bluuebunny/crossref_metadata_2025 huggingface dataset:
What Do We Know and Need to Know About Weaning in Sheep? An Overview of Weaning Practises, Stress and Welfare
Authors: Freitas-de-Melo Aline , Orihuela Agustín , Hötzel Maria José , Ungerfeld Rodolfo
Published: February 2022

Artificial weaning is the separation of the mother and her lamb, involving the forced ending of suckling and milk supply by the ewes to their lambs. Artificial weaning time varies depending on the purpose of each sheep farm and the characteristics of the lambs, including age and weight of the lambs, and their ability to eat solid food. Artificial weaning is performed from 24 h postpartum until around the age of natural weaning (up to 12 mo of age). Artificial weaning results in the breaking of the ewe-lamb bond, the end of suckling and the complete replacement of milk by solid food, frequently added to changes in both the physical and social environment. It triggers behavioural, physiological and immunological changes that generate negative consequences on the health of both ewes and lambs, as well as on the growth of the lambs, rising animal welfare concerns. As artificial weaning is considered one of the most stressful situations in the life of farm mammals, it is important to consider the factors involved in those responses to develop adequate strategies and improve sheep welfare at weaning. The most frequently used method is the abrupt separation of the ewes and their lambs. However, the adaptation of the animals after weaning can be improved by alternative weaning methods (e.g., progressive, two-steps weaning and mixed regimes), hormonal treatments (e.g., administration of progesterone), and pre- and postweaning management (e.g., the use of creeping feeding, and the presence of conspecifics or humans after weaning). This review presents and summarises information on the stress response and animal welfare issues at artificial weaning in sheep and some management practises that can be used to reduce these problems. The major points included are the ewe-lamb bond at birth and during the lactation period; the stress response at weaning; the factors involved in the stress response at weaning; the different types and weaning methods and their repercussions on animal welfare; and some strategies that can be used to improve sheep welfare at weaning. Lastly, we propose directions for research needed to develop practical alternatives to minimise sheep's stress response at weaning.
Traditional Chinese Medicine Compound-Loaded Materials in Bone Regeneration
Authors: Shi Guiwen , Yang Chaohua , Wang Qing , Wang Song , Wang Gaoju , Ao Rongguang , Li Dejian
Published: February 2022

Bone is a dynamic organ that has the ability to repair minor injuries via regeneration. However, large bone defects with limited regeneration are debilitating conditions in patients and cause a substantial clinical burden. Bone tissue engineering (BTE) is an alternative method that mainly involves three factors: scaffolds, biologically active factors, and cells with osteogenic potential. However, active factors such as bone morphogenetic protein-2 (BMP-2) are costly and show an unstable release. Previous studies have shown that compounds of traditional Chinese medicines (TCMs) can effectively promote regeneration of bone defects when administered locally and systemically. However, due to the low bioavailability of these compounds, many recent studies have combined TCM compounds with materials to enhance drug bioavailability and bone regeneration. Hence, the article comprehensively reviewed the local application of TCM compounds to the materials in the bone regeneration in vitro and in vivo. The compounds included icariin, naringin, quercetin, curcumin, berberine, resveratrol, ginsenosides, and salvianolic acids. These findings will contribute to the potential use of TCM compound-loaded materials in BTE.
Development and Theoretical Underpinnings of the PRIORITY Intervention: A Parenting Intervention to Prevent Disordered Eating in Children and Young People With Type 1 Diabetes
Authors: O’Donnell Nicola R. , Satherley Rose-Marie , John Mary , Cooke Debbie , Hale Lucy S. , Stewart Rose , Jones Christina J.
Published: February 2022

Children and young people (CYP) with type 1 diabetes (T1D) are twice as likely to develop disordered eating (T1DE) and clinical eating disorders than those without. This has significant implications for physical and mental health, with some eating disorders associated with repeated diabetic ketoacidosis and higher HbA1c levels, both of which are life threatening. There is currently limited psychological support for CYP and families with T1D but increasingly, policy and practice are suggesting disordered eating in T1D may be effectively prevented through psychological intervention. We describe the development and theoretical underpinnings of a preventative psychological intervention for parents of CYP aged 11-14, with T1D. The intervention was informed by psychological theory, notably the Information Motivation Behaviour Skills model and Behaviour Change Technique Taxonomy. The intervention was co-developed with an expert advisory group of clinicians, and families with T1D. The manualised intervention includes two online group workshops, and supplementary online materials. The intervention continues to evolve, and feasibility findings will inform how best to align the intervention with routine care in NHS diabetes teams. Early detection and intervention are crucial in preventing T1DE, and it is hoped that the current intervention can contribute to improving the psychological and physical wellbeing of young people and families managing T1D.
Immune Infiltration in Gastric Cancer Microenvironment and Its Clinical Significance
Authors: Zhang An Zhi , Yuan Xin , Liang Wei Hua , Zhang Hai Jun , Li Ya , Xie Yu Fang , Li Jiang Fen , Jiang Chen Hao , Li Fan Ping , Shen Xi Hua , Pang Li Juan , Zou Hong , Zhou Wen Hu , Li Feng , Hu Jian Ming
Published: February 2022

Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+T cells, activated CD4+memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.
Systematic Analysis of Molecular Characterization and Clinical Relevance of Liquid–Liquid Phase Separation Regulators in Digestive System Neoplasms
Authors: Zhang Yaxin , Li Jie , Feng Dan , Peng Xiaobo , Wang Bin , Han Ting , Zhang Yingyi
Published: February 2022

Background: The role of liquid–liquid phase separation (LLPS) in cancer has also attracted more and more attention, which is found to affect transcriptional regulation, maintaining genomic stability and signal transduction, and contribute to the occurrence and progression of tumors. However, the role of LLPS in digestive system tumors is still largely unknown.

Results: Here, we characterized the expression profiles of LLPS regulators in 3 digestive tract tumor types such as COAD, STAD, and ESCA with The Cancer Genome Atlas (TCGA) data. Our results for the first time showed that LLPS regulatory factors, such as Brd4, FBN1, and TP53, were frequently mutated in all types of digestive system tumors. Variant allele frequency (VAF) and APOBEC analysis demonstrated that genetic alterations of LLPS regulators were related to the progression of digestive system neoplasms (DSNs), such as TP53, NPHS1, TNRC6B, ITSN1, TNPO1, PML, AR, BRD4, DLG4, and PTPN1. KM plotter analysis showed that the mutation status of LLPS regulators was significantly related to the overall survival (OS) time of DSNs, indicating that they may contribute to the progression of DSN. The expression analysis of LLPS regulatory factors showed that a variety of LLPS regulatory factors were significantly dysregulated in digestive system tumors, such as SYN2 and MAPT. It is worth noting that we first found that LLPS regulatory factors were significantly correlated with tumor immune infiltration of B cells, CD4+ T cells, and CD8+ T cells in digestive system tumors. Bioinformatics analysis showed that the LLPS regulators’ expression was closely related to multiple signaling, including the ErbB signaling pathway and T-cell receptor signaling pathway. Finally, several LLPS signatures were constructed and had a strong prognostic stratification ability in different digestive gland tumors. Finally, the results demonstrated the LLPS regulators’ signature score was significantly positively related to the infiltration levels of CD4+ T cells, neutrophil cells, macrophage cells, and CD8+ T cells.

Conclusion: Our study for the first time showed the potential roles of LLPS regulators in carcinogenesis and provide novel insights to identify novel biomarkers for the prediction of immune therapy and prognosis of DSNs.
Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer
Authors: Liu Zaoqu , Xu Hui , Ge Xiaoyong , Weng Siyuan , Dang Qin , Han Xinwei
Published: February 2022

Studies have demonstrated that non–MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non–MSI-H/pMMR CRC is vital. In this study, using three independent public cohorts and a clinical in-house cohort, we developed and validated a microsatellite stable–associated signature (MSSAS). The initial signature establishment was performed in GSE39582 (n = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas–CRC (n = 312), GSE39084 (n = 54), and in-house cohort (n = 146). As a result, MSSAS was proven to be an independent risk factor for overall survival and relapse-free survival in non–MSI-H/pMMR CRC. Receiver operating characteristic analysis showed that MSSAS had a stable and accurate performance in all cohorts for 1, 3, and 5 years, respectively. Further analysis suggested that MSSAS performed better than age, gender, and the T, N, M, and AJCC stages, adjuvant chemotherapy, tumor mutation burden, neoantigen, and TP53, KRAS, BRAF, and PIK3CA mutations. The clinical validation was executed to further ensure the robustness and clinical feasibility of this signature. In conclusion, MSSAS might be a robust and promising biomarker for advancing clinical management of non–MSI-H/pMMR CRC.
Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion
Authors: Cheuk Yin Celeste , Xu Shihao , Zhu Dong , Luo Yongsheng , Chen Tian , Chen Juntao , Li Jiawei , Shi Yi , Zhang Yi , Rong Ruiming
Published: February 2022

Background: Accumulating evidence indicates that mesenchymal stem cells (MSCs) are precursors of myofibroblasts, which play a vital role in renal fibrosis. The close interaction between MSCs and other immune cells regulates the development of multiple fibrosis-related diseases. However, the effect of myeloid-derived suppressor cells (MDSCs) on MSCs remains unexplored. Here, we investigated the effect of MDSCs on the myofibroblastic differentiation of MSCs.

Methods: MSCs were induced to undergo myofibroblastic differentiation with transforming growth factor beta 1 (TGF-β1). M-MDSCs and G-MDSCs were sorted by flow cytometry. Supernatants derived from MDSCs were administered to cultured bone marrow MSCs (BM-MSCs) undergoing TGF-β1-induced myofibroblastic differentiation. Myofibroblastic differentiation was evaluated by immunostaining. The expression of fibrosis-related genes was determined by quantitative PCR and western blot analysis. In vitro, M-MDSC supernatant or M-MDSC supernatant with interleukin (IL)-15 mAbs was administered following unilateral renal ischemia-reperfusion injury (IRI) to observe the myofibroblast differentiation of renal resident MSCs (RRMSCs) in a murine model.

Results: Myofibroblastic differentiation of MSCs was hindered when the cells were treated with MDSC-derived supernatants, especially that from M-MDSCs. The inhibitory effect of M-MDSC supernatant on the myofibroblastic differentiation of MSCs was partially mediated by IL-15-Ras-Erk1/2-Smad2/3 signaling. Treatment with M-MDSC supernatant ameliorated renal fibrosis and myofibroblastic differentiation in RRMSCs through IL-15. Additionally, M-MDSC supernatant increased M-MDSC infiltration in the kidney in a mouse IRI model. M-MDSC supernatant downregulated the adhesion and migration marker CD44 on the cell membrane of MSCs via IL-15.

Conclusion: M-MDSC-derived supernatant inhibited the TGF-β1-induced myofibroblastic differentiation of MSCs through IL-15. Our findings shed new light on the effect of MDSCs on myofibroblastic differentiation and adhesion of MSCs, which might provide a new perspective in the development of treatment strategies for renal fibrosis.
An Integrated Analysis of the Identified PRPF19 as an Onco-immunological Biomarker Encompassing the Tumor Microenvironment, Disease Progression, and Prognoses in Hepatocellular Carcinoma
Authors: Yang Ming , Qiu Yiwen , Yang Yi , Wang Wentao
Published: February 2022

Background: Targeting the mRNA splicing process has been identified as a therapeutic strategy for human cancer. PRPF19 is an RNA binding protein that is involved in pre-mRNA processing and repairing DNA damage; the aberrant expression of PRPF19 is potentially associated with carcinogenesis. However, the biological role of PRPF19 in hepatocellular carcinoma (HCC) is still elusive.

Methods: Data obtained from TCGA, Oncomine, and GEO were used to investigate the PRPF19 expression level and its role in tumor immune infiltration, prognosis, and the tumor progression of cohorts from HCC. Using various databases and tools (UALCAN, TIMER, TISMO, and PathCards), we presented the potential mechanisms of PFPF19 upregulation, PRPF19-related pathways, and its biological functions in liver cancer.

Results: For HCC, PRPF19 expression was found upregulated both in single tumor cells and tissues. Furthermore, the increased expression of PRPF19 was significantly correlated to clinical characteristics: advanced stage, vascular invasion, high AFP, and poor prognosis of HCC. According to the tumor-immunological analysis, we found that PRPF19 is positively correlated with infiltrating myeloid-derived suppressor cells (MDSCs). Moreover, the microenvironment of HCC tissues with high expression of PRPF19 is highly immunosuppressive (lower T-lymphocytes, multiple immune checkpoints upregulated). Patients with high expression of PRPF19 and high MDSCs had a worse survival prognosis as well. TP53 mutation may have a positive effect on PRPF19 expression via decreased promoter methylation of PRPF19. By TF-mRNA network analysis, key transcription factors (TFs) in TC-NER and PCS pathways (PRPF19 involved) were identified.

Conclusion: This work implied that PRPF19 is associated with tumor immune evasion and progression, and serves as a prognostic marker for worse clinical outcomes with HCC. Thus, this critical regulator could serve as a potential therapeutic target of HCC.
Trace Element-Augmented Titanium Implant With Targeted Angiogenesis and Enhanced Osseointegration in Osteoporotic Rats
Authors: Yan Ran , Li Jinhua , Wu Qianju , Zhang Xiangkai , Hu Longwei , Deng Yuwei , Jiang Ruixue , Wen Jin , Jiang Xinquan
Published: February 2022

Deteriorated bone quality in osteoporosis challenges the success of implants, which are in urgent need for better early osseointegration as well as antibacterial property for long-term stability. As osteoporotic bone formation tangles with angiogenic clues, the relationship between osteogenesis and angiogenesis has been a novel therapy target for osteoporosis. However, few designs of implant coatings take the compromised osteoporotic angiogenic microenvironment into consideration. Here, we investigated the angiogenic effects of bioactive strontium ions of different doses in HUVECs only and in a co-culture system with BMSCs. A proper dose of strontium ions (0.2–1 mM) could enhance the secretion of VEGFA and Ang-1 in HUVECs as well as in the co-culture system with BMSCs, exhibiting potential to create an angiogenic microenvironment in the early stage that would be beneficial to osteogenesis. Based on the dose screening, we fabricated a bioactive titanium surface doped with zinc and different doses of strontium by plasma electrolytic oxidation (PEO), for the establishment of a microenvironment favoring osseointegration for osteoporosis. The dual bioactive elements augmented titanium surfaces induced robust osteogenic differentiation, and enhanced antimicrobial properties. Augmented titanium implant surfaces exhibited improved bone formation and bone–implant contact under comprehensive assessment of an in vivo bone–implant interface. In conclusion, zinc- and strontium-augmented titanium surface benefits the osseointegration in osteoporosis via promoting osteogenic differentiation, exerting antibacterial efficacy, and stimulating early angiogenesis.
Released Parasite-Derived Kinases as Novel Targets for Antiparasitic Therapies
Authors: Silvestre Anne , Shintre Sharvani Shrinivas , Rachidi Najma
Published: February 2022

The efficient manipulation of their host cell is an essential feature of intracellular parasites. Most molecular mechanisms governing the subversion of host cell by protozoan parasites involve the release of parasite-derived molecules into the host cell cytoplasm and direct interaction with host proteins. Among these released proteins, kinases are particularly important as they govern the subversion of important host pathways, such as signalling or metabolic pathways. These enzymes, which catalyse the transfer of a phosphate group from ATP onto serine, threonine, tyrosine or histidine residues to covalently modify proteins, are involved in numerous essential biological processes such as cell cycle or transport. Although little is known about the role of most of the released parasite-derived kinases in the host cell, they are examples of kinases hijacking host cellular pathways such as signal transduction or apoptosis, which are essential for immune response evasion as well as parasite survival and development. Here we present the current knowledge on released protozoan kinases and their involvement in host-pathogen interactions. We also highlight the knowledge gaps remaining before considering those kinases - involved in host signalling subversion - as antiparasitic drug targets.
Learning From Agility, Partnership and Innovation During the Covid-19 Pandemic: A Perspective From Industry
Authors: Cárdenas Ana María , Roger-Dalbert Celine
Published: February 2022

Two years after the COVID-19 pandemic started, the world continues to adapt to the profound effects that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had on our lives. As the global crisis took hold, many looked to the medical technology/device industry for guidance and solutions. All while the industry itself, was disrupting its own processes and activities. In order to evolve and deliver accelerated innovation the industry had to be agile, resilient and collaborative with the broader healthcare community and technology partners. Now comes a time when we will start to see what changes were temporary and which ones will become part of the new process, but one thing is certain, we will not be going back to where we were pre-pandemic.
Challenges to Elephant Connectivity From Border Fences in the World's Largest Transfrontier Conservation Area
Authors: Naidoo Robin , Beytell Piet , Brennan Angela , Kilian Werner , McCulloch Graham , Stronza Amanda , Taylor Russell , Tsholofelo Chief , Songhurst Anna
Published: February 2022

To more effectively protect biodiversity and promote sustainable development, transfrontier conservation areas (TFCAs) aim to enhance wildlife flows across national borders. This is true of the world's largest terrestrial TFCA, the Kavango-Zambezi (KAZA), home to half of Africa's savannah elephants that move across five countries in a mixed-use landscape. We used GPS tracking data from >100 collared elephants to evaluate how fences between Namibia and Botswana impact transboundary connectivity in KAZA. For female elephants these fences formed an impenetrable boundary, with no exchange between animals collared in Botswana and those collared in Namibia. Male elephants did cross border fences, although they remained a partial boundary, with 7 of 21 males accounting for most crossings. Our results suggest a review of fence alignment and de-commissioning of some fencing separating Namibia and Botswana, combined with increased support for fence-free interventions that reduce wildlife-livestock interactions, should be considered to meet the objectives of KAZA.
Association of Residential Proximity to the Coast With Incident Myocardial Infarction: A Prospective Cohort Study
Authors: Xiao-dong Zhuang , Shao-zhao Zhang , Xun Hu , Xin-xue Liao , Li-zhen Liao
Published: February 2022

Background

Little is known about how the residential distance to the coast is associated with incident myocardial infarction (MI) and which mechanisms may explain the association. We aim to explore this association using data from a prospective, population-based cohort with unprecedented sample size, and broad geographical coverage.

Methods

In this study, 377,340 participants from the UK Biobank were included.

Results

It was shown that 4,059 MI occurred during a median 8.0 years follow-up. Using group (<1 km) as reference, group (20–50 km) was associated with a lower risk of MI (hazard ratio, HR 0.79, 95% CI 0.64–0.98) and a U-shaped relation between distance to the coast and MI was shown with the low-risk interval between 32 and 64 km (pnon−linear = 0.0012). Using participants of the intermediate region (32–64 km) as a reference, participants of the offshore region (<32 km) and inland region (>64 km) were both associated with a higher risk of incident MI (HR 1.12, 95% CI 1.04–1.21 and HR 1.09, 95% CI 1.01–1.18, respectively). HR for offshore region (<32 km) was larger in subgroup with low total physical activity (<24 h/week) (HR 1.24, 95% CI 1.09–1.42, pinteraction = 0.043). HR for inland region (>64 km) was larger in subgroup in urban area (HR 1.12, 95% CI 1.03–1.22, pinteraction = 0.065) and in subgroup of high nitrogen dioxide (NO2) air pollution (HR 1.29, 95% CI 1.11–1.50, pinteraction = 0.021).

Conclusion

We found a U-shaped association between residential distance to the coast and incident MI, and the association was modified by physical activity, population density, and air pollution.
Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review
Authors: Wu Na-Qiong , Shi Hui-Wei , Li Jian-Jun
Published: February 2022

The function of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), a novel plasma protein, has mainly been involved in cholesterol metabolism in the liver, while, more interestingly, recent data have shown that PCSK9 also took part in the modulation of inflammation, which appeared to be another explanation for the reduction of cardiovascular risk by PCSK9 inhibition besides its significant effect on lowering lower-density lipoprotein cholesterol (LDL-C) concentration. Overall, a series of previous studies suggested an association of PCSK9 with inflammation. Firstly, PCSK9 is able to induce the secretion of proinflammatory cytokines in macrophages and in other various tissues and elevated serum PCSK9 levels could be observed in pro-inflammatory conditions, such as sepsis, acute coronary syndrome (ACS). Secondly, detailed signaling pathway studies indicated that PCSK9 positively regulated toll-like receptor 4 expression and inflammatory cytokines expression followed by nuclear factor-kappa B (NF-kB) activation, together with apoptosis and autophagy progression. Besides, PCSK9 enhanced and interacted with scavenger receptors (SRs) of inflammatory mediators like lectin-like oxidized-LDL receptor-1 (LOX-1) to promote inflammatory response. Additionally, several studies also suggested that the role of PCSK9 in atherogenesis was intertwined with inflammation and the interacting effect shown between PCSK9 and LOX-1 was involved in the inflammatory response of atherosclerosis. Finally, emerging clinical trials indicated that PCSK9 inhibitors could reduce more events in patients with ACS accompanied by increased inflammatory status, which might be involved in its attenuating impact on arterial plaque. Hence, further understanding of the relationship between PCSK9 and inflammation would be necessary to help prevent and manage the atherosclerotic cardiovascular disease (ASCVD) clinically. This review article will update the recent advances in the link of PCSK9 with inflammation.
Prognostic Value of Global Longitudinal Strain in Asymptomatic Aortic Stenosis: A Systematic Review and Meta-Analysis
Authors: Wang Yuan , Zhang Minghui , Chen Hui , Li Hongwei
Published: February 2022

Backgrounds

The presence of impaired global longitudinal strain (GLS) may be a valuable bio-marker in the early diagnosis for left ventricle (LV) impairment, which would help scrutinize asymptomatic aortic stenosis (AS) patients with high risk of adverse outcomes, such as major adverse cardiovascular events (MACE).

Methods

The study was prospectively registered in PROPSERO (CRD 42021223472). Databases, such as Pubmed, Embase, Cochrane Library, Web of science, and Scopus were searched for studies evaluating the impact of impaired GLS on MACE, all-cause mortality, and aortic valve replacement (AVR) in asymptomatic AS. Hazard ratios (HRs) with 95% CIs were calculated with meta-analysis for binary variants. Meta-regression, subgroup analysis, and sensitivity analyses were applied as needed to explore the heterogeneity.

Results

Eventually, a total of nine studies reporting 1,512 patients were enrolled. Compared with the normal GLS group, impaired GLS significantly increased MACE (HR = 1.20, 95% CI: 1.10–1.30, I2 = 79%) with evident heterogeneity, all-cause mortality (HR = 1.42, 95% CI: 1.24–1.63), and AVR (HR = 1.17, 95% CI: 1.07–1.28). Subgroup analyses stratified by left ventricular ejection fraction (LVEF) > 50% or LVEF without precise cut-off point found that compared with the normal GLS group, impaired GLS remarkably increased MACE both in two subgroups (LVEF > 50%: HR: 1.22, 95% CI: 1.05–1.50; LVEF without cutpoint: HR: 1.25, 95% CI: 1.05–1.50). The results stratified by AS severity (mild/moderate and severe) or follow-up time resembled those stratified by LVEF. In addition, when subgroup analysis was stratified by mean aortic valve pressure gradient (MG ≥ 40 mm Hg and MG <40 mm Hg), compared with normal GLS, impaired GLS significantly increased MACE both in two subgroups (MG ≥ 40 mm Hg: HR: 3.41, 95% CI: 1.64–7.09; MG below 40 mm Hg: HR: 3.17, 95% CI: 1.87–5.38). Moreover, the effect sizes here were substantially higher than those in the former two stratified factors.

Conclusions

The presence of impaired GLS substantially worsens the outcomes for adverse cardiovascular events in asymptomatic patients with AS regardless of LVEF or AS severity or follow-up time or mean aortic valve pressure gradient, which highlights the importance of incorporating impaired GLS into risk algorithms in asymptomatic AS.

Systematic Review Registration

PROSPERO (registration number: CRD42021223472).
Balancing Gender Bias in Job Advertisements With Text-Level Bias Mitigation
Authors: Hu Shenggang , Al-Ani Jabir Alshehabi , Hughes Karen D. , Denier Nicole , Konnikov Alla , Ding Lei , Xie Jinhan , Hu Yang , Tarafdar Monideepa , Jiang Bei , Kong Linglong , Dai Hongsheng
Published: February 2022

Despite progress toward gender equality in the labor market over the past few decades, gender segregation in labor force composition and labor market outcomes persists. Evidence has shown that job advertisements may express gender preferences, which may selectively attract potential job candidates to apply for a given post and thus reinforce gendered labor force composition and outcomes. Removing gender-explicit words from job advertisements does not fully solve the problem as certain implicit traits are more closely associated with men, such as ambitiousness, while others are more closely associated with women, such as considerateness. However, it is not always possible to find neutral alternatives for these traits, making it hard to search for candidates with desired characteristics without entailing gender discrimination. Existing algorithms mainly focus on the detection of the presence of gender biases in job advertisements without providing a solution to how the text should be (re)worded. To address this problem, we propose an algorithm that evaluates gender bias in the input text and provides guidance on how the text should be debiased by offering alternative wording that is closely related to the original input. Our proposed method promises broad application in the human resources process, ranging from the development of job advertisements to algorithm-assisted screening of job applications.
OCT and OCT Angiography Offer New Insights and Opportunities in Schizophrenia Research and Treatment
Authors: Green Kyle M. , Choi Joy J. , Ramchandran Rajeev S. , Silverstein Steven M.
Published: February 2022

The human retina and retinal imaging technologies continue to increasingly gain the attention of schizophrenia researchers. With the same embryologic origin as the brain, the retina offers a window into neurovascular changes that may underlie disease. Recently, two technologies that have already revolutionized the field of ophthalmology, optical coherence tomography (OCT), and a functional extension of this, optical coherence tomography angiography (OCTA), have gained traction. Together, these non-invasive technologies allow for microscopic imaging of both structural and vascular features of the retina. With ease of use and no side effects, these devices are likely to prove powerful digital health tools in the study and treatment of schizophrenia. They may also prove key to discovering disease relevant biomarkers that underly neurodevelopmental and neurodegenerative aspects of conditions such as schizophrenia.
The Spring Heat Source Over the Qinghai–Tibetan Plateau Linked With the Winter Warm Arctic–Cold Siberia Pattern Impacting Summer Drought in China
Authors: Yang Yumeng , Zhao Liang , Shen Xinyong , Xiao Ziniu , Li Qingquan
Published: February 2022

The atmospheric heat source over the Qinghai–Tibetan Plateau (QTP) in spring has an important impact on the climate of the surrounding regions. However, there have been few systematic studies of the dominant mode of the heat source and the cross-seasonal connections with the preceding winter and following summer. Using a distinct empirical orthogonal function (DEOF) decomposition method, we obtained the leading mode of the spring heat source over the QTP and the surrounding regions and analyzed its precursors in the previous winter and lagging effects in the following summer. Our results show that the first mode (DEOF1) was characterized by a warm plateau and cold surrounding regions. The positive phase was significantly associated with the warm Arctic–cold Siberia (WACS) pattern (r = 0.39, p = .01) and the La Niña-like SST anomaly in the Pacific in the preceding winter and the following East Asian subtropical summer monsoon (r = –0.44, p = .01), resulting in a widespread drought in China during the following summer. The cold anomaly in Siberia and the warm anomaly at mid-to low latitudes in winter associated with the WACS pattern coincide with the DEOF1 mode of the heat source over the QTP and its surroundings through change of meridional temperature gradient and wave-flow interactions. A mid-latitude wave train excited by the WACS and the thermal difference in the meridional direction of the spring DEOF1 mode caused high-pressure anomalies over the QTP and the mid-latitude region of East Asia, influencing central and eastern China. This anomaly was not conducive to the northward advancement of the East Asian summer monsoon, resulting in drought in most of China in spring and summer. The cross-seasonal relationship between the main mode of the spring heat source on the QTP and the preceding winter WACS pattern and the following East Asian summer monsoon can be used as a reference in climate prediction studies.
Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors
Authors: Damanti Sarah , Cilla Marta , Tuscano Bruno , De Lorenzo Rebecca , Manganaro Giuseppina , Merolla Aurora , Pacioni Giacomo , Pomaranzi Chiara , Tiraferri Valeria , Martinenghi Sabina , Vitali Giordano , Bosi Emanuele , Conte Caterina , Giustina Andrea , Tresoldi Moreno , Rovere Querini Patrizia
Published: February 2022

Background

acute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients.

Methods

cross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality.

Results

two hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 – 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004).

Discussion

we described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.
Pregnancy Outcomes in Thyroid Cancer Survivors: A Propensity Score-Matched Cohort Study
Authors: Cao Qi , Zhu Huili , Zhang Jiani , Li Yujing , Huang Wei
Published: February 2022

Background

Some female thyroid cancer survivors wish to become pregnant following their cancer treatment. Current studies have shown inconsistent results on pregnancy outcomes in these survivors; however, detailed information on the pathological type, treatment, and gestational thyroid function of these patients are not yet well documented, making the refined assessment of the influence of a history of thyroid cancer and related treatments on pregnancy outcomes challenging.

Objective

To investigate the risk of adverse pregnancy outcomes in thyroid cancer survivors.

Methods

This was a retrospective cohort study. We included all women aged between 19 and 45 years old who delivered between January 2019 and June 2020 in West China Second University Hospital of Sichuan University. Women with tumors other than thyroid cancer or other thyroid diseases were excluded. The included women were divided into survivors of thyroid cancer (survivors) and women without any history of thyroid disease (controls). Propensity score matching and logistic regression were used to control confounding variables.

Results

All 18,332 women who met the inclusion criteria were included in the study (96 survivors of papillary thyroid cancer and 18,236 controls). After propensity score matching, 96 survivors and 192 controls were included. The survivors had higher levels of free thyroxine (15.47 [13.61–17.67] vs. 14.38 [13.20–15.81] pmol/mL; P<0.001) and higher levels of thyroid peroxidase antibodies (TPOAb) (43.55 [31.43–71.43] vs. 35.95 [28.00–48.03] U/mL; P=0.008) but similar levels of thyroid stimulating hormone (1.46 [0.56–3.15] vs. 1.36 [0.81–1.92] mIU/mL; P=0.142) than the controls. There were no significant differences in adverse pregnancy outcomes between survivors and controls. Fetal macrosomia was lower among survivors (OR: 0.077, 95% CI: 0.009–0.668. P=0.020) than controls. Additionally, survivors had reduced weight gain during pregnancy (13.0 [10.0–15.0] vs. 14.00 [11.00–16.00] kg, P=0.005) and reduced placental weight (563.0 [514.5–620.0] vs. 572.0 [520.0–650.0] g, P=0.019), albeit with small absolute differences. Thyroidectomy or radioiodine therapy did not adversely affect pregnancy outcomes.

Conclusion

A history of treated papillary thyroid cancer was not associated with adverse pregnancy outcomes.
Pharmacological Evaluation of Melanocortin 2 Receptor Accessory Protein 2 on Axolotl Neural Melanocortin Signaling
Authors: Wang Xiaozhu , Xue Song , Lei Xiaowei , Song Wenqi , Li Lei , Li Xuan , Fu Yanbin , Zhang Cong , Zhang Hailin , Luo Yao , Wang Meng , Lin Gufa , Zhang Chao , Guo Jing
Published: February 2022

The Melanocortin-3 receptor (MC3R) and Melanocortin-4 receptor (MC4R), two members of the key hypothalamic neuropeptide signaling, function as complex mediators to control the central appetitive and energy homeostasis. The melanocortin 2 receptor accessory protein 2 (MRAP2) is well-known for its modulation on the trafficking and signaling of MC3R and MC4R in mammals. In this study, we cloned and elucidated the pharmacological profiles of MRAP2 on the regulation of central melanocortin signaling in a relatively primitive poikilotherm amphibian species, the Mexican axolotl (Ambystoma mexicanum). Our results showed the higher conservation of axolotl mc3r and mc4r across species than mrap2, especially the transmembrane regions in these proteins. Phylogenetic analysis indicated that the axolotl MC3R/MC4R clustered closer to their counterparts in the clawed frog, whereas MRAP2 fell in between the reptile and amphibian clade. We also identified a clear co-expression of mc3r, mc4r, and mrap2 along with pomc and agrp in the axolotl brain tissue. In the presence of MRAP2, the pharmacological stimulation of MC3R by α-MSH or ACTH significantly decreased. MRAP2 significantly decreased the cell surface expression of MC4R in a dose dependent manner. The co-localization and formation of the functional complex of axolotl MC3R/MC4R and MRAP2 on the plasma membrane were further confirmed in vitro. Dramatic changes of the expression levels of mc3r, mrap2, pomc, and agrp in the fasting axolotl hypothalamus indicated their critical roles in the metabolic regulation of feeding behavior and energy homeostasis in the poikilotherm aquatic amphibian.
Associations of Dietary Inflammatory Index With Prediabetes and Insulin Resistance
Authors: Shu Yanling , Wu Xiaocong , Wang Jiating , Ma Xiang , Li Huawen , Xiang Yun
Published: February 2022

Background and Aims

Previous studies suggested that dietary inflammatory index (DII) was associated with a variety of adverse health conditions. However, less is known about the role of DII in prediabetes and insulin resistance (IR). Therefore, this study aimed to investigate whether DII is associated with prediabetes and IR in American adults.

Method and Results

DII scores were calculated using the average of two 24-hour dietary recalls. Linear regression models were performed to evaluate the associations of DII with markers of Type 2 diabetes (T2D) risk, and the associations of DII with prediabetes and IR were estimated using logistic regression model. The diet of the participants showed an anti-inflammatory potential, with a mean DII score of −0.14 (range: −5.83 to +5.32). After controlling for multiple potential confounders, DII scores were positively associated with fasting plasma glucose (FPG) (β: 0.009; 95%CI: 0.005 to 0.012), fasting serum insulin (FSI) (β: 0.083; 95%CI: 0.067 to 0.099) and homeostatic model assessment of insulin resistance (HOMA-IR) (β: 0.092; 95%CI: 0.075 to 0.109). Participants in the highest tertile of DII score have increased odds of prediabetes (OR: 1.40; 95%CI: 1.17 to 1.69; P for trend <0.001) and IR (OR: 1.79; 95%CI: 1.49 to 2.14; P for trend <0.001) compared with those in the first tertile of DII score.

Conclusions

This study indicates that DII was positively associated with FPG, FSI, and HOMA-IR, and a more pro-inflammatory diet was related to increased odds of insulin resistant and prediabetes.
Statistical Atlases and Automatic Labeling Strategies to Accelerate the Analysis of Social Insect Brain Evolution
Authors: Arganda Sara , Arganda-Carreras Ignacio , Gordon Darcy G. , Hoadley Andrew P. , Pérez-Escudero Alfonso , Giurfa Martin , Traniello James F. A.
Published: February 2022

Current methods used to quantify brain size and compartmental scaling relationships in studies of social insect brain evolution involve manual annotations of images from histological samples, confocal microscopy or other sources. This process is susceptible to human bias and error and requires time-consuming effort by expert annotators. Standardized brain atlases, constructed through 3D registration and automatic segmentation, surmount these issues while increasing throughput to robustly sample diverse morphological and behavioral phenotypes. Here we design and evaluate three strategies to construct statistical brain atlases, or templates, using ants as a model taxon. The first technique creates a template by registering multiple brains of the same species. Brain regions are manually annotated on the template, and the labels are transformed back to each individual brain to obtain an automatic annotation, or to any other brain aligned with the template. The second strategy also creates a template from multiple brain images but obtains labels as a consensus from multiple manual annotations of individual brains comprising the template. The third technique is based on a template comprising brains from multiple species and the consensus of their labels. We used volume similarity as a metric to evaluate the automatic segmentation produced by each method against the inter- and intra-individual variability of human expert annotators. We found that automatic and manual methods are equivalent in volume accuracy, making the template technique an extraordinary tool to accelerate data collection and reduce human bias in the study of the evolutionary neurobiology of ants and other insects.
Achromatic Cues Are Important for Flower Visibility to Hawkmoths and Other Insects
Authors: van der Kooi Casper J. , Kelber Almut
Published: February 2022

Studies on animal colour vision typically focus on the chromatic aspect of colour, which is related to the spectral distribution, and disregard the achromatic aspect, which is related to the intensity (“brightness”) of a stimulus. Although the chromatic component of vision is often most reliable for object recognition because it is fairly context independent, the achromatic component may provide a reliable signal under specific conditions, for example at night when light intensity is low. Here we make a case for the importance of achromatic cues in plant-pollinator signalling, based on experimental data on naïve Deilephila elpenor and Macroglossum stellatarum hawkmoths, optical modelling and synthesising published experiments on bees, flies, butterflies and moths. Our experiments show that in ecologically relevant light levels hawkmoths express a strong preference for brighter stimuli. Published experiments suggest that for flower-visiting bees, butterflies, moths and flies, achromatic cues may be more important for object detection than often considered. Our optical modelling enabled disentangling the contribution of pigments and scattering structures to the flower’s achromatic contrast, and illustrates how flower anatomy and background are important mediating factors. We discuss our findings in the context of the often-assumed dichotomy between detection and discrimination, chromatic versus achromatic vision, and the evolution of floral visual signals.
Contrasting Effects of Chronic Anthropogenic Disturbance on Activity and Species Richness of Insectivorous Bats in Neotropical Dry Forest
Authors: Meramo Katarina , Ovaskainen Otso , Bernard Enrico , Silva Carina Rodrigues , Laine Veronika N. , Lilley Thomas M.
Published: February 2022

For prioritizing conservation actions, it is vital to understand how ecologically diverse species respond to environmental change caused by human activity. This is particularly necessary considering that chronic human disturbance is a threat to biodiversity worldwide. Depending on how species tolerate and adapt to such disturbance, ecological integrity and ecosystem services will be more or less affected. Bats are a species-rich and functionally diverse group, with important roles in ecosystems, and are therefore recognized as a good model group for assessing the impact of environmental change. Their populations have decreased in several regions, especially in the tropics, and are threatened by increasing human disturbance. Using passive acoustic monitoring, we assessed how the species-rich aerial insectivorous bats—essential for insect suppression services—respond to chronic human disturbance in the Caatinga dry forests of Brazil, an area potentially harboring ca. 100 bat species (nearly 50% are insectivorous), but with > 60% its area composed of anthropogenic ecosystems under chronic pressure. Acoustic data for bat activity was collected at research sites with varying amounts of chronic human disturbance (e.g., livestock grazing and firewood gathering). The intensity of the disturbance is indicated by the global multi-metric CAD index (GMDI). Using Animal Sound Identifier (ASI) software, we identified 18 different bat taxon units. Using Hierarchical Modeling of Species Communities (HMSC), we found trends in the association of the disturbance gradient with species richness and bat activity: species richness was higher at sites with higher human disturbance, whereas bat activity decreased with increasing human disturbance. Additionally, we observed taxon-specific responses to human disturbance. We conclude that the effects of chronic anthropogenic disturbance on the insectivorous bat fauna in the Caatinga are not homogeneous and a species-specific approach is necessary when assessing the responses of local bats to human disturbances in tropical dry forests, and in other biomes under human pressure.