bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doubly Robust Estimation under Possibly Misspecified Marginal Structural Cox Model
Authors: Luo Jiyu , Rava Denise , Bradic Jelena , Xu Ronghui 
Published: November 2024

SUMMARY
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

Abstract

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 &lt; 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 &gt; 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.
Capital nationality and long-run economic development
Authors: Klein Martins Guilherme 
Published: November 2024

Abstract
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

Abstract

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 &lt; 23.6 kg/m2, but decreased among men with BMI &gt; 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

Abstract

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

Abstract
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

Abstract

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 &lt; 5 × 10−9). Hip shape SNPs were also associated (P &lt; 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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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.