bluuebunny/crossref_metadata_2025 huggingface dataset:
DMEK after penetrating keratoplasty: cohort with DMEK grafts and descemetorhexis larger than full-thickness graft
Authors: Steindor F. A. , Menzel-Severing J. , Borrelli M. , Schrader S. , Geerling G.
Published: April 2022

Purpose

The study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface.

Methods

A monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface (i.e., in host tissue) between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed.

Results

Eleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002).

Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months (range 6 to 39 months, p < 0.001, n = 8) after surgery.

Conclusion

DMEK can be successfully used to treat endothelial cell failure after PK, and can provide good postoperative results with regards to visual acuity. This study shows that stripping of Descemet’s membrane (DM) peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival.
Magma fragmentation: a perspective on emerging topics and future directions
Authors: Jones Thomas J. , Cashman Katharine V. , Liu Emma J. , Rust Alison C. , Scheu Bettina
Published: April 2022

The breaking apart of magma into fragments is intimately related to the eruptive style and thus the nature and footprint of volcanic hazards. The size and shape distributions of the fragments, in turn, affect the efficiency of heat transfer within pyroclastic plumes and currents and the settling velocity, and so the residence time, of particles in the atmosphere. Fundamental work relating the glass transition to the fragmentation of magmas remains at the heart of conceptual and numerical models of volcanic eruptions. Current fragmentation criteria, however, do not predict the sizes and shapes of the resulting fragments, or fully account for the multiphase nature of magmas or ways in which magma can break in a fluidal manner or by thermal stress. The pulsatory, non-steady state nature of some eruptions, and related interactions with these fragmentation criteria, also requires further investigation. Here, we briefly review some recent advances in the field of magma fragmentation and provide a perspective on how integrated field, experimental and numerical modelling studies can address key outstanding challenges.
Postresuscitation care and prognostication after cardiac arrest—Does sex matter?
Authors: Hasslacher Julia , Ulmer Hanno , Lehner Georg , Klein Sebastian , Mayerhoefer Timo , Bellmann Romuald , Joannidis Michael
Published: April 2022

Background

There are conflicting results concerning sex-specific differences in the post-cardiac arrest period. We investigated the sex distribution of patients after successful cardiopulmonary resuscitation (CPR), differences in treatment, complications, outcome and sex-specific performance of biomarkers for prognostication of neurological outcome.

Methods

Prospective observational study including cardiac-arrest (CA) patients treated with mild therapeutic hypothermia (MTH) at 33 °C for 24 h or normothermia. We investigated common complications including pneumonia and acute kidney injury (AKI) and neuron-specific enolase, secretoneurin and tau protein as biomarkers of neurological outcome, which was assessed with the cerebral performance categories score at hospital discharge.

Results

Out of 134 patients 26% were female. Women were significantly older (73 years, interquartile range (IQR) 56–79 years vs. 62 years, IQR 53–70 years; p = 0.038), whereas men showed a significantly higher rate of pneumonia (29% vs. 6%; p = 0.004) and a trend towards higher rates of AKI (62% vs. 45%; p = 0.091). Frequency of MTH treatment was not significantly different (48% vs. 31%; p = 0.081). Female sex was not associated with neurological outcome in multivariable analysis (p = 0.524). There was no significant interaction of sex with prognostication of neurological outcome at 24, 48 and 72 h after CPR. At the respective time intervals pinteraction for neuron-specific enolase was 0.524, 0.221 and 0.519, for secretoneurin 0.893, 0.573 and 0.545 and for tau protein 0.270, 0.635, and 0.110.

Conclusion

The proportion of female patients was low. Women presented with higher age but had fewer complications during the post-CA period. Female sex was not associated with better neurological outcome. The performance of biomarkers is not affected by sex.
Inter- and intraobserver reliabilities and critical analysis of the osteoporotic fracture classification of osteoporotic vertebral body fractures
Authors: Schönrogge Maria , Lahodski Vadzim , Otto Ronny , Adolf Daniela , Damm Robert , Sitte-Zöllner Albrecht , Piatek Stefan
Published: April 2022

Purpose

The Osteoporotic Fracture Working Group (Spine Division of the German Orthopaedic and Trauma Society) has developed a classification system for osteoporotic thoracolumbar fractures, namely the osteoporotic fracture (OF) classification system. The purpose of this study was to determine the inter- and intraobserver reliabilities of the OF classification system for osteoporotic vertebral body fractures (VFs) at a level-one trauma centre.

Methods

Conventional radiography, magnetic resonance imaging (MRI), and computed tomography (CT) scans of 54 consecutive women who sustained an osteoporotic VF were analysed by six orthopaedic traumatologists with varying levels of experience. The inter- and intraobserver reliabilities of the OF classification system were determined using intraclass correlation coefficients (ICCs) and Cohen’s kappa.

Results

The overall interobserver reliability of the OF classification system was good (ICC, 0.62 [0.51, 0.72]). The intraobserver reliability was found to be substantial (overall weighted Cohen’s kappa estimate [95% confidence interval {CI}] = 0.74 [0.67, 0.80]) and better when the radiography, MRI, and CT scans were assessed together than when only the radiography and MRI scans were evaluated, although the difference was not significant.

Conclusion

The OF classification system is easy to use. It shows good interobserver reliability and substantial intraobserver reliability if diagnostic prerequisites (conventional radiography, MRI, and CT scans) are met.
Early Cretaceous ultramafic-alkaline-carbonatite magmatism in the Shillong Plateau-Mikir Hills, northeastern India – a synthesis
Authors: Srivastava Rajesh K. , Guarino Vincenza , Melluso Leone
Published: April 2022

A comprehensive mineralogical, geochemical and isotopic review of six ultramafic-alkaline-carbonatite magmatic intrusions of the Shillong Plateau (Sung Valley, Jasra, Swangkre-Rongjeng, and Mawpyut) and Mikir Hills (Samchampi-Samteran and Barpung) is presented here, using the published data. These intrusions emplaced ca. 115–102 Ma ago, thus are significantly younger than the tholeiitic flood basalts erupted in Rajmahal-Sylhet province (ca. 118–115 Ma). The intrusive lithologies vary from ultramafic (dunites, clinopyroxenites, melilitolites) to mafic (ijolites, gabbrossensu lato, shonkinites), to felsic (syenites, nepheline syenites) and carbonatites (mostly calcite-rich varieties). The volcanic-subvolcanic facies (lamprophyres, phonolites) are not abundant. The range of chemical compositions of the magmatic phases in the various assemblages is notable; the intrusive rocks are thus the result of crystallization of magmas from variably evolved, independent liquid-lines-of descent, generally of alkaline/strongly alkaline lineages and sodic-to-potassic in affinity. The large variations of the Sr–Nd isotopic ratios of the silicate intrusive rocks (sensu lato) suggest a role of shallow-level crustal contamination during their formation. The carbonatites of the Sung Valley and Samchampi-Samteran have different isotope ratios than the associated silicate rocks, have some isotopic affinity with the Group I tholeiitic basalts of Rajmahal Traps and have an ultimate genesis in a carbonate-bearing lithospheric mantle.
Two new neoavian taxa with contrasting palaeobiogeographical implications from the early Miocene St Bathans Fauna, New Zealand
Authors: Worthy Trevor H. , Scofield R. Paul , Salisbury Steven W. , Hand Suzanne J. , De Pietri Vanesa L. , Archer Michael
Published: April 2022

Two new neoavian landbirds are reported from the early Miocene St Bathans Fauna from New Zealand.Aegotheles zealandivetussp. nov. is described from several bones, among which, notably, the tarsometatarsus shows more similarity to New Guinean taxa than to Australian—New Zealand species.Zealandornis relictusgen. et sp. nov. is described from a distal end of a humerus and placed in the new family Zealandornithidae, tentatively among the ‘higher landbirds’ Telluraves, with most similarity to coliiforms. The humerus is of similar size to that of species ofColiusand its gracile shaft and very shallow sulcus scapulotricipitalis suggests reduced flying ability. The new species ofAegothelesreinforces the Australasian nature of the Zealandian fauna, while in contrast,Zealandornis relictusgen. et sp. nov. appears to have no close relatives. It is as distinct as Acanthisittidae and Strigopidae among birds, or Leiopelmatidae and Sphenodontidae among the herpetofauna, and like them, represents a similar relictual taxon. Together they confer a highly evolutionarily distinctive nature to the Zealandian fauna concomitant with a minimal 60 million years of isolation.
Molecular analysis reveals multiple native and alien Phoxinus species (Leusciscidae) in the Netherlands and Belgium
Authors: Palandačić Anja , Witman Kars , Spikmans Frank
Published: April 2022

Fresh waters are among the most endangered ecosystems, one of the problems being the lack of data on biodiversity. In the center of the missing knowledge are cryptic species, two (or more) species classified as a single one due to their (seemingly) indistinguishable morphology. Lack of research and stabilizing selection are reflected in the cryptic diversity of the genus Phoxinus (Leusciscidae), the studies of which have intensified over the last two decades and reveal undetected taxonomic complexity. Moreover, some of the Phoxinus lineages act as invasive species, while others are endangered by their alien counterparts. Minnows have been intentionally (as food for predatory fish species) or unintentionally (with other fries) stocked causing hybridisation zones in Norway, Portugal, Spain, France, Italy, Germany and Austria. Given that genetic identity and lineage assignment of Phoxinus from Belgium and the Netherlands have not been researched, the goal of the study was to examine available samples from known localities in the area in order to infer- whether they are native or not. For this purpose, the barcoding region cytochrome oxidase I, another mitochondrial gene cytochrome b, a nuclear recombination activating gene 1 and a combination of these markers from a wider neighboring region were analyzed. The study found four different Phoxinus species/lineages occurring in Belgium and the Netherlands: P. phoxinus, P. csikii, P. septimaniae and genetic lineage 11 (possibly P.cf. morella). While the first seem to be native, the other three were probably introduced.
Tracing carbon and nitrogen microbial assimilation in suspended particles in freshwaters
Authors: Mena-Rivera Leonardo , Lloyd Charlotte E. M. , Reay Michaela K. , Goodall Tim , Read Daniel S. , Johnes Penny J. , Evershed Richard P.
Published: April 2022

The dynamic interactions between dissolved organic matter (DOM) and particulate organic matter (POM) are central in nutrient cycling in freshwater ecosystems. However, the molecular-level mechanisms of such interactions are still poorly defined. Here, we study spatial differences in the chemical (i.e., individual proteinaceous amino acids) and microbial (i.e., 16S rRNA) composition of suspended sediments in the River Chew, UK. We then applied a compound-specific stable isotope probing (SIP) approach to test the potential assimilation of 13C,15N-glutamate (Glu) and 15N-NO3− into proteinaceous biomass by particle-associated microbial communities over a 72-h period. Our results demonstrate that the composition of suspended particles is strongly influenced by the effluent of sewage treatment works. Fluxes and percentages of assimilation of both isotopically labelled substrates into individual proteinaceous amino acids showed contrasting dynamics in processing at each site linked to primary biosynthetic metabolic pathways. Preferential assimilation of the organic molecule glutamate and evidence of its direct assimilation into newly synthesised biomass was obtained. Our approach provides quantitative molecular information on the mechanisms by which low molecular weight DOM is mineralised in the water column compared to an inorganic substrate. This is paramount for better understanding the processing and fate of organic matter in aquatic ecosystems.
Equity, justice and the SDGs: lessons learnt from two decades of INEA scholarship
Authors: Gupta Joyeeta , Gupta Aarti , Vegelin Courtney
Published: April 2022

Environmental justice issues have been incrementally but consistently covered within this journal in the last two decades. This article reviews theoretical and empirical approaches to justice in INEA scholarship in order to identify trends and draw lessons for the interpretation and implementation of the 2030 Agenda and for living within environmental limits. Our review traces how justice considerations were initially covered within new institutionalist scholarship on collective action and social practices, to conceptualizing justice as ‘access and allocation’, to newer notions of planetary justice. We link these trends to scholarship on diverse epistemologies and typologies of justice, including conservative, corrective, distributive and procedural justice, and examine their operationalization within the empirical domains of climate, water and sustainable development. In concluding, we draw out implications for the 2030 Sustainable Development Agenda. We argue that a just approach is essential to living within environmental limits, with greater synergies needed between collective action and social practice approaches. While justice can be unpacked for practical and political reasons into access and allocation, we find that (procedural) access considerations are more politically palatable in practice than a concern with allocation (distributive justice), which remains much more contested. As such, dominant approaches promote ‘conservative’ or thin market-based notions of justice. We conclude by noting that just allocation is a precondition to just access. A failure to prioritize and achieve more corrective and distributive forms of justice will, without doubt, contribute to exacerbating global ecological degradation.
Development and consensus testing of quality indicators for geriatric pharmacotherapy in primary care using a modified Delphi study
Authors: Sato Noriko , Fujita Kenji , Kushida Kazuki , Chen Timothy F.
Published: April 2022

BackgroundPolypharmacy is associated with an increased risk of adverse drug events in older people. Although national guidance on geriatric pharmacotherapy exists in Japan, tools to routinely monitor the quality of care provided by community pharmacists are lacking.AimTo develop a set of quality indicators (QIs) to measure the quality of care provided by community pharmacists in improving geriatric pharmacotherapy in primary care in Japan, using a modified Delphi study.MethodThe development of QIs for the Japanese community pharmacy context followed a two–step process: national guidance review and consensus testing using a modified Delphi study. The latter involved two rounds of rating with a face–to–face meeting between the rounds. Ten experts in geriatric pharmacotherapy in primary care were recruited for the panel discussion. QIs were mapped to three key taxonomies and frameworks: the Anatomical Therapeutic Chemical (ATC) classification system, problems and causes of drug–related problems (DRPs) taxonomy and Donabedian’s framework.ResultsA total of 134 QIs for geriatric pharmacotherapy were developed. This QI set included 111 medicine specific indicators, covering medicines in 243 third–level ATC classifications. QIs were classified into the problem of treatment safety (80%) and causes of drug selection (38%) based on validated classification for DRPs. In Donabedian's framework, most QIs (82%) were process indicators. There were no structure indicators.ConclusionA set of 134 QIs for geriatric pharmacotherapy was rigorously developed. Measurement properties of these QIs will be evaluated for feasibility, applicability, room for improvement, sensitivity to change, predictive validity, acceptability and implementation issues in a subsequent study.
Uptake of silicon in barley under contrasting drought regimes
Authors: Wade Ruth N. , Donaldson Sarah M. , Karley Alison J. , Johnson Scott N. , Hartley Sue E.
Published: April 2022

Purpose

Silicon (Si) accumulation in plant tissues plays a vital role in alleviating biotic and abiotic stresses, including drought. Temperate regions are predicted to experience reductions in the quantity and frequency of rainfall events, potentially impacting plant Si uptake via the transpiration stream. Despite the importance for predicting plant responses to Si amendments, the effects of changes in rainfall patterns on Si uptake in cereals have not been characterised.

Methods

Five watering regimes were applied based on predicted precipitation scenarios, varying the quantity of water delivered (ambient, 40% or 60% reduction) and watering frequency (40% reduction in quantity, applied 50% or 25% of ambient frequency), and the effects on growth and leaf Si concentrations of a barley landrace and cultivar were determined.

Results

Reductions in the quantity of water reduced plant growth and yield, whereas reducing the watering frequency had little impact on growth, and in some cases partially ameliorated the negative effects of drought. Reductions in quantity of water lowered leaf Si concentrations in both the cultivar and landrace, although this effect was alleviated under the drought/deluge watering regime. The landrace had greater leaf Si concentration than the cultivar regardless of watering regime, and under ambient watering deposited Si in all cells between trichomes, whereas the cultivar exhibited gaps in Si deposition.

Conclusion

The impact of future reductions in rainfall on barley productivity will depend upon how the water is delivered, with drought/deluge events likely to have smaller effects on yield and on Si uptake than continuous drought.
University leagues alongside rankings
Authors: Banász Zsuzsanna , Kosztyán Zsolt T. , Csányi Vivien V. , Telcs András
Published: April 2022

University rankings can both orient and disorient potential students. In rankings, universities with very different characteristics are compared, which makes interpretation difficult. We propose the application of a clustering method, which creates groups of universities that are close to each other with respect to a subset of indicators, but the indicators also show homogeneity with respect to the universities in that group. We call such groups leagues. These leagues are defined by the data themselves and are not based on subjective criteria. We demonstrate our proposition using one member of the family of the two-way clustering method, namely, biclustering. The case we present is based on the Round University Ranking (RUR) 2020 dataset. The use of leagues could provide better guidance not only for potential applicants but also for university funding organizations and policy-makers. Our case study led to a somewhat surprising observation. In the top league (based on the RUR data and indicators), the three most important indicators measure reputation, not scientific or educational performance.
Immune Activation in Pregnant Rats Affects Brain Glucose Consumption, Anxiety-like Behaviour and Recognition Memory in their Male Offspring
Authors: Guerrin Cyprien G. J. , Shoji Alexandre , Doorduin Janine , de Vries Erik F. J.
Published: April 2022

Purpose

Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for other developmental psychiatric disorders, such as autism and bipolar disorder. Schizophrenia patients were reported to have altered brain metabolism and neuroinflammation. However, the link between prenatal infection, altered brain inflammation and metabolism, and schizophrenia remains unclear. In this project, we aimed to evaluate whether there are changes in brain glucose consumption and microglia activation in the offspring of pregnant rats exposed to maternal immune activation (MIA), and if so, whether these changes occur before or after the initiation of schizophrenia-like behaviour.

Procedures

Pregnant rats were treated with the viral mimic polyinosinic-polycytidylic acid (MIA group) or saline (control group) on gestational day 15. Static PET scans of the male offspring were acquired on postnatal day (PND) 21, 60, and 90, using [11C]-PK11195 and deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) as tracers to measure TSPO expression in activated microglia and brain glucose consumption, respectively. On PND60 and PND90, anxiety-like behaviour, recognition memory, and sensorimotor gating were measured using the open field test (OFT), novel object recognition test (NOR), and prepulse inhibition test (PPI).

Results

[18F]-FDG PET demonstrated that MIA offspring displayed higher brain glucose consumption in the whole brain after weaning (p = 0.017), and in the frontal cortex during late adolescence (p = 0.001) and adulthood (p = 0.037) than control rats. [11C]-PK11195 PET did not reveal any changes in TSPO expression in MIA offspring. Prenatal infection induced age-related behavioural alterations. Adolescent MIA offspring displayed a more anxious state in the OFT than controls (p = 0.042). Adult MIA offspring showed recognition memory deficits in the NOR (p = 0.003). Our study did not show any PPI deficits.

Conclusions

Our results suggest that prenatal immune activation changed neurodevelopment, resulting in increased brain glucose consumption, but not in microglia activation. The increased brain glucose consumption in the frontal cortex of MIA offspring remained until adulthood and was associated with increased anxiety-like behaviour during adolescence and recognition memory deficits in adulthood.
Targeted Therapy for Melanomas Without BRAF V600 Mutations
Authors: Menzer Christian , Hassel Jessica C.
Published: April 2022

Opinion statement

Modern therapy of advanced melanoma offers effective targeted therapeutic options in the form of BRAF plus MEK inhibition for patients with BRAF V600 mutations. For patients lacking these mutations, checkpoint inhibition remains the only first-line choice for treatment of metastatic disease. However, approximately half of patients do not respond to immunotherapy, requiring effective options for a second-line treatment. Advances in genetic profiling have found other possible target molecules, especially a wide array of rare non-V600 BRAF mutations which may respond to available targeted therapy.

More information on the characteristics of such mutants is needed to further assess the efficacy of targeted therapies in the metastatic and adjuvant setting of advanced melanoma. Thus, it may be helpful to classify known BRAF mutations by their kinase activation status and dependence on alternative signaling pathways. While BRAF V600 mutations appear to have an overall more prominent role of kinase activity for tumor growth, non-V600 BRAF mutations show great differences in kinase activation and, hence, response to BRAF plus MEK inhibition. When BRAF-mutated melanomas rely on additional signaling molecules such as RAS for tumor growth, greater benefit may be expected from MEK inhibition than BRAF inhibition. In other cases, mutations of c-kit or NRAS may serve as important pharmacological targets in advanced melanoma. However, since benefit from currently available targeted therapies for non-V600 mutants is usually inferior regarding response and long-term outcome, checkpoint inhibitors remain the standard recommended first-line therapy for these patients.

Herein, we review the current clinical data for characteristics and response to targeted therapy of melanomas lacking a V600 BRAF mutation.
Conservative initial postoperative anticoagulation strategy after HeartMate 3 left ventricular assist device implantation
Authors: Damman Kevin , van den Broek Stan A. J. , Mecozzi Gianclaudio , Droogh Joep M. , Metz Ethel , Oude Lansink Annemieke , Krikken Jan A. , Erasmus Michiel E. , Kuijpers Michiel
Published: April 2022

Introduction

Although anticoagulation therapy is mandated after implantation of a left ventricular assist device (LVAD), postoperative bleedings and reoperations occur relatively frequently and are associated with worse outcomes. We evaluated the use of a conservative postoperative anticoagulation protocol in patients implanted with a HeartMate 3 (HM3) LVAD.

Methods

In a single-centre retrospective analysis of postoperative outcomes after HM3 LVAD implantation, a standard (old) anticoagulation protocol (i.e. early, full-dose anticoagulation with low-molecular weight heparin and overlapping vitamin K antagonist) was compared with a new conservative anticoagulation protocol (i.e. slow initiation of vitamin K antagonists without overlapping heparin). Main outcomes were changes in international normalised ratio (INR), lactate dehydrogenase (LDH), bleeding and/or tamponade events requiring reoperation, length of stay and adverse events.

Results

In total, 73 patients (48 in old vs 25 in new protocol group) were evaluated. Mean age was 56 years (standard deviation 13) and most patients (78%) were males. Changes in INR and LDH in the first 14 days were similar in both groups (p = 0.50 and p = 0.997 for interaction, respectively). Number of bleeding/tamponade events requiring reoperation was lower in the new than in the old protocol group (4% vs 33%, p = 0.005). Postoperative 30-day mortality was similar, and we observed no thromboembolic events. Median (25th–75th percentiles) total length of postoperative hospital stay (27 (25–41) vs 21 (19–27) days, p < 0.001) and length of intensive care unit stay (5 (2–9) vs 2 (2–5) days, p = 0.022) were significantly shorter in the new protocol group.

Conclusion

These retrospective data suggest that conservative slow initiation of anticoagulation therapy after HM3 LVAD implantation is associated with less bleeding/tamponade events requiring reoperation, a similar safety profile and a shorter duration of stay than the currently advised standard anticoagulation protocol.
Mitigating off-target distribution and enhancing cytotoxicity in breast cancer cells with alpha-ketoglutaric acid-modified Fe/Mg-CA nanoparticles
Authors: Haque Sheikh Tanzina , Karim Md. Emranul , Othman Iekhsan , Chowdhury Ezharul Hoque
Published: April 2022

Purpose

In this work, pH-sensitive alpha-ketoglutaric acid-modified Fe/Mg-carbonate apatite (α-KAM-Fe/Mg-CA) NPs were introduced and found to be capable of promoting the selective delivery of cancer-killing drug doxorubicin (DOX) in breast cancer cells, while simultaneously mitigating DOX toxicity on normal cells.

Methods

As part of the characterization and evaluation of α-KAM-Fe/Mg-CA NPs to target breast cancer cells, a series of assessments were performed, which included size measurements, morphological analysis, FTIR, cytotoxicity assessment, hemolysis, drug binding, cellular uptake, and pH-responsive drug release tests. Liquid chromatography-mass spectrometry was used to conduct the protein corona analysis of α-KAM-Fe/Mg-CA using 10% FBS (fetal bovine serum) and mice plasma. Furthermore, to investigate the distribution of DOX-loaded α-KAM-Fe/Mg-CA NPs in major tissues and the tumor, a biodistribution investigation was conducted in mammary tumor-induced Balb/c mouse models 24 h after the intravenous administration of DOX-loaded α-KAM-Fe/Mg-CA NPs.

Results

The in vitro pH-dependent release of DOX over time demonstrated that α-KAM-Fe/Mg-CA NPs were pH-responsive and degraded rapidly at acidic pH levels. When compared to free DOX, the DOX-loaded α-KAM-Fe/Mg-CA NPs demonstrated a potent antiproliferative effect on breast cancer cells. Confocal microscopy confirmed the effective internalization of DOX-loaded α-KAM-Fe/Mg-CA NPs in breast cancer cells. The protein corona analysis revealed an affinity for dysopsonins (serum albumin, apolipoproteins) and transport proteins that may assist in extending their blood circulation period. Furthermore, biodistribution data of DOX-loaded α-KAM-Fe/Mg-CA NPs in the mammary tumor-induced Balb/c mouse model indicated extended circulation in the bloodstream, reduced non-target distribution in major tissues, and increased drug accumulation in the tumor.

Conclusion

The results obtained suggest that α-KAM-Fe/Mg-CA NPs may emerge as a prospective candidate for delivering therapeutic cargos to treat malignant mammary tumors.
Numerical integration of neutrosophic valued function by Gaussian quadrature methods
Authors: Biswas Suvankar , Moi Sandip , Sarkar Smita Pal
Published: April 2022

In this article, different types of Gaussian quadrature methods have been presented to find the numerical integration of a neutrosophic valued function. A new definition of the distance between two neutrosophic number has been defined and it has been proved that the distance and the set of all neutrosophic number form a complete metric space. Also, the definition of neutrosophic continuity on a closed-bounded interval has been defined in the sense of $$(\alpha ,\beta ,\gamma )$$

(
α
,
β
,
γ
)

-cut. This is the first time, when the Gauss–Legendre integration, Gauss–Chebyshev integration and Gauss–Laguerre integration rule have been discussed in neutrosophic environment. In the first test example, the comparison between one-point, two-point and three-point Gauss–Legendre integration rules have been presented in terms of tables and figures. Also, in the second example, the comparison between one-point, two-point Gauss–Chebyshev and Gauss–Laguerre integration rules have been discussed.
Copyright and Digital Teaching Exceptions in the EU: Legislative Developments and Implementation Models of Art. 5 CDSM Directive
Authors: Priora Giulia , Jütte Bernd Justin , Mezei Péter
Published: April 2022

Article 5 of the 2019 EU Directive on Copyright in the Digital Single Market (CDSM) attempted to modernize the regime of copyright exceptions and limitations related to teaching activities. Its aim is to enhance the flexibility behind permitted uses to the benefit of educational institutions regarding their digital and cross-border teaching. The pressing need for such a legislative reform was confirmed by the outbreak of the COVID-19 pandemic, which dramatically moved teaching environments to online platforms. This paper dissects Art. 5 CDSM Directive unveiling three layers of analysis. First, the substance, logic, and promises of the new provision are introduced. Second, it identifies diverging national implementation models, developing a comparative study of the Hungarian, German, and Italian experiences. Third, drawing from the comparative study, the paper provides fundamental guidance in understanding whether Art. 5 CDSM Directive can be considered an evolution or, rather, a devolution of the copyright teaching exceptions in Europe. Focusing on the systematic concerns arising from the new provision, its embedded limits, and the strategic uses of the licensing carve-out, we conclude that the EU legislature has only partially achieved the goal of striking a more European, modern, and sustainable balance between copyright protection and the right to education in the digital environment.
Boundary and Eisenstein cohomology of $$G_2(\mathbb {Z})$$
Authors: Bajpai Jitendra , Guan Lifan
Published: April 2022

In this article, Eisenstein cohomology of the arithmetic group $$G_2(\mathbb {Z})$$

G
2

(
Z
)

with coefficients in any finite dimensional highest weight irreducible representation has been determined. This is accomplished by studying the cohomology of the boundary of the Borel–Serre compactification.
Fungal-derived compounds and mycogenic nanoparticles with antimycobacterial activity: a review
Authors: Tapfuma Kudzanai Ian , Nyambo Kudakwashe , Baatjies Lucinda , Keyster Marshal , Mekuto Lukhanyo , Smith Liezel , Allie Nasiema , Loxton Andre Gareth , Malgas-Enus Rehana , Mavumengwana Vuyo
Published: April 2022

Tuberculosis (TB) is a persistent lung infection caused by Mycobacterium tuberculosis. The disease is characterized by high mortality rates of over 1 million per year. Unfortunately, the potency and effectiveness of currently used anti-TB drugs is gradually decreasing due to the constant development of persistence and resistance by M. tuberculosis. The adverse side effects associated with current anti-TB drugs, along with anti-TB drug resistance, present an opportunity to bio-prospect novel potent anti-TB drugs from unique sources. Fundamentally, fungi are a rich source of bioactive secondary metabolites with valuable therapeutic potential. Enhancing the potency and effectiveness of fungal-based anti-TB drug leads by chemical synthesis and/or modification with nanomaterials, may result in the discovery of novel anti-TB drugs. In this review, the antimycobacterial activity of fungal-derived compounds and mycogenic nanoparticles are summarized. Numerous fungal-derived compounds as well as some mycogenic nanoparticles that exhibit strong antimycobacterial activity that is comparable to that of approved drugs, were found. If fully explored, fungi holds the promise to become key drivers in the generation of lead compounds in TB-drug discovery initiatives.
A new acoustoelastic model for velocity-hydrostatic-pressure in rocks based on general acoustoelastic theory for elastic solids
Authors: Tian Jiayong , Ma Hongfei , Wang Mi
Published: April 2022

Acoustoelastic model based on classic acoustoelastic theory of solids fails to describe rock acoustoelasticity, where wave velocities in rocks has complex non-linear relations with the applied hydrostatic pressure. In order to extend acoustoelastic model into better prediction for rock acoustoelasticity, a new acoustoelastic model is presented based on general acoustoelasticity of elastic solids having complicated constitutive law of rocks, which combines third-order elastic constants of compact rocks with the exponential terms for the influence of pore/cracks in rocks. The data for P- and S-wave velocities of diabase and greywacke samples subjected to the pressure up to 400 MPa are taken as examples to validate the presented model. The results show that the presented model could not only predict rock acoustoelasticity but also be linked with frequently-used empirical model and meso-mechanical model. The intrinsic connection among mechanical parameters, acoustical parameters, and meso-mechanical parameters could be established clearly, which will benefit the determination of high-resolution constitutive law and the compliant porosity by the measured ultrasonic-wave velocities of rock samples.

Article Highlights

General acoustoelasticity of elastic solids having complicated constitutive law yields a new acoustoelastic model of rock acoustoelasticity.

New model predicts better non-linear characteristics of rock acoustoelasticity.

New model benefits for high-resolution evaluation of constitutive law and meso-mechanical parameters for rocks.
Gödel's Incompleteness Theorems
Authors: Kennedy Juliette
Published: April 2022

This Element takes a deep dive into Gödel's 1931 paper giving the first presentation of the Incompleteness Theorems, opening up completely passages in it that might possibly puzzle the student, such as the mysterious footnote 48a. It considers the main ingredients of Gödel's proof: arithmetization, strong representability, and the Fixed Point Theorem in a layered fashion, returning to their various aspects: semantic, syntactic, computational, philosophical and mathematical, as the topic arises. It samples some of the most important proofs of the Incompleteness Theorems, e.g. due to Kuratowski, Smullyan and Robinson, as well as newer proofs, also of other independent statements, due to H. Friedman, Weiermann and Paris-Harrington. It examines the question whether the incompleteness of e.g. Peano Arithmetic gives immediately the undecidability of the Entscheidungsproblem, as Kripke has recently argued. It considers set-theoretical incompleteness, and finally considers some of the philosophical consequences considered in the literature.
Healthcare-associated infections in Veterans Affairs acute-care and long-term healthcare facilities during the coronavirus disease 2019 (COVID-19) pandemic
Authors: Evans Martin E. , Simbartl Loretta A. , Kralovic Stephen M. , Clifton Marla , DeRoos Kathleen , McCauley Brian P. , Gauldin Natalie , Flarida Linda K. , Gamage Shantini D. , Jones Makoto M. , Roselle Gary A.
Published: April 2022

Objective:

To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs) reported from 128 acute-care and 132 long-term care Veterans Affairs (VA) facilities.

Methods:

We compared central-line–associated bloodstream infections (CLABSIs), ventilator-associated events (VAEs), catheter-associated urinary tract infections (CAUTIs), methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile infections and rates reported from each facility monthly to a centralized database before the pandemic (February 2019 through January 2020) and during the pandemic (July 2020 through June 2021).

Results:

Nationwide VA COVID-19 admissions peaked in January 2021. Significant increases in the rates of CLABSIs, VAEs, and MRSA all-site HAIs (but not MRSA CLABSIs) were observed during the pandemic in acute-care facilities. There was no significant change in CAUTI rates, and C. difficile rates significantly decreased. There were no significant increases in HAIs in long-term care facilities.

Conclusions:

The COVID-19 pandemic had a differential impact on HAIs of various types in VA acute care, with many rates increasing. The decrease in CDI HAIs may be due, in part, to evolving diagnostic testing. The minimal impact of COVID-19 in VA long-term facilities may reflect differences in patient numbers and acuity and early recognition of the impact of the pandemic on nursing home residents leading to increased vigilance and optimization of infection prevention and control practices in that setting. These data support the need for building and sustaining conventional infection prevention and control strategies before and during a pandemic.
Developing Irelands first National Student Mental Health and Suicide Prevention Framework for Higher Education
Authors: Surdey J. , Byrne D. , Fox T.
Published: April 2022

This article focuses on the development of Ireland’s first National Student Mental Health and Suicide Prevention Framework for Higher Education. There is growing concern for student mental health in higher education nationally and globally. The majority of students are aged between 18 and 24, which is identified as a high-risk group for mental health difficulties. Recent surveys of student mental illness, mental distress, and low well-being have been recognized by the World Health Organization, the Union of Students in Ireland National Report on Student Mental Health in Third Level Education, the My World survey and the My World 2 study. The Higher Education Authority in Ireland made a commitment to the Department of Health Connecting for Life (Ireland’s National Strategy to Reduce Suicide 2015–2020) to form national guidelines for suicide prevention in higher education. In order to deliver on this commitment, The National Student Mental Health and Suicide Prevention Framework was developed. The Framework is informed by international evidence and was the product of a collaborative cross sector and cross disciplinary team including health professionals, government representatives, educators, students, policy makers, community organizations, researchers and clinicians.
Scale-dependent particle clustering in transitional wake flow
Authors: Shi Zhaoyu , Jiang Fengjian , Zhao Lihao , Andersson Helge I.
Published: April 2022

Dispersion and mixing of inertial point particles in the unsteady and three-dimensional wake of a circular cylinder at$Re=200$are investigated via one-way coupled simulations. The presence of streamwise-oriented vortical braids originating from the mode A instability in the transition regime has a profound impact on the particle dynamics and preferential concentration in the near wake. Particles trapped between the Kármán rollers and the streamwise braids form an inner layer of densely concentrated particles, while discrete particle clumps on the otherwise thin ribbon-like clusters between two consecutive Kármán rollers are another manifestation of the streamwise braids. The effect of particle inertia on the size of clusters and voids ascribed to centrifugal ejection is examined by volume-averaged Voronoï analysis. A distinct dependence on Stokes number ($Sk$) is seen at the cluster scale, whereas the void scale exhibits self-similarity. New physics-based threshold values of clusters and voids are distinctly different from the probability-distribution-based threshold at cluster scale. Increasing inertia is found to suppress particle acceleration more than deceleration. The particle velocity is further suppressed by the presence of the streamwise vortical braids. The effects of particle inertia vary non-monotonically in$Sk$with the strongest effect at$Sk=1$when most particles tend to reside in high-strain/low-vorticity regions.
Hydraulic control of flow in a multi-passage system connecting two basins
Authors: Tan S. , Pratt L.J. , Voet G. , Cusack J.M. , Helfrich K.R. , Alford M.H. , Girton J.B. , Carter G.S.
Published: April 2022

When a fluid stream in a conduit splits in order to pass around an obstruction, it is possible that one branch will be critically controlled while the other remains not so. This is apparently the situation in Pacific Ocean abyssal circulation, where most of the northward flow of Antarctic bottom water passes through the Samoan Passage, where it is hydraulically controlled, while the remainder is diverted around the Manihiki Plateau and is not controlled. These observations raise a number of questions concerning the dynamics necessary to support such a regime in the steady state, the nature of upstream influence and the usefulness of rotating hydraulic theory to predict the partitioning of volume transport between the two paths, which assumes the controlled branch is inviscid. Through the use of a theory for constant potential vorticity flow and accompanying numerical model, we show that a steady-state regime similar to what is observed is dynamically possible provided that sufficient bottom friction is present in the uncontrolled branch. In this case, the upstream influence that typically exists for rotating channel flow is transformed into influence into how the flow is partitioned. As a result, the partitioning of volume flux can still be reasonably well predicted with an inviscid theory that exploits the lack of upstream influence.
Re-Conceptualizing the Rule of Law in Africa: Metaphors of the Tool and the Causeway
Authors: Nwoke Uchechukwu , Ukwueze Festus Okechukwu , Odinkonigbo Jirinwayo Jude , Obi-Ochiabutor Clara C.
Published: April 2022

The rule of law embodies two basic metaphors: the tool and the causeway. Under the tool metaphor, the rule of law is applied more as an instrument of power, while in the causeway metaphor, the law emphasizes a form of relationship between state and society where “ground rules” are established, not just for electoral politics but for the daily transactions and commercial necessities of individuals. The choice between these two metaphors has always been crucial for the legal and political development of democratic states. This article argues that in many African states, the rule of law is presently used as a tool, and contends that if this superficial perception is discarded, in favour of concentrating instead on the more expansive causeway metaphor, the continent will stand the chance of building more modern democratic states that can compare favourably with other consolidated democracies across the globe.
Good Housing for Good “Married Life”: Privacy, Transnational Anti-Communism, and Postwar Housing in South Korea
Authors: Heo Na Sil
Published: April 2022

This article examines postwar housing in South Korea as a transnational project in the Cold War milieu. Privacy (p’ŭraibŏshi) became a central architectural concern in South Korea after the Korean War (1950–53), as Korean architects negotiated their understanding of good, modern housing in the midst of deepening interactions with American architectural knowledge. A call for the construction of independent children's rooms was linked to the belief that good housing should also ensure the sexual privacy of the married couple. This article argues that architects construed privacy to be a value that was attached to liberal democracies and that reflected postwar fantasies and desires for a democratic living in contradistinction to its North Korean counterpart. In this way, housing became a site of transnational anti-communism, as architects and aspiring homeowners invested much energy in the ideological and material construction of privacy as a salient feature of modern housing.