bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of bivalent mRNA booster vaccination and previous infection in older adults during Omicron period: real-world evidence
Authors: España Pedro-Pablo , Castillo-Sintes Idoia , Legarreta Maria J , Bilbao-González Amaia , Larrea Nere , Gascon Maria , Uranga Ane , Artaraz Amaia , Garcia-Asensio Julia , Quintana Jose M ,   the COVID-Health Basque Country Research Group, Portuondo Janire , Garcia Julia , Bilbao González Amaia , Castillo Sintes Idoia , Quintana Jose M , García-Gutierrez Susana , Legarreta Maria J , Gascón María , Larrea Nere , Gonzalez Nerea , Martin Josune , España Pedro Pablo , Uranga Ane
Published: November 2024

Background

The effectiveness of booster bivalent vaccines against the Omicron variant, particularly amongst older patients, remains uncertain.

Objective

We sought to compare the relative effectiveness of a fourth dose of vaccine using bivalent messenger ribonucleic acid (mRNA), by comparing patients who had and had not received this dose.

Methods

We conducted a matched retrospective cohort study to assess the risk of COVID-19 infection, hospitalization and death of people aged >60 years with four doses as compared to those with only three doses. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). We adjusted by age, sex, nursing-home, comorbidities, primary care setting and previous episodes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We also investigated the impact of prior SARS-CoV-2 infection within each cohort, using the same methodology.

Results

The administration of a fourth bivalent mRNA vaccine dose conferred significant additional protection against COVID-19 infection (HR: 0.479; 95% CI: 0.454–0.506), hospitalization (HR: 0.393; 95% CI: 0.348–0.443) and 30-day mortality (HR: 0.234; 95% CI: 0.171–0.318), as compared to individuals who had received only a third monovalent vaccine dose. In both cohorts, a prior history of COVID-19 infection involves lower risk of COVID-infection, hospitalization and death.

Conclusions

During the period of Omicron predominance, receiving a bivalent booster vaccine as a fourth dose, as compared to receiving only three doses of a monovalent mRNA vaccine, provides significant extra protection against COVID-19 infection, hospitalization and mortality. Antecedents of SARS-CoV-2 prior to vaccination involves a notable reduction in the above COVID-19 outcomes.
Using Double Negative Controls to Adjust for Healthy User Bias in a Recombinant Zoster Vaccine Safety Study
Authors: Li Kendrick , Emerman Iris , Cook Andrea J , Fireman Bruce H , Sundaram Maria , Tseng Hung-Fu X , Weintraub Eric S , Yu Onchee , Nelson Jennifer L , Shi Xu
Published: November 2024

Unmeasured confounding is a major concern in many epidemiologic studies that are not randomized. Negative control methods can detect and reduce confounding by leveraging the proxies of the unmeasured confounders, including negative control outcomes (NCO) and exposures (NCE). An NCO is presumably unaffected by the exposure of interest but would be associated with unmeasured confounders; an NCE presumably does not affect the outcome of interest but would be associated with unmeasured confounders. A recently proposed double negative control method leverages both NCO and NCE for unmeasured confounding bias. To demonstrate this relatively new methodology in pharmacoepidemiologic studies, we re-analyzed data from a prior safety study of Recombinant Zoster Vaccine (RZV). The prior study compared risk of safety outcomes of RZV versus unvaccinated comparators, using logistic regression with propensity score adjustment. We identified NCOs and NCEs that could be used to adjust for unmeasured confounding bias that could arise if RZV recipients are incomparable to the comparators due to unmeasured factors. The double negative control analysis yielded relative risk estimates slightly closer to 1.0 than those reported previously, providing additional evidence of RZV safety that is less vulnerable to unmeasured confounding.
Doubly Robust Estimation under Possibly Misspecified Marginal Structural Cox Model
Authors: Luo Jiyu , Rava Denise , Bradic Jelena , Xu Ronghui
Published: November 2024

In this paper we consider the marginal structural Cox model, which has been widely used for analyzing observational studies with survival outcomes. The standard inverse probability weighting method under the model hinges upon a propensity score model for the treatment assignment, and a censoring model which incorporates both the treatment and the covariates. In such settings model misspecification can often occur, and the Cox regression model’s non-collapsibility has historically posed challenges when striving to guard against model misspecification through augmentation. We introduce a novel joint augmentation to the martingale-based full data estimating functions, and develop rate double robustness which allows the use of machine learning and non-parametric methods to overcoming the challenges of non-collapsibility. We closely examine its theoretical properties to guarantee rootn inference for the estimand. The estimator extends naturally to estimating a time-average treatment effect when the proportional hazards assumption fails, and we show that it satisfies both the assumption-lean and the well-specification criteria in the context of a causal estimand for censoring survival data; that is, it is a functional of the potential outcome distributions only, and does not depend on the treatment assignment mechanism, or the covariate distribution, or the censoring mechanism. The martingale based augmentation approach is also applicable to many semiparametric failure time models. Finally, its application to a dataset reveals insights into the impact of mid-life alcohol consumption on mortality in later life.
Trends in cutaneous malignant melanoma incidence, mortality and survival over three decades: a population-based study in Southern Spain
Authors: Ródenas-Herranz Teresa , Rodriguez-Barranco Miguel , Petrova Dafina , Pérez-Gómez Beatriz , Ruiz-Villaverde Ricardo , Sánchez María-José
Published: November 2024

Background

Cutaneous malignant melanoma (CMM) represents a global public health problem. Epidemiological studies about CMM trends tend to focus on single indicators or lack information about tumour characteristics that can help gain a more thorough understanding of CMM epidemiology.

Objectives

To fill this gap, we studied CMM trends in incidence, mortality and survival over three decades and that considered sex, age and tumour characteristics.

Methods

Data were obtained for all patients with a new diagnosis of CMM during 1985–2017 from the population-based cancer registry in Granada (Southern Spain) and for deaths owing to CMM from the Ministry of Health of the Spanish government. Incidence, mortality and survival estimates were obtained according to sex, age group, anatomical site, histological type, Breslow index and Clark level. Observed and net survival were calculated for 1, 3 and 5 years using the Kaplan–Meier and Pohar–Perme methods, respectively. Log-linear jointpoint regression was used to assess temporal trends in age-standardized rates of incidence and mortality.

Results

Between 1985 and 2017, 2446 patients aged ≥ 15 years were newly diagnosed with CMM. There was a significant increase in incidence, both in males and females (annual percentage of change 4.4% and 3.7%, respectively), mainly in superficial spreading and nodular melanomas, and more pronounced among those with < 1 mm Breslow index. Mortality rates increased, mainly driven by increases among males and individuals ≥ 65 years old. Nodular melanoma had the worst prognosis, with a 5-year net survival of 62.7% in the period 2008–2017 compared with survival > 90% for other subtypes. Overall 5-year net survival improved from 78.3% in 1985–1997 to 88.6% in 2008–2017, with a clear trend by Breslow index.

Conclusions

The incidence of melanoma in early stages in Southern Spain has increased over recent decades. This has been accompanied by noticeable improvements in mortality and survival, especially among younger age groups, suggesting the potential effectiveness of prevention strategies and new treatment regimens.
State-of-the-Art Review: Ocular Infections
Authors: Barshak Miriam B , Durand Marlene L , Gupta Akash , Mohareb Amir M , Dohlman Thomas H , Papaliodis George N
Published: November 2024

Collaborations between ophthalmologists and infectious disease specialists are critical for optimizing care of many patients with eye infections. We review challenges in common and uncommon eye infections to promote better understanding of these infections and prioritize areas for further research.
Capital nationality and long-run economic development
Authors: Klein Martins Guilherme
Published: November 2024

This article reviews different literature strands and performs empirical tests to identify new stylized facts on how capital ownership, particularly its nationality, relates to long-run economic development. The results indicate that low- and middle-income countries with larger foreign capital stock in 1980 had lower economic growth over the next four decades. The estimations also suggest that these economies developed a less specialized export basket, which became relatively more concentrated in low-tech goods. The results are inverted to high-income economies, for which the relationship is positive for GDP growth and export specialization and complexity. These stylized facts are in line with (and can be interpreted as a test to) the hypothesis proposed by Alice Amsden’s seminal book ‘The Rise of the Rest’ (2001) to explain different growth trajectories among developing countries. The results can also be interpreted in light of theoretical and empirical evidence that foreign capital might reinforce static comparative advantages in developing economies, particularly in middle-income ones.
Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses
Authors: Narinx Nick , Marriott Ross J , Murray Kevin , Adams Robert J , Ballantyne Christie M , Bauer Douglas C , Bhasin Shalender , Biggs Mary L , Cawthon Peggy M , Couper David J , Dobs Adrian S , Flicker Leon , Hankey Graeme J , Hannemann Anke , Wilkening Robin , Martin Sean A , Matsumoto Alvin M , Ohlsson Claes , O'Neill Terence W , Orwoll Eric S , Shores Molly M , Steveling Antje , Travison Thomas G , Wittert Gary A , Wu Frederick C W , Antonio Leen , Vanderschueren Dirk , Yeap Bu B
Published: November 2024

Objective

Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and “free” T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Design

This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study.

Methods

Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses.

Results

Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (−57.2 pmol/L [95% confidence interval, −69.4, −44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (−24.7 pmol/L [−29.1, −20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (−18.4 pmol/L [−27.6, −9.3]) and in men who formerly smoked (−5.7 pmol/L [−8.9, −2.6]), were in poor general health (−14.0 pmol/L [−20.1, −7.8]), and had diabetes (−19.6 pmol/L [−23.0, −16.3]), cardiovascular disease (−5.8 pmol/L [−8.3, −3.2]), or cancer (−19.2 pmol/L [−24.4, −14.1]).

Conclusions

Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.
General anaesthesia and deep sedation for monopolar pulsed field ablation using a lattice-tip catheter combined with a novel three-dimensional mapping system
Authors: Rillig Andreas , Hirokami Jun , Moser Fabian , Bordignon Stefano , Rottner Laura , Shota Tohoku , My Ilaria , Urbani Andrea , Lemoine Marc , Kheir Joseph , Schenker Niklas , Urbanek Lukas , Govorov Katarina , Schaack David , Obergassel Julius , Riess Jan , Ismaili Djemail , Kirchhof Paulus , Ouyang Feifan , Schmidt Boris , Reissmann Bruno , Chun Kyoung-Ryul Julian , Metzner Andreas
Published: November 2024

Aims

A novel three-dimensional mapping platform combined with a lattice-tip catheter that can toggle between monopolar pulsed field ablation (PFA) and radiofrequency energy delivery was recently launched. So far, the system was predominantly applied in general anaesthesia (GA), not in deep sedation.

Methods and results

Patients with symptomatic paroxysmal or persistent atrial fibrillation (AF) were enrolled, and pulmonary vein isolation (PVI) and ablation of additional linear lesion sets were performed either in GA or in deep sedation. Pulsed field ablation was applied exclusively to perform ipsilateral PVI. A total of 63 patients (35% female, 75% persistent AF, mean age 64 ± 9 years) were included in the analysis with 23 patients treated in GA and 40 patients in deep sedation. Acute efficacy was comparable in both groups with a PVI rate of 100%. Additional 74 lesion sets were performed in the total cohort. Mean procedure and lab occupancy time in the GA and deep sedation group was 96 ± 24 min vs. 100 ± 23 min (P = 0.52) and 165 ± 40 min vs. 131 ± 35 min (P = 0.0008). Mean dose area product was 489 (216;1093) vs. 452 (272;882) cGycm2 in the GA and the deep sedation group (P = 0.82). There was one conversion from deep sedation to GA. There were no map shifts observed in any group. Pericardial tamponade occurred in one patient of the deep sedation group.

Conclusion

The use of a novel ablation platform in conjunction with a lattice-tip catheter in deep sedation is feasible, effective, and associated with significantly shorter lab occupancy time when compared with GA.
Selection on sporulation strategies in a metapopulation can lead to coexistence
Authors: Proulx Stephen R , Sakal Taom , Reitz Zach L , Thomasson Kelly M
Published: November 2024

In constant environments, the coexistence of similar species or genotypes is generally limited. In a metapopulation context, however, types that utilize the same resource but are distributed along a competition–colonization trade-off can coexist. Prior work used a generic trade-off between within-deme competitive ability and between-deme dispersal ability. We show that sporulation in yeasts and other microbes can create a natural trade-off such that strains that initiate sporulation at higher rates suffer in terms of within-deme competition but benefit in terms of between deme dispersal. Using chemostat dynamics within patches, we first show that the rate of sporulation determines the colonization ability of the strain, with colonization ability increasing with sporulation rate up to a point. Metapopulation stability of a single strain exists in a defined range of sporulation rates. We pairwise invasability plots to show that coexistence of strains with different sporulation rates generally occurs, but that the set of sporulation rates that can potentially coexist is smaller than the set that allows for stable metapopulations. We also show how a continuous set of strains can coexist and verify our conclusions with numerical calculations and stochastic simulations. Stable variation in sporulation rates is expected under a wide range of ecological conditions.
The genetic architecture of hip shape and its role in the development of hip osteoarthritis and fracture
Authors: Faber Benjamin G , Frysz Monika , Zheng Jaiyi , Lin Huandong , Flynn Kaitlyn A , Ebsim Raja , Saunders Fiona R , Beynon Rhona , Gregory Jennifer S , Aspden Richard M , Harvey Nicholas C , Lindner Claudia , Cootes Timothy , Evans David M , Davey Smith George , Gao Xin , Wang Sijia , Kemp John P , Tobias Jonathan H
Published: November 2024

Objectives

Hip shape is thought to be an important causal risk factor for hip osteoarthritis and fracture. We aimed to identify genetic determinants of hip shape and use these to assess causal relationships with hip osteoarthritis.

Methods

Statistical hip shape modelling was used to derive 10 hip shape modes (HSMs) from DXA images in UK Biobank and Shanghai Changfeng cohorts (ntotal = 43 485). Genome-wide association study meta-analyses were conducted for each HSM. Two-sample Mendelian randomisation (MR) was used to estimate causal effects between HSM and hip osteoarthritis using hip fracture as a positive control.

Results

Analysis of the first 10 HSMs identified 203 independent association signals (P < 5 × 10−9). Hip shape SNPs were also associated (P < 2.5 × 10−4) with hip osteoarthritis (n = 26) and hip fracture (n = 4). Fine mapping implicated SMAD3 and PLEC as candidate genes that may be involved in the development of hip shape and hip osteoarthritis. MR analyses suggested there was no causal effect between any HSM and hip osteoarthritis, however there was evidence that HSM2 (more obtuse neck-shaft angle) and HSM4 (wider femoral neck) have a causal effect on hip fracture (ORIVW method 1.27 [95% CI 1.12–1.44], P = 1.79 × 10−4 and ORIVW 0.74 [0.65–0.84], P = 7.60 × 10−6 respectively).

Conclusions

We report the largest hip shape GWAS meta-analysis that identifies hundreds of novel loci, some of which are also associated with hip osteoarthritis and hip fracture. MR analyses suggest hip shape may not cause hip osteoarthritis but is implicated in hip fractures. Consequently, interventions targeting hip shape in older adults to prevent hip osteoarthritis may prove ineffective.
Tomato HAIRY MERISTEM4, expressed in the phloem, is required for proper shoot and fruit development
Authors: Khedia Jackson , Vishwakarma Abhay Pratap , Galsurker Ortal , Corem Shira , Gupta Suresh Kumar , Arazi Tzahi
Published: November 2024

The HAIRY MERISTEM (HAM) gene family encodes Type I and II GRAS domain transcriptional regulators in plants. Type II HAMs, predominantly expressed in meristems and regulated by microRNA171, are essential for maintaining undifferentiated meristems, a role conserved across various species. Conversely, the functions of Type I HAMs have been less characterized. In this study, we investigated the role of SlHAM4, a Type I HAM in tomato. CRISPR-induced SlHAM4 loss-of-function mutations (slham4CR) resulted in shoot and fruit abnormalities, which were fully reversed by reintroducing SlHAM4, driven by its native promoter, into the mutant background. Mutant abnormalities included simpler leaves and increased anthocyanin pigmentation in the leaf and sepal primordia, reminiscent of phenotypes observed in certain Arabidopsis mutants with compromised phloem. In addition, slham4CR plants produced significantly smaller fruits with a subset developing catface-like scars, attributed to tears that occurred in the pericarp of setting fruits. Using a GUS reporter gene driven by the native SlHAM4 promoter, we found that SlHAM4 is predominantly expressed in phloem tissues. Consistent with this, transcriptome analysis of mutant anthesis ovaries revealed specific downregulation of genes implicated in phloem development and function, particularly those expressed in companion cells. However, histological analysis showed no obvious abnormalities in phloem vasculature. Taken together, our data suggest that SlHAM4 plays a role in shoot and fruit development likely by regulating genes essential for phloem function.
SoNAC72-SoMYB44/SobHLH130 module contributes to flower color fading via regulating anthocyanin biosynthesis by directly binding to the SoUFGT1 promoter in lilac (Syringa oblata)
Authors: Wang Jinxuan , Wang Xin , Ma Bo , Leng Pingsheng , Wu Jing , Hu Zenghui
Published: November 2024

The fading of flower color is caused by changes of anthocyanin content during flower development in many plants, including lilac (Syringa oblata). However, the molecular regulatory mechanism of this phenomenon is still poorly understood. UDP-glucose: flavonoid 3-O-glucosyltransferase (UFGT) has a pivotal role in the formation of stable anthocyanins. Here, SoUFGT1 and three transcription factors, SoMYB44, SobHLH130, and SoNAC72, were identified and verified to participate in anthocyanin production in lilac. Overexpressing SoMYB44 promoted SoUFGT1 expression in lilac petals. The yeast one-hybrid (Y1H) and dual-luciferase (Dual-LUC) assays demonstrated that SoMYB44 activated SoUFGT1, thereby bolstering anthocyanin accumulation. The overexpression and silencing of SoNAC72 in petals revealed that it facilitated anthocyanin accumulation. The Y1H and Dual-LUC assays verified that SoNAC72 was capable of directly binding to the SoMYB44 promoter to activate the latter’s expression. In addition, SobHLH130 was also displayed to mediate anthocyanin accumulation in petals. By using yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays, the interaction between SoMYB44 and SobHLH130 was confirmed. These results corroborated that SoNAC72 regulates SoMYB44 expression, and SoMYB44 interacts with SobHLH130 to trigger SoUFGT1 expression in lilac, which then contributes to their anthocyanin accumulation. In sum, along with lilac flower development, the lower expression of SoNAC72 and SobHLH130 reduces SoMYB44 transcripts and depresses transcriptional regulation of SoUFGT1, thus diminishing anthocyanin biosynthesis, leading to the fading of petal color. These study’s findings provide valuable new insight for understanding the formation and regulatory mechanisms of flower color in lilac.
Genotype III-Based Japanese Encephalitis Vaccines Exhibit Diminished Neutralizing Response to Reemerging Genotype V
Authors: Lee Ah-Ra , Kim Woo-Jin , Choi Haeyoun , Kim Sang-Hyun , Hong Su-Yeon , Shim Sang-Mu , Lee Hee Il , Song Jae Min , Kim Seong-Jun , Ishikawa Tomohiro , Kang Ji-Man , Eom Hyeon-Seok , Seo Sang-Uk
Published: November 2024

Background

Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge.

Methods

Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing seroresponse to GV isolates.

Results

Serum from immunocompromised pediatric patients vaccinated with an inactivated JE vaccine showed higher 50% plaque reduction neutralization test geometric mean titer (GMT) against GIII Nakayama (11 358; 95% confidence interval [CI], 1790–29 658), but lower GMTs against GV isolates: GV Muar (499; 95% CI, 0–2437), GV 43279 (308; 95% CI, 159–582), and GV 43413 (231; 95% CI, 108–738). Similarly, 32 healthy volunteers receiving a live attenuated JE vaccine achieved 100% seroprotection against GIII Nakayama with GMT of 338 (95% CI, 304–651) at 1 month postvaccination. However, GMTs against GV isolates were 123 (95% CI, 102–446) for GV Muar, 81 (95% CI, 63–168) for GV 43279, and 107 (95% CI, 100–322) for GV 43413, not achieving 100% seroprotection against these isolates. At 6 months postvaccination, GMT against Nakayama increased to 696 (95% CI, 409–2353), while remaining similar for GV isolates.

Conclusions

Our study underscores that current GIII-based vaccines do not provide comparable protection against GV JEVs, impacting individuals in both current and potential endemic regions, as well as travelers to these regions.
Portfolios, pools and public intervention—IP strategies for a greener future?
Authors: Mocanu Alex
Published: November 2024

The Paris Agreement 2015 recognizes the importance of technology in addressing the threat of climate change. Article 10 specifically states that: ‘[a]ccelerating encouraging and enabling innovation is critical for an effective, long-term global response to climate change.’ However, what the Agreement fails to consider is how to resolve the tension between intellectual property rights, technology transfer and climate change. Renewable firms are facing growing pressure to develop and ensure transfer of green technology on a global scale—but at what cost to their IP rights? This article analyses whether renewable firms will rely on either patents or trade secrecy as the primary means of IP protection. We argue that patents will remain the central form of IP protection due to their strategic application: (i) to settle disputes via licensing agreements and (ii) to control technology development in the standardization process. Patents, via the mechanism of patent pools, provide the perfect balance between addressing the global public interest in tackling climate change and protecting private proprietary rights.
Cellulose degradation in Glenea cantor (Fabricius) (Coleoptera: Cerambycidae): functional characterization of GcEGaseZ7 and Cellulase reveals a novel enzymatic activity
Authors: Su Ran-Ran , Lan Tai-Hui , Pan Bi-Qiong , Zheng Xia-Lin , Lu Wen , Wang Xiao-Yun
Published: November 2024

Glenea cantor (Fabricius) is an important forest pest that mainly attacks kapok trees, breaking down cellulose and lignin through 3 enzyme activities: endoglucanase, filter paper enzyme, and cellobiase. In this study, we unveiled the cloning and expression of 10 endoglucanase genes, GcEGase5A1, GcEGase5A2, GcEGaseZ2, GcEGaseZ3, GcEGaseZ4, GcEGaseZ5, GcEGaseZ7, GcEGaseZ8, GcEGaseZ9, and Cellulase, all of which exhibit enzymatic activities in G. cantor. These findings indicated that Cellulase shares sequence homology with beetle GHF45, whereas the other 9 endoglucanase genes are homologous to beetle GHF5. GcEGaseZ4 presented the highest expression in the foregut. In contrast, GcEGase5A2 and Cellulase presented peak expression in the midgut. Furthermore, GcEGaseZ7 was identified as the most highly expressed endoglucanase in the hindgut. Functional assays confirmed the ability of GcEGaseZ7 and Cellulase to degrade cellulose, and their cellulase activities were 75.57 ± 1.21 U/mg and 344.79 ± 6.91 U/mg, respectively. These results enhance our understanding of the complex cellulase system in insects and provide insights into the efficient digestion of cellulosic materials by wood-consuming insects. This research also has potential applications in bioenergy production and the development of biomaterials from lignocellulosic biomass.
Developmental stage and level of submersion in water impact the viability of lone star and winter tick eggs
Authors: Alhawsawi Maher Ramadan I , Lewis David A , Frigard Ronja A , Smith Ellen M , Sivakumar Jaishna , Sharma Ajay M , Nantz Adalynn R , Sabile Chloe Elizabeth G , Kennedy Jasmine , Loni Rashi , LeFevre Gabrielle , Vaka Akshita , Leanza Quinn , Kelley Melissa , Stacey Crystal L , Santhosh Richa A , Catlett Nathan , Cady Tabitha L , Rizvi Raaidh S , Wagner Zach , Olafson Pia U , Benoit Joshua B
Published: November 2024

Female ticks deposit large egg clusters that range in size from hundreds to thousands. These egg clusters are restricted to a deposition site as they are stationary, usually under leaf litter and other debris. In some habitats, these sites can be exposed to periodic flooding. When the clusters of tick eggs are disturbed, they may float to the surface or remain underneath organic debris entirely submerged underwater. Here, we examined the viability of egg clusters from winter ticks, Dermacentor albipictus, and lone star ticks, Amblyomma americanum, when partially or fully submerged in water and in relation to the developmental stages of the eggs under lab conditions. In general, egg clusters that were older and partially submerged had a higher viability than fully submerged, younger eggs. Of the two species, A. americanum was more resistant to water exposure. These studies highlight that egg clusters for certain tick species can remain viable when exposed to water for at least two weeks. These results also suggest that distribution by flooding of egg clusters could occur for some species and water submersion will differentially impact tick egg survival based on the specific developmental stage of exposure and species.
UNHCR–state relations: transfer of authority over refugee status determination
Authors: Ozkul Derya , Welfens Natalie
Published: November 2024

In over 50 states, United Nations High Commissioner for Refugees (UNHCR) conducts refugee status determination (RSD) but engages in various ‘capacity building’ initiatives to ultimately transfer or ‘hand over’ authority over RSD to states. In this article, we examine the recently concluded RSD-handover process in Turkey as a case study to analyse the power dynamics between UNHCR and states. Drawing on constructionist theories of international organizations and practice theory, we examine handovers as the interplay between UNHCR promoting RSD norms and practices and states’ interpretation and adaptation of the latter. Based on desk-based research and interviews with UNHCR officials, we outline the RSD-handover in Turkey in three stages and show that both parties engage in ongoing negotiations within an evolving community of practice. Using a multifaceted theorization of authority, we argue that even if formally delegated authority over RSD is transferred, the broader authority and power relations operate in a co-constituted way between the two parties.
Optimization and scaling up of extracellular polysaccharide production by submerged culture of Ganoderma lucidum on starch-containing medium using response surface methodology and laboratory bioreactors of various designs
Authors: Tikhomirova Tatyana S , Taraskevich Maxim R , Lepekhin Yuriy A , Shevelyova Marina P , Nemashkalov Vitaliy A
Published: November 2024

Basidiomycetes, known for their production of bioactive compounds, traditionally use simple sugars for fermentation. However, their ability to degrade complex plant polysaccharides through enzyme secretion presents potential for the use of renewable raw materials. This study focused on the optimization of exopolysaccharide (EPS) production and efficient substrate consumption by Ganoderma lucidum using response surface methodology (RSM). Using an optimized medium containing 15 g⋅l−1 wheat starch, 0.375 g⋅l−1 NH4Cl, and 0.75 g⋅l−1 CaCl2 (C/N ratio of 40), a significant increase in EPS concentration from 121.1 ± 10.2 mg⋅l−1 to 229.0 ± 20.3 mg⋅l−1 and starch degradation degree (SDD) from 9.1% to 57.6% was achieved after 9 d of submerged cultivation. Scale-up experiments were conducted in both column and stirred tank bioreactors, employing submerged and immobilized cultivation modes. Submerged cultivation in the column bioreactor yielded the highest process desirability of 0.56, achieving EPS concentration of 192.5 ± 5.4 mg⋅l−1 and 60.2% SDD within 7 d. These results highlight the potential of the used column bioreactor for efficient and rapid EPS production. Notably, bioreactor experiments revealed local maxima in EPS content at specific time points, suggesting that cell wall degradation, potentially induced by shear stress, may contribute to the release of polysaccharides into the culture broth.
Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC–MS/MS
Authors: Mendes Marisa I , Wolf Nicole I , Rudinger-Thirion Joëlle , Lenz Dominic , Frugier Magali , Verloo Patrick , Mandel Hanna , Manor Joshua , Kassel Rachel , Corpeleijn Willemijn E , van der Rijt Sanne , Schroor Elsbeth M , van Dooren Silvy J M , Staufner Christian , Salomons Gajja S , Smith Desirée E C
Published: November 2024

In recent years, pathogenic variants in ARS genes, encoding aminoacyl-tRNA synthetases (aaRSs), have been associated with human disease. Patients harbouring pathogenic variants in ARS genes have clinical signs partly unique to certain aaRSs defects, partly overlapping between the different aaRSs defects. Diagnosis relies mostly on genetics and remains challenging, often requiring functional validation of new ARS variants. In this study, we present the development and validation of a method to simultaneously determine aminoacylation activities of all cytosolic aaRSs (encoded by ARS1 genes) in one single cell lysate, improving diagnosis in suspected ARS1 disorders and facilitating functional characterization of ARS1 variants of unknown significance. As proof of concept, we show enzyme activities of five individuals with variants in different ARS1 genes, demonstrating the usability and convenience of the presented method.
Neutralizing the IL-7Rα limits injury in experimental ANCA-associated glomerulonephritis
Authors: Alikhan Maliha A , Kishimoto Kazuya , Wong Limy , Prakongtham Peemapat , Auden Alana , O'Sullivan Kim M , Jaw Juli , Kitching A Richard
Published: November 2024

Background and hypothesis

Increased T-cell interkeukin (IL)-7Rα signalling is associated with a poorer prognosis in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These studies examined the functional role of IL-7Rα (CD127) in experimental glomerulonephritis mediated by anti-myeloperoxidase (MPO) T-cell autoimmunity. We hypothesized that T cells would express IL-7Rα in the kidney and that blocking the function of IL-7Rα, without cellular depletion, would be protective.

Methods

Mice were immunized with mouse MPO, then low-dose sheep anti-mouse basement membrane globulin was administered to trigger glomerulonephritis. Flow cytometry and RNA-sequencing characterized intrarenal CD127+-expressing CD4+ and CD8+ T cells in mice with anti-MPO glomerulonephritis. To assess the functional role of IL-7Rα, mice with established anti-MPO autoimmunity were treated with anti-IL-7Rα antibodies.

Results

Control ovalbumin-immunized mice given anti-basement membrane globulin developed minimal injury, while MPO-immunized mice given anti-basement membrane globulin developed albuminuria with glomerular and tubulointerstitial injury. Numbers of intrarenal IL-7Rα+ (CD127+) CD4+ and CD8+ T cells were increased in mice with anti-MPO glomerulonephritis. There were 3738 and 2726 genes differentially expressed between intrarenal CD127−PD-1+ and CD127+PD-1− CD8+ and CD4+ T cells, respectively, with substantially overlapping differentially expressed genes between CD8+ and CD4+ T cells. Both CD127−PD-1+ CD8+ and CD4+ T cells were enriched for previously described T-cell exhaustion signatures associated with prognosis in autoimmune disease. As effector memory T cells drive inflammation, we blocked the IL-7Rα after inducing anti-MPO autoimmunity. Anti-IL-7Rα antibodies limited histological injury, and reduced albuminuria numbers of glomerular and interstitial leucocytes, with reduced intrarenal chemokine and pro-inflammatory cytokine expression.

Conclusions

Intrarenal effector memory and exhausted CD4+ and CD8+ T cells are present in experimental anti-MPO glomerulonephritis. Neutralizing effector T cells via the IL-7Rα after the induction of autoimmunity limits intrarenal inflammation and disease. IL-7Rα may be a therapeutic target in ANCA-associated vasculitis.
Reactions to a Hypothetical Reduced Nicotine Content Cigarette Policy Among Sexual- and Gender-Minoritized Communities: A Concept Mapping Study
Authors: Sawyer-Mays Ashlee N , Combs Madison , Anbil Akansha , Rudy Alyssa K , Lee Joseph G L , Breland Alison , Soule Eric K
Published: November 2024

Background

People who identify as sexual- and/or gender-minoritized (SGM) individuals have a high prevalence of cigarette smoking. This study used concept mapping to examine anticipated reactions to a hypothetical cigarette nicotine reduction policy among SGM individuals in the United States.

Aims and Methods

In 2022, SGM individuals who reported past-month cigarette smoking (mean age = 33.3) were recruited from 44 US states through Craigslist advertisements to complete an online study. Participants brainstormed statements completing the prompt, “If all cigarettes sold in the United States only had half the nicotine in them that they do now, a specific action I would take or a specific reaction I would have is….” Participants sorted statements by theme and rated statements based on how likely each reaction would be for them. Ninety participants completed at least one part of the study (56, 64, and 73 participants completed brainstorming, sorting, and rating, respectively).

Results

Participants generated 100 statements that were organized into seven thematic clusters using multidimensional scaling and hierarchical cluster analysis. The clusters fell into three broad categories: (1) Thoughts and Reactions to the Ban, (2) Positive Preparations and Action Strategies, and (3) Maintaining Substance Use. The highest-rated clusters among participants were Questioning and Wondering (M = 4.63), Negative Reactions (M = 4.38), and Increasing Intake (M = 4.30), while the lowest-rated cluster was Improving Public Health (M = 3.56).

Conclusions

A policy reducing nicotine content in cigarettes may have a positive impact on SGM individuals who smoke. Health communication campaigns highlighting the purpose and goals of the policy may increase receptiveness to a policy.

Implications

People who identify as SGM individuals have a higher prevalence of cigarette smoking compared to those who do not identify as SGM individuals. A policy reducing the nicotine content in cigarettes may promote smoking cessation or prevent cigarette initiation and, thus, may have a greater impact on SGM people who smoke. However, data from the current study indicate that SGM individuals may be suspicious of the intentions of a policy setting a reduced nicotine content cigarette product standard. This study demonstrates that, while a reduced-nicotine content cigarette policy may have positive public health impacts, regulators should consider how the policy will be communicated to the public to increase the acceptability and effectiveness of the policy.
Divergence in vocalizations indicates cryptic speciation in Camptostoma tyrannulets
Authors: Lima Rafael Dantas , Vaz Ruan Vieira
Published: November 2024

The tyrant flycatcher genus Camptostoma currently comprises 2 visually similar species: C. imberbe (Northern Beardless-Tyrannulet), ranging from the southern United States to Costa Rica, and C. obsoletum (Southern Beardless-Tyrannulet), found from Costa Rica to Uruguay. Vocal and genetic differences have suggested that C. obsoletum may include multiple species, but no analysis of acoustic trait variation has been conducted within the genus. We analyzed a geographically comprehensive sample of sound recordings to measure geographic variation in vocalizations across the genus, testing the hypothesis that C. obsoletum includes multiple species. We find that Camptostoma comprises 8 vocally distinct populations, 2 within C. imberbe and 6 within C. obsoletum. These populations exhibit diagnostic differences in multiple different vocalizations, including vocalization types that are typically species-specific in the Tyrannidae. Their range limits and contact zones largely correspond with known dispersal barriers, ecotones, and suture zones, with little evidence of gene flow between adjacent populations. Our results strongly suggest that Camptostoma comprises as many as 8 vocally distinct biological species, underscoring the underestimated diversity of species in birds with conservative plumage evolution.
Leveraging automated technologies for law-making in Italy: Generative AI and constitutional challenges
Authors: Citino Ylenia Maria
Published: November 2024

As GenAI use intensifies, it is necessary to start reflecting on how AI might affect parliamentary work. The paper describes the paradigmatic case of the Italian Chamber of Deputies as one of the first parliaments to implement GenAI technologies in the legislative procedure. The goal of the research is to identify the constitutional challenges and seek remedies to them. The integration of information technology into daily parliamentary activities intersects with the democratic underpinnings of political representation, such as neutrality, transparency, and political legitimacy. At the same time, digitization affects the invisible dimension of parliamentary work, which goes beyond codified rules of procedures and remains confidential. Still, it is crucial for the smooth functioning of parliamentary assemblies. The remainder of this paper is structured into four sections. After a brief explanation of how GenAI works, it describes why parliaments have to be dealt with distinctively and what the current AI practices embraced by the Italian Parliament are. It provides an in-depth insight into the functioning of software used for processing amendments in the legislative procedure. In the end, it assesses the existing practices from a constitutional standpoint.
Tools to understand hypoxia responses in plant tissues
Authors: Panicucci Gabriele , Barreto Pedro , Herzog Max , Lichtenauer Sophie , Schwarzländer Markus , Pedersen Ole , Weits Daan A
Published: November 2024

Our understanding of how low oxygen (O2) conditions arise in plant tissues and how they shape specific responses has seen major advancement in recent years. Important drivers have been (1) the discovery of the molecular machinery that underpins plant O2 sensing; and (2) a growing set of dedicated tools to define experimental conditions and assess plant responses with increasing accuracy and resolution. While some of those tools, such as the Clark-type O2 electrode, were established decades ago, recent customization has set entirely new standards and enabled novel research avenues in plant hypoxia research. Other tools, such as optical hypoxia reporters and O2 biosensor systems, have been introduced more recently. Yet, their adoption into plant hypoxia research has started to generate novel insight into hypoxia physiology at the tissue and cellular levels. The aim of this update is to provide an overview of the currently available and emerging tools for O2 hypoxia measurements in plants, with an emphasis on high-resolution analyses in living plant tissues and cells. Furthermore, it offers directions for future development and deployment of tools to aid progress with the most pressing questions in plant hypoxia research.
Diabetic Foot Ulcer Beyond Wound Closure: Clinical Practice Guideline
Authors: Wendland Deborah M , Altenburger Elizabeth A , Swen Shelley B , Haan Jaimee D
Published: November 2024

A total of 37.3 million Americans have diabetes, and 96 million more have prediabetes. Hyperglycemia, the hallmark of diabetes, increases the risk for diabetes-related complications, including skin breakdown and cardiovascular disease. Many clinical practice guidelines exist, but there are gaps regarding the best approaches to assess physical fitness and mobility in adults with diabetes; incorporate exercise into the care plan; and reload the diabetic foot after ulcer closure has occurred to avoid ulcer reoccurrence. The purpose of this clinical practice guideline was to review and assess previously published guidelines and address gaps within the guidelines specific to the following: best screening tools/tests and interventions to prevent a future reulceration, best screening tools and interventions to assess and address mobility impairments, best tools to measure and interventions to address reduced physical fitness and activity, best approach to reloading the foot after ulceration closure and, finally, whether improvement in physical fitness will positively change quality of life and health care costs. The Guidelines Development Group performed a systematic literature search and review of the literature. A total of 701 studies were identified. Following duplicate removal and exclusion for irrelevance, 125 studies underwent full-text review, and 38 studies were included. Recommendations were developed using a software assistant created specifically for guideline recommendation development. Recommendations resulted for physical fitness and activity inclusion and measurement for adults with diabetes and with or without foot ulceration. Exercise and physical activity should be prescribed according to the physiologic response of an adult with diabetes to exercise and preferences for optimizing long-term quality of life and reduce health care costs. Reloading following diabetic foot ulcer closure should include maximal offloading, especially during the first 3 months; loading should be titrated using a footwear schedule. Further research is necessary in the areas of exercise in the wound healing process and the assessment of methods to reload a newly reepithelialized ulcer to prevent recurrence.
Altered default-mode and frontal-parietal network pattern underlie adaptiveness of emotion regulation flexibility following task-switch training
Authors: Gao Wei , Biswal Bharat , Zhou Xinqi , Xiao Zhibing , Yang Jiemin , Li Yanping , Yuan JiaJin
Published: November 2024

Emotion regulation flexibility (ERF) refers to one’s ability to respond flexibly in complex environments. Adaptiveness of ERF has been associated with cognitive flexibility, which can be improved by task-switching training. However, the impact of task-switching training on ERF and its underlying neural mechanisms remain unclear. To address this issue, we examined the effects of training on individuals’ adaptiveness of ERF by assessing altered brain network patterns. Two groups of participants completed behavioral experiments and resting-state fMRI before and after training. Behavioral results showed higher adaptiveness scores and network analysis observed a higher number of connectivity edges, in the training group compared to the control group. Moreover, we found decreased connectivity strength within the default mode network (DMN) and increased connectivity strength within the frontoparietal network (FPN) in the training group. Furthermore, the task-switch training also led to decreased DMN–FPN interconnectivity, which was significantly correlated to increased adaptiveness of ERF scores. These findings suggest that the adaptiveness of ERF can be supported by altered patterns with the brain network through task-switch training, especially the increased network segregation between the DMN and FPN.
Mission cocreation or domination? Explorative and exploitative forces in shaping the Dutch circular agriculture mission
Authors: Klerkx Laurens , Begemann Stephanie , Janssen Matthijs
Published: November 2024

One largely neglected focus in the analysis of mission-oriented innovation policies is mission cocreation between stakeholder groups advocating different solution directions. In this paper, we introduce the innovation management concept of ambidexterity to study how mission cocreation in different mission arenas is influenced by actors aiming to continue existing innovation pathways (exploitative innovation) and actors advocating alternative pathways (explorative innovation). Our case study on the Dutch circular agriculture mission highlights how an initial top-down strategy development was dominated by exploitative forces, despite ambitions to secure broad stakeholder participation. Government-led efforts to still engage exploration-minded actors, and restore ambidexterity, were hampered by potential contributors feeling excluded from the policy process. These findings underline the risk that openness of missions, required for broad stakeholder involvement, might also reinforce pre-existing contestation and innovation pathways. Overall, our findings demonstrate a trade-off between maximizing efficiency and speed versus obtaining novel perspectives and wide societal legitimacy.