bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Uplift and Exhumation of the Southeastern Tibetan Plateau: Evidence from Low‐Temperature Thermochronology
Authors: WU Limin , PENG Touping , FAN Weiming , ZHAO Guochun , GAO Jianfeng , DONG Xiaohan , PENG Shili , MIN Kang , MYINT Tin Aung
Published: April 2024

Since the Cenozoic, the Tibetan Plateau has experienced large‐scale uplift and outgrowth due to the India–Asia collision. However, the mechanism and timing of these tectonic processes still remain debated. Here, using apatite fission track dating and inverse thermal modeling, we explore the mechanism of different phases of rapid cooling for different batholiths and intrusions in the southeastern Tibetan Plateau. In contrast to previous views, we find that the coeval granitic batholith exposed in the same tectonic zone experienced differential fast uplift in different sites, indicating that the present Tibetan Plateau was the result of differential uplift rather than the entire lithosphere uplift related to lithospheric collapse during Cenozoic times. In addition, we also suggest that the 5–2 Ma mantle‐related magmatism should be regarded as the critical trigger for the widely coeval cooling event in the southeastern Tibetan Plateau, because it led to the increase in atmospheric CO2 level and a hotter upper crust than before, which are efficient for suddenly fast rock weathering and erosion. Finally, we propose that the current landform of the southeastern Tibetan Plateau was the combined influences of tectonic and climate.
An epigenetic candidate–gene association study of parental styles in suicide attempters with substance use disorders
Authors: Chrétienneau Clara , Spindola Leticia M. , Vorspan Florence , Lagerberg Trine Vik , Marie‐Claire Cynthia , Bellivier Frank , Mouly Stéphane , Laplanche Jean‐Louis , Bloch Vanessa , Le Hellard Stéphanie , Icick Romain
Published: April 2024

Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic–pituitary–adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi‐structured interview. Parental style was patient‐reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in OXTR, CRH and NTF3 significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from FKBP5 and SOCS3 significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients.
Larval competition between three endemic fruit flies (Diptera: Tephritidae) of differing phylogenetic relatedness
Authors: Kay Bianca J. , Harris Colin , Clarke Anthony R.
Published: April 2024

Within a fruit, fruit fly larvae can be subject to scramble competition, in which density‐dependent effects can influence the fitness of subsequent adults. While there is significant research on tephritid interspecific larval competition, it has been conducted in invasive situations where the species are evolutionarily novel to each other. There has been no published research investigating larval competitive interactions between naturally coexisting, endemic species. We ran laboratory‐based, intraspecific and interspecific larval competition trials involving three co‐occurring Bactrocera species of differing genetic relatedness and also measured aspects of juvenile development rate to test possible mechanisms of competitive difference. Larval density had an influence on intraspecific competition in Bactrocera tryoni, Bactrocera neohumeralis and Bactrocera jarvisi, with a decreasing percentage of pupation with increasing larval density. Interspecific competition between B. tryoni and B. neohumeralis, and between B. tryoni and B. jarvisi was influenced by the interaction between species and density. The intensity of competition between B. tryoni and B. neohumeralis was minimal but high between B. tryoni and B. jarvisi. B. jarvisi produced larger eggs and had faster initial larval growth rates than the other two species, but it took the longest time for pupation to occur. Our results conflict with theory, as the greatest competition was observed between the two more distantly related species (B. tryoni and B. jarvisi) rather than between the two most closely related species (B. tryoni and B. neohumeralis). Further, and contrary to other studies, egg size, hatch rate and larval growth rate did not provide B. jarvisi with a competitive advantage; thus, larval size does not appear to be a mechanism of larval competition between B. tryoni and B. jarvisi.
Whole‐genome resequencing uncovers diversity and selective sweep in Kazakh cattle
Authors: Xu Lei , Zhang Yunyun , Guo Yang , Chen Qiuming , Zhang Menghua , Chen Hong , Geng Juan , Huang Xixia
Published: April 2024

The Kazakh cattle in the Xinjiang Uygur Autonomous Region of China are highly adaptable and have multiple uses, including milk and meat production, and use as draft animals. They are an excellent original breed that could be enhanced by breeding and hybrid improvement. However, the genomic diversity and signature of selection underlying the germplasm characteristics require further elucidation. Herein, we evaluated 26 Kazakh cattle genomes in comparison with 103 genomes of seven other cattle breeds from regions around the world to assess the Kazakh cattle genetic variability. We revealed that the relatively low linkage disequilibrium at large SNP distances was strongly correlated with the largest effective population size among Kazakh cattle. Using population structural analysis, we next demonstrated a taurine lineage with restricted Bos indicus introgression among Kazakh cattle. Notably, we identified putative selected genes associated with resistance to disease and body size within Kazakh cattle. Together, our findings shed light on the evolutionary history and breeding profile of Kazakh cattle, as well as offering indispensable resources for germplasm resource conservation and crossbreeding program implementation.
Differential price pass‐through in organic and conventional fresh fruit and vegetable markets
Authors: Li Qingxiao , Çakır Metin , Beatty Timothy K. M. , Park Timothy A.
Published: April 2024

Organic food production growth has remained relatively slow compared to organic retail sales growth in the United States. This paper questions whether the conduct of downstream agents plays any role in explaining the difference. Mainly, we shed light on structural differences between organic and conventional fresh fruit and vegetable markets by examining differential price pass‐through rates. We estimate a rolling‐window retail pricing model using retail and wholesale price data from five metropolitan statistical areas with terminal markets in the United States. We find that pass‐through rates are 10 to 15 percentage points lower in the organic market, and the differences are statistically significant. We also find that the gap between pass‐through rates narrows as the organic market share increases. Our results suggest the organic market is significantly less competitive than the conventional market. The implication is that farmers may have less incentive to convert to organic farming as they may not capture the full retail price premium consumers pay.
Trans men can achieve adequate muscular development through low‐dose testosterone therapy: A long‐term study on body composition changes
Authors: Tominaga Yusuke , Kobayashi Tomoko , Matsumoto Yuko , Moriwake Takatoshi , Oshima Yoshitaka , Okumura Misa , Horii Satoshi , Sadahira Takuya , Katayama Satoshi , Iwata Takehiro , Nishimura Shingo , Bekku Kensuke , Edamura Kohei , Sugimoto Morito , Kobayashi Yasuyuki , Watanabe Masami , Namba Yuzaburo , Matsumoto Yosuke , Nakatsuka Mikiya , Araki Motoo
Published: April 2024

Background

Transgender individuals undergo the gender‐affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long‐term safety and efficacy of GAHT.

Objectives

To investigate the long‐term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose.

Materials and methods

Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low‐dose group (≤ 62.5 mg/wk) to a high‐dose group (> 62.5 mg/wk).

Results

Of 291 participants, 188 patients (64.6%) were in the low‐dose group and 103 (35.4%) in the high‐dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high‐dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long‐term, dose‐dependent side effects such as polycythemia or dyslipidemia.

Conclusion

Long‐term GAHT for trans men is safe and effective. Low‐dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.
Choroidal hyperpermeability patterns correlate with disease severity in central serous chorioretinopathy: CERTAIN study report 2
Authors: Pauleikhoff Laurenz J. B. , Diederen Roselie M. H. , Chang‐Wolf Jennifer M. , Moll Annette C. , Schlingemann Reinier O. , van Dijk Elon H. C. , Boon Camiel J. F.
Published: April 2024

Purpose

Choroidal vascular hyperpermeability (CVH) on indocyanine green angiography (ICGA) is a hallmark feature of central serous chorioretinopathy (CSC). We identified three distinct CVH phenotypes in CSC: uni‐focal indistinct signs of choroidal hyperpermeability (uni‐FISH) with one focal area of CVH, multiple areas of focal CVH (multi‐FISH), and diffuse hyperpermeability covering most of the posterior pole (DISH). This report investigates the distribution of these phenotypes and their association with signs of disease chronicity.

Methods

The CERTAIN study is a monocentric, retrospective study on consecutive CSC patients referred to a large tertiary referral centre that underwent ultra‐widefield (UWF) and 55° ICGA. Two independent graders assessed CVH patterns based on mid‐ to late‐phase UWF and 55° ICGA with a third grader acting as referee.

Results

Of the 167 eyes of 91 patients included in this study, 43 (26%) showed uni‐FISH, 87 (52%) multi‐FISH, and 34 (20%) showed DISH based on UWF ICGA. Median age (40 vs. 45 vs. 57; p < 0.001) and logMAR visual acuity (0 vs. 0 vs. 0.1, p < 0.001) differed significantly in‐between groups, as did the occurrence of cystoid retinal degeneration (PCRD; 0% vs. 1% vs. 18%, p < 0.001) or diffuse atrophic RPE alterations (DARA; 0% vs. 17% vs. 29%, p < 0.001). The same was true when grading was based on 55° ICGA.

Conclusions

The CVH patterns of uni‐FISH, multi‐FISH, and DISH are typical of CSC. These patterns correlate with established signs of CSC chronicity. Their predictive role in treatment response and prognosis remains to be evaluated.
Moral obligation, autonomous motivation and vaccine hesitancy: Highlighting moral obligation increases reactance in hesitant individuals
Authors: Pavey Louisa , Rotella Amanda , Vallée‐Tourangeau Gaelle
Published: April 2024

Vaccine hesitancy is widespread, and developing effective communication strategies that encourage hesitant individuals to choose vaccination is essential. This pre‐registered research aimed to examine associations among moral obligation, autonomous motivation, vaccination intentions and reactance, and to test messages highlighting moral obligation and autonomy support. In Study 1, participants who had not received a Covid‐19 vaccine (N = 1036) completed measures of autonomous motivation, moral obligation, reactance, intentions to vaccinate and vaccine hesitancy. Autonomous motivation and moral obligation emerged as strong independent predictors of lower reactance, lower hesitancy and greater vaccination intentions. In Study 2 (N = 429), the participants received a vaccination‐promoting message that highlighted moral obligation versus personal protection and used autonomy supportive versus controlling language. Messages with autonomy‐supportive language and highlighting personal protection elicited lower reactance and greater perceived legitimacy compared to messages with controlling language and highlighting moral obligation. All messages elicited greater reactance and lower perceived legitimacy compared to an information‐only message, and there were no effects of message type on vaccination intentions or vaccine hesitancy. The research has implications for the design of communications encouraging vaccination in hesitant individuals and suggests caution should be taken when developing messages to encourage vaccination in hesitant individuals.
Firing technology and physicochemical basis for porcelain from the Xing kiln in the late sixth century
Authors: Zong Ruofei , Lu Xiaoke , Li Weidong , Xu Changsong
Published: April 2024

The rise of porcelain industry in northern China and the subsequent emergence of white porcelain production during the Northern dynasties (386–581 CE) played a pivotal role in shaping the historical trajectory of Chinese ceramics. Xing kiln is one of China's earliest and most representative white porcelain kilns. Herein, we investigated 23 porcelain sherds from the Neiqiu Xing kiln site during the late Northern dynasties and the early Sui dynasty (550–600 CE) from the perspective of firing temperature, firing atmosphere, and microstructure using a dilatometer, X‐ray photoelectron spectroscopy, and scanning electron microscopy. The results show that the early Xing porcelains were fired at high firing temperatures exceeding 1200°C with a reducing flame, and the adjustment of temperature promotes the emergence of early white porcelain. Moreover, the higher firing temperature of early Xing porcelain leads to the dominance of a glassy phase within the glaze, and the high bonding strength of the glaze and body caused by the body–glaze interaction layer formed with dense anorthite crystals. Overall, these findings provide valuable insights into the firing technology in the Xing kiln and even in North China during the late sixth century.
Robot‐assisted intracorporeal ileal conduit urinary diversion: A two‐center comparative study of Bricker versus Wallace ureteroileal anastomosis
Authors: Kadoriku Fumiya , Sasaki Yutaro , Fukuta Kyotaro , Nishiyama Mitsuki , Utsunomiya Seiya , Kobayashi Saki , Shiozaki Keito , Daizumoto Kei , Ueno Yoshiteru , Seto Kosuke , Tomida Ryotaro , Kusuhara Yoshito , Fukawa Tomoya , Nakanishi Ryoichi , Yamaguchi Kunihisa , Yamamoto Yasuyo , Izaki Hirofumi , Takahashi Masayuki , Furukawa Junya
Published: April 2024

Introduction

This study was performed to evaluate the differences in the perioperative results, renal function, and incidence of hydronephrosis over time between the use of Bricker anastomosis and Wallace anastomosis for robot‐assisted intracorporeal ileal conduit urinary diversion (RICIC).

Methods

Fifty‐five patients who underwent RICIC at two institutions were evaluated (Bricker, n = 23; Wallace, n = 32). We investigated changes in estimated glomerular filtration rate and hydronephrosis before surgery and at 3, 6, and 12 months after surgery.

Results

The patients in the Bricker group were significantly older than those in the Wallace group. The urinary diversion time was significantly longer in the Bricker group. No significant difference in postoperative renal function was observed. Additionally, no significant difference was observed in the incidence of postoperative hydronephrosis. However, the incidence of right hydronephrosis tended to be high overall, especially in the Wallace group. No patients in either group required repair surgery or ureteral stent placement.

Conclusions

In patients undergoing RICIC, there was no difference in postoperative renal function or the incidence of hydronephrosis between Wallace and Bricker anastomosis. Symptomatic hydronephrosis was not observed in either group. The present study showed that each method was equally effective and safe.
Exploring genital and pregenital musculature in Synthesiomyia nudiseta (Diptera: Muscidae: Reinwardtiinae): Insights into evolutionary relationships with subfamily Azeliinae
Authors: Ovtshinnikova O. G. , Ivorra T. , Sorokina V. S.
Published: April 2024

The male genital, pregenital skeleton, musculature of male terminalia, and the ovipositor were studied in Synthesiomyia nudiseta (Wulp). A comparison was conducted between the terminal segments and muscles of S. nudiseta and previously studied species of the subfamily Azeliinae. Notable differences were found between previously studied species of the subfamily Azeliinae and Synthesiomyia + Muscina. These differences correspond to apomorphic character states in Synthesiomyia + Muscina, including the large size of the ejaculatory apodeme and the powerful constrictors of the ejaculatory apodeme M 23; the completely membranous sternite VI; the membrane connection of the muscle ISM 5 (lower); the small size of pregonites and postgonites; and the joints of the phallapodeme muscles М 21 at the base of the hypandrial arms. Based on these differences, Synthesiomyia + Muscina can be assigned to the subfamily Reinwardtiinae, as has been confirmed by recent molecular studies. However, similarities in the set of pregenital muscles and the set of phallapodeme muscles between Synthesiomyia + Muscina and the Azeliinae were also noted. These similarities may be considered as plesiomorphic character states, indicating their phylogenetic relationship. It can be argued that Reinwardtiinae + Azeliinae constitute sister groups and occupy the basal position within the family Muscidae.
Adding the epigenomic signature to the prognostic jigsaw of myelodysplastic neoplasm?
Authors: Gill Harinder
Published: April 2024

Defining mechanisms of resistance to hypomethylating agents (HMAs) and biomarkers predictive of treatment response remains challenging in myelodysplastic neoplasm (MDS). Currently available prognostic tools that predict overall survival and transformation to acute myeloid leukaemia have not been powered to predict responses to HMAs. Noguera‐Castells et al. comprehensively characterized the epigenomic profile in patients with MDS treated with azacitidine and described a methylation signature‐based prognostic tool in predicting responses to azacitidine.

Commentary on: Noguera‐Castells et al. DNA methylation profiling of myelodysplastic syndromes and clinical response to azacitidine: a multicentre retrospective study. Br J Haematol 2024;204:1838‐1843.
Phylogenetic analysis of viviparity, matrotrophy, and other reproductive patterns in chondrichthyan fishes
Authors: Blackburn Daniel G. , Hughes Daniel F.
Published: April 2024

The reproductive diversity of extant cartilaginous fishes (class Chondrichthyes) is extraordinarily broad, reflecting more than 400 million years of evolutionary history. Among their many notable reproductive specialisations are viviparity (live‐bearing reproduction) and matrotrophy (maternal provision of nutrients during gestation). However, attempts to understand the evolution of these traits have yielded highly discrepant conclusions. Here, we compile and analyse the current knowledge on the evolution of reproductive diversity in Chondrichthyes with particular foci on the frequency, phylogenetic distribution, and directionality of evolutionary changes in their modes of reproduction. To characterise the evolutionary transformations, we amassed the largest empirical data set of reproductive parameters to date covering nearly 800 extant species and analysed it via a comprehensive molecular‐based phylogeny. Our phylogenetic reconstructions indicated that the ancestral pattern for Chondrichthyes is ‘short single oviparity’ (as found in extant holocephalans) in which females lay successive clutches (broods) of one or two eggs. Viviparity has originated at least 12 times, with 10 origins among sharks, one in batoids, and (based on published evidence) another potential origin in a fossil holocephalan. Substantial matrotrophy has evolved at least six times, including one origin of placentotrophy, three separate origins of oophagy (egg ingestion), and two origins of histotrophy (uptake of uterine secretions). In two clades, placentation was replaced by histotrophy. Unlike past reconstructions, our analysis reveals no evidence that viviparity has ever reverted to oviparity in this group. Both viviparity and matrotrophy have arisen by a variety of evolutionary sequences. In addition, the ancestral pattern of oviparity has given rise to three distinct egg‐laying patterns that increased clutch (brood) size and/or involved deposition of eggs at advanced stages of development. Geologically, the ancestral oviparous pattern arose in the Paleozoic. Most origins of viviparity and matrotrophy date to the Mesozoic, while a few that are represented at low taxonomic levels are of Cenozoic origin. Coupled with other recent work, this review points the way towards an emerging consensus on reproductive evolution in chondrichthyans while offering a basis for future functional and evolutionary analyses. This review also contributes to conservation efforts by highlighting taxa whose reproductive specialisations reflect distinctive evolutionary trajectories and that deserve special protection and further investigation.
Possible incomplete penetrance of Xq28 int22h‐1/int22h‐2 duplication
Authors: Billes Alexis , Pujalte Mathilde , Jedraszak Guillaume , Amsallem Daniel , Boudry‐Labis Elise , Boute Odile , Bouquillon Sonia , Brischoux‐Boucher Elise , Callier Patrick , Coutton Charles , Denizet Anne‐Laude Avice , Dieterich Klaus , Kuentz Paul , Lespinasse James , Mazel Benoît , Morin Gilles , Amram Florence , Pennamen Perrine , Rio Marlène , Piard Juliette , Putoux Audrey , Rama Mélanie , Roze‐Guillaumey Virginie , Schluth‐Bolard Caroline , Till Marianne , Trouvé Chloé , Vieville Gaëlle , Rooryck Caroline , Sanlaville Damien , Chatron Nicolas
Published: April 2024

Xq28 int22h‐1/int22h‐2 duplication is the result of non‐allelic homologous recombination between int22h‐1/int22h‐2 repeats separated by 0.5 Mb. It is responsible for a syndromic form of intellectual disability (ID), with recurrent infections and atopic diseases. Minor defects, nonspecific facial dysmorphic features, and overweight have also been described. Half of female carriers have been reported with ID, whereas all reported evaluated born males present mild to moderate ID, suggesting complete penetrance. We collected data on 15 families from eight university hospitals. Among them, 40 patients, 21 females (one fetus), and 19 males (two fetuses), were carriers of typical or atypical Xq28 int22h‐1/int22h‐2 duplication. Twenty‐one individuals were considered asymptomatic (16 females and 5 males), without significantly higher rate of recurrent infections, atopia, overweight, or facial dysmorphism. Approximately 67% live‐born males and 23% live‐born female carriers of the typical duplication did not have obvious signs of intellectual disability, suggesting previously undescribed incomplete penetrance or low expression in certain carriers. The possibility of a second‐hit or modifying factors to this possible susceptibility locus is yet to be studied but a possible observational bias should be considered in assessing such challenging X‐chromosome copy number gains. Additional segregation studies should help to quantify this newly described incomplete penetrance.
Effects of plant taxonomic position on soil nematode communities in Antarctica
Authors: Zhang Anning , Song Hongxian , Liu Ziyang , Cui Hanwen , Ding Haitao , Chen Shuyan , Xiao Sa , An Lizhe , Cardoso Pedro
Published: April 2024

Antarctica terrestrial ecosystems are facing the most threats from global climate change, which is altering plant composition greatly. These transformations may cause major reshuffling of soil community composition, including functional traits and diversity, and therefore affect ecosystem processes in Antarctica. We used high‐throughput sequencing analysis to investigate soil nematodes under 3 dominant plant functional groups (lichens, mosses, and vascular plants) and bare ground in the Antarctic region. We calculated functional diversity of nematodes based on their diet, life histories, and body mass with kernel density n‐dimensional hypervolumes. We also calculated taxonomic and functional beta diversity of the nematode communities based on Jaccard dissimilarity. The presence of plants had no significant effect on the taxonomic richness of nematodes but significantly increased nematode functional richness. The presence of plants also significantly decreased taxonomic beta diversity (homogenization). Only mosses and vascular plants decreased nematode functional beta diversity, which was mostly due to a decreased effect of the richness difference component. The presence of plants also increased the effect of deterministic processes potentially because environmental filtering created conditions favorable to nematodes at low trophic levels with short life histories and small body size. Increasing plant cover in the Antarctic due to climate change may lead to increased diversity of nematode species that can use the scarce resources and nematode taxonomic and functional homogenization. In a future under climate change, community restructuring in the region is possible.
Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers
Authors: Liu Tianxing , Hashizume Kensei , Krieg Eva , Chen Huijun , Mukaida Yuki , Thelen Kirstin , Friedrichs Frauke , Willmann Stefan , Schwers Stephan , Solms Alexander , Yu Rosie
Published: April 2024

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.c.) injection to healthy participants. The studies included participants from diverse ethnic backgrounds (Caucasian, Japanese, and Chinese). Fesomersen demonstrated good safety and tolerability in all three studies. No major bleeding events were observed. After single‐dose s.c. injection, fesomersen was rapidly absorbed into the systemic circulation, with maximum fesomersen‐equivalent (fesomersen‐eq) concentrations (Cmax) in plasma observed within a few hours. After reaching Cmax, plasma fesomersen‐eq concentrations declined in a biphasic fashion. The PD analyses showed that the injection of fesomersen led to dose‐dependent reductions in FXI activity and increases in activated partial thromboplastin time (aPTT). The maximum observed PD effects were reached between Day 15 and 30, and FXI activity and aPTT returned to near‐baseline levels by Day 90 after a single dose. The PK/PD profiles after a single injection were similar among the various ethnic groups. Collectively, the study results suggest that fesomersen has a favorable safety profile and predictable and similar PK and PD profiles across Chinese, Japanese, and Caucasian participants.
Luther and the “Repair of Chalcedon”1
Authors: Hinlicky Paul R.
Published: April 2024

Luther's Christology has long been suspected of deviating from the Chalcedonian Definition. Analysis of the suspicions raises in turn questions about Chalcedon as an incoherent compromise between the forces of Cyril and Leo. Complicating the issue is the metaphysical rendering of hypostasis as suppositum in medieval Western scholasticism. Luther's theopaschite Christology presses for the “repair” of Chalcedon by situating the Antiochene concern for Christ's human obedience within the divine self‐donation of the Eternal Son according to the Alexandrians. In a Trinitarian Christology incorporating the Antiochene concern for the human obedience of Christ, there would be no competition between the personal union of the divine Son in taking on human body and soul and the Holy Spirit anointing this assumed flesh to create of it the new Adam.
What climate litigation reveals about judicial competence
Authors: de Lange Douwe
Published: April 2024

In recent years, the US and the Netherlands have been on opposing sides of the spectrum regarding climate litigation. Dutch courts, in several revolutionary climate cases, have been an arena of societal change, whilst climate claims in the US have been largely unsuccessful. In a way this difference seems strange, because the US judiciary has the power of constitutional review, whilst the Dutch judiciary does not. Against that background, this paper extensively compares the doctrines of judicial competence regarding political questions in both jurisdictions. As a comparative framework, this paper uses three judicial phases, namely: the institutional phase, the substantial phase, and the remedial phase. Climate litigation reveals that the Dutch doctrine of judicial competence is focused on the substantial and remedial phases, which has allowed it more freedom in reviewing climate litigation. On the other hand, climate litigation reveals that the US doctrine of judicial competence is focused on a strict institutional phase, dominated by the Political Question Doctrine (PQD). The main contribution of this paper to the constitutional debate is that climate litigation reveals fundamental differences in doctrines of judicial competence. This is not only an important takeaway for future climate litigation, but also, in terms of the Radbruch formula, for other potential gaps between the executive and justice.
The effects of advanced glycation end‐products on skin and potential anti‐glycation strategies
Authors: Wang Lingyu , Jiang Yanfei , Zhao Chunyue
Published: April 2024

The advanced glycation end‐products (AGEs) are produced through non‐enzymatic glycation between reducing sugars and free amino groups, such as proteins, lipids or nucleic acids. AGEs can enter the body through daily dietary intake and can also be generated internally via normal metabolism and external stimuli. AGEs bind to cell surface receptors for AGEs, triggering oxidative stress and inflammation responses that lead to skin ageing and various diseases. Evidence shows that AGEs contribute to skin dysfunction and ageing. This review introduces the basic information, the sources, the metabolism and absorption of AGEs. We also summarise the detrimental mechanisms of AGEs to skin ageing and other chronic diseases. For the potential strategies for counteracting AGEs to skin and other organs, we summarised the pathways that could be utilised to resist glycation. Chemical and natural‐derived anti‐glycation approaches are overviewed. This work offers an understanding of AGEs to skin ageing and other chronic diseases and may provide perspectives for the development of anti‐glycation strategies.
Cloud‐based provenance framework for duplicates identification and data quality enhancement
Authors: Khan Fakhri Alam
Published: April 2024

Cloud computing revolutionizes data management by offering centralized repositories or services accessible over the Internet. These services, hosted by a single provider or distributed across multiple entities, facilitate seamless access for users and applications. Additionally, cloud technology enables federated search capabilities, allowing organizations to amalgamate data from diverse sources and perform comprehensive searches. However, such integration often leads to challenges in data quality and duplication due to structural disparities among datasets, including variations in metadata. This research presents a novel provenance‐based search model designed to enhance data quality within cloud environments. The model expands the traditional concept of a single canonical URL by incorporating provenance data, thus providing users with diverse search options. Leveraging this model, the study conducts inferential analyses to improve data accuracy and identify duplicate entries effectively. To verify the proposed model, two research paper datasets from Kaggle and DBLP repositories are utilized, and the model effectively identifies duplicates, even with partial queries. Tests demonstrate the system's ability to remove duplicates based on title or author, in both single and distributed dataset scenarios. Traditional search engines struggle with duplicate content, resulting in biased results or inefficient crawling. In contrast, this research uses provenance data to improve search capabilities, overcoming these limitations.
Uppermost global tree elevations are primarily limited by low temperature or insufficient moisture
Authors: Xie Yuyang , Shen Zehao , Wang Tao , Malanson George P. , Peñuelas Josep , Wang Xiaoyi , Chen Xiangwu , Liang Eryuan , Liu Hongyan , Yang Mingzheng , Ying Lingxiao , Zhao Fu , Piao Shilong
Published: April 2024

The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi‐observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing‐season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two‐thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.
Microbial evolution—An under‐appreciated driver of soil carbon cycling
Authors: Abs Elsa , Chase Alexander B. , Manzoni Stefano , Ciais Philippe , Allison Steven D.
Published: April 2024

Although substantial advances in predicting the ecological impacts of global change have been made, predictions of the evolutionary impacts have lagged behind. In soil ecosystems, microbes act as the primary energetic drivers of carbon cycling; however, microbes are also capable of evolving on timescales comparable to rates of global change. Given the importance of soil ecosystems in global carbon cycling, we assess the potential impact of microbial evolution on carbon‐climate feedbacks in this system. We begin by reviewing the current state of knowledge concerning microbial evolution in response to global change and its specific effect on soil carbon dynamics. Through this integration, we synthesize a roadmap detailing how to integrate microbial evolution into ecosystem biogeochemical models. Specifically, we highlight the importance of microscale mechanistic soil carbon models, including choosing an appropriate evolutionary model (e.g., adaptive dynamics, quantitative genetics), validating model predictions with ‘omics’ and experimental data, scaling microbial adaptations to ecosystem level processes, and validating with ecosystem‐scale measurements. The proposed steps will require significant investment of scientific resources and might require 10–20 years to be fully implemented. However, through the application of multi‐scale integrated approaches, we will advance the integration of microbial evolution into predictive understanding of ecosystems, providing clarity on its role and impact within the broader context of environmental change.
Green deserts, but not always: A global synthesis of native woody species regeneration under tropical tree monocultures
Authors: Simões Laura H. P. , Guillemot Joannès , Ronquim Carlos C. , Weidlich Emanuela W. A. , Muys Bart , Fuza Matheus S. , Lima Renato A. F. , Brancalion Pedro H. S.
Published: April 2024

Tree monocultures constitute an increasing fraction of the global tree cover and are the dominant tree‐growing strategy of forest landscape restoration commitments. Their advantages to produce timber are well known, but their value for biodiversity is highly controversial and context dependent. Therefore, understanding whether, and in which conditions, they can harbor native species regeneration is crucial. Here, we conducted meta‐analyses based on a global survey of the literature and on a database created with local, unpublished studies throughout Brazil to evaluate the regeneration potential of native species under tree monocultures and the way management influences this regeneration. Native woody species regeneration under tree monocultures harbors a substantial fraction of the diversity (on average 40% and 68% in the global and Brazilian surveys, respectively) and abundance (on average 25% and 60% in the global and Brazilian surveys, respectively) of regeneration observed in natural forests. Plantations with longer rotation lengths, composed of native tree species, and located adjacent to forest remnants harbor more species. Pine plantations harbor more native individuals than eucalypt plantations, and the abundance of regenerating trees is higher in sites with higher mean temperatures. Species–area curves revealed that the number of woody species under pine and eucalypt plantations in Brazil is 606 and 598 species, respectively, over an aggregated sampled area of ca. 12 ha. We highlight that the understory of tree monocultures can harbor a considerable diversity of regenerating native species at the landscape and regional scales, but this diversity strongly depends on management. Long‐rotation length and favorable location are key factors for woody regeneration success under tropical tree monocultures. Therefore, tree monocultures can play a role in forest landscape restoration and conservation, but only if they are planned and managed for achieving this purpose.
High plasma interleukin‐6 level, but not IL‐6 gene variants, as a predictive marker for the development of hepatocellular carcinoma in a Moroccan population
Authors: Tanouti Ikram‐Allah , Fellah Hassan , Haddaji Asmaa , Zerrad Chaimaa , Tahiri Mohamed , Badre Wafaa , Nfaoui Khaoula , Pineau Pascal , Benjelloun Soumaya , Ezzikouri Sayeh
Published: April 2024

Chronic inflammation triggered by hepatitis B (HBV) and hepatitis C (HCV) viruses elevates interleukin 6 (IL‐6) levels, activating pathways that cause liver damage and contribute to hepatocellular carcinoma (HCC) development. In this study, we assessed IL‐6 levels and explored the correlation between the rs1800795 and rs1800797 variants of the IL‐6 gene and the risk of developing HCC. We conducted a case–control study involving 314 participants. Among them, 157 were HCC patients (94 anti‐HCV, 22 HBsAg and 41 metabolic dysfunction‐associated steatotic liver disease [MASLD]) and 157 controls. Genotyping for IL‐6 rs1800795 and rs1800797 polymorphisms was performed using real‐time polymerase chain reaction (PCR). Additionally, plasma IL‐6 levels were determined using enzyme‐linked immunosorbent assay. The IL‐6 levels were notably higher in patients compared to controls (p < .0001). Among HCC patients, those with MASLD exhibited higher plasma IL‐6 levels than those with HCV and HBV (p = .003). In male HCC patients, IL‐6 levels were significantly elevated compared to controls (p < .0001). Similarly, female patients showed significantly higher IL‐6 levels compared to female controls, though still lower than in male HCC patients (p = .023). However, no significant difference was observed in IL‐6 levels between male and female HCC patients (p = .129). Contrastingly, the genotype and allele distributions of the rs1800795 and rs1800797 polymorphisms in the IL‐6 gene displayed no association with HCC development (all p > .05). In Moroccan HCC patients, chronic liver inflammation is characterized by elevated levels of IL‐6, potentially playing a role in the progression of liver disease and tumourigenesis.
Laboratory assessment of antiphospholipid syndrome: Laboratory data
Authors: Kobylecki Camilla J. , Vedel‐Krogh Signe , Afzal Shoaib , Goetze Jens P.
Published: April 2024

Introduction

Thorough assessment of the antiphospholipid syndrome (APS) includes retesting of positive antiphospholipid antibody (aPL) tests after at least 12 weeks, and a full antiphospholipid antibody profile. To what extent this work‐up is done in clinical practice is unknown.

Methods

Data on 25 116 in‐ and out‐hospital patients tested for the presence of lupus anticoagulant (LA), the aPL which most strongly correlates with thrombosis, was extracted from the laboratory information system of the only laboratory that performs LA tests in the Capital Region, Denmark. We estimated fraction of repeated tests, tests repeated within the recommended time span, and fraction with a full aPL profile.

Results

Out of 25 116 patients, 843 were positive for LA (3.3%), and 3948 results were inconclusive (16%). Only 51% (95% CI of the proportion: 48%–54%) (n = 431) of positive tests were repeated. The proportion of inconclusive LA test results increased from 13% (12%–15%) in 2009 to 20% (19%–22%) in 2020. Out of the positive tests repeated within the first year, only 60/353 (17%; 13%–21%) were repeated within 12–16 weeks; 177/353 (50%; 45%–55%) were re‐tested within the first 12 weeks of first positive test result. The proportion of patients with a full antiphospholipid antibody profile increased from 161/1978 (8%) in 2010 to 1041/1978 (43%) in 2020.

Conclusion

We found several issues with the laboratory workup of APS. This indicates a need for increased awareness of comprehensive laboratory assessment of possible APS as well as a closer collaboration between the laboratory and clinicians.
A systematic review exploring healthcare professionals' perceptions of take‐home naloxone dispensing in acute care areas
Authors: Osinski Karen , Afseth Janyne
Published: April 2024

Aims

To explore healthcare professionals' perceptions and experiences of take‐home naloxone initiatives in acute care settings to gain an understanding of issues facilitating or impeding dispensing.

Design

Systematic literature review.

Data Sources

Cochrane, MEDLINE and CINAHL were searched from 15/03/2021 to 18/03/2021, with a follow‐up search performed via PubMed on 22/03/2021. The years 2011 to 2021 were included in the search.

Review Methods

A systematic literature review focused on qualitative studies and quantitative survey designs. Synthesis without meta‐analysis was undertaken using a thematic analysis approach.

Results

Seven articles from the United States of America (5), Australia (1) and Canada (1) with 750 participants were included in the review. Results indicate ongoing stigma towards people who use drugs with preconceived moral concerns regarding take‐home naloxone. There was confusion regarding roles and responsibilities in take‐home naloxone dispensing and patient education. Similarly, there was a lack of clarity over logistical and financial issues.

Conclusion

Take‐home naloxone is a vital harm reduction initiative. However, barriers exist that prevent the optimum implementation of these initiatives.

Impact

What is already known:

Deaths due to opioid overdose are a global health concern, with take‐home naloxone emerging as a key harm reduction scheme.

Globally, less than 10% of people who use drugs have access to treatment initiatives, including take‐home naloxone.

An optimum point of distribution of take‐home naloxone is post‐acute hospital care.

What this paper adds:

There is role confusion regarding responsibility for the provision of take‐home naloxone and patient education. This is exacerbated by inconsistent provision of training and education for healthcare professionals.

Logistical or financial concerns are common and moral issues are prevalent with some healthcare professionals questioning the ethics of providing take‐home naloxone.

Stigma towards people who use drugs remains evident in some acute care areas which may impact the use of this intervention.

Implications for practice/policy:

Further primary research should examine what training and education methods are effective in improving the distribution of take‐home naloxone in acute care.

Education should focus on reduction of stigma towards people who use drugs to improve the distribution of take‐home naloxone.

Standardized care guidelines may ensure interventions are offered equally and take‐home naloxone ‘champions’ could drive initiatives forward, with support from harm reduction specialists.

Reporting Method

This has adhered to the PRISMA reporting guidelines for systematic reviews.

Patient or Public Contribution

No patient or public contribution.
Annual health checks for people with intellectual disabilities: An exploration of experiences, follow‐up and self‐management of health conditions
Authors: Cavanagh Dawn E. , Northway Ruth , Todd Stuart
Published: April 2024

Background

Little is known about how health issues identified at the annual health check (AHC) are followed up and addressed, how participants self‐manage their health in between AHCs, and what support they receive. This research aimed to explore this.

Methods

People with intellectual disabilities (n = 12), and/or their supporters residing in Wales, were interviewed following their AHC and again at 6 and 11 months. A recurrent cross‐sectional thematic analysis was undertaken.

Results

Five main themes emerged from interview one: going for a health check, issues identified, and actions taken, supporting the self‐management of health, the personal context, and addressing health inequities. Four main themes emerged from follow‐up interviews: follow‐up, supporting the self‐management of health, the need for reasonably adjusted health services, and going for another health check.

Conclusion

A broader system of support around the AHC is required if people are to achieve or maintain the best possible health.