bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers of peanut allergy in children over time
Authors: Foong Ru‐Xin , Du Toit George , van Ree Ronald , Bahnson Henry T. , Radulovic Suzana , Craven Jo , Kwok Matthew , Jama Zainab , Versteeg Serge A. , Brough Helen A. , Logan Kirsty , Perkin Michael R. , Flohr Carsten , Lack Gideon , Santos Alexandra F.
Published: June 2024

Background

Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population‐based cohort.

Methods

Participants were recruited from the EAT and EAT‐On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7–12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7–12 years. PA status was determined at the 7–12 year time point.

Results

The prevalence of PA was 2.1% at 7–12 years. Between 3 and 7–12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut‐sIgE, Ara h 2‐sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut‐sIgE, Ara h 2‐sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut‐sIgE and Ara h 2‐sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut‐sIgE from 36 months to 7–12 years, but MAT remained low. PS children had low biomarkers across time.

Conclusions

In this cohort, few children outgrow or develop new PA between 36 months and 7–12 years. Children with persistent PA have raised SPT, peanut‐sIgE, Ara h 2‐sIgE and MAT evident from infancy that consistently increase over time.
“So that we may be counted”
Authors: Farrukhi Ghazal Asif
Published: June 2024

In 2017 a seemingly small change in Pakistan's questionnaire for the upcoming national census sparked vociferous debates about religious identity and the politics of recognition. The questionnaire added “Scheduled Caste” as a separate religion, whereas previously it had appeared as a Hindu subcategory. Some saw this bureaucratic shift as a cynical attempt to further diminish Pakistan's precarious Hindu minority, reopening old wounds about religious nationalism. Anti‐caste progressives, however, saw an opportunity to imagine alternative political horizons for minority citizenship. How do untimely state projects render new political aspirations legible? As shown through ethnographic attention to rumors, enumerative practices, and census campaigns, the tools of bureaucratic documentation can reactivate unsettled histories, helping people imagine new possibilities from the state's margins.
Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients
Authors: Okda Sherouk M. , El‐Bassiouny Noha A. , El Amrawy Ahmed Mahmoud , Salahuddin Ahmad , Elonsy Sohila M. , Kassem Amira B.
Published: June 2024

Aims

Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients.

Methods

This is an open‐label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real‐time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography–fluorescence detector.

Results

Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL,P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8,P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL,P = .037).

Conclusion

There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.
Challenges for the improvement of valganciclovir prophylaxis in solid organ transplantation and the possible role of therapeutic drug monitoring in adults
Authors: van Vugt Lukas K. , Hesselink Dennis A. , de Winter Brenda C. M.
Published: June 2024

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy. Additionally, valganciclovir resistance has emerged among CMV strains, which complicates the treatment of CMV infections. Furthermore, the use of valganciclovir is associated with myelotoxicity, which can lead to the premature withdrawal of prophylaxis. It is important to address these current issues in order to improve the standard care after solid organ transplantation. This paper will therefore discuss the clinical practice of valganciclovir prophylaxis, elaborate on its issues and suggest how to improve the current prophylactic strategy with a possible role for therapeutic drug monitoring.
Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats
Authors: Bi Guofang , Liang Fengting , Wu Ting , Wang Peng , Jiang Xiaowen , Hu Shuang , Wu Chenghua , Zhou Wenhong , Guo Jiayin , Yang Xiao , Fang Jian‐hong , Chen Wenying , Bi Huichang
Published: June 2024

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug‐metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent‐specific PXR agonist pregnenolone‐16α‐carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two‐thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation‐induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN‐induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up‐regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body.
Outcomes of active surveillance for Japanese patients with prostate cancer (PRIAS‐JAPAN)
Authors: Kato Takuma , Matsumoto Ryuji , Yokomizo Akira , Tohi Yoichiro , Fukuhara Hiroshi , Fujii Yoichi , Mori Keiichiro , Sato Takuma , Inokuchi Junichi , Hashine Katsuyoshi , Sakamoto Shinichi , Kinoshita Hidefumi , Inoue Koji , Tanikawa Toshiki , Utsumi Takanobu , Goto Takayuki , Hara Isao , Okuno Hiroshi , Kakehi Yoshiyuki , Sugimoto Mikio
Published: June 2024

Objective

To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)‐JAPAN study, a prospective observational study for Japanese patients, initiated in 2010.

Patients and Methods

At the beginning, inclusion criteria were initially low‐risk patients, prostate‐specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow‐up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments.

Results

As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64–73) years, 5.3 (4.5–6.6) ng/mL, 0.15 (0.12–0.17) ng/mL, and 1 (1–2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re‐biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re‐biopsies were 29%, 30%, 35% and 25%, respectively. The 1‐, 5‐ and 10‐year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer.

Conclusion

Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded.
Soil–plant–gall relationships: from gall development to ecological patterns
Authors: Arriola Ígor Abba , Costa Elaine Cotrim , de Oliveira Denis Coelho , Isaias Rosy Mary dos Santos
Published: June 2024

The adaptive nature of the galler habit has been tentatively explained by the nutrition, microenvironment, and enemy hypotheses. Soil attributes have direct relationships with these three hypotheses at the cellular and macroecological scales, but their influence has been restricted previously to effects on the nutritional status of the host plant on gall richness and abundance. Herein, we discuss the ionome patterns within gall tissues and their significance for gall development, physiology, structure, and for the nutrition of the gallers. Previous ecological and chemical quantification focused extensively on nitrogen and carbon contents, evoking the carbon‐nutrient defence hypothesis as an explanation for establishing the plant–gall interaction. Different elements are involved in cell wall composition dynamics, antioxidant activity, and regulation of plant–gall water dynamics. An overview of the different soil–plant–gall relationships highlights the complexity of the nutritional requirements of gallers, which are strongly influenced by environmental soil traits. Soil and plant chemical profiles interact to determine the outcome of plant–herbivore interactions and need to be addressed by considering not only the soil features and galler nutrition but also the host plant's physiological traits. The quantitative and qualitative results for iron metabolism in gall tissues, as well as the roles of iron as an essential element in the physiology and reproduction of gallers suggest that it may represent a key nutritional resource, aligning with the nutrition hypothesis, and providing an integrative explanation for higher gall diversity in iron‐rich soils.
The role of perceived powerlessness and other barriers to climate action
Authors: Pickering Gary J. , Dale Gillian
Published: June 2024

The impacts of anthropogenic climate change are rapidly worsening, but current efforts to mitigate this crisis are insufficient. Therefore, it is critically important to understand how to motivate more individuals to take action to protect against future climate change impacts. This study examines the individual‐level factors that predict motivations to act, as well as potential barriers to action in a sample of Canadian adults. Participants completed a questionnaire that assessed a) demographics; b) climate change knowledge, opinions, and scepticism; and c) psychological factors that may impede action. The responses were analyzed to determine the factors that explain whether individuals would change their actions in light of climate change and to what extent climate change considerations impact their actions. Predictors of action included how informed individuals were about climate change, perceived severity of its effects, perceived urgency to act, and climate change scepticism. The strongest predictor was perceived powerlessness; individuals who felt a sense of powerlessness were less likely to change their actions and reported that the threat of climate change had less influence over their behaviours. Powerlessness in turn was associated with age and political affiliation. Implications of these findings, and possible solutions to overcome the barrier of perceived powerlessness, are discussed.
Inflammatory response in traumatic brain and spinal cord injury: The role of XCL1‐XCR1 axis and T cells
Authors: Zhang Mingkang , Han Xiaonan , Yan Liyan , Fu Yikun , Kou Hongwei , Shang Chunfeng , Wang Junmin , Liu Hongjian , Jiang Chao , Wang Jian , Cheng Tian
Published: June 2024

Background

Traumatic brain injury (TBI) and spinal cord injury (SCI) are acquired injuries to the central nervous system (CNS) caused by external forces that cause temporary or permanent sensory and motor impairments and the potential for long‐term disability or even death. These conditions currently lack effective treatments and impose substantial physical, social, and economic burdens on millions of people and families worldwide. TBI and SCI involve intricate pathological mechanisms, and the inflammatory response contributes significantly to secondary injury in TBI and SCI. It plays a crucial role in prolonging the post‐CNS trauma period and becomes a focal point for a potential therapeutic intervention. Previous research on the inflammatory response has traditionally concentrated on glial cells, such as astrocytes and microglia. However, increasing evidence highlights the crucial involvement of lymphocytes in the inflammatory response to CNS injury, particularly CD8+ T cells and NK cells, along with their downstream XCL1‐XCR1 axis.

Objective

This review aims to provide an overview of the role of the XCL1‐XCR1 axis and the T‐cell response in inflammation caused by TBI and SCI and identify potential targets for therapy.

Methods

We conducted a comprehensive search of PubMed and Web of Science using relevant keywords related to the XCL1‐XCR1 axis, T‐cell response, TBI, and SCI.

Results

This study examines the upstream and downstream pathways involved in inflammation caused by TBI and SCI, including interleukin‐15 (IL‐15), interleukin‐12 (IL‐12), CD8+ T cells, CD4+ T cells, NK cells, XCL1, XCR1+ dendritic cells, interferon‐gamma (IFN‐γ), helper T0 cells (Th0 cells), helper T1 cells (Th1 cells), and helper T17 cells (Th17 cells). We describe their proinflammatory effect in TBI and SCI.

Conclusions

The findings suggest that the XCL1‐XCR1 axis and the T‐cell response have great potential for preclinical investigations and treatments for TBI and SCI.
Hippocampal mitophagy contributes to spatial memory via maintaining neurogenesis during the development of mice
Authors: Xu Le , Saeed Saboor , Ma Xinxu , Cen Xufeng , Sun Yifei , Tian Yanan , Zhang Xuhong , Zhang Danhua , Tang Anying , Zhou Hetong , Lai Jianbo , Xia Hongguang , Hu Shaohua
Published: June 2024

Background

Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of mitophagy in spatial memory mediated by neurogenesis during development.

Methods

Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among mitophagy, neurogenesis, and behavioral performance during development.

Results

The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of mitophagy in adult mice with UMI‐77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of mitophagy with Mdivi‐1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory.

Conclusion

The observed decline in spatial memory in adult mice is associated with decreased mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing mitophagy to counteract age‐ or disease‐related cognitive decline.
Disrupted individual‐level morphological brain network in spinal muscular atrophy types 2 and 3
Authors: Li Yufen , Nie Huirong , Xiang Pei , Shen Wanqing , Yan Mengzhen , Yan Cui , Su Shu , Qian Long , Liang Yujian , Tang Wen , Yang Zhiyun , Li Yijuan , Chen Yingqian
Published: June 2024

Background and Objective

Spinal muscular atrophy (SMA) is one of the most common monogenic neuromuscular diseases, and the pathogenesis mechanisms, especially the brain network topological properties, remain unknown. This study aimed to use individual‐level morphological brain network analysis to explore the brain neural network mechanisms in SMA.

Methods

Individual‐level gray matter (GM) networks were constructed by estimating the interregional similarity of GM volume distribution using both Kullback–Leibler divergence‐based similarity (KLDs) and Jesen‐Shannon divergence‐based similarity (JSDs) measurements based on Automated Anatomical Labeling 116 and Hammersmith 83 atlases for 38 individuals with SMA types 2 and 3 and 38 age‐ and sex‐matched healthy controls (HCs). The topological properties were analyzed by the graph theory approach and compared between groups by a nonparametric permutation test. Additionally, correlation analysis was used to assess the associations between altered topological metrics and clinical characteristics.

Results

Compared with HCs, although global network topology remained preserved in individuals with SMA, brain regions with altered nodal properties mainly involved the right olfactory gyrus, right insula, bilateral parahippocampal gyrus, right amygdala, right thalamus, left superior temporal gyrus, left cerebellar lobule IV–V, bilateral cerebellar lobule VI, right cerebellar lobule VII, and vermis VII and IX. Further correlation analysis showed that the nodal degree of the right cerebellar lobule VII was positively correlated with the disease duration, and the right amygdala was negatively correlated with the Hammersmith Functional Motor Scale Expanded (HFMSE) scores.

Conclusions

Our findings demonstrated that topological reorganization may prioritize global properties over nodal properties, and disrupted topological properties in the cortical–limbic‐cerebellum circuit in SMA may help to further understand the network pathogenesis underlying SMA.
Continuous identity authentication protocol against quantum attacks in satellite integrated smart grid
Authors: Huang Chao , Yang Min , Li Bo , Yu Lin
Published: June 2024

To address the issue of low efficiency caused by the repeated use of quantum attack resistant static identity authentication methods in a satellite integrated smart grid, this paper proposes a quantum attack resistant continuous identity authentication protocol. First, in the initial authentication stage, in order to reduce computational complexity, the key encryption mechanism in the CRYSTALS‐Kyber algorithm was improved and combined with the NTRU message recovery digital signature scheme to construct a lattice based explicit AKE (Kyber NTRU. AKE), which achieved mutual authentication and negotiated shared tokens. Second, in the continuous authentication stage, incorporating quantum attack resistant tokens into the current algorithm to improve authentication efficiency. The formal analysis results indicate that compared to the weakly forward secure Kyber.AKE in the CRYSTALS‐Kyber algorithm, Kyber‐NTRU.AKE achieves complete forward secrecy, while the non‐formal analysis results demonstrate the security of the continuous authentication phase. Through theoretical analysis and efficiency comparison with Cyber.AKE, the analysis shows that the Cyber‐NTRU.AKE has higher computational and communication efficiency than Cyber.AKE.
Breast tumor detection using multi‐feature block based neural network by fusion of CT and MRI images
Authors: Kumari Bersha , Nandal Amita , Dhaka Arvind
Published: June 2024

Radiologists and clinicians must automatically examine breast and tumor locations and sizes accurately. In recent years, several neural network‐based feature fusion versions have been created to improve medical image segmentation. Multi‐modal image fusion photos may efficiently identify tumors. This work uses image fusion to identify computed tomography and magnetic resonance imaging alterations. A Gauss‐log ratio operator is recommended for difference image production. The Gauss‐log ratio and log ratio difference image complement the objective of improving the difference map through image fusion. The feature change matrix extracts edge, texture, and intensity from each picture pixel. The final change detection map classifies feature vectors as “changed” or “unchanged” which has been mapped for high‐resolution or low‐resolution pixels. This paper proposes a multi‐feature blocks (MFB) based neural network for multi‐feature fusion. This neural network modeling approach globalizes pixel spatial relationships. MFB‐based feature fusion also aims to capture channel interactions between feature maps. The proposed technique outperforms state‐of‐the‐art approaches which have been discussed in detail in experimental results section.
Protein phosphatase SCP4 regulates cartilage development and endochondral osteogenesis via FoxO3a dephosphorylation
Authors: Wang Pinger , Zou Kaiao , Cao Jin , Zhang Zhengmao , Yuan Wenhua , Chen Jiali , Xu Jianbo , Zou Zhen , Chen Di , Ruan Hongfeng , Feng Jianying , Lin Xia , Jin Hongting
Published: June 2024

The regulatory mechanisms involved in embryonic development are complex and yet remain unclear. SCP4 represents a novel nucleus‐resident phosphatase identified in our previous study. The primary aim of this study was to elucidate the function of SCP4 in the progress of cartilage development and endochondral osteogenesis. SCP4−/− and SCP4Col2ER mice were constructed to assess differences in bone formation using whole skeleton staining. ABH/OG staining was used to compare chondrocyte differentiation and cartilage development. Relevant biological functions were analysed using RNA‐sequencing and GO enrichment, further validated by immunohistochemical staining, Co‐IP and Western Blot. Global SCP4 knockout led to abnormal embryonic development in SCP4−/− mice, along with delayed endochondral osteogenesis. In parallel, chondrocyte‐specific removal of SCP4 yielded more severe embryonic deformities in SCP4Col2ER mice, including limb shortening, reduced chondrocyte number in the growth plate, disorganisation and cell enlargement. Moreover, RNA‐sequencing analysis showed an association between SCP4 and chondrocyte apoptosis. Notably, Tunnel‐positive cells were indeed increased in the growth plates of SCP4Col2ER mice. The deficiency of SCP4 up‐regulated the expression levels of pro‐apoptotic proteins both in vivo and in vitro. Additionally, phosphorylation of FoxO3a (pFoxO3a), a substrate of SCP4, was heightened in chondrocytes of SCP4Col2ER mice growth plate, and the direct interaction between SCP4 and pFoxO3a was further validated in chondrocytes. Our findings underscore the critical role of SCP4 in regulating cartilage development and endochondral osteogenesis during embryonic development partially via inhibition of chondrocytes apoptosis regulated by FoxO3a dephosphorylation.
Cerebral palsy and neurodevelopmental disorders with motor disabilities: Similar but not synonymous
Authors: Lumsden Daniel E.
Published: June 2024

This letter to the editor is a response to the letter to the editor by Cooper et al. on pages 1390–1391 of this issue.
Genetic variants of LEAP2 are associated with anthropometric traits and circulating insulin‐like growth factor‐1 concentration: A UK Biobank study
Authors: Andreoli María F. , Gentreau Mélissa , Rukh Gull , Perello Mario , Schiöth Helgi B.
Published: June 2024

Aim

To test the hypothesis that liver‐expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity.

Methods

Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin‐like growth factor‐1 (IGF‐1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex‐stratified analyses were also conducted.

Results

Five SNPs showed positive associations with obesity‐related traits. rs57880964 was associated with body mass index (BMI) and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF‐1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF‐1 concentration in both sexes.

Conclusions

These findings reveal sex‐specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF‐1 concentration.
Planting long‐lived trees in a warming climate: Theory shows the importance of stage‐dependent climatic tolerance
Authors: Erlichman Adèle , Sandell Linnea , Otto Sarah P. , Aitken Sally N. , Ronce Ophélie
Published: June 2024

Climate change poses a particular threat to long‐lived trees, which may not adapt or migrate fast enough to keep up with rising temperatures. Assisted gene flow could facilitate adaptation of populations to future climates by using managed translocation of seeds from a warmer location (provenance) within the current range of a species. Finding the provenance that will perform best in terms of survival or growth is complicated by a trade‐off. Because trees face a rapidly changing climate during their long lives, the alleles that confer optimal performance may vary across their lifespan. For instance, trees from warmer provenances could be well adapted as adults but suffer from colder temperatures while juvenile. Here we use a stage‐structured model, using both analytical predictions and numerical simulations, to determine which provenance would maximize the survival of a cohort of long‐lived trees in a changing climate. We parameterize our simulations using empirically estimated demographic transition matrices for 20 long‐lived tree species. Unable to find reliable quantitative estimates of how climatic tolerance changes across stages in these same species, we varied this parameter to study its effect. Both our mathematical model and simulations predict that the best provenance depends strongly on how fast the climate changes and also how climatic tolerance varies across the lifespan of a tree. We thus call for increased empirical efforts to measure how climate tolerance changes over life in long‐lived species, as our model suggests that it should strongly influence the best provenance for assisted gene flow.
Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation
Authors: Kilcoyne Isabelle , Nieto Jorge , Nottle Bridget F. , Flynn Harriet , Knych Heather K.
Published: June 2024

Background

Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb.

Objectives

The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin.

Study design

Randomised cross‐over in vivo experiment.

Methods

Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2‐week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30‐min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography–tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay.

Results

Measurable concentrations of morphine were apparent in the RCJ of all horses. Median CMAX of morphine in the M group was 4753.1 (2115.7–14 934.5) ng/mL and 4477 (3434.3–7363) ng/mL in the MA group (p = 0.5). Median CMAX of synovial amikacin was 322.6 (157.5–1371.6 μg/mL).

Main limitations

Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included.

Conclusions

IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side‐effects.
The novel prognostic marker SPOCK2 regulates tumour progression in melanoma
Authors: Kang Ji Young , Cho Hyeijin , Gil Minchan , Lee Haeryung , Park Soochul , Kim Kyung Eun
Published: June 2024

Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal‐like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1‐MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.
Interplay between diabetes mellitus and atopic dermatitis
Authors: Lei Dongyun , Zhang Jiechen , Zhu Tingting , Zhang Litao , Man Mao‐Qiang
Published: June 2024

Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.
Interparental conflict trajectories across various child residence arrangements when parents live apart
Authors: Holt Tonje , Helland Maren Sand , Larsen Linda , Gustavson Kristin , Smyth Bruce
Published: June 2024

In Norway, as in most Western countries, a growing proportion of parents living apart choose shared residence for their children. The aim of this study was to investigate trajectories of five interparental conflict dimensions across four child residence arrangement groups (and three combination groups) to improve understanding of different conflict trajectories when parents live apart. We used data from the Dynamics of Family Conflict study. Families (N = 1136) were recruited from 37 family counseling centers across Norway. Parents answered questionnaires in three waves: Wave 1 (December 2017 through August 2019); Wave 2 (November 2019 through January 2021); and Wave 3 (April through May 2021). Mixed effects analyses indicated that (a) for all conflict dimensions, there was less conflict and more cooperation over time across all residence arrangements; (b) except for children's involvement in conflict, the conflict dimensions did not develop differently over time between residence arrangements; (c) families with arrangements in which one parent had minority time (1%–14% and 15%–34%) were more likely to report children being involved in their parents' arguments over time than the 35%–49% and 50/50 residence groups; (d) for families with high relational risk pattern, children's involvement in conflict did not decline in either a high (1–34%) or a low degree (35%–49%) of sharing; and (e) families with a violent risk pattern and low degree of sharing (1%–34%) had the steepest decrease in conflict frequency/intensity over time. Even with an average decrease in destructive conflict dimensions over time, the findings point to the need for providing support for parents with complex needs, particularly for parents with a high relational risk pattern.
Working on what works: A critical reflection on the past, present, and future of parenting education programs for divorcing and separating parents
Authors: Markham Melinda Stafford , Ferraro Anthony J.
Published: June 2024

In this commentary, we revisit the current state of research on parenting education programs for divorcing and separating parents and reflect on what scholars have recommended as priorities for future research. We then explore how the collection of articles in this special issue advance those priorities in meaningful ways. Topics addressed include recommendations for parenting education program content, parenting education to better meet families' needs, and measurement of program effectiveness. Implications for practitioners, family court professionals, and researchers are discussed.
Urea fertilization for potentializing beef cattle performance in agroforestry systems in the humid tropics
Authors: Figueiredo Thaís Lima , Apolinário Valéria Xavier de Oliveira , Coelho Janerson José , Muniz Luciano Cavalcante , Sousa Maria Karoline de Carvalho Rodrigues de , Souza Raabe Alves , Carneiro Giselle Cristina da Silva , Vilhena Natannael Castro , Costa Joaquim Bezerra , Dubeux Jose Carlos Batista
Published: June 2024

This study hypothesized that urea fertilization could optimize animal performance in an agroforestry system. This study evaluated how increasing rates of N fertilization (0, 100, 200, and 400 kg N ha−1 year−1) using urea (CH4N2O) affected forage mass, nutritive value, and beef cattle (Bos indicus) performance in an agroforestry system with Massai grass (Megathyrsus maximus Jacq. cv. Massai) and legume tree (Mimosa caesalpiniifolia Benth.), in the humid tropic region of Brazil, over 2‐year period. The experiment was carried out in a randomized complete block design with four treatments (N fertilizer rates) and three replications. Forage mass was positive and linearly affected by N fertilization (p = .0236, R2 = 0.92), ranging from 1297 to 1583 kg DM ha−1 under 0 and 400 kg N ha−1 year−1, respectively. There was greater average forage mass during the rainy period (1826 kg ha−1) (p < .05). Crude protein in green forage mass increased linearly (p = .0041, R2 = 0.91) in function of the N applied. Cattle average daily gain showed a positive quadratic response to the rates of N applied (p = .0298, R2 = 0.97), ranging from 0.46 kg to 0.68 kg animal day−1; and the gain per area increased linearly from 1.84 to 2.68 kg LW ha−1 day−1 (p = .0640, R2 = 0.96). The findings indicate that applying 200 kg N ha−1 year−1, split‐applied during the rainy season, would yield acceptable outcomes in terms of forage mass, nutritive value, and animal performance for this type of agroforestry system.
Advancing the Use of Suction Lysimeters to Inform Soil Leaching and Remediation of PFAS Source Zones
Authors: Rayner John L. , Lee Amanda , Corish Stephen , Leake Simon , Bekele Elise , Davis Greg B.
Published: June 2024

Porewater in soil vadose zones is an integrator of the fundamental processes governing the transport and partitioning of per and poly‐fluoroalkyl substances (PFAS) as they move from source zones to groundwater. Suction lysimeters are being advanced as a method to provide reliable and representative PFAS porewater samples, to inform PFAS leaching and for monitoring remedial approaches. We report outcomes of lysimeter investigations across 3 sites and 18 lysimeters within fine‐textured soil profiles. Soil cores were recovered from the same locations, and PFAS concentrations in soils and lysimeter porewater were compared and compared with prior laboratory investigations. Variable concentration distributions with depth of PFAS in soils were found with a maximum sum of PFAS of ~56 mg/kg dominated by perfluorooctane sulfonic acid (PFOS). The maximum sum of PFAS in porewater was 13.5 mg/L. Comparison across all collocated soil and porewater concentrations did not provide consistent trends. PFAS mass fractions within lysimeter porewater samples were much higher for most PFAS than mass fractions determined from laboratory investigations, but the fraction was lower for PFOS. The results indicate preferential recovery of individual shorter chain PFAS via leaching at lower liquid: soil ratios such as those experienced under suction during recovery of porewater by lysimeters. Suggestions are offered to advance the use of suction lysimeters in promoting porewater PFAS concentrations as an alternative for regulatory compliance, and in closing the gap between field and laboratory approaches. There is merit in using lysimeters at PFAS field sites with improvements and considerations embraced.
LANGUAGE—HISTORY—PRESENCE
Authors: ALONZI LUIGI
Published: June 2024

This article deals with the use of language in historiography and with this usage's implications for the conception of history and the historiographical operation/practice. Whereas theorists of “presence” believe that “presence” and “reality” can be grasped in spoken language and written texts, thus generally considering them as a medium that enables access to a “reality” that lies beyond texts and language, I argue that language and texts should themselves be considered as a “reality.” We need to distinguish the process of “presentification” performed by words from the presence of language as a lexical and physical reality; though the two aspects are strictly connected, the presence of language needs to be emphasized as a lexical‐semantic system and as a thing in the world. In this article, I consider language as a “living witness” of the narrated events; it is a presence in the moment that events occurred and a presence that is still present. We should think of language as we think of the material world around us—that is, as a transformed landscape that contains present and absent pasts. Historians of “presence” consider the meanings associated with language as a major obstacle obstructing the understanding of history in a new unmediated way; to some extent, this article is an attempt to hold meaning and presence together.
Investigations on kaolin mixtures: Impact on mullite formation kinetics and microstructure evolution
Authors: Sadli Nabil , May Abdelghani , Hamidouche Mohamed , Henniche Abdelkhalek , Belhouchet Hocine , Boudouh Hassane
Published: June 2024

This study evaluates Algerian kaolin (Djebel Debbagh (DD1) and Tamazart (KT2)) as potential substitutes for commercial kaolin (Lab) in the production of mullite‐based ceramics. Three compositions were prepared by incorporating the appropriate percentage of alumina to each calcined kaolin to achieve stoichiometric mullite precursors. The phase evolution of individual kaolin powders, as well as their mixtures with alumina, depends strongly on the calcination temperature and kaolin impurities. The differential scanning calorimetry combined with thermogravimetric analysis (TGA) showed lower secondary mullite formation temperature for the KT2‐based mixture. However, X‐ray diffraction revealed a complete mullitization in DD1 mixture. The K2O hindered cristobalite formation and reduced secondary mullite formation rate. Microstructure analysis showed lath‐shaped primary mullite and equi‐axed secondary mullite particles. After sintering at 1600°C, The KT2‐based sample (M3) exhibited higher density (3.013 g/cm3) and hardness (9.9 GPa), whereas the DD2‐based sample (M2) showed moderate densification (2.91 g/cm3) and higher flexural strength (159.42 MPa). Impurities (mainly Fe2O3, and K2O) promoted liquid phase sintering, resulting in greater densification in M3, whereas M2 showed more homogeneous microstructure, refined grains, and lower glassy phase content, contributing to enhanced strength.
Communication in organizations: An overview and provocations
Authors: Izak Michal , Case Peter , Ybema Sierk
Published: June 2024

The role that communication plays in social organization and processes of organizing has received considerable scholarly attention from multiple disciplines over several decades. This paper provides a review of the diverse literature that has sought to contribute to the understanding of communication and its implication for management and organization studies. An analysis of the SCOPUS database for the period 1980–2022 enabled us to cluster reference material and identify five perspectives which emerge from a review of the literature: communication as transfer, discourse, conversation (analysis), narrative, and Communicative Constitution of Organizations. These categories are not intended to be exhaustive, but they do provide a useful critical heuristic for navigating a field of study that might otherwise appear overwhelming. To map the terrain's theoretical underpinnings, our study also adopted a problematizing approach to the review which revealed various conspicuous conceptual and empirical absences at a ‘field level’ which merit further attention. The paper offers provocations and suggestions that we expect will inform future studies of organizational communication. Possibilities for developing the field include paying attention to: (a) paralinguistic dimensions of communication; (b) communication in relation to actual work practices; (c) monologic communication and (d) organizational communication in non‐Western contexts.
Effectiveness and predictors of weight loss response to phentermine plus lifestyle modifications among youth in a paediatric weight management clinical setting
Authors: Bomberg Eric M. , Clark Justin , Rudser Kyle D. , Gross Amy C. , Kelly Aaron S. , Fox Claudia K.
Published: June 2024

Background

Anti‐obesity medications (AOMs) are promising lifestyle modification (LSM) adjuncts for obesity treatment, and phentermine is commonly prescribed in paediatric weight management clinics. Determining ‘real‐world’ AOM effectiveness and characteristics predicting response is important.

Objectives

We sought to describe phentermine plus LSM effectiveness and identify baseline characteristics predicting response.

Methods

This was a retrospective cohort study among youth seen in a US academic‐based weight management clinic from 2012 to 2020. Baseline characteristics (e.g., body mass index (BMI), liver transaminases, eating‐related behaviours) and outcomes (%BMI of 95th percentile (%BMIp95), BMI, %BMI change, weight) were determined through electronic health records and intake surveys.

Results

Among 91 youth prescribed phentermine plus LSM over 8 years (mean %BMIp95 150%), %BMIp95 was statistically significantly reduced at 1.5, 3, 6 and 12 months (peak reduction 10.9 percentage points at 6 months; p < 0.001). Considering multiple comparisons, the presence of baseline elevated alanine aminotransferase was associated with statistically significant smaller 1.5‐month %BMIp95 reductions (p = 0.001) and higher food responsiveness with smaller 3‐ (p = 0.001) and 6‐month (p < 0.001) reductions.

Conclusions

Phentermine plus LSM reduced %BMIp95 among youth in a weight management clinic, and baseline characteristics may help determine those more or less likely to respond. Prospective studies are needed to further characterize effectiveness and confirm response predictors.