bluuebunny/crossref_metadata_2025 huggingface dataset:
The performance of general practice in the English National Health Service (NHS): an analysis using Starfield's framework for primary care
Authors: Fisher Rebecca , Alderwick Hugh
Published: February 2024

General practice in the English National Health Service (NHS) is in crisis. In response, politicians are proposing fundamental reform to the way general practice is organized. But ideas for reform are contested, and there are conflicting interpretations of the problems to be addressed. We use Barbara Starfield's “4Cs” framework for high-performing primary care to provide an overall assessment of the current role and performance of general practice in England. We first assessed theoretical alignment between Starfield's framework and the role of general practice in England. We then assessed actual performance using publicly available national data and targeted literature searches. We found close theoretical alignment between Starfield's framework and the model of NHS general practice in England. But, in practice, its model of universal comprehensive care risks being undermined by worsening and inequitable access, while continuity of care is declining. Underlying causes of current challenges in general practice in England appear more closely linked to under-resourcing than the fundamental design of the system. General practice in England must evolve, but wholesale re-organization is likely to damage and distract. Instead, policymakers should focus on adequately resourcing general practice while supporting general practice teams to improve the quality and coordination of local services.
Defensive alteration of root exudate composition by grafting Prunus sp. onto resistant rootstock contributes to reducing crown gall disease
Authors: Chen Lin , Bian Lusen , Ma Qinghua , Li Ying , Wang Xinghong , Liu Yunpeng
Published: February 2024

Grafting is a traditional and significant strategy to suppress soil-borne diseases, such as the crown gall disease caused by tumorigenic Agrobacterium and Rhizobium. Root exudates and the rhizosphere microbiome play critical roles in controlling crown gall disease, but their roles in suppressing crown gall disease in grafted plants remain unclear. Here, disease-susceptible cherry rootstock ‘Gisela 6’ and disease-resistant cherry rootstock ‘Haiying 1’ were grafted onto each other or self-grafted. The effect of their root exudates on the soil microbiome composition and the abundance of pathogenic Agrobacterium were studied. Grafting onto the disease-resistant rootstock helped to reduce the abundance of pathogenic Agrobacterium, accompanied by altering root exudation, enriching potential beneficial bacteria, and changing soil function. Then, the composition of the root exudates from grafted plants was analyzed and the potential compounds responsible for decreasing pathogenic Agrobacterium abundance were identified. Based on quantitative measurement of the concentrations of the compounds and testing the impacts of supplied pure chemicals on abundance and chemotaxis of pathogenic Agrobacterium and potential beneficial bacteria, the decreased valine in root exudates of the plant grafted onto resistant rootstock was found to contribute to decreasing Agrobacterium abundance, enriching some potential beneficial bacteria and suppressing crown gall disease. This study provides insights into the mechanism whereby grafted plants suppress soil-borne disease.
Banana MabHLH28 positively regulates the expression of softening-related genes to mediate fruit ripening independently or via cooperating with MaWRKY49/111
Authors: Wu Chaojie , Cai Danling , Li Jun , Lin Zengxiang , Wei Wei , Shan Wei , Chen Jianye , Lu Wangjin , Su Xinguo , Kuang Jianfei
Published: February 2024

Texture softening is a physiological indicator of fruit ripening, which eventually contributes to fruit quality and the consumer’s acceptance. Despite great progress having been made in identification of the genes related to fruit softening, the upstream transcriptional regulatory pathways of these softening-related genes are not fully elucidated. Here, a novel bHLH gene, designated as MabHLH28, was identified because of its significant upregulation in banana fruit ripening. DAP-Seq analysis revealed that MabHLH28 bound to the core sequence of ‘CAYGTG’ presented in promoter regions of fruit softening-associated genes, such as the genes related to cell wall modification (MaPG3, MaPE1, MaPL5, MaPL8, MaEXP1, MaEXP2, MaEXPA2, and MaEXPA15) and starch degradation (MaGWD1 and MaLSF2), and these bindings were validated by EMSA and DLR assays. Transient overexpression and knockdown of MabHLH28 in banana fruit resulted in up- and down-regulation of softening-related genes, thereby hastening and postponing fruit ripening. Furthermore, overexpression of MabHLH28 in tomato accelerated the ripening process by elevating the accumulation of softening-associated genes. In addition, MabHLH28 showed interaction withMaWRKY49/111 and itself to form protein complexes, which could combinatorically strengthen the transcription of softening-associated genes. Taken together, our findings suggest that MabHLH28 mediates fruit softening by upregulating the expression of softening-related genes either alone or in combination with MaWRKY49/111.
Genome-wide methylation, transcriptome and characteristic metabolites reveal the balance between diosgenin and brassinosteroids in Dioscorea zingiberensis
Authors: Li Zihao , Li Yi , Geng Luyu , Wang Jiachen , Ouyang Yidan , Li Jiaru
Published: February 2024

Diosgenin (DG) is a bioactive metabolite isolated from Dioscorea species, renowned for its medicinal properties. Brassinosteroids (BRs) are a class of crucial plant steroidal hormones. Cholesterol and campesterol are important intermediates of DG and BR biosynthesis, respectively. DG and BRs are structurally similar components; however, the regulatory network and metabolic interplays have not been fully elucidated. In an effort to decode these complex networks, we conducted a comprehensive study integrating genome-wide methylation, transcriptome and characteristic metabolite data from Dioscorea zingiberensis. Leveraging these data, we were able to construct a comprehensive regulatory network linking DG and BRs. Mass spectrometry results enabled us to clarify the alterations in cholesterol, campesterol, diosgenin, and castasterone (one of the major active BRs). The DG content decreased by 27.72% at 6 h after brassinolide treatment, whereas the content increased by 85.34% at 6 h after brassinazole treatment. Moreover, we pinpointed DG/BR-related genes, such as CASs, CYP90s, and B3-ARFs, implicated in the metabolic pathways of DG and BRs. Moreover, CASs and CYP90s exhibit hypomethylation, which is closely related to their high transcription. These findings provide robust evidence for the homeostasis between DG and BRs. In conclusion, our research revealed the existence of a balance between DG and BRs in D. zingiberensis. Furthermore, our work not only provides new insights into the relationship between the two pathways but also offers a fresh perspective on the functions of secondary metabolites.
The impact of energy consumption on carbon emissions intensity in China: evidence from a dynamic panel quantile regression model
Authors: Hou Jian , Yang Shenyang , Fan Guoliang , Xu Hongxia
Published: February 2024

China, being the largest global emitter of carbon, faces significant challenges in mitigating carbon emissions from energy consumption. The empirical findings reveal that the impact of energy consumption intensity and energy consumption structure on carbon emissions intensity is positively correlated with quantile levels and shows heterogeneous effects in different regions. Employing an energy consumption structure as a threshold variable to examine the impact of energy consumption intensity on carbon emissions intensity, we identify a significant single threshold effect in both the full sample and the western sample. Based on empirical research findings, this paper proposes specific policy recommendations.
Metabolomic Characteristics of Nontuberculous Mycobacterial Pulmonary Disease
Authors: Kim Jungeun , Chae Woori , Kim Joong-Yub , Yim Jae-Joon , Cho Joo-Youn , Kwak Nakwon
Published: February 2024

Background

The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD–specific metabolic pathways using serum metabolomics to understand disease pathogenesis.

Methods

Mass spectrometry–based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling.

Results

Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group.

Conclusions

In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches.
Nonsurgical Treatment of Postburn Hypopigmentation: A Literature Review
Authors: Lupon Elise , Berkane Yanis , Bertheuil Nicolas , Cetrulo Curtis L , Vaillant Camille , Chaput Benoît , Camuzard Olivier , Lellouch Alexandre G
Published: February 2024

The treatment of postburn hypopigmentation was primarily surgical before the advent of new technologies. Medical devices and therapies are emerging to manage scar sequelae that can be disfiguring and associated with severe psychosocial impact. These innovations have been poorly investigated for hypopigmentation, but they represent a real hope. We reviewed all articles published on Pubmed up to June 2022. Included studies had to specifically focus on treating postburn hypopigmented scars. All articles evaluating transient solutions such as make-up, and articles describing inflammation-linked hypopigmentation with no etiological details or no burn injury history were excluded. Through this review, we have highlighted 6 different types of nonsurgical treatments reported in postburn leukoderma potentially allowing definitive results. Electrophoto-biomodulation or E light (combining intensive pulsed light, radiofrequency, and cooling), topical daylight psoralen UVA therapy, and lasers (fractional lasers using pulse energies or CO2FL devices, lasers-assisted drug delivery as local bimatoprost and tretinoin or pimecrolimus) have been explored with encouraging results in hypopigmented burns. Finally, other promising medical strategies include using FK506, a nonsteroidal anti-inflammatory drug, to induce melanogenesis or using melanocyte-stimulating hormones with fractional laser-assisted drug deliveries, which are expected to emerge soon.
Revolutionizing the latent heat storage: Boosting discharge performance with innovative undulated phase change material containers in a vertical shell-and-tube system
Authors: Sultan Hakim S , Mohammed Hayder I , Biswas Nirmalendu , Togun Hussein , Ibrahem Raed Khalid , Mahdi Jasim M , Yaïci Wahiba , Keshmiri Amir , Talebizadehsardari Pouyan
Published: February 2024

This paper examines the impact of various parameters, including frames, zigzag number, and enclosure shape, on the solidification process and thermal energy storage rate of a vertical phase change material (PCM) container. The study also assesses the effects of the flow rate of the heat transfer fluid as well as changing the materials of the PCM between RT35 and RT35HC. In addition, the study compares the framed versus unframed systems and, subsequently, the best case was tested with various zigzag pitch numbers before changing the zigzag-shaped structure to arc and reversed-arc. The findings are examined by contrasting the different scenarios’ liquid fractions, temperature distributions, solidification rates, and heat storage rates. The results show that the framed geometry is 66% faster to reach the target temperature compared with the unframed geometry and employing a zigzag enclosure in a PCM can significantly improve the solidification time and heat recovery rate. As the number of pitches in the zigzag enclosure increases, the improvement rate decreases but still improves the solidification time and heat recovery rate. The reversed-arc-shaped structure has the best performance compared with the other undulated surfaces. For the system with RT35HC, the discharge time is 55% higher compared with that of the system with RT35, while the discharge rate is 8.2% higher for the former during the first 3000 s of the discharging process.
Border carbon adjustment compliance and the WTO: the interactional evolution of law
Authors: Durel Laurie
Published: February 2024

International law and its understanding can evolve outside of treaties, but little is known about the elements that can explain these changes. This paper looks at the debate on border carbon adjustment (BCA) compatibility with the World Trade Organization (WTO) and argues that international law depends on the actors’ perceptions, which can change over time. It applies an interactional international law framework to explain how a policy that was once deemed incompatible with WTO rules is now considered ‘WTO-compliant’ by the European Union. A discourse network analysis is conducted based on debates from the WTO and the literature over 24 years. Results show that since 2012, the legal literature has increasingly been more confident that BCA could be WTO-compatible, despite the absence of significant changes in WTO case law during the same period. This increase in support was sustained by an expanded practice of legality and a perceived lack of legality of applicable WTO rules. This research offers new insights into the dynamics of international law. It provides new methodological avenues for scholars seeking to trace the evolution of law and legal understanding through formal and informal processes.
The ZmNF-YC1–ZmAPRG pathway modulates low phosphorus tolerance in maize
Authors: Bai Yang , Yang Qiuyue , Gan Yuling , Li Mei , Zhao Zikun , Dong Erfei , Li Chaofeng , He Di , Mei Xiupeng , Cai Yilin
Published: February 2024

Phosphorus (P) is an essential nutrient for plant growth and yield. Low phosphate use efficiency makes it important to clarify the molecular mechanism of low P stress. In our previous studies, a P efficiency gene ZmAPRG was identified. Here, we further screened the upstream regulator ZmNF-YC1 of ZmAPRG by yeast one hybrid (Y1H) assay, and found it was a low inorganic phosphorus (Pi)-inducible gene. The results of dual luciferase assays, expression analysis, and ChIP-qPCR assays showed that ZmNF-YC1 is a positive regulator of ZmAPRG. Overexpression of ZmNF-YC1 improved low P tolerance, whereas knockout of ZmNF-YC1 decreased low P tolerance in maize. Bimolecular fluorescence complementation (BiFC), yeast two hybrid (Y2H) assay, and yeast three hybrid (Y3H) assay further showed that ZmNF-YC1 can interact with ZmNF-YB14, and recruit ZmNF-YA4/10 to form NF-Y complexes. Transcriptional activation assay confirmed that the NF-Y complexes can activate the promoters of ZmAPRG. Meanwhile, transcriptome and metabolome analyses indicated that overexpression of ZmAPRG improves low P tolerance by regulating lipid composition and photosynthetic capacity, and chlorophyll fluorescence parameters provided evidence in support of this hypothesis. Furthermore, overexpression of ZmAPRG increased grain yield in inbred and hybrid maize under low P conditions. Taken together, our research revealed a low P tolerance mechanism of the ZmNF-YC1–ZmAPRG pathway.
Topological bias: how haloes trace structural patterns in the cosmic web
Authors: Bermejo Raul , Wilding Georg , van de Weygaert Rien , Jones Bernard J T , Vegter Gert , Efstathiou Konstantinos
Published: February 2024

We trace the connectivity of the cosmic web as defined by haloes in the Planck-Millennium simulation using a persistence and Betti curve analysis. We normalize clustering up to the second-order correlation function and use our systematic topological analysis to correlate local information and properties of haloes with their multiscale geometrical environment of the cosmic web (elongated filamentary bridges and sheetlike walls). We capture the multiscale topology traced by the halo distribution through filtrations of the corresponding Delaunay tessellation. The resulting nested alpha shapes are sensitive to the local density, perfectly outline the local geometry, and contain the complete information on the multiscale topology. We find a remarkable linear relationship between halo masses and topology: haloes of different mass trace environments with different topological signature. This is a topological bias, an environmental structure bias independent of the halo clustering bias associated with the two-point correlation function. This mass-dependent linear scaling relation allows us to take clustering into account and determine the overall connectivity from a limited sample of galaxies. The presence of topological bias has major implications for the study of voids and filaments in the observed distribution of galaxies. The (infra)structure and shape of these key cosmic web components will strongly depend on the underlying galaxy sample. Their use as cosmological probes, with their properties influenced by cosmological parameters, will have to account for the subtleties of topological bias. This is of particular relevance with the large upcoming galaxy surveys such as DESI, Euclid, and the Vera Rubin telescope surveys.
A multiband look at ultraluminous X-ray sources in NGC 7424
Authors: Soria Roberto , Cheng Siying , Pakull Manfred W , Motch Christian , Russell Thomas D
Published: February 2024

We studied the multiband properties of two ultraluminous X-ray sources (2CXO J225728.9−410211 = X-1 and 2CXO J225724.7−410343 = X-2) and their surroundings, in the spiral galaxy NGC 7424. Both sources have approached X-ray luminosities LX ∼ 1040 erg s−1 at some epochs. Thanks to a more accurate astrometric solution (based on Australia Telescope Compact Array and Gaia data), we identified the point-like optical counterpart of X-1, which looks like an isolated B8 supergiant (M ≈ 9M⊙, age ≈30 Myr). Instead, X-2 is in a star-forming region (size of about 100 pc × 150 pc), near young clusters and ionized gas. Very large telescope long-slit spectra show a spatially extended region of He ii λ4686 emission around the X-ray position, displaced by about 50 pc from the brightest star cluster, which corresponds to the peak of lower ionization line emission. We interpret the He ii λ4686 emission as a signature of X-ray photoionization from the ULX, while the other optical lines are consistent with UV ionization in an ordinary He ii region. The luminosity of this He++ nebula puts it in the same class as other classical photoionized ULX nebulae such as those around Holmberg II X-1 and NGC 5408 X-1. We locate a strong (5.5 GHz luminosity $\nu \, L_{\nu } \approx 10^{35}$ erg s−1), steep-spectrum, unresolved radio source at the peak of the low-ionization lines, and discuss alternative physical scenarios for the radio emission. Finally, we use WISE data to obtain an independent estimate of the reddening of the star-forming clump around X-2.
Cool and data-driven: an exploration of optical cool dwarf chemistry with both data-driven and physical models
Authors: Rains Adam D , Nordlander Thomas , Monty Stephanie , Casey Andrew R , Rojas-Ayala Bárbara , Žerjal Maruša , Ireland Michael J , Casagrande Luca , McKenzie Madeleine
Published: February 2024

Detailed chemical studies of F/G/K – or solar-type – stars have long been routine in stellar astrophysics, enabling studies in both Galactic chemodynamics and exoplanet demographics. However, similar understanding of the chemistry of M and late-K dwarfs – the most common stars in the Galaxy – has been greatly hampered both observationally and theoretically by the complex molecular chemistry of their atmospheres. Here, we present a new implementation of the data-driven Cannon model, modelling Teff, log g, [Fe/H], and [Ti/Fe] trained on low–medium resolution optical spectra (4000–7000  Å) from 103 cool dwarf benchmarks. Alongside this, we also investigate the sensitivity of optical wavelengths to various atomic and molecular species using both data-driven and theoretical means via a custom grid of MARCS synthetic spectra, and make recommendations for where MARCS struggles to reproduce cool dwarf fluxes. Under leave-one-out cross-validation, our Cannon model is capable of recovering Teff, log g, [Fe/H], and [Ti/Fe] with precisions of 1.4 per cent, $\pm 0.04\,$ dex, $\pm 0.10\,$ dex, and $\pm 0.06\,$ dex respectively, with the recovery of [Ti/Fe] pointing to the as-yet mostly untapped potential of exploiting the abundant – but complex – chemical information within optical spectra of cool stars.
Semi-analytic modelling of Pop. III star formation and metallicity evolution – I. Impact on the UV luminosity functions at z = 9–16
Authors: Ventura Emanuele M , Qin Yuxiang , Balu Sreedhar , Wyithe J Stuart B
Published: February 2024

We implemented Population III (Pop. III) star formation in mini-haloes within the Meraxes semi-analytic galaxy formation and reionization model, run on top of a N-body simulation with L = 10 h−1 cMpc with 20483 particles resolving all dark matter haloes down to the mini-haloes (∼105 M⊙). Our modelling includes the chemical evolution of the IGM, with metals released through supernova-driven bubbles that expand according to the Sedov–Taylor model. We found that SN-driven metal bubbles are generally small, with radii typically of 150 ckpc at z = 6. Hence, the majority of the first galaxies are likely enriched by their own star formation. However, as reionization progresses, the feedback effects from the UV background become more pronounced, leading to a halt in star formation in low-mass galaxies, after which external chemical enrichment becomes more relevant. We explore the sensitivity of the star formation rate density and stellar mass functions to the unknown values of free parameters. We also discuss the observability of Pop. III dominated systems with JWST, finding that the inclusion of Pop. III galaxies can have a significant effect on the total UV luminosity function at z = 12–16. Our results support the idea that the excess of bright galaxies detected with JWST might be explained by the presence of bright top-heavy Pop. III dominated galaxies without requiring an increased star formation efficiency.
Unveiling the origins of galactic bars: insights from barred and unbarred galaxies
Authors: López Paula D , Scannapieco Cecilia , Cora Sofía A , Gargiulo Ignacio D
Published: February 2024

A significant fraction of local galaxies exhibit stellar bars, non-axisymmetric structures composed of stars, gas, and dust. Identifying key differences between the properties of barred and unbarred galaxies can uncover clues about the conditions for triggering bar formation. We explore the early stages of bar formation in a small sample of disc barred galaxies extracted from the TNG50 cosmological simulation, and compare their properties to those of unbarred galaxies. According to our results, the most important difference between barred and unbarred galaxies is that the former have systematically higher fractions of stellar to dark matter mass in their inner regions, from very early stages and prior to the formation of the bars. They harbour high initial gas content, fostering increased star formation rates and leading to a central mass concentration that grows faster over time compared to unbarred galaxies. Examining the evolution of the halo spin within $10\, \mathrm{ckpc}$ reveals that barred galaxies have higher angular momentum transfer from the disc to the halo. Curiously, both barred and unbarred galaxies share similar initial low values of the halo spin, consistent with those proposed in the literature for bar formation. Furthermore, we evaluate existing stability criteria to capture the complexity of the process, and investigate the effects of mergers, flybys, and environment as possible drivers of bar formation. We find no clear link between mergers and disc instabilities resulting in the formation of bars, even though some of the simulated barred galaxies might have been influenced by these events.
Cytonuclear Interactions and Subgenome Dominance Shape the Evolution of Organelle-Targeted Genes in the Brassica Triangle of U
Authors: Kan Shenglong , Liao Xuezhu , Lan Lan , Kong Jiali , Wang Jie , Nie Liyun , Zou Jun , An Hong , Wu Zhiqiang
Published: February 2024

The interaction and coevolution between nuclear and cytoplasmic genomes are one of the fundamental hallmarks of eukaryotic genome evolution and, 2 billion yr later, are still major contributors to the formation of new species. Although many studies have investigated the role of cytonuclear interactions following allopolyploidization, the relative magnitude of the effect of subgenome dominance versus cytonuclear interaction on genome evolution remains unclear. The Brassica triangle of U features 3 diploid species that together have formed 3 separate allotetraploid species on similar evolutionary timescales, providing an ideal system for understanding the contribution of the cytoplasmic donor to hybrid polyploid. Here, we investigated the evolutionary pattern of organelle-targeted genes in Brassica carinata (BBCC) and 2 varieties of Brassica juncea (AABB) at the whole-genome level, with particular focus on cytonuclear enzyme complexes. We found partial evidence that plastid-targeted genes experience selection to match plastid genomes, but no obvious corresponding signal in mitochondria-targeted genes from these 2 separately formed allopolyploids. Interestingly, selection acting on plastid genomes always reduced the retention rate of plastid-targeted genes encoded by the B subgenome, regardless of whether the Brassica nigra (BB) subgenome was contributed by the paternal or maternal progenitor. More broadly, this study illustrates the distinct selective pressures experienced by plastid- and mitochondria-targeted genes, despite a shared pattern of inheritance and natural history. Our study also highlights an important role for subgenome dominance in allopolyploid genome evolution, even in genes whose function depends on separately inherited molecules.
COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)—a Randomized Controlled Clinical Trial
Authors: Le Michelle , Khoury Lauren , Lu Yang , Prosty Connor , Cormier Maxime , Cheng Mathew P , Fowler Robert , Murthy Srinivas , Tsang Jennifer L Y , Ben-Shoshan Moshe , Rahme Elham , Golchi Shirin , Dendukuri Nandini , Lee Todd C , Netchiporouk Elena
Published: February 2024

Background

Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties.

Objective

We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.

Methods

This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization.

Results

Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events.

Conclusions

These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission.

ClinicalTrials.gov ID: NCT04720612
A Somatic BRCA2-Mutated Pancreatic Adenocarcinoma With Sustained Exceptional Response to Modified FOLFIRINOX
Authors: Jamison Jacob K , May Michael S , Raufi Alexander G , Luk Lyndon , Wong Winston , Mundi Prabhjot S , Manji Gulam A
Published: February 2024

Homologous recombination repair (HRR) pathway deficiency opens multiple therapeutic avenues within pancreatic cancer. Patients with HRR deficiency–associated gene mutations such as BRCA1, BRCA2, and PALB2 are more susceptible to platinum-based chemotherapies and in those with somatic BRCA mutations, PARP inhibitor therapy prolongs progression-free survival. The case discussed herein illustrates the therapeutic opportunities offered through the identification of HRR deficiency in pancreatic cancer, as well as the challenges associated with treatment and prevention of central nervous system metastases in long-term survivors of pancreatic cancer.
Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS
Authors: Shore Neal D , Gratzke Christian , Feyerabend Susan , Werbrouck Patrick , Carles Joan , Vjaters Egils , Tammela Teuvo L J , Morris David , Aragon-Ching Jeanny B , Concepcion Raoul S , Emmenegger Urban , Fleshner Neil , Grabbert Markus , Lietuvietis Vilnis , Mahammedi Hakim , Cruz Felipe M , Paula Adriano , Pieczonka Christopher , Rannikko Antti , Richardet Martin , Silveira Glauco , Kuss Iris , Le Berre Marie-Aude , Verholen Frank , Sarapohja Toni , Smith Matthew R , Fizazi Karim
Published: February 2024

Background

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment.

Patients and Methods

Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval–specific new and cumulative event rates were determined during the first 24 months of the double-blind period.

Results

Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months.

Conclusion

Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment–related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment.

Trial number

ClinicalTrials.gov identifier NCT02200614
Rhetoric and Political Theory
Authors: Meyers Peter Alexander
Published: February 2024

The purpose of this chapter is to make a general statement about the conduct of political theory, illustrated by reference to a particular instance. Rhetoric properly understood is a mode of inquiry into civic life. The conditions for such inquiry change in modern times with the emergence of new forms of human relationship. Rousseau modernizes the scope and content of rhetorical inquiry by identifying the fact of society as its central object and by disseminating a new discourse around that term with unmatched success and influence. Rhetorical interests are taken over in and after the eighteenth century by the new social sciences. Sociology in this capacious sense provides a new fundamental terrain for political theory. Rousseau aligns himself in many ways with rhetorical traditions as he seeks to refigure citizenship. He therefore exemplifies, perhaps more than any “modern” before the twentieth century, the connection this volume seeks to articulate. Those who reject Rousseau’s imbrication of “the social” and “the political” have misunderstood both. By resituating Rousseau’s project with respect to rhetorical interests, we may correct this error and find a new way forward for political theory.
Whitman and the Poetics of Democracy
Authors: Erkkila Betsy
Published: February 2024

This chapter examines Whitman’s democratic poetics, his attempt to create a democratic language, form, content, and myth commensurate with the experimental politics of the American republic, to embody in his poetic persona America’s unique political identity, and to engage the reader as an active participant in the process of poetic and democratic creation. The chapter explores the roots of Whitman’s democratic poetics in the radical political and aesthetic thought of the American and the French Revolutions. Focusing on Leaves of Grass as a language experiment grounded in the idioms of the spoken language, this essay also examines the various democratizing strategies Whitman used to individualize, equalize, and connect people, labor, body, sex, and kosmos in an overall pattern of many in one that highlights the role of the reader and the future in the ongoing process of personal, poetic, and democratic creation.
TRANSPARENT TESTA GLABRA2 defines trichome cell shape by modulating actin cytoskeleton in Arabidopsis thaliana
Authors: Liu Lu , Wang Yali , Cao Weihua , Yang Lan , Zhang Chi , Yuan Lanxin , Wang Dan , Wang Wenjia , Zhang Hongchang , Schiefelbein John , Yu Fei , An Lijun
Published: February 2024

The Arabidopsis (Arabidopsis thaliana) TRANSPARENT TESTA GLABRA2 (TTG2) gene encodes a WRKY transcription factor that regulates a range of development events like trichome, seed coat, and atrichoblast formation. Loss-of-function of TTG2 was previously shown to reduce or eliminate trichome specification and branching. Here, we report the identification of an allele of TTG2, ttg2-6. In contrast to the ttg2 mutants described before, ttg2-6 displayed unique trichome phenotypes. Some ttg2-6 mutant trichomes were hyper-branched, whereas others were hypo-branched, distorted, or clustered. Further, we found that in addition to specifically activating R3 MYB transcription factor TRIPTYCHON (TRY) to modulate trichome specification, TTG2 also integrated cytoskeletal signaling to regulate trichome morphogenesis. The ttg2-6 trichomes displayed aberrant cortical microtubules (cMTs) and actin filaments (F-actin) configurations. Moreover, genetic and biochemical analyses showed that TTG2 could directly bind to the promoter and regulate the expression of BRICK1 (BRK1), which encodes a subunit of the actin nucleation promoting complex suppressor of cyclic AMP repressor (SCAR)/Wiskott–Aldrich syndrome protein family verprolin homologous protein (WAVE). Collectively, taking advantage of ttg2-6, we uncovered a function for TTG2 in facilitating cMTs and F-actin cytoskeleton-dependent trichome development, providing insight into cellular signaling events downstream of the core transcriptional regulation during trichome development in Arabidopsis.
A systematic evaluation of physical activity and diet policies in Scotland: results from the 2021 Active Healthy Kids Report Card
Authors: Tomaz Simone A , Reilly John J , Johnstone Avril , Hughes Adrienne , Robertson Jenni , Craig Leone C A , Bardid Farid
Published: February 2024

Background

Policymaking regarding physical activity (PA) and diet plays an important role in childhood health promotion. This study provides a detailed examination of Scottish government and policy for child and adolescent PA and diet and discusses strengths and areas for improvement.

Methods

Scottish policy documents (n = 18 [PA]; n = 10 [diet])—published in 2011–20—were reviewed for grading using an adapted version of the Health-Enhancing Physical Activity Policy Audit Tool Version 2.

Results

There is clear evidence of leadership and commitment to improving PA and diet and tackling obesity in children and adolescents. The allocation of funds and resources for policy implementation has increased substantially over the past decade. Progress through early key stages of public policymaking—policy agenda and formation—has improved. However, there is limited information on later key stages, including policy monitoring and evaluation.

Conclusions

Childhood PA and diet are a clear priority in Scotland, and PA and diet policies clearly support the desire to achieve other goals, including reducing inequalities and increasing active travel in Scotland. Nonetheless, future policies should be further strengthened through clear(er) plans of implementation, and monitoring and evaluation to support their societal impact.
The Causal Impact of Socio-Emotional Skills Training on Educational Success
Authors: Sorrenti Giuseppe , Zölitz Ulf , Ribeaud Denis , Eisner Manuel
Published: February 2024

We study the long-term effects of a randomized intervention targeting children's socio-emotional skills. The classroom-based intervention for primary school children has positive impacts that persist for over a decade. Treated children become more likely to complete academic high school and enrol in university. Two mechanisms drive these results. Treated children show fewer attention deficit/hyperactivity disorder symptoms: they are less impulsive and less disruptive. They also attain higher grades, but they do not score higher on standardized tests. The long-term effects on educational attainment thus appear to be driven by changes in socio-emotional skills rather than cognitive skills.
Electroencephalographic slowing during REM sleep in older adults with subjective cognitive impairment and mild cognitive impairment
Authors: Lam Aaron Kin Fu , Carrick James , Kao Chien-Hui , Phillips Craig L , Zheng Yi Zhong , Yee Brendon J , Kim Jong Won , Grunstein Ronald R , Naismith Sharon L , D’Rozario Angela L
Published: February 2024

Study Objectives

In older adults with Alzheimer’s disease, slowing of electroencephalographic (EEG) activity during REM sleep has been observed. Few studies have examined EEG slowing during REM in those with mild cognitive impairment (MCI) and none have examined its relationship with cognition in this at-risk population.

Methods

Two hundred and ten older adults (mean age = 67.0, SD = 8.2 years) underwent comprehensive neuropsychological, medical, and psychiatric assessment and overnight polysomnography. Participants were classified as subjective cognitive impairment (SCI; n = 75), non-amnestic MCI (naMCI, n = 85), and amnestic MCI (aMCI, n = 50). REM EEG slowing was defined as (δ + θ)/(α + σ + β) power and calculated for frontal, central, parietal, and occipital regions. Analysis of variance compared REM EEG slowing between groups. Correlations between REM EEG slowing and cognition, including learning and memory, visuospatial and executive functions, were examined within each subgroup.

Results

The aMCI group had significantly greater REM EEG slowing in the parietal and occipital regions compared to the naMCI and SCI groups (partial η2 = 0.06, p < 0.05 and 0.06, p < 0.05, respectively), and greater EEG slowing in the central region compared to SCI group (partial η2 = 0.03, p < 0.05). Greater REM EEG slowing in parietal (r = −0.49) and occipital regions (r = −0.38 [O1/M2] and −0.33 [O2/M1]) were associated with poorer visuospatial performance in naMCI.

Conclusions

REM EEG slowing may differentiate older adults with memory impairment from those without. Longitudinal studies are now warranted to examine the prognostic utility of REM EEG slowing for cognitive and dementia trajectories.
Empagliflozin Ameliorates the Impaired Osteogenic Differentiation Ability of Adipose-Derived Stem Cells in Diabetic Osteoporosis by Activating Autophagy
Authors: Yang Shuanglin , Lin Ya , Xie Yuping , Fu Ting , Wu Tianli , Lan Xiaorong , Lou Fangzhi , Xiao Jingang
Published: February 2024

Adipose-derived stem cells (ASCs) from diabetic osteoporosis (DOP) mice showed impaired osteogenic differentiation capacity. Recent studies have shown that in addition to antidiabetic drugs, sodium-glucose co-transporter inhibitor-2 (SGLT-2), empagliflozin, can play multipotent roles through various mechanisms of action. In this study, we aimed to investigate the effects and underlying mechanisms of empagliflozin on osteogenic differentiation of ASCs in DOP mice. Our results showed that osteogenic differentiation potential and autophagy activity weakened in DOP-ASCs when compared to controls. However, empagliflozin enhanced autophagy flux by promoting the formation of autophagosomes and acidification of autophagic lysosomes, resulting in an increase in LC3-II expression and a decrease in SQSTM1 expression. Furthermore, empagliflozin contributed to the reversal of osteogenesis inhibition in DOP-ASCs induced by a diabetic microenvironment. When 3-methyladenine was used to block autophagy activity, empagliflozin could not exert its protective effect on DOP-ASCs. Nonetheless, this study demonstrated that the advent of cellular autophagy attributed to the administration of empagliflozin could ameliorate the impaired osteogenic differentiation potential of ASCs in DOP mice. This finding might be conducive to the application of ASCs transplantation for promoting bone fracture healing and bone regeneration in patients with DOP.
Embryonic stem cell related gene regulates alternative splicing of transcription factor 3 to maintain human embryonic stem cells’ self-renewal and pluripotency
Authors: Xie Wen , Liu Weidong , Wang Lei , Li Shasha , Liao Zilin , Xu Hongjuan , Li Yihan , Jiang Xingjun , Ren Caiping
Published: February 2024

Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.
A Lack of Workplace Resources for Social Workers in Schools
Authors: Dull Jennifer
Published: February 2024

Social workers support youth in schools, but there is a lack of research that explores the supports that are offered to these helpers. Research suggests workplace coping resources for social workers in other environments that may help buffer the effects of stress; however, there is a significant lack of research on the availability of these resources. The purpose of this study was to determine common available resources to social workers in schools. A total of 100 public school social workers were surveyed using the Workplace Resource Questionnaire for School Social Workers (designed for this study). The study’s findings indicate a significant lack of workplace resources for school social workers; only 27 percent of participants reported regularly available resources outside their schools, and 18 percent and fewer reported resources regularly available in their schools. There was a range in how significant participants felt each resource would support their coping, but many participants felt the resources would support their coping at least minimally. Participants suggested training topics and other resources they felt would help their coping with stress while in the workplace.
Intraoperative lung protection: strategies and their impact on outcomes
Authors: Simonte Rachele , Cammarota Gianmaria , De Robertis Edoardo
Published: February 2024

Purpose of review

The present review summarizes the current knowledge and the barriers encountered when implementing tailoring lung-protective ventilation strategies to individual patients based on advanced monitoring systems.

Recent findings

Lung-protective ventilation has become a pivotal component of perioperative care, aiming to enhance patient outcomes and reduce the incidence of postoperative pulmonary complications (PPCs). High-quality research has established the benefits of strategies such as low tidal volume ventilation and low driving pressures. Debate is still ongoing on the most suitable levels of positive end-expiratory pressure (PEEP) and the role of recruitment maneuvers. Adapting PEEP according to patient-specific factors offers potential benefits in maintaining ventilation distribution uniformity, especially in challenging scenarios like pneumoperitoneum and steep Trendelenburg positions. Advanced monitoring systems, which continuously assess patient responses and enable the fine-tuning of ventilation parameters, offer real-time data analytics to predict and prevent impending lung complications. However, their impact on postoperative outcomes, particularly PPCs, is an ongoing area of research.

Refining protective lung ventilation is crucial to provide patients with the best possible care during surgery, reduce the incidence of PPCs, and improve their overall surgical journey.