation to create shallow NV centre ensembles in high-quality CVD diamond
Authors: Ngandeu Ngambou Midrel Wilfried , Perrin Pauline , Balasa Ionut , Brinza Ovidiu , Valentin Audrey , Mille Vianney , Bénédic Fabien , Goldner Philippe , Tallaire Alexandre , Achard Jocelyn
Published: October 2022

The negatively charged nitrogen-vacancy centre (so-called NV-centre) in diamond is one of the most promising systems for applications in quantum technologies because of the possibility to optically manipulate and read out the spin state of this defect, even at room temperature. Nevertheless, obtaining high NV densities (>500 ppb) close to the surface (5–20 nm) while maintaining good spin properties remain challenging. In this work we rely on a versatile ion implantation system allowing both implanting nitrogen using N2
+ and creating vacancies with He+ ion bombardment at variable energies and fluence to create shallow NV ensembles. By optimizing the ion irradiation conditions as well as the surface preparation prior to treatment we successfully increase the amount of created colour centres while demonstrating narrow magnetic resonance linewidths.
Autophagy Reduces the Degradation and Promotes Membrane Localization of Occludin to Enhance the Intestinal Epithelial Tight Junction Barrier against Paracellular Macromolecule Flux
Authors: Saha Kushal , Subramenium Ganapathy Ashwinkumar , Wang Alexandra , Michael Morris Nathan , Suchanec Eric , Ding Wei , Yochum Gregory , Koltun Walter , Nighot Meghali , Ma Thomas , Nighot Prashant
Published: October 2022

Background and Aims

Functional loss of the gut epithelium’s paracellular tight junction [TJ] barrier and defective autophagy are factors potentiating inflammatory bowel disease [IBD]. Previously, we showed the role of autophagy in enhancing the intestinal TJ barrier via pore-forming claudin-2 degradation. How autophagy regulates the TJ barrier-forming proteins remains unknown. Here, we investigated the role of autophagy in the regulation of occludin, a principal TJ component involved in TJ barrier enhancement.

Results

Autophagy induction using pharmacological activators and nutrient starvation increased total occludin levels in intestinal epithelial cells, mouse colonocytes and human colonoids. Autophagy induction enriched membrane occludin levels and reduced paracellular permeability of macromolecules. Autophagy-mediated TJ barrier enhancement was contingent on the presence of occludin as OCLN−/− nullified its TJ barrier-enhancing effect against macromolecular flux. Autophagy inhibited the constitutive degradation of occludin by preventing its caveolar endocytosis from the membrane and protected against inflammation-induced TJ barrier loss. Autophagy enhanced the phosphorylation of ERK-1/2 and inhibition of these kinases in Caco-2 cells and human colonic mucosa prevented the macromolecular barrier-enhancing effects of autophagy. In vivo, autophagy induction by rapamycin enhanced occludin levels in wild-type mouse intestines and protected against lipopolysaccharide- and tumour necrosis factor-α-induced TJ barrier loss. Disruption of autophagy with acute Atg7 knockout in adult mice decreased intestinal occludin levels, increasing baseline colonic TJ permeability and exacerbating the effect of experimental colitis.

Conclusion

Our data suggest a novel role of autophagy in promoting the intestinal TJ barrier by increasing occludin levels in an ERK1/2 mitogen-activated protein kinase-dependent mechanism.
A crisis like no other? Unmet needs in healthcare during the first wave of the COVID-19 crisis in Austria
Authors: Schmidt Andrea E , Rodrigues Ricardo , Simmons Cassandra , Steiber Nadia
Published: October 2022

Background

Many patients experienced restricted access to healthcare during the Coronavirus Disease 2019 (COVID-19) pandemic. This study is among the first to provide systematic evidence on the existence of subjective unmet needs (SUN) in different population groups during the pandemic.

Methods

Using data on individuals aged 20–64 and living in Austria from the AKCOVID survey (June 2020) and the ‘European Social Survey’ (2015), SUN were compared between 2015 and 2020, either related to the pandemic (fear of infection, provider closed or treatment postponed) or not (barriers related to knowledge, affordability, time and reachability). Multinomial logistic regression models identified determinants of SUN during the pandemic, adjusting for socio-demographics, socio-economic status and self-reported health.

Results

Shares of the population with SUN in 2020 substantially exceeded SUN in 2015. Excess unmet needs were mostly attributable to the pandemic. Postponed treatments and closed providers were the most important reasons for SUN in June 2020. Older age groups (50–64 years), inactive and retired people were most likely to report pandemic-related SUN. We did not find socio-economic differences in pandemic-related SUN.

Conclusions

The pandemic resulted in a supply-side shock to healthcare, with vulnerabilities emerging especially among older people, people with poor health and/or people no longer active on the labour market. Further research could focus on health system resilience and the possibilities to improve management of healthcare services during pandemics without widening inequalities while maintaining population health.
Telomere-to-telomere genome assembly of bitter melon (Momordica charantia L. var. abbreviata Ser.) reveals fruit development, composition and ripening genetic characteristics
Authors: Fu Anzhen , Zheng Yanyan , Guo Jing , Grierson Donald , Zhao Xiaoyan , Wen Changlong , Liu Ye , Li Jian , Zhang Xuewen , Yu Ying , Ma Hong , Wang Qing , Zuo Jinhua
Published: October 2022

Momordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.
Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy
Authors: Alqahtani Hajar , Alghamdi Ahlam , Alobaidallah Nouf , Alfayez Amal , Almousa Rawan , Albagli Rawan , Shamas Nour , Farahat Fayssal , Mahmoud Ebrahim , Bosaeed Mohammad , Abanamy Reem
Published: October 2022

Background

Carbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%.

Method

This single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE).

Results

A total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ± OXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ± OXA-48).

Conclusions

This was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.
O-GlcNAcylation is a gatekeeper of porcine myogenesis
Authors: Kirkpatrick Laila T , Daughtry Morgan R , El-Kadi Samer , Shi Tim Hao , Gerrard David E
Published: October 2022

Although it has long been known that growth media withdrawal is a prerequisite for myoblast differentiation and fusion, the underpinning molecular mechanism remains somewhat elusive. Using isolated porcine muscle satellite cells (SCs) as the model, we show elevated O-GlcNAcylation by O-GlcNAcase (OGA) inhibition impaired SC differentiation (D5 P < 0.0001) but had unnoticeable impacts on SC proliferation. To explore the mechanism of this phenotype, we examined the expression of the transcription factor myogenin, a master switch of myogenesis, and found its expression was downregulated by elevated O-GlcNAcylation. Because insulin/IGF-1/Akt axis is a strong promoter of myoblast fusion, we measured the phosphorylated Akt and found that hyper O-GlcNAcylation inhibited Akt phosphorylation, implying OGA inhibition may also work through interfering with this critical differentiation-promoting pathway. In contrast, inhibition of O-GlcNAc transferase (OGT) by its specific inhibitor had little impact on either myoblast proliferation or differentiation (P > 0.05). To confirm these in vitro findings, we used chemical-induced muscle injury in the pig as a model to study muscle regenerative myogenesis and showed how O-GlcNAcylation functions in this process. We show a significant decrease in muscle fiber cross sectional area (CSA) when OGA is inhibited (P < 0.05), compared to nondamaged muscle, and a significant decrease compared to control and OGT inhibited muscle (P < 0.05), indicating a significant impairment in porcine muscle regeneration in vivo. Together, the in vitro and in vivo data suggest that O-GlcNAcylation may serve as a nutrient sensor during SC differentiation by gauging cellular nutrient availability and translating these signals into cellular responses. Given the importance of nutrition availability in lean muscle growth, our findings may have significant implications on how muscle growth is regulated in agriculturally important animals.
Circulating Levels of C1q/TNF-Related Protein 3 (CTRP3) and CTRP9 in Gestational Diabetes and Their Association with Insulin Resistance and Inflammatory Cytokines
Authors: Fadaei Reza , Goodarzi Golnoosh , Yarahmadi Sahar , Allahyari Pooneh , Fallah Soudabeh , Moradi Nariman
Published: October 2022

Objective

Gestational diabetes mellitus (GDM) is closely related to obesity, adipose tissue, and adipokines. Adiponectin-homologous adipokines with anti-inflammatory properties, including C1q/TNF-related protein 3 (CTRP3) and CTRP9, regulate glucose and lipid metabolism, which was measured in pregnant women with GDM with the aim to assess their circulating levels and their relation with inflammatory cytokines and other biochemical data.

Methods

Serum levels of CTRP3, CTRP9, adiponectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured in 43 subjects with GDM and 42 healthy controls by enzyme-linked immunosorbent assay.

Results

Serum levels of adiponectin and CTRP3 were lower in GDM subjects than in controls, whereas CTRP9, TNF-α, and IL-6 showed higher concentrations in subjects with GDM than in controls. In the subjects with GDM, there was a significant association of CTRP3 with homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, and triglycerides, whereas CTRP9 is associated with TNF-α and HOMA-IR.

Conclusion

The differences in the assessed levels of CTRP3 and CTRP9 suggest a possible relation with the pathogenesis of GDM, in particular insulin resistance, which showed significant association with both adipokines.
Targeting integrin α2 as potential strategy for radiochemosensitization of glioblastoma
Authors: Korovina Irina , Vehlow Anne , Temme Achim , Cordes Nils
Published: October 2022

Background

Glioblastoma (GBM) is a fast-growing primary brain tumor characterized by high invasiveness and resistance. This results in poor patient survival. Resistance is caused by many factors, including cell-extracellular matrix (ECM) interactions. Here, we addressed the role of adhesion protein integrin α2, which we identified in a high-throughput screen for novel potential targets in GBM cells treated with standard therapy consisting of temozolomide (TMZ) and radiation.

Methods

In our study, we used a range of primary/stem-like and established GBM cell models in vitro and in vivo. To identify regulatory mechanisms, we employed high-throughput kinome profiling, Western blotting, immunofluorescence staining, reporter, and activity assays.

Results

Our data showed that integrin α2 is overexpressed in GBM compared to normal brain and, that its deletion causes radiochemosensitization. Similarly, invasion and adhesion were significantly reduced in TMZ-irradiated GBM cell models. Furthermore, we found that integrin α2-knockdown impairs the proliferation of GBM cells without affecting DNA damage repair. At the mechanistic level, we found that integrin α2 affects the activity of activating transcription factor 1 (ATF1) and modulates the expression of extracellular signal-regulated kinase 1 (ERK1) regulated by extracellular signals. Finally, we demonstrated that integrin α2-deficiency inhibits tumor growth and thereby prolongs the survival of mice with orthotopically growing GBM xenografts.

Conclusions

Taken together our data suggest that integrin α2 may be a promising target to overcome GBM resistance to radio- and chemotherapy. Thus, it would be worth evaluating how efficient and safe the adjuvant use of integrin α2 inhibitors is to standard radio(chemo)therapy in GBM.
Punishing Atrocity Crimes in Transitional Contexts: Advancing Discussions on Adequacy of Alternative Criminal Sanctions Using the Case of Colombia
Authors: Mayans-Hermida Beatriz E , Holá Barbora
Published: October 2022

Criminal trials and proportional prison sentences are generally seen as the most suitable way to deal with perpetrators of atrocity crimes. Notwithstanding, traditionally conceived criminal penalties, such as imprisonment, may discourage active responsibility-taking by offenders, disaffect victims by not meeting their needs and impede meaningful engagement between perpetrators and survivors. Arguably, alternative criminal sanctions may be appropriate punishment even for atrocity crimes when tried in transitional societies. Using the case of Colombia, this article analyses the justifications of punishment for atrocities in transitional contexts and discusses the adequacy of alternative criminal sanctions as penalties for atrocity crimes. It concludes that under certain conditions, alternative sanctions can be a viable punishment option that may promote active responsibility-taking and contribute to repairing harm, reintegrating offenders into the community and (re)constructing relationships while serving expressive rationales.
Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment
Authors: Kim Jinyong , Chang Euijin , Park Song Yi , Lee Dae-Won , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Oh Myoung-don , Park Wan Beom , Lee Kyung-Hun , Im Seock-Ah
Published: October 2022

Background

Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies.

Materials and Methods

In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments.

Results

Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy.

Conclusion

Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.
Epigenetic nature of Arabidopsis thaliana telomeres
Authors: Vaquero-Sedas María I , Vega-Palas Miguel A
Published: October 2022

The epigenetic features of defined chromosomal domains condition their biochemical and functional properties. Therefore, there is considerable interest in studying the epigenetic marks present at relevant chromosomal loci. Telomeric regions, which include telomeres and subtelomeres, have been traditionally considered heterochromatic. However, whereas the heterochromatic nature of subtelomeres has been widely accepted, the epigenetic status of telomeres remains controversial. Here, we studied the epigenetic features of Arabidopsis (Arabidopsis thaliana) telomeres by analyzing multiple genome-wide ChIP-seq experiments. Our analyses revealed that Arabidopsis telomeres are not significantly enriched either in euchromatic marks like H3K4me2, H3K9ac, and H3K27me3 or in heterochromatic marks such as H3K27me1 and H3K9me2. Thus, telomeric regions in Arabidopsis have a bimodal chromatin organization with telomeres lacking significant levels of canonical euchromatic and heterochromatic marks followed by heterochromatic subtelomeres. Since heterochromatin is known to influence telomere function, the heterochromatic modifications present at Arabidopsis subtelomeres could play a relevant role in telomere biology.
Genomic screening reveals ubiquitin-like modifier activating enzyme 1 as a potent and druggable target in c-MYC-high triple negative breast cancer models
Authors: Jacob Sheeba , Turner Tia H , Cai Jinyang , Floros Konstantinos V , Yu Ann K , Coon Colin M , Khatri Rishabh , Alzubi Mohammad A , Jakubik Charles T , Bouck Ynes M , Puchalapalli Madhavi , Shende Mayuri , Dozmorov Mikhail G , Boikos Sosipatros A , Hu Bin , Harrell J Chuck , Benes Cyril H , Koblinski Jennifer E , Costa Carlotta , Faber Anthony C
Published: October 2022

Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer (BC)-related deaths, despite accounting for only 10% to 15% of total BC cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the ubiquitin-like modifier activating enzyme 1 (UBA1). Targeting UBA1 with the first-in-class UBA1 inhibitor TAK-243 induced unresolvable endoplasmic reticulum (ER)-stress and activating transcription factor 4 (ATF4)-mediated upregulation of proapoptotic NOXA, leading to cell death. c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. Moreover, in an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden, indicating UBA1 is a potential new target in TNBC expressing high levels of c-MYC.