bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the roles of amphiregulin and transforming growth factor β1 in microvasculature-like formation in human granulosa-lutein cells
Authors: Li Hui , Chang Hsun-Ming , Li Saijiao , Klausen Christian , Shi Zhendan , Leung Peter C.K.
Published: August 2022

Vascular endothelial-cadherin (VE-cadherin) is an essential component that regulates angiogenesis during corpus luteum formation. Amphiregulin (AREG) and transforming growth factor β1 (TGF-β1) are two intrafollicular factors that possess opposite functions in directing corpus luteum development and progesterone synthesis in human granulosa-lutein (hGL) cells. However, whether AREG or TGF-β1 regulates the VE-cadherin expression and subsequent angiogenesis in the human corpus luteum remains to be elucidated. Results showed that hGL cells cultured on Matrigel spontaneously formed capillary-like and sprout-like microvascular networks. Results of specific inhibitor treatment and small interfering RNA-mediated knockdown revealed that AREG promoteed microvascular-like formation in hGL cells by upregulating the VE-cadherin expression mediated by the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase1/2 (ERK1/2) signaling pathway. However, TGF-β1 suppressed microvascular-like formation in hGL cells by downregulating VE-cadherin expression mediated by the activin receptor-like kinase (ALK)5-Sma- and Mad-related protein (SMAD)2/3/4 signaling pathway. Collectively, this study provides important insights into the underlying molecular mechanisms by which TGF-β1 and AREG differentially regulate corpus luteum formation in human ovaries.
Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems
Authors: Hejabi Faranak , Abbaszadeh Mohammad Sadegh , Taji Shirinsadat , O’Neill Andrew , Farjadian Fatemeh , Doroudian Mohammad
Published: August 2022

In recent decades, clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) has become one of the most promising genome-editing tools for therapeutic purposes in biomedical and medical applications. Although the CRISPR/Cas system has truly revolutionized the era of genome editing, the safe and effective delivery of CRISPR/Cas systems represents a substantial challenge that must be tackled to enable the next generation of genetic therapies. In addition, there are some challenges in the in vivo delivery to the targeted cells/tissues. Nanotechnology-based drug delivery systems can be employed to overcome this issue. This review discusses different types and forms of CRISPR/Cas systems and the current CRISPR/Cas delivery systems, including non-viral carriers such as liposomes, polymeric, and gold particles. The focus then turns to the viral nanocarriers which have been recently used as a nanocarrier for CRISPR/Cas delivery.
Antifungal effects and active compounds of the leaf of Allium mongolicum Regel
Authors: Qu Huan , Guo Zhen , Ma Li , Zhang Xiu , Ma Haijun , Chen Yang
Published: August 2022

Taking plant metabolites as material to develop new biological fungicides is still an important mission for pesticide development, and the preliminary study confirmed that Allium mongolicum showed a certain inhibitory effect on plant pathogens. In this study, the antifungal activity of extracts of A. mongolicum was studied and the compounds were isolated, purified, and identified by HPLC, NMR, and ESI-MS. The methanol extract of A. mongolicum exhibited certain inhibitory activity against almost all nine tested pathogens at concentration of 0.5 mg/ml. Sixteen compounds were isolated and purified from the extract, which were identified as nine flavonoids, six phenolic acids, and an amino acid. Among them, cinnamic acid derivatives 1, 2, and 3 and flavonoids 7, 8, 9, and 13 were separated in A. mongolicum for the first time.
Combined resistance training with aerobic training improves physical performance in patients with coronary artery disease: A secondary analysis of a randomized controlled clinical trial
Authors: Kambic Tim , Šarabon Nejc , Lainscak Mitja , Hadžić Vedran
Published: August 2022

Background

The efficacy of combined resistance training (RT) and aerobic training (AT) compared with AT alone is well established in cardiac rehabilitation (CR); however, it remains to be elucidated whether RT load (high load [HL] vs. low load [LL]) modifies the outcomes. The aim of our study was to investigate the effects of HL-RT and LL-RT combined with AT in comparison to AT alone on body composition and physical performance in patients with coronary artery disease (CAD) enrolled in phase II CR.

Methods

We randomized 79 patients with a stable CAD to 12 weeks of lower limb LL-RT + AT (35–40% of one repetition maximum [1-RM]; n = 28), HL-RT + AT (70–80% of 1-RM; n = 26), or AT (n = 25). Fifty-nine patients (75% men) with mean (standard deviation) age 61 (8) years and left ventricular ejection fraction 53 (9)% completed LL-RT (n = 19), HL-RT (n = 21) and AT (n = 19). Body composition and physical performance (upper and lower submaximal muscle strength, flexibility, balance, and mobility) were measured at baseline and post-training.

Results

Training intervention had no significant impact on time × group interaction in the body composition measures. There was a significant time × group interaction for the gait speed test, chair sit-and-reach test, arm curl test, Stork balance test, up and go test, STS-5, and 6-min walk distance (p-values ≤ 0.001–0.04) following the training intervention. After the training intervention, HL-RT improved gait speed (+12%, p = 0.044), arm curl (+13%, p = 0.037), and time of Up and Go test (+9%, p < 0.001) to a greater extent compared with AT group, while there was a greater improvement in time of Up and Go test (+18%, p < 0.001) and time of five sit-to-stand tests (+14%, p = 0.016) following LL-RT when compared with AT. There were no differences between HL-RT and LL-RT in post-training improvement in any of the physical performance measures.

Conclusion

The combination of AT with HL-RT or LL-RT promoted similar improvements in physical performance, which were superior to AT. Therefore, both types of combined AT and RT can be applied to patients with CAD.

Clinical trial registration

[https://clinicaltrials.gov/ct2/show/NCT04638764] Identifier [NCT04638764].
Prognostic value of ventricular longitudinal strain in patients undergoing transcatheter aortic valve replacement: A systematic review and meta-analysis
Authors: Xiao Yangjie , Bi Wenjing , Qiao Wei , Wang Xin , Li Ying , Ren Weidong
Published: August 2022

Introduction

Strain obtained by speckle tracking echocardiography (STE) can detect subclinical myocardial impairment due to myocardial fibrosis (MF) and is considered a prognostic marker. Aortic stenosis (AS) is not only a valve disease, but also a cardiomyopathy characterized by MF. The purpose of this study was to systematically review and analyze ventricular strain as a predictor of adverse outcomes in patients with AS undergoing transcatheter aortic valve replacement (TAVR).

Methods

PubMed, Embase, and the Cochrane library were searched for studies that investigated the prognostic value of impaired ventricular strain on patients with AS undergoing TAVR with all-cause mortality (ACM) and major adverse cardiovascular events (MACE). Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated to assess the role of left (LVLS) and right (RVLS) ventricular longitudinal strain in the prognostic prediction of patients with AS undergoing TAVR. Sensitivity and subgroup analysis was performed to assess heterogeneity.

Results

Twelve studies were retrieved from 571 citations for analysis. In total, 1,489 patients with a mean age of 82 years and follow-up periods varying between 1 year and 8.5 years were included. Meta-analysis showed the impaired LVLS from eight studies was associated with an increased risk for combined ACM and MACE (OR: 1.08, 95% CI: 1–1.16; p = 0.037), and ACM alone (HR: 1.08, 95% CI: 1.01–1.16; p = 0.032). Impaired RVLS from four studies was associated with an increased risk of combined ACM and MACE (OR: 1.08, 95% CI: 1.02–1.14; p < 0.01), and ACM alone (HR: 1.07, 95% CI: 1.02–1.12; p < 0.01).

Conclusions

This meta-analysis demonstrated that ventricular strain, including LVLS and RVLS, had a substantial prognostic value in ACM or combined ACM and MACE, which could be used as a valid marker for risk stratification in patients with AS undergoing TAVR.
Treatment and prognosis of Scimitar syndrome: A retrospective analysis in a single center of East China
Authors: Wang Kai , Xu Xinyi , Liu Tingliang , Gao Wei , Guo Ying
Published: August 2022

Background

Scimitar syndrome is a rare congenital cardiovascular malformation; its optimal management remains controversial. This study aims to present the clinical experience of this disease in our center.

Methods

We undertook a retrospective review of 34 patients with Scimitar syndrome documented at our institution between January 2013 and December 2018. The patients' clinical characteristics, management, and prognosis data were collected and analyzed.

Results

Thirty-four patients, including 16 males and 18 females, were enrolled with a median age at diagnosis of 7 months and a follow-up period of 22.5 months. The infantile form of Scimitar syndrome presents more tendency for pulmonary hypertension (PH), pulmonary vein stenosis (PVS), and mortality than the adult form. Of the 15 patients who underwent surgical correction of the Scimitar vein, four had post-operation PVS. There was no significant difference in the stenosis incidence between baffle repair and Scimitar vein reimplantation groups. Eight patients received interventional catheter therapy, including occlusion of aortopulmonary collateral arteries (APCs) and other intracardiac malformations, without the following surgery. The overall mortality rate was 20.5% (7 of 34) over the study period. High-risk factors of death included age at diagnosis (p = 0.000), PH (p = 0.007) and PVS (p = 0.014).

Conclusions

Infantile Scimitar syndrome needs intense suspicion for early diagnosis and multidisciplinary treatment. Interventional treatment of Scimitar syndrome alleviates pulmonary artery pressure and progression during infancy. Baffle repair and direct reimplantation of the Scimitar vein used in the surgical treatment of Scimitar syndrome are safe and have similar effects. Age at diagnosis, PH, and PVS are high-risk factors for death in Scimitar syndrome.
Governance of Clinical AI applications to facilitate safe and equitable deployment in a large health system: Key elements and early successes
Authors: Liao Frank , Adelaine Sabrina , Afshar Majid , Patterson Brian W.
Published: August 2022

One of the key challenges in successful deployment and meaningful adoption of AI in healthcare is health system-level governance of AI applications. Such governance is critical not only for patient safety and accountability by a health system, but to foster clinician trust to improve adoption and facilitate meaningful health outcomes. In this case study, we describe the development of such a governance structure at University of Wisconsin Health (UWH) that provides oversight of AI applications from assessment of validity and user acceptability through safe deployment with continuous monitoring for effectiveness. Our structure leverages a multi-disciplinary steering committee along with project specific sub-committees. Members of the committee formulate a multi-stakeholder perspective spanning informatics, data science, clinical operations, ethics, and equity. Our structure includes guiding principles that provide tangible parameters for endorsement of both initial deployment and ongoing usage of AI applications. The committee is tasked with ensuring principles of interpretability, accuracy, and fairness across all applications. To operationalize these principles, we provide a value stream to apply the principles of AI governance at different stages of clinical implementation. This structure has enabled effective clinical adoption of AI applications. Effective governance has provided several outcomes: (1) a clear and institutional structure for oversight and endorsement; (2) a path towards successful deployment that encompasses technologic, clinical, and operational, considerations; (3) a process for ongoing monitoring to ensure the solution remains acceptable as clinical practice and disease prevalence evolve; (4) incorporation of guidelines for the ethical and equitable use of AI applications.
Forecasting and communicating the dispersion and fallout of ash during volcanic eruptions: lessons from the September 20, 2020 eruptive pulse at Sangay volcano, Ecuador
Authors: Bernard Benjamin , Samaniego Pablo , Mastin Larry , Hernandez Stephen , Pino Gerardo , Kibler Jamie , Encalada Marjorie , Hidalgo Silvana , Vizuete Nicole
Published: August 2022

Volcanic ash is a hazard to human health and activities. Accurate and timely forecasts coupled with effective communication about the dispersion and fallout of volcanic ash during explosive events are essential to reduce impacts on local communities and limit economic losses. In this study, we present the first detailed description of an eruptive pulse at Sangay volcano and its eruption source parameters. The eruptive pulse on September 20, 2020, started at about 9:20 UTC and lasted between 90 and 100 min, producing an eruptive column that rapidly separated into (1) a higher (15.2 km above sea level, asl), gas-rich cloud moving east-southeast and (2) a lower (12.2 km asl), ash-rich cloud moving west and causing ash fallout up to 280 km from the volcano. Field data collected immediately after the event allow estimating the volume of bulk tephra to be between 1.5 and 5.0 × 106 m3, corresponding to a volcanic explosivity index of 2. The eruptive pulse, identified as violent Strombolian, emitted andesitic ash that was more mafic than products ejected by Sangay volcano in recent decades. Component analysis and glass chemistry of juvenile particles support the hypothesis that this event excavated deeper into the upper conduit compared to typical Strombolian activity at Sangay volcano, while grain-size analysis allows reconstruction of the total grain-size distribution of the fallout deposit. The discrepancies between the ash fallout simulations performed with the Ash3D online tool and the actual deposit are mainly the result of inaccurate pre- and syn-eruptive configurations and highlight the importance of additional processes such as aggregation. Communication products issued during the event included (1) several standard short reports, (2) volcano observatory notices for aviation, (3) social media posts, and (4) a special report providing the results of the ash fallout simulation. Although communication was effective with the authorities and the connected population, an effort must be made to reach the most vulnerable isolated communities for future events. This study shows that forecasting ash dispersion and fallout during volcanic eruptions can guide early warnings and trigger humanitarian actions, and should become a standard in volcano observatories worldwide.
Water consumption patterns of 110 cities in the Yangtze River Economic Belt in 2015
Authors: Sun Boyang , Li Fapeng
Published: August 2022

How to formulate scientific and effective water-saving policies is of great significance for the sustainable water consumption. As a country with the largest water consumption in the world, China has been committed to formulating scientific and effective water-saving policies. However, due to geospatial variations of water consumption in different regions, how to formulate targeted and efficient water-saving policies which suit for different local characteristics has always been a key issue to be solved. In a quest to understand the water consumption patterns, this study first adopted a dual evaluation index system combining Gini coefficient and Global Moran’s Index to classify different types of water consumption. Taking 110 cities in the Yangtze River Economic Belt as research objects, the water consumption of 110 cities was divided into nine types. According to each type, a targeted water-saving policy is given. This study provides important theoretical support for the efficient management of water resources in the Yangtze River Economic Belt, and provides reference for water resources management in other regions at the same time.
Lifetime risk and health-care burden of diabetic ketoacidosis: A population-based study
Authors: Ebrahimi Fahim , Kutz Alexander , Christ Emanuel Remigius , Szinnai Gabor
Published: August 2022

Objective

Diabetic ketoacidosis (DKA) is a life-threatening complication of both type 1 and type 2 diabetes. We aimed to assess population-based rates, trends and outcomes of patients with DKA.

Design and methods

This is a nationwide cohort study using hospital discharge claims data from 2010 to 2018 in Switzerland. Incidence rates and in-hospital outcomes of DKA were analyzed throughout lifetime for children (0-9 years), adolescents (10-19 years), and adults (20-29, 30-59, and 60-90 years). Analyses were stratified for type of diabetes mellitus and sex.

Results

In total, 5,544 hospitalizations with DKA were identified, of whom 3,847 were seen in patients with type 1 diabetes and 1,697 in type 2 diabetes. Incidence rates of DKA among patients with type 1 diabetes were highest during adolescence with 17.67 (girls) and 13.87 (boys) events per 100,000 person-years (incidence rate difference [IRD]: -3.80 [95% CI, -5.59 to -2.02]) and decreased with age in both sexes thereafter. Incidence rates of DKA in patients with type 2 diabetes were low up to an age of 40 years and rose to 5.26 (females) and 6.82 (males) per 100,000 person-years in adults aged 60-90 years. Diabetic ketoacidosis was associated with relevant health-care burden independent of age, sex, or type of diabetes. The population-based incidence rate of DKA increased over time from 7.22 per 100,000 person-years in 2010 to 9.49 per 100,000 person-years in 2018.

Conclusions

In type 1 diabetes highest incidence rates of DKA hospitalizations were observed among adolescent females. In comparison, in patients with type 2 diabetes the risk for DKA steadily increased with age with higher rates in adult males. Over the 9 year study period, incidence rates of DKA were increasing irrespective of type of diabetes. DKA was associated with a high burden of disease reflected by high rates of intensive care unit admission, prolonged hospital stay and high mortality rates, especially in elderly.
Risk of infections in patients with NAFLD and Type 2 Diabetes under treatment with SGLT2 inhibitors and relationship with liver outcomes: A retrospective case-control study
Authors: Bañares Juan , Manzano-Nuñez Ramiro , Prió Alba , Rivera-Esteban Jesús , Camps-Relats Laura , Villarejo Ana , Ruiz-Ortega Lourdes , Pons Mònica , Ciudin Andreea , Salcedo María Teresa , Vargas Víctor , Genescà Joan , Pericàs Juan M.
Published: August 2022

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries, with its incidence growing parallel to the epidemics of obesity and type 2 diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are becoming a cornerstone in the management of cardiovascular health and some studies suggest the potential role in NAFLD. However, patients under treatment with SGLT2i are at risk of developing genitourinary fungal infections (GFIs). Moreover, both NAFLD and SGLT2i have a strong influence on the immune system, and therefore the risk of infections other than GFIs could be increased in NAFLD patients treated with SGLT2i. We aimed to examine the possible association of SGLT2i with infections and hepatic outcomes in NAFLD patients.

Methods

We conducted a case-control study including NAFLD patients with T2DM visited at the Liver Unit outpatient clinic from 2016 to 2021 with a minimum follow-up of 6 months by selecting 65 patients receiving SGLT2i and 130 matched patients with other types of antidiabetic treatment.

Results

During follow-up, GFIs were significantly higher in the SGLT2i group (15.4% vs. 3.8%; p=0.008), whereas there were no differences in the occurrence of overall infections (41.5% vs. 30%; p=0.1) nor in other types of specific infections. In the multivariable analysis, treatment with SGLT2i was not independently associated with higher odds of overall infection. On the other hand, SGLT2i patients showed a significantly lower incidence of hepatic events (1.5% vs. 10.7%; p=0.02). There were no significant different in all-cause mortality between cases and controls.

Conclusions

NAFLD patients with T2DM receiving SGLT2i more frequently presented GFIs, whereas the incidence of other types of infections was not found to be higher than in other patients with NAFLD and T2DM treated with other drugs. Moreover, SGLT2i-treated patients had a lower occurrence of hepatic events. Further studies are warranted to validate our data.
Infectious diseases associated with pediatric type 1 diabetes mellitus: A narrative review
Authors: Piccolo Gianluca , De Rose Elena Lucia , Bassi Marta , Napoli Flavia , Minuto Nicola , Maghnie Mohamad , Patti Giuseppa , d’Annunzio Giuseppe
Published: August 2022

Diabetes mellitus (DM) has been frequently associated with an impaired immune response against infectious agents, making affected patients at risk for more severe disease and sometimes causing worse outcomes. The recent COVID-19 pandemic has seriously affected patients with both diabetes, in particular those carrying comorbidities or with poor glycemic control. As regards pediatric diabetes mellitus, the availability of more accurate and technological tools for glycemic management and the improved markers of metabolic control might mitigate the negative impact of infections. Notably, good metabolic control of diabetes since its diagnosis reduces not only the risk of microangiopathic complications but also of impaired immune response to infectious diseases. Therefore, vaccinations are strongly recommended. Our paper aims to provide the most updated evidence regarding infectious diseases in type 1 pediatric DM.
Health-related quality of life in long-term differentiated thyroid cancer survivors: A cross-sectional Tunisian-based study
Authors: Missaoui Abdel Mouhaymen , Hamza Fatma , Maaloul Mohamed , Charfi Hana , Ghrissi Wiem , Abid Mohamed , Guermazi Fadhel
Published: August 2022

Background and Aim

The incidence of differentiated thyroid cancer (DTC) has risen dramatically worldwide. Despite an excellent prognosis, the growing DTC survivors’ community often features poor health-related quality of life (HRQoL), which challenges long-term DTC care, particularly in developing Southern Mediterranean and African countries. We aimed to assess the HRQoL and to investigate its determinants in disease-free Tunisian DTC survivors.

Methods

We conducted a three-month cross-sectional study that included 266 patients diagnosed with DTC. We assessed the HRQoL in eligible participants using the short form–36 health survey, in comparison with 76 healthy controls.

Results

The 86 eligible DTC survivors were predominantly female (89.5%) with an average age of 44.3 ± 12.5 years. Physical-functioning (PF), role-physical (RP), and pain domains were substantially altered compared to the reference population. Age was negatively associated with PF, RP, role-emotional (RE), and social functioning (SF). Tumor size and lymph node metastases affected general health and PF, respectively. The cancer-free survival duration was positively correlated with mental health (MH). Poor neck scar healing and persistent post-operative hypoparathyroidism significantly deteriorate MH. Pain perception was positively correlated with the radioactive iodine cumulative dose. Subclinical hyperthyroidism significantly reduced PF and RP scores. TSH suppression was negatively and strongly correlated with MH and SF scores.

Conclusion

HRQoL is substantially reduced in DTC survivors compared to the normative Tunisian population. These results could be extrapolated to similar individuals in other South Mediterranean and African countries. The development of coordinated multidisciplinary aftercare interventions in this region is warranted to preserve HRQoL in DTC survivors.
Neutronics performance improvement based on the small lead-based fast reactor SLBR-50
Authors: Zhao Chen , Lou Lei , Zhang Bin , Zhou Bingyan , Wang Lianjie , Peng Xingjie
Published: August 2022

The design of high-performance lead-based fast reactors (LFRs) has become a hotspot in the advanced reactor system. This study evaluates the neutronics performance improvement based on the small LFR SLBR-50. Parameter sensitivity analyses are conducted, including height-to-diameter ratio (H/D), reflector assembly arrangement, and pitch-to-diameter ratio in fuel assembly, fuel material, and fuel enrichment partitioning. Numerical results of eigenvalue in burnup procedure, assembly power distribution, and energy spectrum are analyzed using the Monte-Carlo code RMC. Our findings indicate that the fuel material, fuel partitioning, and H/D are the three most important factors in LFR design. The neutronics performance analyses will assist in LFR design.
Evapotranspiration and land surface temperature of typical urban green spaces in a semi-humid region: Implications for green management
Authors: Li Xinhao , Li Yiran , Di Suchuang , Niu Yong , Zhang Chuanjie
Published: August 2022

Ecological deterioration and water scarcity motivate people to seek a balance between ecological reserves and water consumption in cities located in Semi-humid regions. This study is designed to develop a method for evaluating cooling water-saving characteristics of green space structures. Land surface temperature (TS), vegetation quantity (VQ) and evapotranspiration (ET) of typical green vegetation structures in 50 plots with an average area of 10,000 m2 were studied. Parameters were obtained based on data from three temporal remote sensing images; the surface energy balance algorithm for land (SEBAL) model, single-channel algorithm, and normalized difference vegetation index (NDVI) were utilized in the calculation. The relationships between the TS, VQ, and ET of green land were explored using regression analysis. A comprehensive index (EWI) was proposed to evaluate the cooling and water-saving abilities of different green space structures. Based on assessment results, species were classified into three: good (EWI ≥ 0.795), common (0.795 > EWI ≥ 0.419), and weak (EWI < 0.419). The characteristics of 17 species or species compositions with good cooling and water-saving abilities were summarized as: 1) a mix of the arbor, shrub, and herb, and 2) complete cover of green space by shrub.
Knockdown of Circ_0037658 Alleviates IL-1β-Induced Osteoarthritis Progression by Serving as a Sponge of miR-665 to Regulate ADAMTS5
Authors: Li Ningbo , Wang Yongsheng , Wu Xuejian
Published: August 2022

Background: Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease which brings great pain to patients and a tremendous burden on the world’s medical resources. Previous reports have indicated that circular RNAs (circRNAs) are involved in the pathogenesis of OA. The purpose of this study was to explore the role and mechanism of circ_0037658 in the OA cell model.

Methods: The content of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) was measured using enzyme-linked immunosorbent assay (ELISA). Cell proliferation ability and apoptosis were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EDU), and flow cytometry assays. Western blot assay was used to measure the protein levels of Bcl-2-related X protein (Bax), cleaved-caspase-3, MMP13, Aggrecan, and ADAMTS5. The expression of circ_0037658, microRNA-665 (miR-665), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay were manipulated to analyze the relationships of circ_0037658, miR-665, and ADAMTS5.

Results: Human chondrocytes (CHON-001 cells) were treated with interleukin-1β (IL-1β) to establish an OA cell model. Circ_0037658 and ADAMTS5 levels were increased, and miR-665 was decreased in OA cartilage samples and IL-1β-treated chondrocyte cells. Moreover, circ_0037658 silencing promoted proliferation and impaired inflammation, apoptosis, and ECM degradation in IL-1β-treated CHON-001 cells. Mechanically, circ_0037658 acted as a sponge for miR-665 to regulate ADAMTS5 expression.

Conclusion: Circ_0037658 knockdown relieved IL-1β-triggered chondrocyte injury via regulating the miR-665/ADAMTS5 axis, promising an underlying therapeutic strategy for OA.
Characterization of aging cancer-associated fibroblasts draws implications in prognosis and immunotherapy response in low-grade gliomas
Authors: Zhou Zijian , Wei Jinhong , Kuang Lijun , Zhang Ke , Liu Yini , He Zhongming , Li Luo , Lu Bin
Published: August 2022

Background: Due to the highly variable prognosis of low-grade gliomas (LGGs), it is important to find robust biomarkers for predicting clinical outcomes. Aging cancer-associated fibroblasts (CAFs) within the senescent stroma of a tumor microenvironment (TME) have been recently reported to play a key role in tumor development. However, there are few studies focusing on this topic in gliomas.

Methods and Results: Based on the transcriptome data from TCGA and CGGA databases, we identified aging CAF-related genes (ACAFRGs) in LGGs by the weighted gene co-expression network analysis (WGCNA) method, followed by which LGG samples were classified into two aging CAF-related gene clusters with distinct prognosis and characteristics of the TME. Machine learning algorithms were used to screen out eight featured ACAFRGs to characterize two aging CAF-related gene clusters, and a nomogram model was constructed to predict the probability of gene cluster A for each LGG sample. Then, a powerful aging CAF scoring system was developed to predict the prognosis and response to immune checkpoint blockage therapy. Finally, the ACAFRGs were verified in two glioma-related external datasets. The performance of the aging CAF score in predicting the immunotherapy response was further validated in two independent cohorts. We also confirmed the expression of ACAFRGs at the protein level in glioma tissues through the Human Protein Atlas website and Western blotting analysis.

Conclusion: We developed a robust aging CAF scoring system to predict the prognosis and immunotherapy response in LGGs. Our findings may provide new targets for therapeutics and contribute to the exploration focusing on aging CAFs.
Innovation in the Breeding of Common Bean Through a Combined Approach of in vitro Regeneration and Machine Learning Algorithms
Authors: Aasim Muhammad , Katirci Ramazan , Baloch Faheem Shehzad , Mustafa Zemran , Bakhsh Allah , Nadeem Muhammad Azhar , Ali Seyid Amjad , Hatipoğlu Rüştü , Çiftçi Vahdettin , Habyarimana Ephrem , Karaköy Tolga , Chung Yong Suk
Published: August 2022

Common bean is considered a recalcitrant crop for in vitro regeneration and needs a repeatable and efficient in vitro regeneration protocol for its improvement through biotechnological approaches. In this study, the establishment of efficient and reproducible in vitro regeneration followed by predicting and optimizing through machine learning (ML) models, such as artificial neural network algorithms, was performed. Mature embryos of common bean were pretreated with 5, 10, and 20 mg/L benzylaminopurine (BAP) for 20 days followed by isolation of plumular apice for in vitro regeneration and cultured on a post-treatment medium containing 0.25, 0.50, 1.0, and 1.50 mg/L BAP for 8 weeks. Plumular apice explants pretreated with 20 mg/L BAP exerted a negative impact and resulted in minimum shoot regeneration frequency and shoot count, but produced longer shoots. All output variables (shoot regeneration frequency, shoot counts, and shoot length) increased significantly with the enhancement of BAP concentration in the post-treatment medium. Interaction of the pretreatment × post-treatment medium revealed the need for a specific combination for inducing a high shoot regeneration frequency. Higher shoot count and shoot length were achieved from the interaction of 5 mg/L BAP × 1.00 mg/L BAP followed by 10 mg/L BAP × 1.50 mg/L BAP and 20 mg/L BAP × 1.50 mg/L BAP. The evaluation of data through ML models revealed that R2 values ranged from 0.32 to 0.58 (regeneration), 0.01 to 0.22 (shoot counts), and 0.18 to 0.48 (shoot length). On the other hand, the mean squared error values ranged from 0.0596 to 0.0965 for shoot regeneration, 0.0327 to 0.0412 for shoot count, and 0.0258 to 0.0404 for shoot length from all ML models. Among the utilized models, the multilayer perceptron model provided a better prediction and optimization for all output variables, compared to other models. The achieved results can be employed for the prediction and optimization of plant tissue culture protocols used for biotechnological approaches in a breeding program of common beans.
Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study
Authors: D’Erasmo Laura , Giammanco Antonina , Suppressa Patrizia , Pavanello Chiara , Iannuzzo Gabriella , Di Costanzo Alessia , Tramontano Daniele , Minicocci Ilenia , Bini Simone , Vogt Anja , Stewards Kim , Roeters Van Lennep Jeanine , Bertolini Stefano , Arca Marcello ,   the Italian and European Working Group on Lomitapide in HoFH
Published: August 2022

Backgroundand aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.

Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) years, with a median treatment duration of 31.0 (IQR 14.0–40.5) months. At baseline, four (44.4%) patients had hypertension, one (11.1%) had diabetes mellitus, two (22.2%) were active smokers, and five (55.5%) reported ASCVD. The baseline LDL-C was 257.0 (IQR, 165.3–309.2) mg/dL. All patients were on statins plus ezetimibe, three were receiving Lipoprotein apheresis (LA), and one was also receiving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The addition of lomitapide (mean dose, 10 mg) resulted in the achievement of a median on-treatment LDL-C of 101.7 mg/dL (IQR, 71.3–138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0 mg/dL (IQR, 43.7–86.7; 73.5% reduction from baseline). During follow-up, one patient stopped both PCSK9i and LA. Recurrence of ASCVD events was reported in one patient. The median on-treatment aspartate transaminase and alanine transaminase values were 31.1 (IQR, 22.6–48.3) U/L and 31.1 (IQR, 27.2–53.8) U/L, respectively. Among six ARH patients with available fibroscan examination, liver stiffness values recorded at the last visit were within the normal range (median, 4.7 KPa; IQR, 3.6–5.3 KPa).

Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.
Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans
Authors: Harley Isaac T. W. , Allison Kristen , Scofield R. Hal
Published: August 2022

Most B cells produced in the bone marrow have some level of autoreactivity. Despite efforts of central tolerance to eliminate these cells, many escape to periphery, where in healthy individuals, they are rendered functionally non-responsive to restimulation through their antigen receptorviaa process termed anergy. Broad repertoire autoreactivity may reflect the chances of generating autoreactivity by stochastic use of germline immunoglobulin gene segments or active mechanisms may select autoreactive cells during egress to the naïve peripheral B cell pool. Likewise, it is unclear why in some individuals autoreactive B cell clones become activated and drive pathophysiologic changes in autoimmune diseases. Both of these remain central questions in the study of the immune system(s). In most individuals, autoimmune diseases arise from complex interplay of genetic risk factors and environmental influences. Advances in genome sequencing and increased statistical power from large autoimmune disease cohorts has led to identification of more than 200 autoimmune disease risk loci. It has been observed that autoantibodies are detectable in the serum years to decades prior to the diagnosis of autoimmune disease. Thus, current models hold that genetic defects in the pathways that control autoreactive B cell tolerance set genetic liability thresholds across multiple autoimmune diseases. Despite the fact these seminal concepts were developed in animal (especially murine) models of autoimmune disease, some perceive a disconnect between human risk alleles and those identified in murine models of autoimmune disease. Here, we synthesize the current state of the art in our understanding of human risk alleles in two prototypical autoimmune diseases – systemic lupus erythematosus (SLE) and type 1 diabetes (T1D) along with spontaneous murine disease models. We compare these risk networks to those reported in murine models of these diseases, focusing on pathways relevant to anergy and central tolerance. We highlight some differences between murine and human environmental and genetic factors that may impact autoimmune disease development and expression and may, in turn, explain some of this discrepancy. Finally, we show that there is substantial overlap between the molecular networks that define these disease states across species. Our synthesis and analysis of the current state of the field are consistent with the idea that the same molecular networks are perturbed in murine and human autoimmune disease. Based on these analyses, we anticipate that murine autoimmune disease models will continue to yield novel insights into how best to diagnose, prognose, prevent and treat human autoimmune diseases.
The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection
Authors: Noto Alessandra , Suffiotti Madeleine , Joo Victor , Mancarella Antonio , Procopio Francesco A. , Cavet Guy , Leung Yvonne , Corpataux Jean-Marc , Cavassini Matthias , Riva Agostino , Stamatatos Leonidas , Gottardo Raphael , McDermott Adrian B. , Koup Richard A. , Fenwick Craig , Perreau Matthieu , Pantaleo Giuseppe
Published: August 2022

Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3+ Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3- Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3- Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3+ Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3+ B cells showed lower rate of somatic hypermutation, as compared to CXCR3- B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.
Unraveling the venom chemistry with evidence for histamine as key regulator in the envenomation by caterpillar Automeris zaruma
Authors: Seldeslachts Andrea , Peigneur Steve , Mebs Dietrich , Tytgat Jan
Published: August 2022

Over the past decades, envenomation by caterpillars of Automeris spp. became an increasing health problem in Latin America. Accidental contact with the stinging spines of these caterpillars cause acute local pain, itching, inflammation and skin rashes that persists for days. Even when the cause is obvious, the exact molecular mechanisms responsible for the observed symptoms are yet to be elucidated. Here, we describe for the first time, an active compound in the venom and the study of the bioactivity of the venom extracted from the spines of the caterpillar Automeris zaruma. Electrophysiological screening of a library of membrane proteins important for pain and itch enabled us to investigate and reveal the mode of action of the venom of A. zaruma. Further mass spectrometric analysis (Q-TOF-MS) made it possible to establish a link between the bioactivity and the components found in the venom. We show that the spine extract of A. zaruma contains histamine that potently activates the four types of the human histamine receptors (H1R, H2R, H3R and H4R) with a selectivity preference towards H3R and H4R. Furthermore, a modulation of the target MRGPRX2 was found. Together, these findings are the first to explain the symptomology of A. zaruma envenomation, enabling us a better understanding of caterpillar envenomation and predict that the hurdle of the scarce efficacy of the currently used antihistaminic drugs can be overcome by including H3R and H4R blockers in the clinical used medication. Such an approach might be used for other caterpillar envenomation in the world and represent a significant improvement for the well-being of the patient.
Molecular characterization and functional analysis of DIGIRR from golden pompano (Trachinotus ovatus)
Authors: Xie Yushuai , Gao Shuangshuang , Cao Yiwen , Ji Yuexin , Zhang Qihuan , Wei Youchuan , Qi Zhitao
Published: August 2022

Mammalian single immunoglobulin (Ig) interleukin-1 receptor related molecule (SIGIRR), an important member of the Toll/interleukin-1 receptor (TIR) family, plays important balancing roles in the inflammatory responses. In the present study, the double Ig interleukin-1 receptor related molecule (DIGIRR), the homologous of SIGIRR, was characterized in golden pompano (Trachinotus ovatus) (termed as trDIGIRR). The full-length cDNA of trDIGIRR was 2,167 bp with an open reading frame (ORF) of 1,572 bp encoding 523 amino acids. The trDIGIRR contained several conserved domains including a signal peptide, two Ig domains, a transmembrane domain and a TIR domain, and shared high sequence identities with its teleost counterparts. Realtime qPCR analysis revealed that the trDIGIRR was distributed in all tissues examined, with high expressions in intestine, liver and head kidney. The expressions of trDIGIRR were induced by Vibrio alginolyticus, lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (poly I:C) challenge. Further analysis revealed that trDIGIRR was mainly located in the cytoplasm. In addition, the co-immunoprecipitation (co-IP) assay identified that trDIGIRR could interact with myeloid differentiation factor 88 (MyD88), but not interact with TIR domain containing adaptor protein inducing interferon-β (TRIF). Our results provide basis for studying the immune role of fish DIGIRR.
Eisenia arborea (Areschoung) domestication and mariculture development on the Pacific coast of Baja California, México
Authors: Zertuche-González José A. , Sandoval-Gil Jose M. , Sánchez-Barredo Mariana , Altamirano-Gómez Zarko , Guzmán-Calderón José M. , Rangel-Mendoza Laura K. , Ladah Lydia B. , Cruz-López Ricardo , Yarish Charles
Published: August 2022

Eisenia arborea (sensu Ecklonia arborea) is the kelp with the greatest latitudinal distribution on the Northeastern Pacific Coast. It is harvested in Mexico in small amounts for abalone farm fodder and occasionally exported to Asia for human consumption. Because the high-energy environment where it naturally grows limits its sustainable harvest, we explored the domestication and cultivation of this kelp on the west coast of Baja California, Mexico. The life history of E. arborea was completed in the laboratory following traditional methods for kelp cultivation. Gametophytes became reproductive approximately 50 days after spore release and sporophytes were visible to the naked eye after 80 days. When sporophytes reached 2–3 cm, they were transplanted to two sites on long-line systems: in an open bay (Todos Santos Bay) and in a shallow coastal lagoon (San Quintín Bay). At both sites, full differentiation occurred 6 to 8 months after deployment, with fertile blades occurring within a year. Once individuals reached maximum size, blades were harvested by pruning. Monthly, regrowth of pruned blades and new blade addition were measured. Pruned individuals reached the same weight as controls in three months. On the basis of these results, a seasonal seeding program was implemented at a third site where the presence of natural Eisenia is rare due to the lack of hard substrate but was hypothesized to provide appropriate conditions for kelp cultivation (Santa María Bay). Cultures were deployed at three different depths and growth was correlated with season, depth, and temperature. Only cultures seeded in winter developed successfully at this site. This study shows that the culture of E. arborea in a variety of ocean conditions is possible; however, site selection and seasonality are important considerations. Because E. arborea is perennial, it can be harvested periodically during the year thereby increasing yield, and because it is the warmest tolerant kelp species, it is an ideal target for ocean farming and commercial cultivation, considering climate change.
Carbon cycling in the East Sea (Japan Sea): A review
Authors: Kim Minkyoung , Hwang Jeomshik , Kim Guebuem , Na Taehee , Kim Tae-Hoon , Hyun Jung-Ho
Published: August 2022

The East Sea (also known as the Japan Sea; hereafter, EJS) is a semi-enclosed marginal sea surrounded by the Korean Peninsula, Russia, and the Japanese Islands. The EJS is connected to the Pacific through shallow straits. Thus, the EJS has its own thermohaline circulation and the characteristic biogeochemistry. The deep overturning circulation plays a critical role in carbon cycling including absorption of atmospheric CO2 and its sequestration into the interior of the sea. The turnover time of the deep EJS (>1000 m) is ~ hundred years and probably varies depending on physical climate forcing. Thus, the effect of climate change on oceanic processes may be more easily detected in the EJS. In this paper, we summarize the current understanding of carbon cycling in the EJS. We focus especially on the Ulleung Basin in the southwestern EJS, from which more extensive data are available. Notable features of carbon cycling in the EJS include the following: primary productivity and the export/production ratio are higher than in the adjacent Pacific; the EJS is a net sink of atmospheric CO2 and anthropogenic CO2 content is ~1% of the dissolved inorganic carbon inventory; dissolved inorganic carbon in the sea interior is mostly supplied by organic matter decomposition rather than CaCO3 dissolution and thus, the deep waters are vulnerable to acidification; N:P molar ratio of the deep waters is ~13, lower than the Redfield ratio; concentration of dissolved organic carbon is significantly higher than in the oceans; and sediment resuspension and lateral transport is an important component of sinking particulate organic carbon (POC) flux. Another important feature is the temporal trends observed for the last few decades. For example, pH, calcium carbonate saturation status, and dissolved oxygen concentration in the sea interior have decreased, whereas dissolved inorganic carbon and likely, the inventory of anthropogenic CO2 have increased. These temporal trends have an implication on better understanding of the processes occurring more slowly in the oceans. Brief suggestions for future research that will improve our understanding of carbon cycling and its variability are provided at the end of the paper.