bluuebunny/crossref_metadata_2025 huggingface dataset:
The Causal Pivot: A Structural Approach to Genetic Heterogeneity and Variant Discovery in Complex Diseases
Authors: Shaw Chad , Williams Christopher , Tan Tao Tao , Di Nicholas , Shulman Joshua , Belmont John W.
Published: November 2024

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages one established causal factor to detect the contribution of a second suspected cause. Specifically, polygenic risk scores (PRS) serve as known causes, while rare variants (RV) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum likelihood procedure for binary and quantitative traits and develop the Causal Pivot Likelihood Ratio Test (CP-LRT) to detect causal signals.

Through simulations, we demonstrate the CP-LRT’s robust power and superior error control compared to alternatives. We apply the CP-LRT to UK Biobank (UKB) data, analyzing three exemplar diseases: hypercholesterolemia (HC, LDL-c ≥ 4.9 mmol/L; nc=24,656), breast cancer (BC, ICD10 C50; nc=12,479), and Parkinson’s disease (PD, ICD10 G20; nc=2,940). For PRS, we utilize UKB-derived values, and for RVs, we analyze ClinVar pathogenic/likely pathogenic variants and loss-of-function mutations in disease-relevant genes:LDLRfor HC,BRCA1for BC, andGBAfor PD. Significant CP-LRT signals were detected for all three diseases. Cross-disease and synonymous variant analyses serve as controls. We further develop ancestry adjustment using matching and inverse probability weighting, and we extend the CP to examine oligogenic burden in the lysosomal storage pathway for PD. The CP reveals an approach to address heterogeneity and is an extensible method for inference and discovery in complex disease genetics.
Longer internal exons tend to have more tandem repeats and more frequently experience insertions and deletions that are mostly in intrinsically disordered regions of the encoded proteins
Authors: Homma Keiichi , Anbo Hiroto , Ota Motonori , Fukuchi Satoshi
Published: November 2024

Insertions and deletions (indels) in eukaryotic proteins are known to preferentially encode intrinsically disordered regions (IDRs), protein regions that by themselves do not form unique three-dimensional structures. As a previous investigation showed that long internal exons tend to encode IDRs in eukaryotes in general, we thought it worthwhile to analyze how indels alter internal exons and affect IDRs of the encoded proteins. For consideration of evolutionary roles indels play, we decided to select indels commonly observed in all variants (“fixed” indels) since indels in minor variants may represent transient aberrations in splicing. Here, by comparison of orthologous variants of closely related species together with those of outgroups, we identified fixed indels in the internal exons in four mammals and two flies. The fixed indels are nearly always nonframeshifting, short, and mostly encode IDRs. On average 51% of inserted and 40% of deleted residues are attributable to alterations in tandem repeats. Deletion tends to occur more frequently than insertion does and indels are generally more prevalent in long internal exons. Tandem repeats occur preferentially in long internal exons, indicating that their alterations account for the high frequency of indels in long internal exons. Also, since tandem repeats mostly encode IDRs, this finding at least partially explains the high incidence of IDRs in long internal exons. We propose that long internal exons had been produced in early eukaryotes mainly by repeat expansion that added IDRs to the encoded proteins but are experiencing frequent indels by alterations in tandem repeats.
Data driven refinement of gene expression signatures for enrichment analysis
Authors: Wenzel Alexander T. , Faraji Farhoud , Sato Kuniaki , Medetgul-Ernar Kwat , Castanza Anthony , Sagatelian Romella , Donepudi Gayathri , Halawa Omar , Wang Jean Y. J. , Gutkind J. Silvio , Tamayo Pablo , Mesirov Jill P.
Published: November 2024

Gene set enrichment methods measure biological process or pathway activation in gene expression data by testing coordinate up- or down-regulation of pathway members in a ranked list of genes. These methods rely on curated, annotated gene sets whose members’ coordinate expression is an indicator of a process or state. We therefore developed the Molecular Signatures Database (MSigDB), a collection of expertly annotated gene sets. While using, enhancing, and expanding MSigDB, we have observed that some gene sets can lack coordinate expression, especially those derived from canonical pathways. To address this challenge, we developed gene set refinement (GSR), a data-driven approach leveraging large-scale multi-omics compendia to extract context-specific sets, deconvolve heterogeneity, and reveal multiple downstream signaling. We applied this method to address cancer biology questions, and demonstrated successful, targeted refinement of existing MSigDB gene sets.
Programmable 3D cell alignment of bioprinted tissue via soft robotic dynamic stimulation
Authors: Rosalia Luca , Mosle Katelyn , Sinha Soham , Du Yi Yi , Solberg Fredrik , Jia Allison , Weiss Jonathan , Tam Tony , Herrmann Jessica E. , Cutkosky Mark , Skylar-Scott Mark
Published: November 2024

Recent breakthroughs in biofabrication have enabled the development of engineered tissues for various organ systems, supporting applications in drug testing and regenerative medicine. However, current approaches do not allow for dynamic mechanical maturation of engineered tissue in 3D. Although uniaxial mechanostimulation techniques have shown promise in generating anisotropic tissues, they fail to recapitulate the biomechanics of complex tissues. As a result, existing biofabricated tissues lack the ability to replicate complex 3D alignment patterns essential for functional biomimicry. Here, we present a soft robotics-driven approach for programmable 3D alignment in 3D bioprinted tissue. Our method introduces the co-printing of biological tissue with a silicone-based soft robot via a custom core-double shell nozzle. The application of 3D, exogenous, dynamic expansion and torsional forces to the tissue via the co-printed silicone robot was found to drive cell alignment. Confocal imaging revealed pronounced anisotropy of the stimulated tissue samples compared to the unstimulated controls. In addition, different cellular orientation patterns resulted from each mode of stimulation, demonstrating the versatility of the soft robotic approach in tailoring the pattern of tissue alignment based on programmed mechanostimulation.
Functionally important binding site for a volatile anesthetic in a voltage-gated sodium channel identified by X-ray crystallography
Authors: Hollingworth David , Herold Karl F. , Kelly Geoff , Mykhaylyk Vitaliy B. , Xiang Jiaxin , Zhang Donghang , Wallace B. A. , Hemmings Hugh C.
Published: November 2024

Volatile general anesthetics are used for inhalational anesthesia in hundreds of millions of surgical procedures annually, yet their mechanisms of action remain unclear. Membrane proteins involved in cell signaling are major targets for anesthetics, and voltage-gated ion channels that mediate neurotransmission, movement, and cognition are sensitive to volatile anesthetics (VAs). In many cases, the effects produced by VAs on mammalian ion channels are reproduced in prokaryotic orthologues, providing an opportunity to investigate VA interactions at high resolution using these structurally simpler prokaryotic proteins. We utilized the bacterial voltage-gated sodium channel (VGSC) NavMs fromMagnetococcus marinusto investigate its interaction with the widely used VA sevoflurane. Sevoflurane interacted directly with NavMs, producing effects consistent with multisite binding models for VA actions on their targets. We report the identification of one of these interactions at atomic detail providing the first high-resolution structure of a VA bound to a voltage-gated ion channel. The X-ray crystal structure shows sevoflurane binding to NavMs within an intramembrane hydrophobic pocket formed by residues from the voltage sensor and channel pore, domains essential for channel gating. Mutation of the dominant sevoflurane binding-site residue within this pocket, and analogous residues found in similar sites in human VGSCs, profoundly affected channel properties, supporting a critical role for this site in VGSC function. These findings provide the basis for future work to understand the role of VA interactions with VGSCs in both the anesthetic and toxic effects associated with general anesthesia.

Significance

While general anesthesia is an essential medical technique, the mechanisms that contribute to its pleiotropic neurological effects of unconsciousness, amnesia, immobility and analgesia remain incompletely understood. Identification of anesthetic binding sites in critical molecular targets like voltage-gated Na+channels is essential to elucidation of the mechanisms involved. Using a combined structural and functional approach, we identify and characterize the first known volatile anesthetic binding site in a voltage-gated ion channel.
Self-consistent quasiparticle
GW
and hybrid functional calculations for Al/InAs/Al heterojunctions: Band offset and spin-orbit coupling effects
Authors: Ness H. , Corsetti F. , Pashov D. , Verstichel B. , Winkler G. W. , van Schilfgaarde M. , Lutchyn R. M.
Published: November 2024

The electronic structure of surfaces and interfaces plays a key role in the properties of quantum devices. Here, we study the electronic structure of realistic Al/InAs/Al heterojunctions using a combination of density functional theory with hybrid functionals and state-of-the-art quasiparticle GW (QSGW) calculations. We find a good agreement between QSGW calculations and hybrid functional calculations, which themselves compare favorably well with angle-resolved photoemission spectroscopy experiments. Our paper confirms the need for well-controlled quality of the interfaces to obtain the needed properties of InAs/Al heterojunctions. A detailed analysis of the effects of spin-orbit coupling on the spin splitting of the electronic states shows a linear scaling in k space, related to the two-dimensional nature of some interface states. The good agreement by QSGW and hybrid functional calculations opens the door towards trustable use of an effective approximation to QSGW for studying very large heterojunctions.

Published by the American Physical Society
2024
Regularized entanglement entropy of electron-positron scattering with a witness photon
Authors: Shivashankara Shanmuka , Gogliettino Grace
Published: November 2024

Regularized quantum information metrics are calculated for the scattering process e−e+→γ,Z→μ−μ+ that has a witness photon entangled with the initial electron-positron state. Unitarity implies the correct regularization of divergences that appear in both the final density matrix and von Neumann entanglement entropies. The entropies are found to quantify uncertainty or randomness. The variation of information, entanglement entropy, and correlation between the muon’s and witness photon’s helicities are found to convey equivalent information. The magnitude of the muon’s expected helicity rises (falls) as the helicity entropy falls (rises). Area, or the scattering cross section, is a source of entropy for the muon’s helicity entropy and momentum entropy. The muon’s differential angular entropy distribution is similar to the differential angular cross section distribution, capturing the forward-backward asymmetry at high center-of-mass energies.

Published by the American Physical Society
2024
Integer Fluxonium Qubit
Authors: Mencia Raymond A. , Lin Wei-Ju , Cho Hyunheung , Vavilov Maxim G. , Manucharyan Vladimir E.
Published: November 2024

We describe a superconducting qubit derived from operating a properly designed fluxonium circuit in a zero magnetic field. The qubit has a frequency of about 4 GHz and an energy relaxation quality factor Q≈0.7×107, even though the dielectric loss quality factor of the circuit components is in the low-105 range. The Ramsey coherence time exceeds 100μs, and the average fidelity of Clifford gates is benchmarked to F>0.999. These figures are expected to improve with optimized fabrication and measurement procedures. Our work establishes a ready-to-use “partially protected” superconducting qubit functioning in the frequency range of conventional transmons.

Published by the American Physical Society
2024
Improving the reliability of small- and wide-angle X-ray scattering measurements of anisotropic precipitates in metallic alloys using sample rotation
Authors: Perrin Thomas , Chahine Gilbert A. , Arnaud Stéphan , Després Arthur , Heugue Pierre , Deschamps Alexis , De Geuser Frédéric
Published: November 2024

Nanometric precipitates in metallic alloys often have highly anisotropic shapes. Given the large grain size and non-random texture typical of these alloys, performing small- and wide-angle X-ray scattering (SAXS/WAXS) measurements on such samples for determining their characteristics (typically size and volume fraction) results in highly anisotropic and irreproducible data. Rotations of flat samples during SAXS/WAXS acquisitions are presented here as a solution to these anisotropy issues. Two aluminium alloys containing anisotropic precipitates are used as examples to validate the approach with a −45°/45° angular range. Clear improvements can be seen on the SAXS I(q) fitting and the consistency between the different SAXS/WAXS measurements. This methodology results in more reliable measurements of the precipitate's characteristics, and thus allows for time- and space-resolved measurements with higher accuracy.
The effects of low boron incorporation on the structural and optical properties of B
x
Ga1−x
N/SiC epitaxial layers
Authors: Romanitan Cosmin , Mickevičius Juras , Comanescu Florin , Gavrila Raluca , Stoian Marius , Varasteanu Pericle , Kadys Arunas , Malinauskas Tadas , Pavelescu Emil-Mihai
Published: November 2024

BGaN epilayers with boron contents up to 5.6% were grown on SiC substrates by metal–organic chemical vapor deposition. The effects of boron incorporation on the structural and optical properties were studied by high-resolution X-ray diffraction (XRD), atomic force microscopy (AFM), Raman spectroscopy and photoluminescence (PL) spectroscopy. XRD reciprocal-space maps around the symmetric 0002 and asymmetric 11 {\overline 2} 4 reflections allowed evaluation of the lattice constants and lattice mismatch with respect to the underlying substrate. XRD rocking curves and AFM measurements indicated the mosaic microstructure of the epilayer. The impact of boron content on crystallite size, tilt and twist is evaluated and the correlation with threading dislocation density is discussed. The deterioration of optical properties with increasing boron content was assessed by Raman and PL spectroscopy.
Deforestation policies in the Brazilian Legal Amazon: an analysis of the PPCDAm using the triple difference method
Authors: Benevit Bruno , da Trindade Carolina Silva , de Melo Junior Roberto Bezerra , Uhr Daniel de Abreu Pereira , Uhr Julia Gallego Ziero
Published: November 2024

Purpose

This study aims to evaluate the effects of the synergy between monitoring technologies and deforestation control policies promoted by the Action Plan for the Prevention and Control of Deforestation in the Legal Amazon (PPCDAm) during its initial stage.

Design/methodology/approach

The triple difference method is employed to explore the differences between the non-metropolitan municipalities with Indigenous lands and other regional municipalities.

Findings

The findings indicate a reduction of approximately 16.1 km² per municipality between 2004 and 2007. This reduction corresponds to a decrease of 10,293 km² in the area of deforestation and a total of 498 million tons of CO2. To ensure the robustness of the results, placebo tests, event study and flexibility in the composition of the groups were conducted. The robustness tests substantiate the findings.

Practical implications

These results emphasize the significance of remote monitoring policies for controlling deforestation in isolated regions and Indigenous lands. Additionally, such results indicate that the policy was cost-effective.

Originality/value

This study innovates by examining the causal impact of the initial phase of the PPCDAm before 2008, a period not focused on existing literature. Further, employing the triple difference method innovates methodologically to assess PPCDAm's effect on deforestation in isolated Amazon areas.
Effects of green innovation ecosystem coopetition, environmental management practices and digital innovation on carbon footprint reduction
Authors: Rosa Fabricia S. , Lunkes Rogério João , Codesso Mauricio , Mendes Alcindo Cipriano Argolo , Costa Gabriel Donadio
Published: November 2024

Purpose

The purpose of this article is to analysis of the effects of green innovation ecosystem coopetition (cooperation and competition), environmental management practices (EMPs) and digital innovation (DI) on carbon footprint reduction.

Design/methodology/approach

To conduct the study, a questionnaire was administered to hotel managers from different regions of Brazil. Data were collected from 197 hotels and analyzed via partial least squares structural equation modeling.

Findings

The results show that green innovation ecosystem cooperation positively and significantly affects EMPs and DI. Green innovation ecosystem competition interactions also benefit the adoption of EMPs. However, they do not significantly influence the use of DI. The results indicate that hotels that are in a scenario of simultaneous competition and collaboration (coopetition) within the green innovation ecosystem can reduce carbon emissions when EMPs and DI are used.

Research limitations/implications

The authors contribute to the literature by showing different pathways for reducing the carbon footprint of hotels. The results expand the authors’ knowledge by showing evidence that cooperation and competition interactions can produce distinct effects, especially on DI. Thus, this study has important practical implications for hotel managers seeking to improve their environmental practices and DI with the help of external multiagent resources and knowledge.

Originality/value

This research contributes to the literature by examining how cooperation and competition interactions in the green innovation ecosystem help in the adoption of environmental management and DI practices.
How to make strategic conversations more AGIL
Authors: Duhamel Francois , Niess Alexander
Published: November 2024

Purpose

This article addresses the role of communication processes in the formulation and implementation of strategic planning. It seeks to delineate a structured approach to define the contents of strategic conversations among internal stakeholders, to achieve actionable outcomes.

Design/methodology/approach

This paper employs a theoretical approach, derived from Talcott Parsons’ AGIL framework, to conceptualize the contents of strategic conversations in a systematic way. Several examples are proposed to illustrate this framework.

Findings

Conversations among internal stakeholders in organizations, to be deemed strategic, should be orientated towards the formulation and implementation of priorities, procedures, prospective sensemaking and value patterns, as well as the media of interaction connecting them.

Originality/value

This paper offers original insights for practitioners and scholars aiming to comprehend strategic value in communication processes, thanks to Parson’s theoretical views, which have been seldom used in the strategic management literature. Our framework has the originality to offer a more comprehensive and systematic view of the topics making conversations strategic in organizations.
Enhancing pricing strategies in the aftermarket sector with machine learning
Authors: Sarode Mohit S. , Kumar Anil , Prasad Abhijit , Shetty Abhishek
Published: November 2024

Purpose

This research explores the application of machine learning to optimize pricing strategies in the aftermarket sector, particularly focusing on parts with no assigned values and the detection of outliers. The study emphasizes the need to incorporate technical features to improve pricing accuracy and decision-making.

Design/methodology/approach

The methodology involves data collection from web scraping and backend sources, followed by data preprocessing, feature engineering and model selection to capture the technical attributes of parts. A Random Forest Regressor model is chosen and trained to predict prices, achieving a 76.14% accuracy rate.

Findings

The model demonstrates accurate price prediction for parts with no assigned values while remaining within an acceptable price range. Additionally, outliers representing extreme pricing scenarios are successfully identified and predicted within the acceptable range.

Originality/value

This research bridges the gap between industry practice and academic research by demonstrating the effectiveness of machine learning for aftermarket pricing optimization. It offers an approach to address the challenges of pricing parts without assigned values and identifying outliers, potentially leading to increased revenue, sharper pricing tactics and a competitive advantage for aftermarket companies.
Artificial intelligence in management education: transformative potential and challenges
Authors: Cook Jared Scott , Cook Jack
Published: November 2024

Purpose

The purpose of this paper is to define artificial intelligence (AI) and examine its history, positive and negative impacts, ethical and social implications and implementation within management education. This paper offers various suggestions for the use of AI, as well as context surrounding the current AI landscape.

Design/methodology/approach

The paper uses a narrative review (Sylvester et al., 2013).

Findings

This paper identifies several areas of AI innovation, including AI tutoring systems, feedback systems for student papers, utilization of AI for innovative lesson plans and the use of AI to predict potential student dropout from a course or institution. In addition, there are significant concerns regarding the lack of ethical guidelines with current AI.

Practical implications

Practical implications include the ability to immediately use certain AI tools to enhance lesson plans as well as enhance student work using AI as a tool.

Originality/value

This paper was originally created as a conference presentation and presented at the society for advancement of management (SAM) International Business Conference before being reworked to be submitted to the journal. All content in this paper is original in their creation.
30 years of terrestrial insect richness patterns across elevation: What have we learned? A global meta‐analysis
Authors: Dolson Sarah J. , Kharouba Heather M.
Published: November 2024

Understanding elevation variation in biodiversity is a classic question in ecology and has implications for understanding climate change impacts on mountain ecosystems. While insects are the largest group of animals, the global trend in insect species richness with elevation is unknown. To date, single studies and taxa‐specific syntheses have provided no single picture, finding variable patterns of insect richness with elevation.

A global synthesis across systems would provide a better understanding of how insect species richness changes with elevation and the possible environmental correlates of those patterns. We used published studies of terrestrial insect elevation gradients from 1990 to 2020 to ask: How do insect species richness change with elevation, and which environmental variables best explain this relationship statistically?

With 1486 sites spanning 151 species richness‐elevation gradients from 80 studies from four diverse insect taxonomic groups and five biomes, we found that overall proportional richness reached a low‐elevation plateau and then decreased. We also show that mean annual temperature and seasonality best explain this trend.

We suggest best practices and areas of interest for the future of insect richness‐elevation studies, including underrepresented groups, geographic areas, and more standardized methods.
High‐intensity ultrasound modification of techno‐functional and structural properties of white finger millet protein fractions
Authors: Shylla Eleonora , Sunil C. K. , Rawson Ashish , Venkatachalapathy N.
Published: November 2024

In this study, albumin, globulin, and glutelin were extracted from white finger millet, and their amino acid content, functional and structural properties were investigated. The protein concentration of albumin, globulin, and glutelin were 76.01%, 74.32%, and 69.55%, respectively. The results showed that all the fractions had a significant amount of essential amino acids. Aqueous protein dispersions (10%, w/v) were treated for 12 min at different ultrasound power levels (100, 200, and 300 W). The solubility, emulsifying, and foaming properties of albumin and glutelin were significantly (p < 0.05) improved after ultrasound treatment (20 kHz) which indicates that ultrasound could unfold protein aggregates. A decrease in particle size, increase in surface hydrophobicity, and zeta potential correlated with improved functional properties. Ultrasound treatment reduced the size of all proteins except for fractions at 300 W and also sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed a significant change in the molecular weight of albumin and glutelin at 300 W. Scanning electron microscopy of treated protein fraction showed distinctive microstructure with irregular structure compared to untreated protein fraction. Although Fourier transform infrared spectroscopy spectra of proteins were similar after ultrasonication, a partial increase in the intensity of the Amide A band was observed. In conclusion, the ultrasound‐treated protein fraction can be used as a high‐value plant‐based emulsifier.
Development, characterization, and comparison of chitosan microparticles as a carrier system for black bean protein hydrolysates with antioxidant capacity
Authors: Alfaro‐Díaz Arturo , Castillo‐Herrera Gustavo A. , Espinosa‐Andrews Hugo , Luna‐Vital Diego , Mojica Luis
Published: November 2024

Peptides in black bean protein hydrolysates (BPHs) exert antioxidant capacity. However, peptides are prone to degradation during processing and digestion. Chitosan (Ch) can protect them and provide a delayed release. This work develops and compares two drying methods producing porous structured Ch microparticles (MPs) as carriers for antioxidant BPH. Ch gels were obtained by ionic gelation and dried by supercritical CO2 solvent displacement or fast‐freeze‐drying methods. The resulting aerogels and fast‐freeze‐dried MPs were structurally characterized, and their swelling and release profiles were obtained at pH 1.2 and 7.4. The antioxidant capacity of systems was determined by 2,2′‐azino‐bis(3‐ethyl‐benzthiazoline‐6‐sulphonic acid) (ABTS) and superoxide radical assays. The results showed BPH‐Ch best complexation conditions occurring at a pH of 4.5 and a 4:1 BPH/Ch ratio. The particle size of the complex was 1047.6 nm, and the entrapment efficiency and loading capacity were 28.2% and 54.3%, respectively. At pH 1.2 and 7.4, the release rate of BPH was lower in aerogel than in fast‐freeze‐dried MPs. Besides, entrapment BPH in Ch significantly reduced the ABTS antioxidant activity IC50 from 35.1 µM Trolox equivalents (TE)/mg to 250.7 and 406.2 µM TE/mg for Ch fast‐freeze‐dried and aerogels, respectively. Superoxide radical inhibition IC50 ranged from 74.6 to 92.9 mM ascorbic acid equivalents/mg in the different samples. BPH‐loaded aerogels presented lower specific surface area (94.7 vs. 138.6 m2/g, p < 0.05) and higher average pore size (26.4 vs. 19.8 nm) than Ch aerogels. Ch aerogel is a promising carrier for delaying the release of common bean antioxidant peptides useful for developing functional foods.

Practical Application

This novel system could act as an ingredient to incorporate antioxidant compounds in different formats to develop delayed‐release nutraceuticals and functional foods, such as bakery, dairy products, or beverages. Along, antioxidant peptide‐loaded aerogels could be used as a slow‐release system for compounds acting as natural preserving antioxidants for food applications such as raw meat products or high‐fat foods.
Gendered enterprise: Women and Australian business history
Authors: Wright Claire E. F.
Published: November 2024

This special issue examines women and Australian business history. Contributions explore women's entrepreneurship in small urban businesses, side hustles, agriculture, and family companies. Articles highlight the importance of women's businesses, as a financial necessity for women, their families, and their communities. Authors examine the barriers for women in business, including legislation, licensing, societal expectations, and discrimination. Articles also explore women's intersections with other demographic characteristics, with access to enterprise mediated by class and the rural–urban divide. Finally, contributions examine the way traditional archives have obscured histories of businesswomen, and the opportunities offered by feminist historical methodologies for studying business history.
The behavioral dimension of CO2 fertilization effect: Evidence from US harvesting records
Authors: Liu Ziheng
Published: November 2024

The CO2 fertilization effect has been demonstrated to boost crop production by enhancing photosynthesis and reducing drought stress. In addition to this biological channel, there is also a behavioral margin for the CO2 fertilization effect that was previously unnoticed. I find evidence that an additional ppm of average CO2 concentration leads to increases in the corn and soybean harvested ratios of .57 and .75 percentage points, respectively. My predictions suggest that, without considering the adjustment in harvesting decision, the crop production benefits from CO2 fertilization effect would be biasedly estimated for both corn and soybeans, which broadens the understanding of farmers’ behavioral responses to environmental stimuli and extends the knowledge on how CO2 would benefit crop production.
The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children—A pivotal phase III trial
Authors: Gappa Monika , Gagnon Rémi , Horak Fritz , Cichocka‐Jarosz Ewa , Dalgaard Terrie , Hargreaves Kate , Mikler Jan , Emeryk Andrzej , Hansen Kirsten Skamstrup , Pfaar Oliver
Published: November 2024

Background

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT‐tablet in a paediatric population (5–17 years) with moderate‐to‐severe AR/C induced by pollen from birch and trees in the birch homologous group.

Methods

Nine hundred and fifty‐two subjects were randomized (1:1) to daily treatment with SQ tree SLIT‐tablet or placebo for up to 52 weeks and had free access to AR/C symptom‐relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS).

Results

SQ tree SLIT‐tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment‐related adverse events were mild or moderate local administration site reactions.

Conclusion

This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT‐tablet in tree pollen‐induced AR/C in a paediatric population (5–17 years).
Early left ventricular unloading during extracorporeal membrane oxygenation in cardiogenic shock: A systematic review and meta‐analysis
Authors: Abuelazm Mohamed , Nawlo Ahmad , Ibrahim Ahmed A. , Amin Ahmed Mazen , Mahmoud Abdelrahman , Elshenawy Salem , Alabdallat Yasmeen Jamal , Turkmani Mustafa , Abdelazeem Basel , Caccamo Marco
Published: November 2024

Background

Left ventricular (LV) unloading is a crucial intervention to decrease the harmful consequences of extracorporeal membrane oxygenation (ECMO) on hemodynamic status in cardiogenic shock (CS) patients. However, a lingering question preoccupies experts: Should we intervene early or wait until clinical deterioration caused by increasing afterload is detected?

Methods

A systematic review and meta‐analysis synthesizing studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 2023. We used R V. 4.3 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42024501643.

Results

Eight studies with 2.117 patients were included. Early/prophylactic LV unloading was associated with a lower incidence of all‐cause mortality [RR: 0.87 with 95% CI (0.79, 0.95), p < 0.01]. However, there was no significant difference between the two groups regarding cardiac mortality [RR: 1.01 with 95% CI (0.68, 1.48), p = 0.98], non‐cardiac mortality [RR: 0.86 with 95% CI (0.46, 1.62), p = 0.64], and in‐hospital mortality [RR: 0.95 with 95% CI (0.86, 1.05), p = 0.30]. There was no significant difference between the two groups regarding ECMO weaning, myocardial recovery, ECMO duration, and length of hospitalization.

Conclusion

Early/prophylactic LV unloading during ECMO for CS patients was associated with a decreased incidence of all‐cause mortality and sepsis or infection, with no effect on ECMO weaning, myocardial recovery, ECMO duration, and hospital length of stay.
A second chance for avatrombopag in chemotherapy‐induced thrombocytopenia
Authors: Al‐Samkari Hanny , Moore Donald C.
Published: November 2024

Chemotherapy‐induced thrombocytopenia (CIT) remains a common complication of cancer therapy with no approved available treatments in most of the world. Although a prior clinical trial of avatrombopag for CIT did not meet its primary end‐point, a report from Galamaga and colleagues raises prospects for a second chance for avatrombopag in CIT, highlighting the differences between nadir and persistent CIT and the importance of patient selection in CIT treatment.

Commentary on: Galamaga et al. Avatrombopag for the treatment of patients with chemotherapy‐induced thrombocytopenia: a case series. Br J Haematol 2025; 206:272‐278.
The prognostic significance of MYC/BCL2 double expression in DLBCL in the genetic classification era
Authors: Wu Yi‐Fan , Yuan Qun‐Hui , Shen Hao‐Rui , Du Kai‐Xin , Shang Chun‐Yu , Li Yue , Zhang Xin‐Yu , Wu Jia‐Zhu , Gao Rui , Wang Li , Li Jian‐Yong , Yin Hua , Liang Jin‐Hua , Xu Wei
Published: November 2024

Double expression (DE) is a World Health Organization‐recognized adverse prognostic factor in diffuse large B‐cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double‐expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression‐free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non‐DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA‐sequencing analyses exhibited upregulation in tumor proliferation‐related pathways in DEL patients, but downregulation in extracellular matrix organization, T‐cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients.
A Comprehensive Analysis on Galantamine Based Hybrids for the Management of Alzheimer's Disease
Authors: Singh Yash Pal , Prasad Sonima , Kumar Harish
Published: November 2024

Alzheimer's disease (AD) is a progressive chronic age‐related neurodegenerative brain disorder characterized by the loss of memory and other cognitive functions. The exact etiology of AD is still under investigation, however several factors such as low level of neurotransmitter acetylcholine (ACh), aggregation of amyloid beta (Aβ) in the form of Aβ plaques, hyperphosphorylation of tau protein into neurofibrillary tangles (NFTs), oxidative stress, and metal ion imbalance are the major hallmarks of this disease. Of the multiple hypotheses for AD, the amyloid‐β (Aβ) and cholinergic hypothesis are the main targeting hypotheses for AD. Some researchers hypothesized that the primary event associated with the cholinergic neurotransmitter (acetylcholine) is memory loss and cognitive impairment. Due to the disease's complicated pathogenesis, long‐term therapy with a single target candidate is futile. As a result, multitargeted and multifunctional therapies have emerged. Various research teams are concentrating on addressing multiple disease factors through hybridization techniques. Consequently, this hybridization approach has been applied to all core scaffolds, including galantamine. In this article, we tried to provide a thorough overview of the most recent developments on galantamine, a prospective AChE inhibitor, and its hybrid analogs as possible therapeutic agents for treating AD. Furthermore, we also provided the design, synthesis, and SAR analysis of the galantamine‐based compounds used in the last decades for the management of AD.
MiR‐107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma
Authors: Kim Byung‐Keun , Yang Min‐Suk , Srivastava Upasna , Piparia Shraddha , Sharma Rinku , Tiwari Anshul , Kho Alvin , Wong Richard , Celedón Juan C. , Weiss Scott T. , McGeachie Michael , Tantisira Kelan
Published: November 2024

Introduction

MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma.

Methods

Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs. We first divided according to HDM sensitisation and then tested whether miRNAs were differentially expressed (DE) between the two groups. Gene enrichment analysis for target genes of the DE miRNAs was then performed to identify potential causal pathways. Replication analysis was performed in the Childhood Asthma Management Program (CAMP), in which expression data of 258 miRNAs in 491 children were available. A mediation analysis was conducted to discern relationships between miRNA and phenotype differences according to HDM sensitisation in GACRS cohort.

Results

There were 906 (80.5%) and 220 (19.5%) subjects in the GACRS HDM+ and HDM– groups. Compared with HDM– participants, those in the HDM+ group were more likely to be severe in variables including pulmonary function, oral corticosteroid use and blood tests. A total of 17 miRNAs were DE (p < 0.05) between the two groups, with miR‐642a‐3p, let‐7c‐5p and miR‐107 most significantly associated with HDM sensitisation. In CAMP, there were 39 DE miRNAs, and increased expression of miR‐107 in HDM+ children was replicated in this cohort. In both GACRS and CAMP, the cadherin‐binding pathway was enriched in an analysis of target genes for DE miRNA. In a mediation analysis, miR‐107 showed significant indirect effects on eosinophil count and total IgE that were mediated by HDM sensitisation.

Conclusion

In children with asthma, miR‐107 is associated with HDM sensitisation. Furthermore, miR‐107 was indirectly associated with total IgE and eosinophil count through HDM sensitisation.
Motivating residents to volunteer for urban waterway restoration: A segmentation approach
Authors: Dorner Zack , McLeod Lynette J. , Milfont Taciano L. , Stahlmann‐Brown Philip , Hine Donald W. , Maris Robbie D. C. , Kitson Jane C. , Tassell‐Matamua Natasha A.
Published: November 2024

Urban landscapes play a crucial role in the health of freshwater ecosystems. The task of protecting and restoring urban freshwater waterways requires concerted efforts from all sectors of society, including volunteers. The recruitment and retention of volunteers is often a challenge for community environmental organizations as urban residents are diverse and influenced by a blend of personal, societal, and environmental factors. We surveyed a representative sample of 1901 urban residents across Aotearoa New Zealand and used the Behaviour Change Wheel framework and audience segmentation to understand the underlying factors influencing volunteering for waterway restoration projects and to identify potential target audiences to recruit new volunteers. We identified four segments within the target audience (“Supportive,” “Receptive but unsure,” “Hesitant and lack opportunity,” and “Reluctant”) each with its own unique profile of capabilities, opportunities, and motivations for volunteering. Recommendations for appropriate intervention designs to increase levels of volunteering include providing tailored messaging and events for those who are “Receptive but unsure” or “Hesitant and lack opportunity” and information about volunteering opportunities to “Supportive” individuals. This knowledge lays the groundwork for future initiatives focused on increasing urbanites' volunteering with community freshwater restoration groups.
Implementing sensor‐based digital health technologies in clinical trials: Key considerations from the eCOA Consortium
Authors: Izmailova Elena S. , Middleton Danielle , Yunis Reem , Lakeland Julia , Sowalsky Kristen , Kling Julia , Ritchie Alison , Guo Christine C. , Byrom Bill , Kern Scottie
Published: November 2024

The increased use of sensor‐based digital health technologies (DHTs) in clinical trials brought to light concerns about implementation practices that might introduce burden on trial participants, resulting in suboptimal compliance and become an additional complicating factor in clinical trial conduct. These concerns may contribute to the lower‐than‐anticipated uptake of DHT deployment and data use for regulatory decision‐making, despite well‐articulated benefits. The Electronic Clinical Outcome Assessment (eCOA) Consortium gathered collective experience on deploying sensor‐based DHTs and supplemented this with relevant literature focusing on mechanisms that may enhance participant compliance. The process for DHT implementation starts with identifying a clinical concept of interest followed by a digital measure selection, defining active or passive data capture and their sources, the number of sensors with respective body location, plus the duration and frequency of use in the context of perceived participant burden. Roundtable discussions among patient groups, physicians, and technology providers prior to protocol development can be very impactful for optimizing trial design. While diversity and inclusion are essential for any clinical trial, patient populations should be considered carefully in the context of trial‐specific aims, requirements, and anticipated patient burden. Minimizing site burden includes assessment of training, research engagement, and logistical burden which needs to be triaged differently for early and late‐stage clinical trials. Additional considerations include sharing trial results with study participants and leveraging publicly available data for compliance modeling. To the best of our knowledge, this report provides holistic considerations for sensor‐based DHT implementation that may optimize participant compliance.
Plasmablastic Lymphoma in the Submandibular Region Diagnosed by FNAC: A Case Report and Literature Review
Authors: de Aquino Sibele Nascimento , de Cáceres Cinthia Veronica Bardález López , Bezerra Hélen Kaline Farias , Vargas Pablo Agustin , Lopes Márcio Ajudarte
Published: November 2024

Objective

This study aims to provide a literature review of FNAC‐diagnosed plasmablastic lymphoma (PBL) cases and present a case of PBL in an HIV patient diagnosed by FNAC.

Methods

A literature review was conducted across eight databases to compile information on FNAC‐diagnosed PBL cases without restricting the site of involvement.

Results

The literature review included 23 PBL, with 13 (56.5%) affecting head and neck region. The mean age of patients was 49 years, with a male‐to‐female ratio of 1.9:1, and 13 (56.5%) patients were HIV positive. Ten (43.5%) of 23 patients tested positive for Epstein–Barr virus (EBV). Twenty‐one FNAC procedures and two cytological smears were performed. Plasmacytoid/plasmablastic morphology was described in seven cases (30.4%). Large cells were observed in 17 cases (73.9%). Pleomorphism was noted in 10 cases (43.5%). A cytological diagnosis of malignancy was achieved in 91.3% of cases. In 20 cases assessed for concordance, complete agreement was found in 8 cases (34.8%), while discordance was noted in 12 cases (65.2%). We also report a case of PBL diagnosed via FNAC in a 55‐year‐old male patient who presented with a painful, hard, nonmobile mass in the left submandibular region, approximately 10 cm in size, with 1 month of evolution. FNAC was performed, and cytologic smears, along with cell block (CB) preparations, were made. After staining with Diff‐Quik, HE and Papanicolaou stain, numerous cells exhibiting plasmacytic morphology were observed. Immunohistochemical analysis showed negativity for LCA, CD3, CD20, Pax5, CD79a, ALK and HHV‐8, and positivity for CD138, MUM1 and Ki‐67 (100%). EBV positivity was also confirmed, leading to a diagnosis of PBL.

Conclusion

This study highlights the efficacy of FNAC in diagnosing PBL. The immunophenotypic profile and morphological features observed through FNAC, combined with immunohistochemistry (IHC) and in situ hybridisation, were crucial for an accurate diagnosis. The literature review underscores the value of FNAC as a diagnostic tool for PBL, demonstrating a high rate of cytological diagnosis and significant cytohistological concordance.
Endoscopic closure using SureClip Traction Band for delayed perforation after colorectal endoscopic submucosal dissection
Authors: Kobayashi Reo , Yoshida Naohisa , Inoue Ken
Published: November 2024

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