bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein domains provide a new layer of information for classifying human variations in rare diseases
Authors: Corcuff Mélanie , Garibal Marc , Desvignes Jean-Pierre , Guien Céline , Grattepanche Coralie , Collod-Béroud Gwenaëlle , Ménoret Estelle , Salgado David , Béroud Christophe
Published: February 2023

Introduction: Using the ACMG-AMP guidelines for the interpretation of sequence variants, it remains difficult to meet the criterion associated with the protein domain, PM1, which is assigned in only about 10% of cases, whereas the criteria related to variant frequency, PM2/BA1/BS1, is reported in 50% of cases. To improve the classification of human missense variants using protein domains information, we developed the DOLPHIN system (https://dolphin.mmg-gbit.eu).

Methods: We used Pfam alignments of eukaryotes to define DOLPHIN scores to identify protein domain residues and variants that have a significant impact. In parallel, we enriched gnomAD variants frequencies for each domains’ residue. These were validated using ClinVar data.

Results: We applied this method to all potential human transcripts’ variants, resulting in 30.0% being assigned a PM1 label, whereas 33.2% were eligible for a new benign support criterion, BP8. We also showed that DOLPHIN provides an extrapolated frequency for 31.8% of the variants, compared to the original frequency available in gnomAD for 7.6% of them.

Discussion: Overall, DOLPHIN allows a simplified use of the PM1 criterion, an expanded application of the PM2/BS1 criteria and the creation of a new BP8 criterion. DOLPHIN could facilitate the classification of amino acid substitutions in protein domains that cover nearly 40% of proteins and represent the sites of most pathogenic variants.
Requirement for ER-mitochondria Ca2+ transfer, ROS production and mPTP formation in L-asparaginase-induced apoptosis of acute lymphoblastic leukemia cells
Authors: Lee Jung Kwon , Rosales Jesusa L. , Lee Ki-Young
Published: February 2023

Acute lymphoblastic leukemia (aLL) is a malignant cancer in the blood and bone marrow characterized by rapid expansion of lymphoblasts. It is a common pediatric cancer and the principal basis of cancer death in children. Previously, we reported that L-asparaginase, a key component of acute lymphoblastic leukemia chemotherapy, causes IP3R-mediated ER Ca2+ release, which contributes to a fatal rise in [Ca2+]cyt, eliciting aLL cell apoptosis via upregulation of the Ca2+-regulated caspase pathway (Blood, 133, 2222–2232). However, the cellular events leading to the rise in [Ca2+]cyt following L-asparaginase-induced ER Ca2+ release remain obscure. Here, we show that in acute lymphoblastic leukemia cells, L-asparaginase causes mitochondrial permeability transition pore (mPTP) formation that is dependent on IP3R-mediated ER Ca2+ release. This is substantiated by the lack of L-asparaginase-induced ER Ca2+ release and loss of mitochondrial permeability transition pore formation in cells depleted of HAP1, a key component of the functional IP3R/HAP1/Htt ER Ca2+ channel. L-asparaginase induces ER Ca2+ transfer into mitochondria, which evokes an increase in reactive oxygen species (ROS) level. L-asparaginase-induced rise in mitochondrial Ca2+ and reactive oxygen species production cause mitochondrial permeability transition pore formation that then leads to an increase in [Ca2+]cyt. Such rise in [Ca2+]cyt is inhibited by Ruthenium red (RuR), an inhibitor of the mitochondrial calcium uniporter (MCU) that is required for mitochondrial Ca2+ uptake, and cyclosporine A (CsA), an mitochondrial permeability transition pore inhibitor. Blocking ER-mitochondria Ca2+ transfer, mitochondrial ROS production, and/or mitochondrial permeability transition pore formation inhibit L-asparaginase-induced apoptosis. Taken together, these findings fill in the gaps in our understanding of the Ca2+-mediated mechanisms behind L-asparaginase-induced apoptosis in acute lymphoblastic leukemia cells.
Cooperation between primary cilia signaling and integrin receptor extracellular matrix engagement regulates progenitor proliferation and neuronal differentiation in the developing cerebellum
Authors: Pittman Anna E. , Solecki David J.
Published: February 2023

Neural progenitors and their neuronal progeny are bathed in extrinsic signals that impact critical decisions like the mode of cell division, how long they should reside in specific neuronal laminae, when to differentiate, and the timing of migratory decisions. Chief among these signals are secreted morphogens and extracellular matrix (ECM) molecules. Among the many cellular organelles and cell surface receptors that sense morphogen and ECM signals, the primary cilia and integrin receptors are some of the most important mediators of extracellular signals. Despite years of dissecting the function of cell-extrinsic sensory pathways in isolation, recent research has begun to show that key pathways work together to help neurons and progenitors interpret diverse inputs in their germinal niches. This mini-review utilizes the developing cerebellar granule neuron lineage as a model that highlights evolving concepts on the crosstalk between primary cilia and integrins in the development of the most abundant neuronal type in the brains of mammals.
Novel virulence factor Cba induces antibody-dependent enhancement (ADE) of Streptococcus suis Serotype 9 infection in a mouse model
Authors: Yang Pengjiang , Yang Lei , Cao Kun , Hu Qian , Hu Yuli , Shi Jun , Zhao Dun , Yu Xinglong
Published: February 2023

Streptococcus suis (SS) is a zoonotic pathogen that affects the health of humans and the development of the pig industry. The SS Cba protein is a collagen adhesin, and a few of its homologs are related to the enhancement of bacterial adhesion. We compared the phenotypes of SS9-P10, SS9-P10 cba knockout strains and its complementary strains in vitro and in vivo and found that knocking out the cba gene did not affect the growth characteristics of the strain, but it significantly reduced the ability of SS to form biofilms, adhesion to host cells, phagocytic resistance to macrophages and attenuated virulence in a mouse infection model. These results indicated that Cba was a virulence related factor of SS9. In addition, Mice immunized with the Cba protein had higher mortality and more serious organ lesions after challenge, and the same was observed in passive immunization experiments. This phenomenon is similar to the antibody-dependent enhancement of infection by bacteria such as Acinetobacter baumannii and Streptococcus pneumoniae. To our knowledge, this is the first demonstration of antibody-dependent enhancement of SS, and these observations highlight the complexity of antibody-based therapy for SS infection.
Relevant mechanisms of MAIT cells involved in the pathogenesis of periodontitis
Authors: Jiang Xinrong , Zhao Qingtong , Huang Zhanyu , Ma Fengyu , Chen Kexiao , Li Zejian
Published: February 2023

Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells that are abundant in the human body, recognize microbial-derived vitamin B metabolites presented by MHC class I-related protein 1 (MR1), and rapidly produce proinflammatory cytokines, which are widely involved in the immune response to various infectious diseases. In the oral mucosa, MAIT cells tend to accumulate near the mucosal basal lamina and are more inclined to secrete IL-17 when activated. Periodontitis is a group of diseases that manifests mainly as inflammation of the gums and resorption of the alveolar bone due to periodontal tissue invasion by plaque bacteria on the dental surface. The course of periodontitis is often accompanied by a T-cell-mediated immune response. This paper discussed the pathogenesis of periodontitis and the potential contribution of MAIT cells to periodontitis.
Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy
Authors: Huang Kai , Mei Kun , Duan Jiahao , Wang Ruting , Yang Chun , Wang Bin , Gu Renjun , Yang Ling
Published: February 2023

Background

Cardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM.

Methods

We downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein–protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR.

Results

Overall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray.

Conclusion

Our study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.
Association of arterial stiffness with a prothrombotic state in uncomplicated nondiabetic hypertensive patients
Authors: Brosolo Gabriele , Da Porto Andrea , Bulfone Luca , Vacca Antonio , Bertin Nicole , Vivarelli Cinzia , Sechi Leonardo A. , Catena Cristiana
Published: February 2023

Background and aims

Past studies reported a significant contribution of a prothrombotic state to the development and progression of target organ damage in hypertensive patients. Stiffening of arterial vessels is associated with aging and hypertension, and additional factors could contribute to this process. This study was designed to examine the relationships between arterial stiffening and the hemostatic and fibrinolytic system.

Methods

In 128 middle-aged, nondiabetic, essential hypertensive patients without major cardiovascular and renal complications, we measured coagulation markers that express the spontaneous activation of the hemostatic and fibrinolytic system and assessed stiffness of the arterial tree by measurement of the carotid/femoral pulse wave velocity (cfPWV) and pulse wave analysis with calculation of the brachial augmentation index (AIx).

Results

Levels of fibrinogen (FBG), D-dimer (D-d), and plasminogen activator-inhibitor 1 (PAI-1) were significantly higher in patients with PWV and AIx above the median of the distribution. FBG, D-d, and PAI-1 were significantly and directly related with both cfPWV and AIx, and multivariate regression analysis indicated that the relationships of D-d and PAI-1 with both cfPWV and AIx and of FBG with AIx, were independent of age, body mass index, severity and duration of hypertension, use of antihypertensive drugs, blood glucose, and plasma lipids.

Conclusion

In middle-aged, uncomplicated, nondiabetic patients with essential hypertension, spontaneous activation of plasma hemostatic cascade and impaired fibrinolysis is significantly and independently associated with stiffening of the arterial tree.
Petrology and phase equilibria of HP/LT eclogite at Gaoqiao, western Dabie and implications for lawsonite development in continental subduction zones
Authors: Lu Xianbin , Xia Bin , Yang Qin , Wu Yuanbao
Published: February 2023

Lawsonite is of great significance for understanding fluid activity, element migration and crust–mantle interactions in subduction zones. Though studies have predicted lawsonite to be present under theP–Tregime during continental subduction, no lawsonite has been documented from natural (U) HP rocks in continental orogenic belt. In this study, we work on HP–LT eclogite (GQ–1 and GQ–2) at Gaoqiao, western Dabie to explore lawsonite formation and preservation during continental subduction and exhumation. Both samples have ubiquitous polymineralic aggregates of epidote/clinozoisite + paragonite/albite ± other minerals showing distinct rectangular or rhombic shapes developed as inclusions in garnet or in the matrix. Combined with recalculated bulk compositions similar to that of ideal lawsonite, we interpret these polymineralic aggregates to be pseudomorphs after lawsonite. Phase equilibrium modelling combined with compositional isopleth thermobarometry have constrained a segment of the prograde to peak stages to evolve from 19.0 to 19.5 kbar, ∼470°C to ∼20.0 kbar, 500C–505°C, then to ∼25 kbar, 530C–555°C in lawsonite stability fields. The progradeP–Tpath shows a two-stageP–Tevolution, with the first stage following a geothermal gradient of ∼7°C/km and the second stage decreasing to ∼6°C/km. Initial exhumation was inferred to follow an isothermal decompression process leading to lawsonite breakdown to form epidote/clinozosite ± paragoniteviathe reaction lawsonite + omphacite→ epidote + glaucophane ± paragonite + H2O at ∼19 kbar, 550°C. ModeledP/T–Xpseudosections calculated atT= 550°C andp= 25 kbar show that, when H2O content in bulk composition is more than 1.1 wt%, a certain amount of lawsonite (>13 mode%) should be present in eclogite. On the other hand, in the compositional range of natural intracontinental plate basalts, variations on O (Fe3+),XMgO[MgO/(MgO+FeO)],XCaO[CaO/(CaO+MgO+FeO+MnO+Na2O)],XNa2O[(Na2O/(CaO+Na2O)] andXAl2O3[Al2O3/(Al2O3+CaO+Na2O)] in bulk compositions have little influence on lawsonite development. In combination with previous studies, we conclude that during continent subduction along low geothermal gradient (<8°C/km), lawsonite could be formed under H2O present conditions. The absence of lawsonite in natural eclogite might be ascribed to retrograde overprint during exhumation.
Study on prevention and control mechanism of runoff water hazard in thick coal seam mining in valley terrain
Authors: Zhang Yunfeng , Qian Chenlong , Wang Xufeng , Chen Xuyang , Chang Zechao , Wang Jiyao , Niu Zhijun
Published: February 2023

During the mining of thick coal seams under the gully slope, the mining-induced fractures are prone to connect with the gully runoff, which may induce potential water hazards and affect underground production. Based on the occurrence characteristics of coal seams and the landform in the gully-developed mining area, the coal seam mining under the slope of Na’er Coal Mine and Baoshan Coal Mine was taken as the engineering background, the seasonal runoff of gullies was considered as the influencing factors of the safe mining, and the spatial relationship between the working face and the gully slope was analyzed when the mining-induced fractures were connected with the gully surface and caused the gully runoff water disaster. The research results show that the occurrence structure of the gully slope has a greater impact on the strata movement of the slope. When the key layer is incomplete, the horizontal sliding and local block overturning of the slope rock strata are strong; when the key layer is complete, the horizontal sliding and local block overturning of the slope rock strata are weakened. According to the safety distance of the working face and the generalized model of safety coal pillar setting, the method of setting the safety coal pillar was used to prevent the connection of slipping cracks of the rock strata at the slope bottom and the gully surface during the slope mining, thus preventing the occurrence of runoff hazards during the thick coal seams mining in the valley terrain. The results can provide a theoretical basis and technical support for the prevention and control of seasonal runoff hazards, as well as a reference for the prevention and control of mining-induced landslides, water conservation mining, and ecological environment protection.
COVID-19 and online distance learning in Malaysia: A blessing or a curse?
Authors: Kamaludin Kamilah , Sundarasen Sheela
Published: February 2023

This study intends to investigate the extent to which students' learning experience has been meaningful and satisfying, and their sentiment on online distance learning due to the implementation of emergency remote teaching (ERT). The study further analyses the causes of Malaysian university students' grievances and challenges and psychological effects in dealing with ERT during the period of the COVID-19 pandemic outbreak and MCO in Malaysia, which prohibited any face-to-face interaction between the period of 18 March 2020 to 30 May 2020. This study employs qualitative methodology in analyzing the content of social media comments following a video post on students' frustration about online distance learning (ODL). Our study provides evidence that ODL, as experienced by the students during the MCO, presented numerous pedagogical, technological, and social challenges which caused a great deal of stress and affects students physically and psychologically. By capturing and analyzing the comments made for a viral video posting of a Malaysian undergraduate student about her personal experience undergoing the ODL, we identify nine factors that contributed adversely to students' learning experience during the ERT period. In more in-depth, we find that the continuous academic assessment tasks, coping with new method of teaching and learning and excessive workload are the main pedagogical challenges. Additionally, technological challenges were present due to lack of reliable internet connection and digital technological equipment and finally, social challenges arise from the lack of family support and understanding, conflicting roles and responsibilities, need for emotional support and unconducive learning environment. Leveraging on the students' experience, we deduced that their encounter with ODL is a reflection of the application of emergency remote teaching (ERT) philosophy.
Refiguring research stories of science identity by attending to the embodied, affective, and non-human
Authors: Rahm Jrène , Gonsalves Allison J.
Published: February 2023

This perspective article draws on conversations with a program coordinator in a community organization that guided the development of an after school Convoclub for girls, which focused on understanding the role of science in their lives. We examine our conversations with the program coordinator to understand how affective placemaking, brought about by engagement in a digital storytelling project, created a new space for girls' engagement in science. We describe these conversations as part of our “research story”—a term intended to highlight the importance of storying in postqualitative methods. We draw on data from a qualitative case study of the co-designed science activities in Convoclub with a special focus on conversations with its program director and our joint work in the design of the club activities over time (i.e., dialogue circles with the six youth participants, a digital storytelling project, and a video documentary about science). Presented in three vignettes, we address the evolution of the club activities and its implications for designing spaces for learning and becoming informal science learning environments supportive of empowering identities in science understood through framing from a posthumanist perspective. Throughout, we consider the implications of refiguring research stories of identity by attending to the mundane yet also emergent stories of assemblages—affectively charged associations of people, places, and things. We consider what this orientation brings not only to the telling of identity stories but also to the co-design of learning spaces and considerations about whose voices and stories are told and heard in science spaces.
Thyroid hormones and carnitine in the second trimester negatively affect neonate birth weight: A prospective cohort study
Authors: Yang Mengmeng , Sun Man , Jiang Chenyu , Wu Qianqian , Jiang Ying , Xu Jian , Luo Qiong
Published: February 2023

Background

Maternal thyroid hormones and carnitine are reported to affect neonate birth weight during the second trimester, which is one of the most important markers for fetal growth and perinatal mortality and morbidity. Nevertheless, the effect of thyroid hormone and carnitine in the second trimester on birth weight has yet to be understood.

Method

This was a prospective cohort study with 844 subjects enrolled during the first trimester. Thyroid hormones, free carnitine (C0), neonate birth weight, as well as other related clinical and metabolic data were collected and assessed.

Results

Pre-pregnancy weight and body mass index (BMI) as well as neonate birth weight were significantly different among different free thyroxine (FT4) level groups. Maternal weight gain and neonate birth weight varied significantly when grouped by different thyroid-stimulating hormone (TSH) levels. There was a significantly positive correlation between C0 and TSH (r = 0.31), free triiodothyronine (FT3) (r = 0.37), and FT4 (r = 0.59) (all P < 0.001). In addition, a significantly negative influence was found between birth weight and TSH (r = −0.48, P = 0.028), so as C0 (r = −0.55, P < 0.001) and FT4 (r = −0.64, P < 0.001). Further assessment detected a stronger combined effect of C0 and FT4 (P < 0.001) and of C0 and FT3 (P = 0.022) on birth weight.

Conclusion

Maternal C0 and thyroid hormones are of great importance in neonate birth weight, and routine examination of C0 and thyroid hormones during the second trimester has a positive effect on the intervention of birth weight.
Insights by which TUDCA is a potential therapy against adiposity
Authors: Freitas Israelle Netto , da Silva Jr Joel Alves , Oliveira Kênia Moreno de , Lourençoni Alves Bruna , Dos Reis Araújo Thiago , Camporez João Paulo , Carneiro Everardo Magalhães , Davel Ana Paula
Published: February 2023

Adipose tissue is an organ with metabolic and endocrine activity. White, brown and ectopic adipose tissues have different structure, location, and function. Adipose tissue regulates energy homeostasis, providing energy in nutrient-deficient conditions and storing it in high-supply conditions. To attend to the high demand for energy storage during obesity, the adipose tissue undergoes morphological, functional and molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a molecular hallmark of metabolic disorders. In this sense, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), a bile acid conjugated to taurine with chemical chaperone activity, has emerged as a therapeutic strategy to minimize adipose tissue dysfunction and metabolic alterations associated with obesity. In this review, we highlight the effects of TUDCA and receptors TGR5 and FXR on adipose tissue in the setting of obesity. TUDCA has been demonstrated to limit metabolic disturbs associated to obesity by inhibiting ER stress, inflammation, and apoptosis in adipocytes. The beneficial effect of TUDCA on perivascular adipose tissue (PVAT) function and adiponectin release may be related to cardiovascular protection in obesity, although more studies are needed to clarify the mechanisms. Therefore, TUDCA has emerged as a potential therapeutic strategy for obesity and comorbidities.
Embryo development and live birth resulted from artificial oocyte activation after microdissection testicular sperm extraction with ICSI in patients with non-obstructive azoospermia
Authors: Zhang Xi , Li Li , Zhang Wenhong , Luo Yang , Mao Yuling , Du Hongzi , Li Lei
Published: February 2023

Introduction

The application of microdissection testicular sperm extraction (micro-TESE) to retrieve the sperm of patients with non-obstructive azoospermia (NOA) has greatly increased. Patients with NOA often have poor quality sperm. Unfortunately, there are few studies on artificial oocyte activation (AOA) performed on patients who successfully retrieved motile and immotile sperm by micro-TESE after intracytoplasmic sperm injection (ICSI). Therefore, this study sought to obtain more comprehensive evidence-based data and embryo development outcomes to aid consultation of patients with NOA who opted to receive assisted reproductive techniques and to determine whether AOA needs to be performed in different motile sperm after ICSI.

Methods

This retrospective study involved 235 patients with NOA who underwent micro-TESE to retrieve adequate sperm for ICSI between January 2018 and December 2020. A total of 331 ICSI cycles were performed in the 235 couples. Embryological, clinical, and neonatal outcomes were demonstrated comprehensively between motile sperm and immotile sperm using AOA and non-AOA treatment.

Results

Motile sperm injection with AOA (group 1) showed significantly higher fertility rate (72.77% vs. 67.59%, p=0.005), 2 pronucleus (2PN) fertility rate (64.33% vs. 60.22%, p=0.036), and miscarriage rate (17.65% vs. 2.44%, p=0.018) compared with motile sperm injection with non-AOA (group 2). Group 1 had comparable available embryo rate (41.29% vs. 40.74%, p=0.817), good embryo rate (13.44% vs. 15.44%, p=0.265), and without an embryo for transfer rate (10.85% vs. 9.90%, p=0.815) compared with group 2. Immotile sperm injection with AOA (group 3) displayed significantly higher fertility rate (78.56% vs. 67.59%, p=0.000), 2PN fertility rate (67.36% vs. 60.22%, p=0.001), without an embryo for transfer rate (23.76% vs. 9.90%, p=0.008), and miscarriage rate (20.00% vs. 2.44%, p=0.014), but significantly lower available embryo rate (26.63% vs.40.74%, p=0.000) and good embryo rate (15.44% vs. 6.99%, p=0.000) compared with group 2. In groups 1, 2, and 3, the rates of implantation (34.87%, 31.85% and 28.00%, respectively; p=0.408), clinical pregnancy (43.87%, 41.00%, and 34.48%, respectively; p=0.360) and live birth (36.13%, 40.00%, and 27.59%, respectively; p=0.194) were similar.

Discussion

For those patients with NOA from whom adequate sperm were retrieved for ICSI, AOA could improve fertilization rate, but not embryo quality and live birth outcomes. For patients with NOA and only immotile sperm, AOA can help achieve acceptable fertilization rate and live birth outcomes. AOA is recommended for patients with NOA only when immotile sperm are injected.
An integrated nomogram combining deep learning, clinical characteristics and ultrasound features for predicting central lymph node metastasis in papillary thyroid cancer: A multicenter study
Authors: Chang Luchen , Zhang Yanqiu , Zhu Jialin , Hu Linfei , Wang Xiaoqing , Zhang Haozhi , Gu Qing , Chen Xiaoyu , Zhang Sheng , Gao Ming , Wei Xi
Published: February 2023

Objective

Central lymph node metastasis (CLNM) is a predictor of poor prognosis for papillary thyroid carcinoma (PTC) patients. The options for surgeon operation or follow-up depend on the state of CLNM while accurate prediction is a challenge for radiologists. The present study aimed to develop and validate an effective preoperative nomogram combining deep learning, clinical characteristics and ultrasound features for predicting CLNM.

Materials and methods

In this study, 3359 PTC patients who had undergone total thyroidectomy or thyroid lobectomy from two medical centers were enrolled. The patients were divided into three datasets for training, internal validation and external validation. We constructed an integrated nomogram combining deep learning, clinical characteristics and ultrasound features using multivariable logistic regression to predict CLNM in PTC patients.

Results

Multivariate analysis indicated that the AI model-predicted value, multiple, position, microcalcification, abutment/perimeter ratio and US-reported LN status were independent risk factors predicting CLNM. The area under the curve (AUC) for the nomogram to predict CLNM was 0.812 (95% CI, 0.794-0.830) in the training cohort, 0.809 (95% CI, 0.780-0.837) in the internal validation cohort and 0.829(95%CI, 0.785-0.872) in the external validation cohort. Based on the analysis of the decision curve, our integrated nomogram was superior to other models in terms of clinical predictive ability.

Conclusion

Our proposed thyroid cancer lymph node metastasis nomogram shows favorable predictive value to assist surgeons in making appropriate surgical decisions in PTC treatment.
Perhaps, perhaps, perhaps: Navigating uncertainty in environmental flow management
Authors: Judd Meegan , Horne Avril C. , Bond Nick
Published: February 2023

Uncertainty can be an impediment to decision making and result in decision paralysis. In environmental flow management, system complexity and natural variability increase uncertainty. Climate change provides further uncertainty and can hinder decision making altogether. Environmental flow managers express reluctance to include climate change adaptation in planning due to large knowledge gaps in hydro-ecological relationships. We applied a hybrid method of hypothetical scenarios and closed ended questions within a survey to investigate ecological trade off decision making behaviours and cognitive processes of environmental flow managers. The scenarios provided were both similar to participants’ past experiences, and others were entirely unprecedented and hence unfamiliar. We found managers were more confident making decisions in situations they are familiar with, and most managers show low levels of confidence in making trade off decisions under uncertain circumstances. When given a choice, the most common response to uncertainty was to gather additional information, however information is often unavailable or inaccessible–either it does not exist, or uncertainties are so great that decisions are deferred. Given future rainfall is likely to be different from the past, environmental flow managers must work to adopt robust decision making frameworks that will increase confidence in decision making by acknowledging uncertainties. This can be done through tools developed to address decision making under deep uncertainty. Adapting these tools and methods to environmental flow management will ensure managers can begin to consider likely, necessary future trade-offs in a more informed, transparent and robust manner and increase confidence in decision making under uncertainty.
The analyzing the role of electric vehicles in urban logistics: A case of China
Authors: Yan Zhu , Ding Huiping , Chen Lu
Published: February 2023

In recent years, the rapid development of electric vehicles has gained widespread attention, and has especially brought new vitality to the fast-growing logistics service industry. Electric vehicles in urban logistics are not only ideal transportation tools but also do not affect the environment. This study thus implements the economic valuation of electric vehicles in urban logistics from the viewpoints of both manufacturers and business users through the investigation of pricing mechanism and discusses the potential for improving policy-making together with the real case in China. The net present value (NPV) approach is used to quantitatively analyze the investment decisions of urban logistics electric vehicles, with government regulation, incentive policy, and carbon emission trading taken into consideration. Our findings provide insights into the decision-making mechanism for commercializing electric vehicles in urban logistics that involves optimizing the government subsidy and transaction price between the manufacturers and business users. The results imply that with rationalized government policy incentives and coordinated transaction price, both manufacturers and business users are expected to achieve their break-even in limited time periods. The carbon cap placed on business users rather than manufacturers would be relatively more conducive to the marketization process.
Type 2 diabetes and glycemic traits are not causal factors of delirium: A two-sample mendelian randomization analysis
Authors: Li Jing , Yang Mingyi , Luo Pan , Wang Gang , Dong Buhuai , Xu Peng
Published: February 2023

This study aims to explore the genetic causal association between type 2 diabetes (T2D) and glycemic traits (fasting glucose [FG], fasting insulin [FI], and glycated hemoglobin [HbA1c]) on delirium using Mendelian randomization (MR). Genome-wide association studies (GWAS) summary data for T2D and glycemic traits were obtained from the IEU OpenGWAS database. GWAS summary data for delirium were obtained from the FinnGen Consortium. All the participants were of European ancestry. In addition, we used T2D, FG, FI, and HbA1c as exposures and delirium as outcomes. A random-effects variance-weighted model (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform MR analysis. In addition, MR-IVW and MR-Egger analyses were used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using MR-Egger regression and MR pleiotropy residual sum and outliers (MR-PRESSO). MR-PRESSO was also used to assess outlier single nucleotide polymorphisms (SNPs). The “leave one out” analysis was used to investigate whether the MR analysis results were influenced by a single SNP and evaluate the robustness of the results. In this study, we conducted a two-sample MR analysis, and there was no evidence of a genetic causal association between T2D and glycemic traits (T2D, FG, FI, and HbA1c) on delirium (all p > 0.05). The MR-IVW and MR-Egger tests showed no heterogeneity in our MR results (all p values >0.05). In addition, The MR-Egger and MR-PRESSO tests showed no horizontal pleiotropy in our MR results (all p > 0.05). The MR-PRESSO results also showed that there were no outliers during the MR analysis. In addition, the “leave one out” test did not find that the SNPs included in the analysis could affect the stability of the MR results. Therefore, our study did not support the causal effects of T2D and glycemic traits (FG, FI, and HbA1c) on delirium risk.
The genetic contribution of the X chromosome in age-related hearing loss
Authors: Naderi Elnaz , Cornejo-Sanchez Diana M. , Li Guangyou , Schrauwen Isabelle , Wang Gao T. , Dewan Andrew T. , Leal Suzanne M.
Published: February 2023

Age-related (AR) hearing loss (HL) is the most common sensory impairment with heritability of 55%. The aim of this study was to identify genetic variants on chromosome X associated with ARHL through the analysis of data obtained from the UK Biobank. We performed association analysis between self-reported measures of HL and genotyped and imputed variants on chromosome X from ∼460,000 white Europeans. We identified three loci associated with ARHL with a genome-wide significance level (p < 5 × 10−8), ZNF185 (rs186256023, p = 4.9 × 10−10) and MAP7D2 (rs4370706, p = 2.3 × 10−8) in combined analysis of males and females, and LOC101928437 (rs138497700, p = 8.9 × 10−9) in the sex-stratified analysis of males. In-silico mRNA expression analysis showed MAP7D2 and ZNF185 are expressed in mice and adult human inner ear tissues, particularly in the inner hair cells. We estimated that only a small amount of variation of ARHL, 0.4%, is explained by variants on the X chromosome. This study suggests that although there are likely a few genes contributing to ARHL on the X chromosome, the role that the X chromosome plays in the etiology of ARHL may be limited.
Complementarity determining regions in SARS-CoV-2 hybrid immunity
Authors: Frans Glynis , Dillaerts Doreen , Dehaemers Tom , Van Elslande Jan , De Leeuw Jonas , Boon Lise , Maes Wim , Callewaert Nico , Calcoen Bas , Ancheva Lina , Cockx Maaike , Geukens Nick , Arat Kusay , Derua Rita , Vermeersch Pieter , Carpentier Sebastien Christian , Bossuyt Xavier
Published: February 2023

Pre-vaccination SARS-CoV-2 infection can boost protection elicited by COVID-19 vaccination and post-vaccination breakthrough SARS-CoV-2 infection can boost existing immunity conferred by COVID-19 vaccination. Such ‘hybrid immunity’ is effective against SARS-CoV-2 variants. In order to understand ‘hybrid immunity’ at the molecular level we studied the complementarity determining regions (CDR) of anti-RBD (receptor binding domain) antibodies isolated from individuals with ‘hybrid immunity’ as well as from ‘naive’ (not SARS-CoV-2 infected) vaccinated individuals. CDR analysis was done by liquid chromatography/mass spectrometry-mass spectrometry. Principal component analysis and partial least square differential analysis showed that COVID-19 vaccinated people share CDR profiles and that pre-vaccination SARS-CoV-2 infection or breakthrough infection further shape the CDR profile, with a CDR profile in hybrid immunity that clustered away from the CDR profile in vaccinated people without infection. Thus, our results show a CDR profile in hybrid immunity that is distinct from the vaccination-induced CDR profile.
Heterogeneity of antibody-secreting cells infiltrating autoimmune tissues
Authors: Giovannini Diane , Belbezier Aude , Baillet Athan , Bouillet Laurence , Kawano Mitsuhiro , Dumestre-Perard Chantal , Clavarino Giovanna , Noble Johan , Pers Jacques-Olivier , Sturm Nathalie , Huard Bertrand
Published: February 2023

The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be pathogenic by themselves and/or propagate the inflammatory reaction. The infiltration of autoimmune tissues by antibody-secreting cells (ASCs) constitutes another dysfunction. The known high dependency of ASCs on the microenvironment to survive combined to the high diversity of infiltrated tissues implies that ASCs must adapt. Some tissues even within a single clinical autoimmune entity are devoid of infiltration. The latter means that either the tissue is not permissive or ASCs fail to adapt. The origin of infiltrated ASCs is also variable. Indeed, ASCs may be commonly generated in the secondary lymphoid organ draining the autoimmune tissue, and home at the inflammation site under the guidance of specific chemokines. Alternatively, ASCs may be generated locally, when ectopic germinal centers are formed in the autoimmune tissue. Alloimmune tissues with the example of kidney transplantation will also be discussed own to their high similarity with autoimmune tissues. It should also be noted that antibody production is not the only function of ASCs, since cells with regulatory functions have also been described. This article will review all the phenotypic variations indicative of tissue adaptation described so for at the level of ASC-infiltrating auto/alloimmune tissues. The aim is to potentially define tissue-specific molecular targets in ASCs to improve the specificity of future autoimmune treatments.
Vulnerability to climate change of managed stocks in the California Current large marine ecosystem
Authors: McClure Michelle M. , Haltuch Melissa A. , Willis-Norton Ellen , Huff David D. , Hazen Elliott L. , Crozier Lisa G. , Jacox Michael G. , Nelson Mark W. , Andrews Kelly S. , Barnett Lewis A.K. , Berger Aaron M. , Beyer Sabrina , Bizzarro Joe , Boughton David , Cope Jason M. , Carr Mark , Dewar Heidi , Dick Edward , Dorval Emmanis , Dunham Jason , Gertseva Vladlena , Greene Correigh M. , Gustafson Richard G. , Hamel Owen S. , Harvey Chris J. , Henderson Mark J. , Jordan Chris E. , Kaplan Isaac C. , Lindley Steven T. , Mantua Nathan J. , Matson Sean E. , Monk Melissa H. , Moyle Peter , Nicol Colin , Pohl John , Rykaczewski Ryan R. , Samhouri Jameal F. , Sogard Susan , Tolimieri Nick , Wallace John , Wetzel Chantel , Bograd Steven J.
Published: February 2023

Introduction

Understanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.

Methods

This study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.

Results

Overall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.

Discussion

As climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.
Transcriptomic analysis provides new insights into the secondary follicle growth in spotted scat (Scatophagus argus)
Authors: Jiang Mou-Yan , Zhou Yi-Fan , Liu Hao , Peng You-Xing , Huang Yuan-Qing , Deng Si-Ping , Huang Yang , Shi Gang , Zhu Chun-Hua , Li Guang-Li , Jiang Dong-Neng
Published: February 2023

Spotted scat (Scatophagus argus) is an important mariculture fish that is of great economic significance in East and Southeast Asia. To date, there are no studies on ovary development and regulation in S. argus. Herein, the ovary transcriptome profiles of S. argus at different stages were constructed, and the genes and pathways potentially involved in secondary follicle growth were identified. A total of 25,426 genes were detected by sequencing the mRNAs from the ovary libraries at stage III (n=3) and IV (n=3). Notably, 2950 and 716 genes were up-regulated and down-regulated in the stage IV ovary, respectively, compared to the stage III ovary. The differentially expressed genes (DEGs) were found to be mostly involved in regulating steroidogenesis, vitellogenesis, lipid metabolism, and meiosis. Up-regulation of steroid hormone synthesis pathway genes (fshr, cyp17a1, and foxl2) and insulin-like growth factor pathway genes (igf1r, ifg2r, igfbp1, igfbp3, and igfbp7) in the ovary at stage IV was possibly the reason for the increased serum estrogen. Moreover, ppara, ppard, fabp3, and lpl were up-regulated in the stage IV ovary and were potentially involved in the lipid droplet formation in the oocyte. Many DEGs were involved in the cellular cycle, meiosis, and cAMP or cGMP synthesis and hydrolysis, indicating that meiosis was restarted at stage IV ovary. In addition, numerous TGF-beta signal pathway genes were up-regulated in the stage IV ovary. This ovary transcript dataset forms a baseline for investigating functional genes associated with oogenesis in S. argus.
Groundwater springs in the German Wadden Sea tidal flat: A fast-track terrestrial transfer route for nutrients and dissolved organic matter
Authors: Carvalho da Silva Roger , Seidel Michael , Dittmar Thorsten , Waska Hannelore
Published: February 2023

Submarine groundwater discharge (SGD) connects fresh groundwater and marine ecosystems and conveys terrestrially derived dissolved organic matter (DOM) and nutrients from land to sea. The connectivity of terrestrial and marine ecosystems via SGD depends strongly on local environmental settings. For example, SGD composition is modified on its transit through the coastal aquifer, with spring-type SGD from highly permeable aquifers presumably being less affected than diffuse discharge systems from sedimentary environments. In our study, we investigated spring-type SGD near Sahlenburg/Cuxhaven, Northern Germany, which passes through fine, unconsolidated tidal sediments before entering the coastal ocean. We characterized groundwater, surface water and seawater endmembers from different seasons and assessed the potential of tidal sediments impacting the biogeochemistry of “fast-track”, point-source groundwater discharge systems. In addition to physicochemical parameters and nutrients, we analyzed the DOM molecular composition via ultrahigh-resolution mass spectrometry (FT-ICR-MS). Our data revealed a widespread physicochemical and geochemical influence of the groundwater springs on the tidal flat, producing low salinity and low dissolved organic carbon (DOC), and high nitrate and high oxygen concentrations not only in the springs, but also in adjacent porewater. From near- to offshore, salinity and DOC concentrations in springs decreased whereas nitrate and oxygen concentrations increased, resembling an inverse estuarine pattern. Furthermore, high nitrate values suggest anthropogenic sources (e.g., agricultural influence) in the surrounding watershed and may stimulate primary productivity in the tidal flat. Humic-like fluorescent DOM (FDOM) abundances and DOM molecular fingerprints indicated inputs of terrestrial DOM from nearshore saltmarsh plants, as well as from the nearby Elbe and Weser estuaries. Our study demonstrated that SGD had a strong geochemical impact even in the vicinity of large rivers, with productive springs actively hindering sulfate and nitrate reduction by flushing otherwise anoxic systems with oxygen. We posit that the geochemical influence of groundwater springs in tidal flats is underestimated because it can extend far beyond their visual discharge points.