bluuebunny/crossref_metadata_2025 huggingface dataset:
Odorant receptor orthologues from moths display conserved responses to cis‐jasmone
Authors: Hou Xiao‐Qing , Jia Zhongqiang , Zhang Dan‐Dan , Wang Guirong
Published: November 2023

In insects, the odorant receptor (OR) multigene family evolves by the birth‐and‐death evolutionary model, according to which the OR repertoire of each species has undergone specific gene gains and losses depending on their chemical environment, resulting in taxon‐specific OR lineage radiations with different sizes in the phylogenetic trees. Despite the general divergence in the gene family across different insect orders, the ORs in moths seem to be genetically conserved across species, clustered into 23 major clades containing multiple orthologous groups with single‐copy gene from each species. We hypothesized that ORs in these orthologous groups are tuned to ecologically important compounds and functionally conserved. cis‐Jasmone is one of the compounds that not only primes the plant defense of neighboring receiver plants, but also functions as a behavior regulator to various insects. To test our hypothesis, using Xenopus oocyte recordings, we functionally assayed the orthologues of BmorOR56, which has been characterized as a specific receptor for cis‐jasmone. Our results showed highly conserved response specificity of the BmorOR56 orthologues, with all receptors within this group exclusively responding to cis‐jasmone. This is supported by the dN/dS analysis, showing that strong purifying selection is acting on this group. Moreover, molecular docking showed that the ligand binding pockets of BmorOR56 orthologues to cis‐jasmone are similar. Taken together, our results suggest the high conservation of OR for ecologically important compounds across Heterocera.
The temporal–spatial expression and functional analysis of three gustatory receptor genes in Solenopsis invicta using sweet and bitter compounds
Authors: Waris Muhammad Irfan , Lei Yanyuan , Qi Guojun , Guan Ziying , Rashied Abdul , Chen Jie , Lyu Lihua
Published: November 2023

The insect gustatory system participates in identifying potential food sources and avoiding toxic compounds. During this process, gustatory receptors (GRs) recognize feeding stimulant and deterrent compounds. However, the GRs involved in recognizing stimulant and deterrent compounds in the red imported fire ant, Solenopsis invicta, remain unknown. Therefore, we conducted a study on the genes SinvGR1, SinvGR32b, and SinvGR28a to investigate the roles of GRs in detecting feeding stimulant and deterrent compounds. In this current study, we found that sucrose and fructose are feeding stimulants and the bitter compound quinine is a feeding deterrent. The fire ant workers showed significant behavior changes to avoid the bitter taste in feeding stimulant compounds. Reverse transcription quantitative real‐time polymerase chain reaction results from developmental stages showed that the SinvGR1, SinvGR32b, and SinvGR28a genes were highly expressed in fire ant workers. Tissue‐specific expression profiles indicated that SinvGR1, SinvGR32b, and SinvGR28a were specifically expressed in the antennae and foreleg tarsi of workers, whereas SinvGR32b gene transcripts were also highly accumulated in the male antennae. Furthermore, the silencing of SinvGR1 or SinvGR32b alone and the co‐silencing of both genes disrupted worker stimulation and feeding on sucrose and fructose. The results also showed that SinvGR28a is required for avoiding quinine, as workers with knockdown of the SinvGR28a gene failed to avoid and fed on quinine. This study first identified stimulant and deterrent compounds of fire ant workers and then the GRs involved in the taste recognition of these compounds. This study could provide potential target gustatory genes for the control of the fire ant.
Vascular calcification inhibitors and cardiovascular events in peritoneal dialysis patients
Authors: Olmaz Refik , Selen Tamer , Gungor Ozkan
Published: November 2023

The prevalence of cardiovascular diseases is high among patients with chronic kidney disease (CKD) and peritoneal dialysis (PD) patients, which increases morbidity and mortality in this population and represents a significant financial burden for both the patients and the healthcare systems. Vascular calcification (VC) is associated with increased morbidity and mortality and VC risk is higher in patients with CKD than in healthy individuals. Calcification inhibitors, compounds that inhibit VC, were discovered as a result of efforts to explain why some patients are spared. It was found that certain proteins (e.g., fetuin‐A, osteopontin, osteoprotegerin, bone morphogenetic protein‐7) inhibit calcification in dialysis patients. In this narrative review, we provide an overview of known calcification inhibitors, describe the relevant regulatory mechanisms, and discuss their relation to VC development in PD patients.
Bioeconomy Transition Pathways – Potential Impacts for the EU Bio‐based Chemicals Sector
Authors: Philippidis George , M'barek Robert , van Zeist Willem‐Jan
Published: November 2023

The European Commission's Green Deal sets out a bold vision to meet the challenges of biodiversity protection and net‐zero emissions, whilst forging a pathway for a circular model of competitive growth and job creation. To achieve these multiple challenges, the bioeconomy has a key role to play, particularly in the deployment of biomass in higher value‐added industrial applications. To support evidence‐based policy modelling, the EU H2020 funded project BioMonitor represents a first step toward both improving data transparency, particularly in bio‐industrial activities, and the creation of a single toolbox for the purpose of performing integrated modelling assessments of the bioeconomy. Comparing with a baseline, this study presents results from a series of medium to long‐term bio‐based industry focused transition narratives. In particular, the focus is on the EU bio‐based chemicals sector employing results from an economy‐wide simulation model from the toolbox, called MAGNET.

Publicly backed fiscal support policies, costing between 0.22–0.25% of EU GDP by 2050, generate notable improvements in EU bio‐based chemical sector production and employment generation, as well as synergetic production increases in advanced generation biofuels. There is evidence of decarbonisation in the EU bio‐based chemicals sector, although more tangible improvements are achieved with the implementation of accompanying climate‐ and sustainable bio‐energy policies.
Prevalence of dengue fever in Saudi Arabia: Jeddah as a case study
Authors: Alyahya Hanan S.
Published: November 2023

Dengue fever is widespread in tropical and subtropical regions, including Saudi Arabia. Aedes aegypti (Diptera: Culicidae) transmits dengue and many other diseases, including chikungunya and Zika. This study provides an overview of dengue fever in Saudi Arabia since the first case was recorded in the early 1990s. In addition, it focuses on the epidemiological situation in Jeddah as a case study to study the spatial distribution of dengue cases using Geographic Information Systems (GIS) techniques over 5 years, from 2019 to 2023. The first recorded case in Saudi Arabia was in October 1993; however, daily data indicates that 2023 is a major epidemic year. The number of infections has reached 4099 so far during the first half of the year, which indicates a significant increase compared to previous years. GIS analysis has unveiled the locations of high infection rates across multiple municipalities, commonly called hotspots, and identified areas where dengue cases remain relatively low. The Inverse Distance Weighted (IDW) tool was used to determine the severity of infection in different areas of Jeddah. The study concluded that factors such as temperature, rainfall, and septic tanks in areas that lack a proper sanitation network are the most contributing factors to the spread of disease vectors and, thus, dengue. Winter rainfall creates conducive breeding environments for dengue mosquito vectors, increasing transmission rates. On the other hand, summer heat accelerates the mosquito life cycle and enhances viral replication, heightening the risk of dengue transmission.
Seasonal heavy metal effects on detoxification and antioxidant gene expression in the urban honeybee
Authors: Gizaw Gashawbeza , Kim YeongHo , Moon KyungHwan , Choi Jong Bong , Mwamula Abraham , Lee Dong Woon , Kim Young Ho , Park Jong Kyun
Published: November 2023

Environmental pollutants are associated with honeybee colony losses and may show seasonal concentration variations with respect to the environment and plants. In this study, we examined arsenic (As), lead (Pb), and mercury (Hg) seasonal variations in honey and honeybees in urban areas. Seasonal trends in detoxification (CYP9Q1, CYP9Q2, and CYP9Q3) and antioxidant genes encoding catalase (CAT) and superoxide dismutase (SOD1) were also determined in honeybees. Accordingly, As, Pb, and Hg concentrations were significantly increased in summer in both honey and honeybee samples when compared with other seasons. Similarly, the expression level of CYP9Q1, CYP9Q2, CYP9Q3, SOD1, and CAT showed a significant increase in summer honeybees. This increased expression level particularly in summer honeybees indicating an increased summer honeybee exposure and adaptive oxidative stress responses to environmental pollutants, including heavy metals due to increased flight activity when compared with other seasons. Thus, active season honeybees were subjected to environmental oxidative and detoxification stressors when exposed to environmental pollutants, including heavy metals.
Optimization of the pulsed vacuum drying process of green walnut husk through temperature adaptive regulation
Authors: Ao Jingfang , Shen Heyu , Cai Yingying , Wang Jun , Xie Yongkang , Luo Anwei
Published: November 2023

This study aimed to optimize the temperature adaptive conditions of pulsed vacuum drying (PVD) for green walnut husk (GWH) to tackle the issues of severe environmental pollution and limited utilization of GWH. The results of the single‐factor experiment revealed that the optimal drying temperature for PVD of GWH was 65°C, with a pulsed ratio of 9 min: 3 min. The drying time decreased from 10.87 to 6.32 h with increasing drying temperature and from 8.83 to 6.23 kW·h/kg with increasing pulsed ratio. Energy consumption also decreased with shorter drying time and shorter vacuum time. Under this optimal variable temperature drying condition, GWH exhibited the highest total active substance content, with respective values of 9.43 mg/g for total triterpenes, 35.68 mg/g for flavonoids, 9.51 mg/g for polyphenols, and 9.55 mg/g for quinones. The experimental drying data of GWH were best fitted by a logarithmic model, with R2 values ranging from 0.9927 to 0.9943. Furthermore, the observed microstructure of GWH corresponded to the variations in total active substance content. This study provided valuable theoretical guidance for addressing environmental pollution associated with GWH and facilitating the industrialization and refinement of GWH drying processes.

Practical Application

There is a growing interest in harnessing the potential value of agricultural waste to transform low‐cost raw materials into high‐value products while mitigating environmental pollution. In this study, for the first time, the effects of variable temperature pulsed vacuum drying on the content of active substances, drying time, and energy consumption of green walnut husk (GWH) were investigated. The findings serve as a theoretical foundation for addressing environmental pollution issues associated with GWH and enabling the industrialization and precision drying of GWH.
Single‐cell RNA sequencing reveals immune microenvironment of small cell lung cancer‐associated malignant pleural effusion
Authors: Wang Shuyan , An Jing , Hu Xueru , Zeng Tingting , Li Ping , Qin Jiangyue , Shen Yongchun , Chen Mei , Wen Fuqiang
Published: November 2023

We used 10 × genomics single‐cell transcriptome sequencing technology to reveal the tumor immune microenvironment characteristics of small cell lung cancer (SCLC) in a patient with malignant pleural effusion (MPE). A total of 8008 high‐quality cells were finally obtained for subsequent bioinformatic analysis, which were divided into 10 cell clusters further identified as B cells, T cells, myeloid cells, NK cells, and cancer cells. Such SCLC related genes as NOTCH1, MYC, TSC22D1, SOX4, BLNK, YBX3, VIM, CD8A, CD8B, and KLF6 were expressed in different degrees during differentiation of T and B cells. Different ligands and receptors between T, B and tumor cells almost interact through MHC II, IL‐16, galectin, and APP signaling pathway.
How to get the most out of phylogenetic imputation without abusing it
Authors: Molina‐Venegas Rafael
Published: November 2023

Phylogenies are viewed as potentially powerful resources to predict missing values in trait datasets, but they are often misused. Critically, many of the imputed values that completely or partially rely on phylogenetic information are trusted without convincingly demonstrating that the data meet the requirements for the predictions to be at least minimally valuable.

I discuss that phylogenetic signal, which is the mainstay of phylogenetic imputation, is often interpreted as ‘strong’ because the outcome of randomization tests has prevailed over the actual strength of the signal in determining whether it is strong or not. This circumstance has led many researchers to infer conclusions based on ‘strong’ signals that are actually way more labile than a phylogenetic random walk (i.e. Brownian motion).

Although trait evolutionary trajectories that nearly fit Brownian motion are typically considered as strongly conserved, the Brownian process is subject to high levels of stochasticity that may render spurious predictions under some circumstances. To my knowledge, very few studies (if any) that rely on phylogenetically imputed information have rigorously evaluated the expected accuracy of individual predictions, despite among‐lineage variability in prediction accuracy can be dramatic even for strongly conserved traits.

Here, I advocate for a Monte‐Carlo approach that is based on trait simulations to assess the prediction accuracy that is expected for each missing value in the traits of interest, which can be continuous or discrete. The framework is presented in a detailed step‐by‐step R tutorial that was conceived for non‐specialized researchers to identify highly likely spurious predictions without the need for advanced technical and statistical skills.

Although phylogenetic imputation has important limitations, I suggest that leveraging advances in our understanding of such hindrances and using the technique with caution and restraint will allow trait‐based research to progress further while sampling efforts continue replacing imputed data.
Including the invisible fraction in whole population studies: A guide to the genetic sampling of unhatched bird eggs
Authors: Morland Fay , Patel Selina , Santure Anna W. , Brekke Patricia , Hemmings Nicola
Published: November 2023

Early embryo mortality has recently been proven to be a significant component of avian reproductive failure. Due to the difficulty in distinguishing eggs, which have suffered early embryo mortality from unfertilised eggs, this cause of reproductive failure has historically been underestimated and overlooked.

We describe methods for recognising and collecting early failed, unhatched eggs from wild bird populations, identifying and isolating embryonic material in unhatched eggs, and efficiently extracting DNA from those samples. We test these methods on unhatched hihi (Notiomystis cincta) eggs collected from the field, which have undergone postmortem incubation.

We obtained DNA yields from early‐stage embryos that are sufficient for a wide range of molecular techniques, including microsatellite genotyping for parentage analysis and sex‐typing. The type of tissue sample taken from the egg affected downstream DNA yields and microsatellite amplification rates. Species‐specific microsatellite markers had higher amplification success rates than cross‐species markers. We make key recommendations for each stage of the sampling and extraction process and suggest potential protocol improvements and modifications.

Genetic and possibly genomic analysis of embryos that die early in development has the potential to advance many fields. The methods described here will allow a more in‐depth exploration of the previously overlooked causes of early embryo mortality in wild populations of birds, including threatened species.
Phenotypic characterization of Indian mustard using agronomic and quality traits under semi‐arid climate
Authors: Singh Aditya Pratap , Majhi Timir , Das Dibakar , Dewanjee Sujaya
Published: November 2023

Indian mustard is an important oilseed crop in India. The productivity of Indian mustard needs to be increased in marginal environments such as in arid and semi‐arid areas to boost production. For this, identification of promising genotypes with high yield and quality under arid and semi‐arid climate is required. In this study, 65 genotypes of Indian mustard were evaluated in Augmented Randomized Block Design in the Purulia district of West Bengal, a mustard growing zone characterized by red laterite soil and semi‐arid climate. Considerable variation was observed between the genotypes for most characters such as number of seeds per siliqua (coefficient of variation [CV] 7.39%), followed by days to first flowering (CV 6.9%) and total number of siliquae (CV 6.43%), respectively. However, variation was less for days to maturity and quality parameters. Strong positive correlations were observed between many traits such as number of branches and number of siliquae on branches (0.82), number of branches and siliquae per plant (0.73), number of branches and yield per plant (0.72), number of siliquae on branches and siliquae per plant (0.91), number of siliquae on branches and seed yield per plant (0.76). Relatively strong negative correlation was observed only between oil and glucosinolate content (−0.60). Most of the traits showed high heritability along with high genetic advance over mean. Principal component analysis and cluster analysis classified the genotypes into six clusters. Based on yield, its components, and other quality parameters, promising genotypes such as Pusa Mahak, Narendra Ageti Rai 4, and JM‐1 were identified. These genotypes may be targeted for further genetic improvement or be incorporated in breeding programmes for developing high‐yielding mustard varieties for arid and semi‐arid climate.
Age‐dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging
Authors: Sun Liang , Li Zhiming , Hu Caiyou , Ding Jiahong , Zhou Qi , Pang Guofang , Wu Zhu , Yang Ruiyue , Li Shenghui , Li Jian , Cai Jianping , Sun Yuzhe , Li Rui , Zhen Hefu , Sun Shuqin , Zhang Jianmin , Fang Mingyan , Chen Zhihua , Lv Yuan , Cao Qizhi , Sun Yanan , Gong Ranhui , Huang Zezhi , Duan Yong , Liu Hengshuo , Dong Jun , Li Junchun , Ruan Jie , Lu Haorong , He Benjin , Li Ninghu , Li Tao , Xue Wenbin , Li Yan , Shen Juan , Yang Fan , Zhao Cheng , Liang Qinghua , Zhang Mingrong , Chen Chen , Gong Huan , Hou Yong , Wang Jian , Zhang Ying , Yang Huanming , Zhu Shida , Xiao Liang , Jin Zhen , Guo Haiyun , Zhao Peng , Brix Susanne , Xu Xun , Jia Huijue , Kristiansen Karsten , Yang Ze , Nie Chao
Published: November 2023

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age‐dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p‐cresol, N‐phenylacetylglutamine, 2‐oxindole, and 4‐aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age‐dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota‐metabolite interplay on renal function and healthy aging.
Long‐term exposure from perinatal life to food‐grade TiO2 alters intestinal homeostasis and predisposes to food allergy in young mice
Authors: Issa Mohammad , Michaudel Chloé , Guinot Marine , Grauso‐Culetto Marta , Guillon Blanche , Lecardonnel Jérôme , Jouneau Luc , Chapuis Céline , Bernard Hervé , Hazebrouck Stephane , Castelli Florence , Fenaille François , Gaultier Eric , Rivière Gilles , Houdeau Eric , Adel‐Patient Karine
Published: November 2023

Background

Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food‐grade titanium dioxide (fg‐TiO2), a common food additive.

Methods

Dams were fed a control versus fg‐TiO2‐enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg‐TiO2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time‐point, using established models. Sensitization to CMP was investigated by measuring β‐lactoglobulin and casein‐specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge.

Results

Perinatal exposure to fg‐TiO2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism.

Conclusions

Long‐term perinatal exposure to fg‐TiO2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect.
Pharmacomechanical thrombectomy of iliofemoral deep vein thrombosis is associated with a low incidence of post‐thrombotic syndrome and perioperative complications
Authors: Larkin Theresa A. , Deen Raeed , Amirnezami Taraneh , Shvartsbart Alisa , Villalba Laurencia
Published: November 2023

Background

Iliofemoral deep venous thrombosis (IFDVT) is associated with an incidence of post‐thrombotic syndrome (PTS) of up to 50%. PTS is associated with high morbidity, impaired quality of life and a significant economic burden. The aim of the current study was to assess the impact of a single session pharmacomechanical thrombectomy (PMT), dedicated venous stents and a risk mitigation protocol on the rate of PTS.

Methods

Between 2015 and 2022, patients presenting with acute or subacute IFDVT treated with the same protocol of single session PMT, dedicated venous stents, and risk‐mitigation measures were included. Procedural success rate, complications, stent patency and incidence of PTS were determined.

Results

Of 60 patients (58 ± 19 years; 65% male), the procedural success rate was 93%, with 7% of patients experiencing complications but no long‐term sequelae or mortality. Most (n = 52; 87%) patients were stented, including 46% across the inguinal ligament. At 3 months post‐procedure, primary, assisted primary and secondary stent patency rates were 89%, 93% and 98%, respectively, with no loss of patency or re‐interventions after that. At latest follow‐up of a median 48 months (n = 32), stent patency rate was 97%, with only three patients (9%) experiencing symptoms of PTS.

Conclusion

Single session PMT, dedicated venous stents and a risk‐mitigation protocol results in high success rate, excellent long‐term stent patency and low incidence of PTS without compromising safety. These results support early intervention for iliofemoral DVT.
Identification of depression and anxiety during pregnancy: A systematic review and meta‐analysis of test accuracy
Authors: Rondung Elisabet , Massoudi Pamela , Nieminen Katri , Wickberg Birgitta , Peira Nathalie , Silverstein Rebecca , Moberg Klas , Lundqvist Martina , Grundberg Åke , Hultcrantz Monica
Published: November 2023

Introduction

Depression and anxiety are significant contributors to maternal perinatal morbidity and a range of negative child outcomes. This systematic review and meta‐analysis aimed to review and assess the diagnostic test accuracy of selected screening tools (Edinburgh Postnatal Depression Scale [EPDS], EPDS‐3A, Patient Health Questionnaire [PHQ‐9]‐, PHQ‐2, Matthey Generic Mood Question [MGMQ], Generalized Anxiety Disorder scale [GAD‐7], GAD‐2, and the Whooley questions) used to identify women with antenatal depression or anxiety in Western countries.

Material and methods

On January 16, 2023, we searched 10 databases (CINAHL, Cochrane Library, CRD Database, Embase, Epistemonikos, International HTA Database, KSR Evidence, Ovid MEDLINE, PROSPERO and PsycINFO); the references of included studies were also screened. We included studies of any design that compared case‐identification with a relevant screening tool to the outcome of a diagnostic interview based on the Diagnostic and Statistical Manual of Mental Disorders, fourth or fifth edition (DSM‐IV or DSM‐5), or the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD‐10). Diagnoses of interest were major depressive disorder and anxiety disorders. Two authors independently screened abstracts and full‐texts for relevance and evaluated the risk of bias using QUADAS‐2. Data extraction was performed by one person and checked by another team member for accuracy. For synthesis, a bivariate model was used. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Registration: PROSPERO CRD42021236333.

Results

We screened 8276 records for eligibility and included 16 original articles reporting on diagnostic test accuracy: 12 for the EPDS, one article each for the GAD‐2, MGMQ, PHQ‐9, PHQ‐2, and Whooley questions, and no articles for the EPDS‐3A or GAD‐7. Most of the studies had moderate to high risk of bias. Ten of the EPDS articles provided data for synthesis at cutoffs ≥10 to ≥14 for diagnosing major depressive disorder. Cutoff ≥10 gave the optimal combined sensitivity (0.84, 95% confidence interval [CI]: 0.75–0.90) and specificity (0.87, 95% CI: 0.79–0.92).

Conclusions

Findings from the meta‐analysis suggest that the EPDS alone is not perfectly suitable for detection of major depressive disorder during pregnancy. Few studies have evaluated the other instruments, therefore, their usefulness for identification of women with depression and anxiety during pregnancy remains very uncertain. At present, case‐identification with any tool may best serve as a complement to a broader dialogue between healthcare professionals and their patients.
Efficacy and safety of upadacitinib for 16‐week extended induction and 52‐week maintenance therapy in patients with moderately to severely active ulcerative colitis
Authors: Panaccione Remo , Danese Silvio , Zhou Wen , Klaff Justin , Ilo Dapo , Yao Xuan , Levy Gweneth , Higgins Peter D. R. , Loftus Edward V. , Chen Su , Gonzalez Yuri Sanchez , Leonard Carolyn , Hébuterne Xavier , Lindsay James O. , Cao Qian , Nakase Hiroshi , Colombel Jean‐Frédéric , Vermeire Séverine
Published: November 2023

Background

Upadacitinib is an oral, selective Janus kinase inhibitor.

Aim

To assess the efficacy and safety of upadacitinib in patients with moderate‐to‐severe ulcerative colitis following 16‐week extended induction therapy, and 52‐week maintenance therapy in patients achieving clinical response after 16‐week extended induction therapy

Methods

Patients without clinical response to 8 weeks' upadacitinib 45 mg once daily induction therapy in two induction trials were eligible for an additional 8 weeks of therapy. Patients achieving clinical response at Week 16 were subsequently re‐randomised (1:1) to upadacitinib 15 or 30 mg once daily for 52‐week maintenance therapy. Efficacy was assessed at induction Week 16 (integrated) and maintenance Week 52; safety was assessed throughout.

Results

Overall, 127/663 (19.2%) patients did not achieve clinical response to upadacitinib 45 mg at Week 8 and received an additional 8 weeks of therapy; 75/127 (59.1%) subsequently achieved clinical response at Week 16 and entered the maintenance trial. At Week 52, 26.5% of patients receiving upadacitinib 15 mg, and 43.6% receiving 30 mg, achieved clinical remission; efficacy was observed across all other endpoints with both doses. Herpes zoster rates increased with longer duration (16 weeks) of exposure to upadacitinib 45 mg during induction compared with the same population during the first 8 weeks. No other new safety signals were observed, and results are otherwise consistent with the known safety profile of upadacitinib.

Conclusions

Patients without clinical response after 8 weeks' upadacitinib 45 mg induction therapy, may benefit from an additional 8 weeks of therapy.

Clinical trial registration: NCT02819635; NCT03653026
A case of hepatitis‐associated aplastic anaemia following living‐donor liver transplantation for fulminant hepatitis showing loss of heterozygosity in the 6p chromosome in the affected liver
Authors: Katagiri Takamasa , Iwasaki Hiroka , Fujieda Atsushi , Kasashima Satomi , Ozaki Satoru , Uemori Mizuho , Ogawa Seishi , Nakao Shinji
Published: November 2023

The mechanisms underlying hepatitis‐associated aplastic anaemia (HAAA) that occurs several weeks after the development of acute hepatitis are unknown. A 20‐year‐old male developed HAAA following living‐donor liver transplantation for fulminant hepatitis. The patient's leucocytes lacked HLA‐class I due to loss of heterozygosity in the short arm of chromosome 6p (6pLOH). Interestingly, the patient's liver cells resected during the transplantation also exhibited 6pLOH that affected the same HLA haplotype as the leucocytes, suggesting that CD8+ T cells recognizing antigens presented by specific HLA molecules on liver cells may have attacked the haematopoietic stem cells of the patient, leading to the HAAA development.
Efficiency or equality? The utilitarianism–egalitarianism trade‐off determines carbon allocation preference
Authors: Huang Lingling , Liu Li , Dang Jianning , Wei Cong , Miao Xiaoyan
Published: November 2023

International carbon allocation confronts the conflict between efficiency and equality. Previous research based on the intergroup bias perspective has attributed carbon allocation preference to the defence of ingroup interests (i.e., national interests) while overlooking the critical role of trade‐offs between competing moral values. Integrating the contingency theory of justice and moral philosophical theories of utilitarianism and egalitarianism, we proposed that the moral‐values trade‐off between utilitarianism and egalitarianism determines carbon allocation preference through justice reasoning. Analysis of large‐scale survey datasets (Study 1) revealed that aggregated national endorsement of utilitarianism over egalitarianism predicted greater efficiency preference in total and per capita carbon emission levels. Study 2 demonstrated that experimentally manipulating endorsement of utilitarianism versus egalitarianism boosted efficiency (vs. equality) preference in carbon allocation, and justice reasoning characterized by enhanced efficiency‐focused justice and diminished equality‐focused justice accounted for these effects. Using a ‘manipulation‐of‐mediator’ design, Study 3 further confirmed the causal link in the mediation model. By highlighting the significance of moral trade‐offs in shaping carbon allocation preference, this research not only provides a novel moral perspective in understanding debates on international carbon allocation but also has important implications for fostering international carbon abatement cooperation.
Structural changes of CA1 pyramidal neurons after stroke in the contralesional hippocampus
Authors: Merino‐Serrais Paula , Plaza‐Alonso Sergio , Hellal Farida , Valero‐Freitag Susana , Kastanauskaite Asta , Plesnila Nikolaus , DeFelipe Javier
Published: November 2023

Significant progress has been made with regard to understanding how the adult brain responds after a stroke. However, a large number of patients continue to suffer lifelong disabilities without adequate treatment. In the present study, we have analyzed possible microanatomical alterations in the contralesional hippocampus from the ischemic stroke mouse model tMCAo 12–14 weeks after transient middle cerebral artery occlusion. After individually injecting Lucifer yellow into pyramidal neurons from the CA1 field of the hippocampus, we performed a detailed three‐dimensional analysis of the neuronal complexity, dendritic spine density, and morphology. We found that, in both apical (stratum radiatum) and basal (stratum oriens) arbors, CA1 pyramidal neurons in the contralesional hippocampus of tMCAo mice have a significantly higher neuronal complexity, as well as reduced spine density and alterations in spine volume and spine length. Our results show that when the ipsilateral hippocampus is dramatically damaged, the contralesional hippocampus exhibits several statistically significant selective alterations. However, these alterations are not as significant as expected, which may help to explain the recovery of hippocampal function after stroke. Further anatomical and physiological studies are necessary to better understand the modifications in the “intact” contralesional lesioned brain regions, which are probably fundamental to recover functions after stroke.
LINE‐1 hypomethylation, increased retrotransposition and tumor‐specific insertion in upper gastrointestinal cancer
Authors: Baba Yoshifumi , Yasuda Noriko , Bundo Miki , Nakachi Yutaka , Ueda Junko , Ishimoto Takatsugu , Iwatsuki Masaaki , Miyamoto Yuji , Yoshida Naoya , Oshiumi Hiroyuki , Iwamoto Kazuya , Baba Hideo
Published: November 2023

The long interspersed nuclear element‐1 (LINE‐1) retrotransposons are a major family of mobile genetic elements, comprising approximately 17% of the human genome. The methylation state of LINE‐1 is often used as an indicator of global DNA methylation levels and it regulates the retrotransposition and somatic insertion of the genetic element. We have previously reported the significant relationship between LINE‐1 hypomethylation and poor prognosis in upper gastrointestinal (GI) cancers. However, the causal relationships between LINE‐1 hypomethylation, retrotransposition, and tumor‐specific insertion in upper GI cancers remain unknown. We used bisulfite‐pyrosequencing and quantitative real‐time PCR to verify LINE‐1 methylation and copy number in tissue samples of 101 patients with esophageal and 103 patients with gastric cancer. Furthermore, we analyzed the LINE‐1 retrotransposition profile with an originally developed L1Hs‐seq. In tumor samples, LINE‐1 methylation levels were significantly lower than non‐tumor controls, while LINE‐1 copy numbers were markedly increased. As such, there was a significant inverse correlation between the LINE‐1 methylation level and copy number in tumor tissues, with lower LINE‐1 methylation levels corresponding to higher LINE‐1 copy numbers. Of particular importance is that somatic LINE‐1 insertions were more numerous in tumor than normal tissues. Furthermore, we observed that LINE‐1 was inserted evenly across all chromosomes, and most often within genomic regions associated with tumor‐suppressive genes. LINE‐1 hypomethylation in upper GI cancers is related to increased LINE‐1 retrotransposition and tumor‐specific insertion events, which may collectively contribute to the acquisition of aggressive tumor features through the inactivation of tumor‐suppressive genes.
A novel iTreg‐related signature for prognostic prediction in lung adenocarcinoma
Authors: Zhang Jian , Li Yan , Yang Yue , Huang Jian , Sun Yue , Zhang Xi , Kong Xianglong
Published: November 2023

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Most patients are diagnosed at an advanced stage, therefore it is crucial to identify novel prognostic biomarkers for LUAD. As important regulatory cells, inducible regulatory T cells (iTregs) play a vital role in immune suppression and are important for the maintenance of immune homeostasis. This study explored the prognostic value and therapeutic effects of iTreg‐related genes in LUAD. Data for LUAD patients, including immune infiltration data, RNA sequencing data, and clinical features, were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and Tumor Immune Single‐cell Hub 2 databases. Immune‐related subgroups with different infiltration patterns and iTreg‐related genes were identified through univariate and multivariate Cox regression analyses and weighted correlation network analysis. Functional enrichment analyses were performed to explore the underlying mechanisms of iTreg‐related genes. A prognostic risk signature was constructed using Cox regression analysis with the least absolute shrinkage and selection operator penalty. The ESTIMATE algorithm was applied to determine the immune status of LUAD patients. We applied the constructed signature to predict chemosensitivity and performed single‐cell RNA sequencing analysis. The infiltration of iTregs was identified as an independent factor for predicting patient outcomes. We constructed a prognostic signature based on seven iTreg‐related genes (GIMAP5, SLA, MS4A7, ZNF366, POU2AF1, MRPL12, and COL5A1), which was applied to subdivide patients into high‐ and low‐risk subgroups. Our results revealed that patients in the iTreg‐related low‐risk subgroup had a better prognosis and possibly greater sensitivity to traditional chemotherapy. Our study provides a novel iTreg‐related signature to elucidate the mechanisms underlying LUAD prognosis and promote individualized chemotherapy treatment.
Interactions of perinatal depression versus anxiety and infants' early temperament trajectories
Authors: Sörensen Ferdinand , Kimmel Mary C. , Brenner Vera , Krägeloh‐Mann Ingeborg , Skalkidou Alkistis , Mahjani Behrang , Fransson Emma
Published: November 2023

This study examines the interplay between maternal depression/anxiety and infant temperament's developmental trajectory in 1687 Swedish‐speaking mother–infant dyads from Uppsala County (2009–2019), Sweden. The sample includes a high proportion of university‐educated individuals and a low share of foreign‐born participants. Maternal depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale during gestational weeks 17 and 32 and postpartum at week 6. Multinomial regression explored associations between maternal variables and infant temperament trajectories at 6 weeks, 12 months, and 18 months. Prenatal anxiety is associated with the high‐rising infant difficult temperament trajectory, while prenatal depression/anhedonia is associated with the stable‐medium trajectory, attenuated postpartum. Associations between infant temperament and maternal mood depended on timing (pre/postpartum) and symptom type (depression/anhedonia vs. anxiety).
Neglecting to consider early emotional development after abuse and/or neglect: Insights and recommendations from child welfare providers
Authors: Edwards Nicole Megan , Panlilio Carlomagno C.
Published: November 2023

Laying a strong foundation for emotional development in children birth to 5 is of critical importance, but the extent to which this is considered following child abuse and/or neglect, foster care placement, reunification, and potential re‐entry into foster care remains unclear. Using a convergent mixed methods design, we investigated perceptions among child welfare professionals given the contributing role they could play in both initiating provider–parent dialogue and connecting families with timely resources to better support early emotional development post‐abuse/neglect. Fifty eight child welfare professionals in an urban, Northeastern County of the USA participated (73% response rate). Survey data and focus group insights shed light on satisfaction with and roadblocks to supporting foster and biological parents in promoting emotional development. A low proportion of respondents offered advice on emotional development, referred families to relevant parent education, or perceived biological or foster parents as extremely prepared. Self‐reported likelihood of providing advice to families was positively associated with access to information on emotional development, years employed, and job satisfaction. Multilevel roadblocks were identified. Results inform systems‐level, family‐centred initiatives and information sharing to better support emotional development post‐abuse and/or neglect.
Integrated model of maternal caregiving in child HIV management in Chinese mother–child dyads living with HIV: A qualitative dyadic analysis
Authors: Ji Shiyun , Zeng Xiaoliang , Chen Chen , Fu Rong , Shen Zhiyong , Li Xiaoming , Yu Nancy Xiaonan
Published: November 2023

Perinatally HIV‐positive (PHIV+) children face challenges arising from their complicated and highly stigmatized chronic illness throughout childhood and adolescence. Caring and support from caregivers are vital, especially from their mothers who also live with HIV. However, little is known regarding how HIV+ mothers coach their PHIV+ children to adjust to HIV. This study used dyadic‐level qualitative analyses of semi‐structured, one‐on‐one interviews among 20 mother–child dyads (n = 40; children aged 12–18 years) living with HIV in southern China. Interviews examined the perspectives of both mothers and children on the maternal caregiving in child HIV management and child adaptation outcomes. Our findings showed that based on a dual‐dimension model of the extent of maternal involvement in child HIV management and the intimacy of the mother–child relationship, four categories of maternal caring emerged among the mother–child dyads: supportiveness (n = 4, 20%), independence (n = 9, 45%), contradiction (n = 4, 20%) and alienation (n = 3, 15%). The PHIV+ children's selected HIV management indicators (including disclosure of HIV status, HIV‐related communication, antiretroviral therapy adherence, stigma coping and emotion management) also showed some variations among these four categories. The integrated model may inform the development of dyadic intervention programmes tailored for mothers and children both living with HIV.
Biallelic variants in the COQ4 gene caused hereditary spastic paraplegia predominant phenotype
Authors: Wei Qiao , Yu Hao , Wang Pei‐Shan , Xie Juan‐Juan , Dong Hai‐Lin , Wu Zhi‐Ying , Li Hong‐Fu
Published: November 2023

Introduction

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in COQ4 have been reported to cause primary CoQ10 deficiency‐7 (COQ10D7), which is a mitochondrial disease.

Aims

We aimed to screened COQ4 variants in a cohort of HSP patients.

Methods

A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants.

Results

In this study, five different COQ4 variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early‐onset pure HSP caused by COQ4 variants. Functional studies in patient‐derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure.

Conclusions

Our findings revealed that bilateral variants in the COQ4 gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4‐related disorders.
Estonian alcohol control legislation in 1990–2020: A narrative review
Authors: Stoppel Relika , Reile Rainer , Ahven Andri , Pärna Kersti
Published: November 2023

Issues

The aim of this narrative review is to provide a detailed, chronological overview on the development of Estonian alcohol control legislation during 1990–2020.

Approach

Qualitative document review focused on six legislative acts central to Estonian alcohol control policy. Distinguishing four policy areas (availability, advertising, taxation and drink‐driving), the review identifies and describes significant changes in these legislative acts and their amendments from 1990 to 2020.

Key Findings

The review identified 51 significant changes in acts regulating either availability, advertising, taxation or drink‐driving in Estonia. Majority of these changes (n = 36) relate to Alcohol Excise Duty Act and the Alcohol Act which regulate the taxation, production and sales of alcohol. Although all six key legislative acts were introduced during the 1990s, only a few significant changes to alcohol control policy were made in this decade. In contrast, the 2000s experienced an intense period of new legislation and amendments followed by 2010s when the main emphasis was on alcohol taxation and advertising.

Implications

During three decades, Estonian alcohol control legislation has gradually evolved to include most evidence‐based measures to reduce the harmful use of alcohol, the effects of the policies on consumption and alcohol‐related harms remain relatively modest.

Conclusion

The liberal and unregulated alcohol control measures in the 1990s have transitioned in the following two decades towards a coherent alcohol policy. While many of the World Health Organization's ‘best buys’ have been successfully implemented, there are still some recommendations which have not been targeted.