bluuebunny/crossref_metadata_2025 huggingface dataset:
Unga kvinnor med intellektuell funktionsnedsättning
Authors: Borgström Åsa
Published: August 2022

Tidigare forskning visar att unga med intellektuell funktionsnedsättning behöver ges möjlighet att utforska och uttrycka olika sociala identiteter, som idag sker på en rad olika arenor. Samtidigt saknas studier som särskilt belyser unga kvinnor med intellektuell funktionsnedsättning och identitetsskapande på digitala arenor. Det övergripande syftet med den här studien är således att studera erfarenheter av självpresentationer som unga kvinnor med intellektuell funktionsnedsättning gör på internet. Ett särskilt fokus riktas åt hur internet och sociala medier kan skapa förutsättningar för alternativa identitetskonstruktioner och hur dessa kan ta sig uttryck för dem. Studien baseras på intervjuer (individuella intervjuer, par-intervjuer och fokusgrupper) med unga kvinnor med intellektuell funktionsnedsättning (n=17). Intervjuerna genomfördes under 2017 och 2018 och intervjupersonerna var mellan 16-21 år. Analysen av materialet är inspirerad av tolkande fenomenologisk analys (Interpretative phenomenological analyses - IPA) och mynnar ut i fyra teman: ”vara sig själv”, ”vara försiktig och undvika visa kroppen”, ”i andras ögon: om låtsasidentitet och att försköna” och ”när bilden inte stämmer överens”. Resultatet tolkas utifrån ett interaktionistiskt perspektiv och synliggör förhandlingar på olika nivåer inom olika områden. Mest framträdande är förhandlingen mellan risk och möjlighet, arenorna online och offline och normalitet och avvikelse. Slutsatsen är att unga kvinnor med intellektuell funktionsnedsättning ger intryck av att befinna sig i ett spänningsfält mellan risk och möjlighet. Det är tydlig att internet å ena sidan utgör en möjlighet att utforska olika identitetsuttryck i samspel med andra. Å andra sidan kan internet liknas vid ett ”minfält” där det gäller att navigera mellan riskerna. Detta leder till en försiktighet som är relevant, men som kan upplevas som hämmande. Sammantaget ställer det stora krav på omgivningen: föräldrar och professionella. De praktiska implikationerna diskuteras utifrån begreppen dialektisk delaktighet och positivt risktagande.
Att förebygga våld och tvång på institutioner genom social inkludering
Authors: Pelto-Piri Veikko , Stranberg Anna
Published: August 2022

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The Development of Cooperation with Foreign Partners as One of the Directions to Accelerate the Implementation of Russia's Priorities in Science, Technology and Education
Authors: Bitkina Inna , Vasilyeva Irina , Rebrova Tatiana , Demidov Andrey
Published: August 2022

Introduction. Under current conditions, it is necessary to specify the priorities of scientific and technological cooperation, both thematic and geographical, to develop an approach to the search for and selection of partners. The article analyzes the existing forms of scientific and technical cooperation of the Russian Federation with foreign countries within the framework of the EAEU. The analysis comprises the following areas of cooperation: an integrated scientific and technological space; joint use of scientific infrastructure; interstate research projects, programs and their financing; digital platforms; exchange of scientific information and popularization of science. The article specifically focuses on the cooperation in the field of intellectual property. Particular attention is paid in the article to intellectual property interactions. Methods. General theoretical methods (analysis, generalization and systemic approach) and private scientific methods (formal-legal, method of interpretation of rules of law) were used. Results and Discussion. The article sets the directions for the development of cooperation between Russia and foreign countries in the scientific and technical sphere, which would make it possible to increase the effectiveness of such cooperation. Regulatory legal acts and treaties by areas of cooperation were systematized in order to assess their coverage of all areas of cooperation. The authors note the poorly developed system for planning the results of international scientific and technical cooperation, and indicators to assess its performance. Conclusion. The key areas of cooperation classified by the implementation horizon into tactical and strategic. Specification for scientific organizations and universities of the tasks and results of international scientific, technological and educational cooperation promotes the effectiveness of such interaction and the national interests of the country.
Skin prick test in milk allergic patients undergoing oral immunotherapy: Does the milk form used for skin tests matter?
Authors: Bukhari Esraa , Gabrielli Sofianne , McCusker Christine , Upton Julia , Grunebaum Eyal , Chan Edmond S. , Beaudette Liane , Langlois Alexandra , Torabi Bahar , Lejtenyi Duncan , Clarke Ann E. , Ke Danbing , Mazer Bruce David , Ben-Shoshan Moshe
Published: August 2022

SPT is the most commonly used confirmatory test for an IgE-mediated milk allergy. However, food SPTs are not standardized. We aimed to assess the accuracy of SPTs with extract, diluted, and undiluted milk to detect desensitization in children with milk allergy undergoing OIT. Children with milk allergy undergoing OIT and controls were recruited from Montreal Children’s Hospital (MCH), British Columbia Children’s Hospital (BCCH) and The Hospital for Sick Children (SickKids). Participants in the active arm received a weekly increase in milk until 200 ml of pure milk was tolerated. SPT using milk extract (Omega), diluted 2% milk (1:10), and undiluted milk was done at the study entry and when 200 ml of pure milk was reached. Participants in the control arm had SPT at study entry and 12 months later before they entered the active arm. Among 53 children who reached 200 ml, the median age was 12 years and 54.7% were males. The mean decrease in wheal size at 200 ml from the baseline was 3.78 mm (95%CI, 2.55–5.01), 5.05 mm (95% CI, 3.68–6.41), and 5.05 mm (95% CI, 3.29–6.80) for milk extract, diluted and undiluted milk respectively. Among 32 controls, the median age was 10 years and 62.5% were males. There was no significant change in wheal diameter over a one-year period regardless of the skin test method. Response to extract behaved similarly to whole food (Diluted and undiluted) and thus can be used to follow sensitization in the context of a desensitization program.
A kernel mixing strategy for use in adaptive Markov chain Monte Carlo and stochastic optimization contexts
Authors: West Graham , Sinkala Zachariah , Wallin John
Published: August 2022

Performing Markov chain Monte Carlo parameter estimation on complex mathematical models can quickly lead to endless searching through highly multimodal parameter spaces. For computationally complex models, one rarely has prior knowledge of the optimal proposal distribution. In such cases, the Markov chain can become trapped near a suboptimal mode, lowering the computational efficiency of the method. With these challenges in mind, we present a novel MCMC kernel which incorporates both mixing and adaptation. The method is flexible and robust enough to handle parameter spaces that are highly multimodal. Other advantages include not having to locate a near-optimal mode with a different method beforehand, as well as requiring minimal computational and storage overhead from standard Metropolis. Additionally, it can be applied in any stochastic optimization context which uses a Gaussian kernel. We provide results from several benchmark problems, comparing the kernel's performance in both optimization and MCMC cases. For the former, we incorporate the kernel into a simulated annealing method and real-coded genetic algorithm. For the latter, we incorporate it into the standard Metropolis and adaptive Metropolis methods.
Seeing is caring – automated assessment of resource use of broilers with computer vision techniques
Authors: van der Eijk Jerine A. J. , Guzhva Oleksiy , Voss Alexander , Möller Matthias , Giersberg Mona F. , Jacobs Leonie , de Jong Ingrid C.
Published: August 2022

Routine monitoring of broiler chickens provides insights in the welfare status of a flock, helps to guarantee minimum defined levels of animal welfare and assists farmers in taking remedial measures at an early stage. Computer vision techniques offer exciting potential for routine and automated assessment of broiler welfare, providing an objective and biosecure alternative to the current more subjective and time-consuming methods. However, the current state-of-the-art computer vision solutions for assessing broiler welfare are not sufficient to allow the transition to fully automated monitoring in a commercial environment. Therefore, the aim of this study was to investigate the potential of computer vision algorithms for detection and resource use monitoring of broilers housed in both experimental and commercial settings, while also assessing the potential for scalability and resource-efficient implementation of such solutions. This study used a combination of detection and resource use monitoring methods, where broilers were first detected using Mask R-CNN and were then assigned to a specific resource zone using zone-based classifiers. Three detection models were proposed using different annotation datasets: model A with annotated broilers from a research facility, model B with annotated broilers from a commercial farm, and model A+B where annotations from both environments were combined. The algorithms developed for individual broiler detection performed well for both the research facility (model A, F1 score > 0.99) and commercial farm (model A+B, F1 score > 0.83) test data with an intersection over union of 0.75. The subsequent monitoring of resource use at the commercial farm using model A+B for broiler detection, also performed very well for the feeders, bale and perch (F1 score > 0.93), but not for the drinkers (F1 score = 0.28), which was likely caused by our evaluation method. Thus, the algorithms used in this study are a first step to measure resource use automatically in commercial application and allow detection of a large number of individual animals in a non-invasive manner. From location data of every frame, resource use can be calculated. Ultimately, the broiler detection and resource use monitoring might further be used to assess broiler welfare.
On the quest for novel bio-degradable plastics for agricultural field mulching
Authors: Dar Sami Ullah , Wu Zizhao , Zhang Linyi , Yu Peirong , Qin Yiheng , Shen Yezi , Zou Yunfan , Poh Leslie , Eichen Yoav , Achmon Yigal
Published: August 2022

Plasticulture, the practice of using plastic materials in agricultural applications, consumes about 6.7 million tons of plastics every year, which is about 2% of the overall global annual plastics production. For different reasons, plastic material used for agriculture is difficult to recycle. Therefore, most of it is either buried in fertile soils, thereby significantly causing deterioration of their properties, or, at best case, end in landfills where its half-life is measured in decades and even centuries. Hence, developing biodegradable plastic materials that are suitable for agricultural applications is a vital and inevitable need for the global human society. In our labs, two types of potentially biodegradable plastic polymer films were prepared and characterized imidazolium in terms of their bio-degradability. In the first approach, polymers made of ionic liquid monomers were prepared using photo radical induced polymerization. The second approach relies on formation of polyethylene-like n-alkane disulfide polymers from 1,ω-di-thiols through thermally activated air oxidation. These two families of materials were tested for their biodegradability in soils by using a simulation system that combines a controlled environment chamber equipped with a respirometer and a proton-transfer-reaction time of flight mass spectrometer (PTR-TOF-MS) system. This system provides a time-dependent and comprehensive fingerprint of volatiles emitted in the degradation process. The results obtained thus far indicate that whereas the ionic-liquid based polymer does not show significant bio-degradability under the test conditions, the building block monomer, 1,10-n-decane dithiol, as well as its disulfide-based polymer, are bio-degradable. The latter reaching, under basic soil conditions and in room temperature, ∼20% degradation within three months. These results suggest that by introduction of disulfide groups into the polyethylene backbone one may be able to render it biodegradable, thus considerably shortening its half-life in soils. Principal component analysis, PCA, of the data about the total volatiles produced during the degradation in soil indicates a distinctive volatile “fingerprint” of the disulfide-based bio-degradable products which comes from the volatile organic compounds portfolio as recorded by the PTR-TOF-MS. The biodegradation volatile fingerprint of this kind of film was different from the “fingerprint” of the soil background which served as a control. These results can help us to better understand and design biodegradable films for agricultural mulching practices.
Mussel-inspired polydopamine decorated alginate dialdehyde-gelatin 3D printed scaffolds for bone tissue engineering application
Authors: Ghorbani Farnaz , Kim Minjoo , Monavari Mahshid , Ghalandari Behafarid , Boccaccini Aldo R.
Published: August 2022

This study utilized extrusion-based 3D printing technology to fabricate calcium-cross-linked alginate dialdehyde-gelatin scaffolds for bone regeneration. The surface of polymeric constructs was modified with mussel-derived polydopamine (PDA) in order to induce biomineralization, increase hydrophilicity, and enhance cell interactions. Microscopic observations revealed that the PDA layer homogeneously coated the surface and did not appear to induce any distinct change in the microstructure of the scaffolds. The PDA-functionalized scaffolds were more mechanically stable (compression strength of 0.69 ± 0.02 MPa) and hydrophilic (contact angle of 26) than non-modified scaffolds. PDA-decorated ADA-GEL scaffolds demonstrated greater durability. As result of the 18-days immersion in simulated body fluid solution, the PDA-coated scaffolds showed satisfactory biomineralization. Based on theoretical energy analysis, it was shown that the scaffolds coated with PDA interact spontaneously with osteocalcin and osteomodulin (binding energy values of −35.95 kJ mol−1 and −46.39 kJ mol−1, respectively), resulting in the formation of a protein layer on the surface, suggesting applications in bone repair. PDA-coated ADA-GEL scaffolds are capable of supporting osteosarcoma MG-63 cell adhesion, viability (140.18% after 7 days), and proliferation. In addition to increased alkaline phosphatase secretion, osteoimage intensity also increased, indicating that the scaffolds could potentially induce bone regeneration. As a consequence, the present results confirm that 3D printed PDA-coated scaffolds constitute an intriguing novel approach for bone tissue engineering.
Enhanced osteogenic activity of titania-modified zirconia implant by ultraviolet irradiation
Authors: Tang Shuang , Wang Yan , Zong Zhenyu , Ding Ning , Zhang Zutai
Published: August 2022

Zirconia is a superior implant material owing to its high mechanical strength, durable corrosion resistance, superior aesthetic effect and excellent biocompatibility. However, the bioactivity of zirconia surfaces remains a great challenge for implant osseointegration. A titania (TiO2) coating was innovatively synthesized on the surface of zirconia by infiltration in a suspension of zirconium oxychloride and titania for dense sintering. Subsequently, the coating was subjected to ultraviolet (UV) light to enhance the biological inertness of zirconia. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and contact angle analysis were conducted to confirm the surface characteristics. Afterwards, in vitro assessments of cell adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells were performed. Zirconia samples were implanted into rat femurs to assess biocompatibility and host tissue response in vivo. Micro-CT evaluation and histological testing were conducted. After UV irradiation, the content of hydroxyl groups and hydrophilicity of TiO2-modified zirconia were significantly increased. The results of in vitro experiments showed that TiO2-modified zirconia subjected to UV light could promote cell proliferation and spreading, enhance ALP activity and the degree of mineralization, and upregulate osteogenesis-related genes. Furthermore, in vivo assessments confirmed that UV-irradiated TiO2-modified zirconia implants maximized the promotion of osseointegration. TiO2-modified zirconia after UV treatment will have broad clinical application prospects in improving the osseointegration of zirconia implants.
Application progress of plant-mediated RNAi in pest control
Authors: Li Xiang , Liu Xiaoguang , Lu Wenhui , Yin Xinming , An Shiheng
Published: August 2022

RNA interference (RNAi)-based biopesticides are novel biologic products, developed using RNAi principles. They are engineered to target genes of agricultural diseases, insects, and weeds, interfering with their target gene expression so as to hinder their growth and alleviate their damaging effects on crops. RNAi-based biopesticides are broadly classified into resistant plant-based plant-incorporated protectants (PIPs) and non-plant-incorporated protectants. PIP RNAi-based biopesticides are novel biopesticides that combine the advantages of RNAi and resistant transgenic crops. Such RNAi-based biopesticides are developed through nuclear or plastid transformation to breed resistant plants, i.e., dsRNA-expressing transgenic plants. The dsRNA of target genes is expressed in the plant cell, with pest and disease control being achieved through plant-target organism interactions. Here, we review the action mechanism and strategies of RNAi for pest management, the development of RNAi-based transgenic plant, and the current status and advantages of deploying these products for pest control, as well as the future research directions and problems in production and commercialization. Overall, this study aims to elucidate the current development status of RNAi-based biopesticides and provide guidelines for future research.
Visualization and evaluation of concrete damage in-service headworks by X-ray CT and non-destructive inspection methods
Authors: Morozova Nadezhda , Shibano Kazuma , Shimamoto Yuma , Tayfur Sena , Alver Ninel , Suzuki Tetsuya
Published: August 2022

The durability of concrete irrigation infrastructures decreases easily due to environmental effects, such as the freeze-thawed process. The degree of damage in concrete is, in most cases, evaluated by an unconfined compression test or ultrasonic test. The limiting states of structures are the result of a gradual accumulation of microdefects during the in-service period, which leads to the initiation and development of macroscopic cracks, loss of performance, and Failure. Therefore, to maintain such structures, it is necessary to properly determine the degree of damage by non-destructive testing. For effective maintenance and management of in-service structures, it is necessary to evaluate not only such mechanical properties as strength but also the degree of damage. Quantitative damage evaluation of concrete is proposed by applying the X-ray CT method and related non-destructive inspection, which is based on estimating cracking damage effects. In this study, the damage evaluation of concrete-core samples is investigated by X-ray CT parameters and the non-destructive parameters. The samples tested were taken from the damaged concrete headwork in Niigata, Japan, about 50 years after its construction. The geometric properties of the concrete matrix were calculated by the analysis of X-ray CT images. After X-ray CT measurement, an ultrasonic test and a resonant frequency test were performed. The dynamic modulus of elasticity was calculated by using ultrasonic pulse velocity and resonant frequency. As a result, based on the relationship between the geometric properties of the concrete matrix and the non-destructive parameters, the accumulation of damage in the samples tested was correlated with the ratio of the total area of cracks to the observation area. In damaged conditions, the high value of its ratio is demonstrated under low ultrasonic pulse velocity. These results suggest that the most sensitive components in a concrete body to the degree of damage are cracks in mortar and the ratio of the total area of cracks to the observation area. These values are affected by the internal actual cracks. Thus, the damage of concrete could be quantitatively evaluated by the geometric properties of the concrete matrix and its physical properties.
Clinical and biochemical characteristics of diabetic ketoacidosis in adults with type 1 or type 2 diabetes at a tertiary hospital in the United Arab Emirates
Authors: Almazrouei Raya , Siddiqua Amatur Rahman , Alnuaimi Mouza , Al-Shamsi Saif , Govender Romona
Published: August 2022

Background

Diabetes ketoacidosis (DKA) is a well-known acute complication of diabetes. This study aims to describe the sociodemographic, clinical, and biochemical characteristics of adult patients with different diabetes types and DKA severities attending a tertiary hospital in the UAE.

Methods

We retrospectively extracted sociodemographic, clinical, and laboratory data from the electronic medical records of 220 adult patients with DKA admitted to Tawam Hospital between January 2017 and October 2020.

Results

The average age was 30.6 ± 16.6 years of whom 54.5% were women, 77.7% were UAE nationals and 77.9% were Type 1 diabetes (T1DM). 12.7% were newly diagnosed with diabetes. Treatment noncompliance (31.4%), and infection (26.4%) were the main precipitating factors. Most patients presented with moderate DKA (50.9%). Compared to T1DM, patients with Type 2 diabetes (T2DM) were older (53.6 vs 23.9 years, p < 0.001), had longer hospital stay (12.1 days vs 4.1 days, p < 0.001), had more complications (52.1%, vs 18.9% p <0.001), and a higher mortality rate (6.3% vs 0.6%, p = 0.035). Patients with severe DKA had a shorter diabetes duration compared to mild and moderate DKA (5.7 vs 11.0 vs 11.7 years, respectively, p = 0.007), while complications were significantly lower in the mild group compared to both the moderate and severe groups (11.6% vs 32.1% vs 33.3%, respectively).

Conclusion

The risk of DKA is higher for patients with T1DM than for those with T2DM. The clinical characteristics and outcomes of patients with T2DM differ from those with T1DM highlighting the importance of educating all patients about DKA.
Association of aging-related genes with prognosis and immune infiltration in pancreatic adenocarcinoma
Authors: Xue Shengbai , Ge Weiyu , Wang Kexuan , Mao Tiebo , Zhang Xiaofei , Xu Haiyan , Wang Yongchao , Yao Jiayu , Li Shumin , Yue Ming , Ma Jingyu , Wang Yanling , Shentu Daiyuan , Cui Jiujie , Wang Liwei
Published: August 2022

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies. Aging is described as the degeneration of physiological function, which is complexly correlated with cancer. It is significant to explore the influences of aging-related genes (ARGs) on PAAD. Based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets, we used univariate Cox regression analysis and acquired eight differentially expressed ARGs with prognostic values. Two molecular subtypes were identified based on these ARGs to depict PAAD patients’ overall survival (OS) and immune microenvironments preliminarily. Cluster 1 had a poor OS as well as a worse immune microenvironment. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we constructed a seven-ARG risk signature based on the TCGA dataset and verified it in Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) to predict the prognoses, immune microenvironments, signal pathways, tumor mutations, and drug sensitivity of PAAD patients. The high-risk group possessed an unfavorable OS compared with that of the low-risk group. We also verified the independence and clinical availability of the risk signature by Cox regression analyses and the establishment of a nomogram, respectively. The higher risk score was associated with several clinical factors such as higher grade and advanced tumor stage as well as lower immunoscore and cluster 1. The negative associations of risk scores with immune, stroma, and estimate scores proved the terrible immune microenvironment in the high-risk group. Relationships between risk score and immune checkpoint gene expression as well as signal pathways provided several therapeutic targets. PAAD patients in the low-risk group possessed lower tumor mutations as well as a higher susceptibility to axitinib and vorinostat. The high-risk group bore a higher TMB and cisplatin and dasatinib may be better options. We used immunohistochemistry and qPCR to confirm the expression of key ARGs with their influences on OS. In conclusion, we identified two ARG-mediated molecular subtypes and a novel seven-ARG risk signature to predict prognoses, immune microenvironments, signal pathways, tumor mutations, and drug sensitivity of PAAD patients.
RNA binding proteins in osteoarthritis
Authors: Yi Qian , Deng Zhenhan , Yue Jiaji , He Jinglong , Xiong Jianyi , Sun Wei , Sun Weichao
Published: August 2022

Osteoarthritis (OA) is a common chronic degenerative joint disease worldwide. The pathological features of OA are the erosion of articular cartilage, subchondral bone sclerosis, synovitis, and metabolic disorder. Its progression is characterized by aberrant expression of genes involved in inflammation, proliferation, and metabolism of chondrocytes. Effective therapeutic strategies are limited, as mechanisms underlying OA pathophysiology remain unclear. Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying OA focused on gene transcription. However, posttranscriptional alterations also play significant function in inflammation and metabolic changes related diseases. RNA binding proteins (RBPs) have been recognized as important regulators in posttranscriptional regulation. RBPs regulate RNA subcellular localization, stability, and translational efficiency by binding to their target mRNAs, thereby controlling their protein expression. However, their role in OA is less clear. Identifying RBPs in OA is of great importance to better understand OA pathophysiology and to figure out potential targets for OA treatment. Hence, in this manuscript, we summarize the recent knowledge on the role of dysregulated RBPs in OA and hope it will provide new insight for OA study and targeted treatment.
Green synthesis of silver nanoparticles and their antibacterial effects
Authors: Xin Xiaoqian , Qi Chunli , Xu Liang , Gao Qin , Liu Xiaowen
Published: August 2022

Antibacterial resistance is by far one of the greatest challenges to global health. Many pharmaceutical or material strategies have been explored to overcome this dilemma. Of these, silver nanoparticles (AgNPs) are known to have a non-specific antibacterial mechanism that renders it difficult to engender silver-resistant bacteria, enabling them to be more powerful antibacterial agents than conventional antibiotics. AgNPs have shown promising antibacterial effects in both Gram-positive and Gram-negative bacteria. The aim of this review is to summarize the green synthesis of AgNPs as antibacterial agents, while other AgNPs-related insights (e.g., antibacterial mechanisms, potential toxicity, and medical applications) are also reviewed.
Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha
Authors: Song Nali , Zheng Xi , Wang Jiapeng , Zhu Li , Wang Chengyao , Cai Le , Ding Zhongtao
Published: August 2022

A new rosane-type diterpenoid (1) along with nine known diterpenoids (2–10), were isolated from the dried roots of Euphorbia nematocypha. The absolute configuration was elucidated from spectroscopic (nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism) and optical-rotation analyses. Cytotoxicity and the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals were determined. Compound 1 showed remarkable cytotoxicity against human cancer cell lines (HeLa, CT26, and HCC 1806) in vitro. The interaction between compound 1 and proteins of ribosomal S6 kinase was revealed using molecular docking and provided valuable insights into the cytotoxic mechanism of action of compound 1. The latter could be developed as a pharmaceutical agent in the future.
Design, Synthesis, and Activity Assays of Cyclin-Dependent Kinase 1 Inhibitors With Flavone Scaffolds
Authors: Fu Lanlan , Mou Jiajia , Deng Yanru , Ren Xiaoliang , Qiu Shuang
Published: August 2022

Cyclin-dependent kinase 1 (CDK1) plays an indispensable role in the whole cell cycle. It has become a new target for cancer therapy. According to the binding mode of a pan-CDK inhibitor, flavopiridol with CDK1, and our previous work, a new series of flavone derivatives were discovered. Among them, compound 2a showed the best CDK1 inhibitory and anti-proliferative potencies in the in vitro activity investigation. The IC50 of 2a against CDK1 was 36.42 ± 1.12 μM vs. 11.49 μM ± 0.56 of flavopiridol. In the anti-proliferation activity assays, 2a exhibited better activity toward RAW264.7 than MCF-7 cells. The results indicated that flavone derivatives, besides inhibiting the growth of tumor cells, can also antagonize inflammatory response. Molecular docking results showed that conformation of 2a can form hydrogen bonds and various hydrophobic interactions with the key amino acid residues of CDK1. It can be used as a promising lead compound for CDK1 inhibitor development.
Molecular characterization of NDM-1-producing carbapenem-resistant E. cloacae complex from a tertiary hospital in Chongqing, China
Authors: Hu Kewang , Zhang Jisheng , Zou Jingbo , Zeng Lingyi , Li Jie , Wang Jianmin , Long Wenzhang , Zhang Xiaoli
Published: August 2022

Background

The aim of this study was to clarify the molecular characterization of NDM-1-producing carbapenem-resistant Enterobacter cloacae complex (CREL) at a teaching hospital in Chongqing, China.

Methods

Antimicrobial susceptibility and resistance genes were analyzed. Epidemiological relationship was analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Conjugation experiments were performed to determine the transferability of plasmids. Whole-genome sequencing (WGS) of strains was implemented, and the genetic environment of the blaNDM-1- and mcr-9-carrying plasmids was analyzed.

Results

A total of 10 blaNDM-1-positive CREL isolates were identified. All isolates harbored multiple resistance genes. ECL68 and ECL78 co-produce blaNDM-1 and mcr-9. Among the four different sequence types (STs) detected, ST1466 was assigned as a novel ST. Six isolates exhibited highly similar PFGE patterns. Conjugation assay proved that all plasmids containing blaNDM-1 or mcr-9 could be transferred to the recipient Escherichia coli. WGS indicated that blaNDM-1 genes were carried by diverse plasmids, including IncHI2/IncN, IncX3, and one unclassified plasmid type. The backbone structure of these plasmids is involved in replication initiation (repAB), partitioning (parABM), and conjugation/type IV secretion (tra/virB). Analysis of the genetic environment showed that blaNDM-1 in three plasmids exhibited a highly similar structure to protype Tn125. Co-existence of blaNDM-1 and the colistin resistance gene mcr-9 was detected in the two isolates, ECL68 and ECL78. In ECL68, blaNDM-1 and mcr-9 were present on the same plasmid while located in two separate plasmids in ECL78. The genetic environment of mcr-9 was organized as IS26-wbuC-mcr-9-IS903-pcoS-pcoE-rcnA-rcnR, and the two-component system encoding genes qseC and qseB was not found in two plasmids, which could explain mcr-9-harboring strains’ colistin susceptibility.

Conclusions

We first report a nosocomial outbreak of NDM-1-producing E. cloacae complex ST177 in China. Conjugative plasmids contributed to the horizontal transfer of antibiotic resistance genes. The prevalence and even coexistence of blaNDM-1 and mcr-9 may further threaten public health. Our results highlight further surveillance for blaNDM-1, and mcr-9 is essential to prevent its dissemination.
High prevalence of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates: A 5-year retrospective study at a Tertiary Hospital in Northern Thailand
Authors: Siriphap Achiraya , Kitti Thawatchai , Khuekankaew Akachai , Boonlao Chalermchai , Thephinlap Chonthida , Thepmalee Chutamas , Suwannasom Nittiya , Khoothiam Krissana
Published: August 2022

Background

The global emergence and spread of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, especially Escherichia coli and Klebsiella pneumoniae, have been recognized as a public health concern as severe infections caused by these microorganisms increase morbidity and mortality. This study aimed to assess the prevalence of ESBL-positive E. coli and K. pneumoniae strains isolated from hospitalized patients in Chiangrai Prachanukroh hospital, Chiangrai province, Thailand.

Methods

This retrospective analysis was conducted from January 2016 to December 2020. A total of 384,001 clinical specimens were collected aseptically and further cultivated on an appropriate medium. All clinical isolates (one isolate per patient) were identified based on standard laboratory methods. Antibiotic susceptibility testing was performed by the Kirby Bauer disc diffusion technique following CLSI guidelines. ESBL production was screened with ceftazidime and cefotaxime discs based on the CLSI recommendations. Phenotypic confirmation of ESBL production was carried out using a double-disc synergy technique following the CLSI standard.

Results

Of a total of 384,001 clinical samples analyzed for bacterial species identification, 11,065 (2.9%) tested positive for E. coli and 5,617 (1.5%) for K. pneumoniae. Approximately 42.5% (4,706/11,065) of E. coli and 30.2% (1,697/5,617) of K. pneumoniae isolates were classified as ESBL producers. A higher proportion of ESBL producers was found in patients older than 60 years and male groups. The highest infection rates of ESBL-positive pathogens were observed among patients in a medical unit. ESBL-producing E. coli and K. pneumoniae isolates were predominantly found in urine and sputum, respectively. ESBL producers exhibited a high resistance rate to ampicillin (99.8–100%), cefazolin (100%), cefotaxime (100%), fluoroquinolones, and trimethoprim/sulfamethoxazole.

Conclusions

This study demonstrated the high prevalence and emerging antibiotic resistance of ESBL-positive E. coli and K. pneumoniae isolates from patients admitted to a provincial hospital in northern Thailand. Most ESBL-producing strains were highly resistant to several antimicrobial agents apart from carbapenems and aminoglycosides. These findings indicated that carbapenems and aminoglycosides should be advised as the first-line drugs of choice for serious infections with ESBL-producing Enterobacterales.
Gender dimension in cardio-pulmonary continuum
Authors: Hernandez Leah , Laucyte-Cibulskiene Agne , Ward Liam J. , Kautzky-Willer Alexandra , Herrero Maria-Trinidad , Norris Colleen M. , Raparelli Valeria , Pilote Louise , Stenvinkel Peter , Kublickiene Karolina ,   the GOING-FWD Consortium
Published: August 2022

Cardio-pulmonary diseases, which were once regarded as a man's illness, have been one of the leading causes of morbidity and mortality for both men and women in many countries in recent years. Both gender and sex influence the functional and structural changes in the human body and therefore play an important role in disease clinical manifestation, treatment choice, and/or response to treatment and prognosis of health outcomes. The gender dimension integrates sex and gender analysis in health sciences and medical research, however, it is still relatively overlooked suggesting the need for empowerment in the medical research community. Latest advances in the field of cardiovascular research have provided supportive evidence that the application of biological variables of sex has led to the understanding that heart disease in females may have different pathophysiology compared to males, particularly in younger adults. It has also resulted in new diagnostic techniques and a better understanding of symptomatology, while gender analysis has informed more appropriate risk stratification and prevention strategies. The existing knowledge in the pulmonary field shows the higher prevalence of pulmonary disorders among females, however, the role of gender as a socio-cultural construct has yet to be explored for the implementation of targeted interventions. The purpose of this review is to introduce the concept of gender dimension and its importance for the cardiopulmonary continuum with a focus on shared pathophysiology and disease presentation in addition to interrelation with chronic kidney disease. The review presents basic knowledge of what gender dimension means, and the application of sex and gender aspects in cardiovascular medicine with a specific focus on early pulmonary development, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Early vascular aging and inflammation have been presented as a potential pathophysiological link, with further interactions between the cardiopulmonary continuum and chronic kidney disease. Finally, implications for potential future research have been provided to increase the impact of gender dimension on research excellence that would add value to everybody, foster toward precision medicine and ultimately improve human health.
Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality
Authors: Ng Cheng Han , Wong Zhen Yu , Chew Nicholas W. S. , Chan Kai En , Xiao Jieling , Sayed Nilofer , Lim Wen Hui , Tan Darren Jun Hao , Loke Ryan Wai Keong , Tay Phoebe Wen Lin , Yong Jie Ning , Kong Gywneth , Huang Daniel Q. , Wang Jiong-Wei , Chan Mark , Dalakoti Mayank , Tamaki Nobuharu , Noureddin Mazen , Siddiqui Mohammad Shadab , Sanyal Arun J. , Muthiah Mark
Published: August 2022

Background and aims

Hypertension (HTN) is a common comorbidity in non-alcoholic fatty liver disease (NAFLD) affecting up to 40% of individuals. However, the impact of HTN and its control on outcomes in NAFLD remains unclear. Therefore, we aimed to examine the impact of HTN on survival outcomes in a longitudinal cohort of NAFLD patients.

Methods

The analysis consisted of adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with data on socio-demographic characteristics and comorbidities. NAFLD was diagnosed with fatty liver index (FLI) and United States-FLI at a cut-off of 60 and 30, respectively in the substantial absence of alcohol use. A multivariate regression analysis was conducted to adjust for confounders.

Results

A total of 45,302 adults were included, and 27.83% were identified to have NAFLD. Overall, 45.65 and 35.12% of patients with NAFLD had HTN and uncontrolled HTN, respectively. A multivariate analysis with confounders demonstrated that hypertensive NAFLD had a significantly increased risk of all-cause mortality (HR: 1.39, CI: 1.14–1.68, p < 0.01) and cardiovascular disease (CVD) mortality (HR: 1.85, CI: 1.06–3.21, p = 0.03). Untreated HTN remained to have a significantly increased risk in all-cause (HR: 1.59, CI: 1.28–1.96, p < 0.01) and CVD mortality (HR: 2.36, CI: 1.36–4.10, p < 0.01) while treated HTN had a non-significant increased risk of CVD mortality (HR: 1.51, CI: 0.87–2.63, p = 0.14) and a lower magnitude of increase in the risk of all-cause mortality (HR: 1.26, CI: 1.03–1.55, p = 0.03).

Conclusion

Despite the significant burden of HTN in NAFLD, up to a fifth of patients have adequate control, and the lack thereof significantly increases the mortality risk. With the significant association of HTN in NAFLD, patients with NAFLD should be managed with a multidisciplinary team to improve longitudinal outcomes.
Concurrent use of statins decreases major bleeding and intracerebral hemorrhage in non-valvular atrial fibrillation patients taking direct oral anticoagulants—A nationwide cohort study
Authors: Wu Hsin-Hsu , Chang Shang-Hung , Lee Tsong-Hai , Tu Hui-Tzu , Liu Chi-Hung , Chang Ting-Yu
Published: August 2022

Background

Statins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins.

Methods

This nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score.

Results

50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72–0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74–0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74–0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66–0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69–0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51–0.89), but not in male patients (IRR 0.87, 95% CI 0.70–1.08).

Conclusions

Among non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.
PlaqView 2.0: A comprehensive web portal for cardiovascular single-cell genomics
Authors: Ma Wei Feng , Turner Adam W. , Gancayco Christina , Wong Doris , Song Yipei , Mosquera Jose Verdezoto , Auguste Gaëlle , Hodonsky Chani J. , Prabhakar Ajay , Ekiz H. Atakan , van der Laan Sander W. , Miller Clint L.
Published: August 2022

Single-cell RNA-seq (scRNA-seq) is a powerful genomics technology to interrogate the cellular composition and behaviors of complex systems. While the number of scRNA-seq datasets and available computational analysis tools have grown exponentially, there are limited systematic data sharing strategies to allow rapid exploration and re-analysis of single-cell datasets, particularly in the cardiovascular field. We previously introduced PlaqView, an open-source web portal for the exploration and analysis of published atherosclerosis single-cell datasets. Now, we introduce PlaqView 2.0 (www.plaqview.com), which provides expanded features and functionalities as well as additional cardiovascular single-cell datasets. We showcase improved PlaqView functionality, backend data processing, user-interface, and capacity. PlaqView brings new or improved tools to explore scRNA-seq data, including gene query, metadata browser, cell identity prediction, ad hoc RNA-trajectory analysis, and drug-gene interaction prediction. PlaqView serves as one of the largest central repositories for cardiovascular single-cell datasets, which now includes data from human aortic aneurysm, gene-specific mouse knockouts, and healthy references. PlaqView 2.0 brings advanced tools and high-performance computing directly to users without the need for any programming knowledge. Lastly, we outline steps to generalize and repurpose PlaqView's framework for single-cell datasets from other fields.
Detecting upland glaciation in Earth’s pre-Pleistocene record
Authors: Soreghan Gerilyn S. , Pfeifer Lily S. , Sweet Dustin E. , Heavens Nicholas G.
Published: August 2022

Earth has sustained continental glaciation several times in its past. Because continental glaciers ground to low elevations, sedimentary records of ice contact can be preserved from regions that were below base level, or subject to subsidence. In such regions, glaciated pavements, ice-contact deposits such as glacial till with striated clasts, and glaciolacustrine or glaciomarine strata with dropstones reveal clear signs of former glaciation. But assessing upland (mountain) glaciation poses particular challenges because elevated regions typically erode, and thus have extraordinarily poor preservation potential. Here we propose approaches for detecting the former presence of glaciation in the absence or near-absence of ice-contact indicators; we apply this specifically to the problem of detecting upland glaciation, and consider the implications for Earth’s climate system. Where even piedmont regions are eroded, pro- and periglacial phenomena will constitute the primary record of upland glaciation. Striations on large (pebble and larger) clasts survive only a few km of fluvial transport, but microtextures developed on quartz sand survive longer distances of transport, and record high-stress fractures consistent with glaciation. Proglacial fluvial systems can be difficult to distinguish from non-glacial systems, but a preponderance of facies signaling abundant water and sediment, such as hyperconcentrated flood flows, non-cohesive fine-grained debris flows, and/or large-scale and coarse-grained cross-stratification are consistent with proglacial conditions, especially in combination with evidence for cold temperatures, such as rip-up clasts composed of noncohesive sediment, indicating frozen conditions, and/or evidence for a predominance of physical over chemical weathering. Other indicators of freezing (periglacial) conditions include frozen-ground phenomena such as fossil ice wedges and ice crystals. Voluminous loess deposits and eolian-marine silt/mudstone characterized by silt modes, a significant proportion of primary silicate minerals, and a provenance from non-silt precursors can indicate the operation of glacial grinding, even though such deposits may be far removed from the site(s) of glaciation. Ultimately, in the absence of unambiguous ice-contact indicators, inferences of glaciation must be grounded on an array of observations that together record abundant meltwater, temperatures capable of sustaining glaciation, and glacial weathering (e.g., glacial grinding). If such arguments are viable, they can bolster the accuracy of past climate models, and guide climate modelers in assessing the types of forcings that could enable glaciation at elevation, as well as the extent to which (extensive) upland glaciation might have influenced global climate.