bluuebunny/crossref_metadata_2025 huggingface dataset:
Service condition of several pedestrian cable-supported bridges in the Rhodopi Mountain of Bulgaria
Authors: Ivanov S D , Georgiev L D
Published: February 2023

This paper describes the service condition of few long span pedestrian suspension bridges in Rhodopi Mountain of Bulgaria. They were built more than 50 years ago and were reconstructed after 35 years of exploitation. Visual inspection was made in the summer of 2021 by the authors. Typical design shortcomings are presented. In conclusion some ideas for the improvement of their condition with respect to their future save exploitation are suggested.
Composite Girders of Classes 1 and 2 With Partial Plasticization
Authors: Dulevski Encho
Published: February 2023

A case of a bridge composite girder is analysed. According to EC4 rules, its cross section is coinciding into class 1 and should be able to resist the design moment in ULS. But after tracking the loading history with gradually increasing the live load up to the design level, it is established, that an early web instability exists before the loading ends. This effect contradicts to some code settings and the case should be considered as a warning to the designers working in similar circumstances.
Study of the behavior of a experimental reinforced concrete slab at different stages of loading from the production of the reinforced concrete slab over it
Authors: Bakardzhiev S
Published: February 2023

This report examines the behavior of a reinforced concrete slab, part of an experimental reinforced concrete structure, under loads derived from the casting of the formwork system of the subsequent plate and from the laid concrete mix in the slab above it. The deflections in the individual stages were measured with the help of dial gauges. The full strength and deformation characteristics of the concretes used in the construction were researched. The behavior at all stages of loading of the slab was studied, including each phase of formwork of the slab above it and the laying of the concrete in the formwork itself. Conclusions have been made about the behavior of the slabs during production using the method for Early striking of reinforced concrete slabs.
The Septemvri-Dobrinishte narrow-gauge railway line – a unique project for Balkans.
Authors: Lepoev M. G.
Published: February 2023

The first section of the narrow-gauge railway line Septemvri-Dobrinishte was put into operation in the distant 1926, and the last sixth stage of it was completed in 1945. It is single line, non-electrified, with a track gauge of 760mm, which makes it unique for Bulgaria and the Balkans. Apart from its track gauge, the line impresses with its spiral ascents, maximum longitudinal slopes - up to 32 ‰, minimum radii of horizontal curves of 50m and the highest station on the Balkan Peninsula, Avramovo 1267.4m above sea level. Within a total length of 125 km, 35 tunnels, 23 bridges, retaining walls and numerous culverts have been built. The article presents the current state of the major engineering facilities along the line - bridges and tunnels, as well as the state of the superstructure of the railway. Its technical characteristics, which makes it a unique achievement, both in terms of transport structural facilities and for railway construction in general, are also commented.
Dual-wavelength chiral metasurfaces based on quasi-bound states in the continuum
Authors: Chen Run , Bi Qianhui , Li Tianyue , Wang Shuming , Zhu Shining , Wang Zhenlin
Published: February 2023

In this paper, we numerically demonstrate a dual-wavelength chiral metasurface with the chirality only existing at two resonant wavelengths, making use of the excitation of two quasi-bound states in the continuum (quasi-BICs). This chiral metasurface is constructed on the basis of photonic crystal slabs with square lattice of circular holes by introducing rectangular holes as perturbations. The two quasi-BICs supported by chiral metasurface are orthogonal to each other, thus the chirality at the two resonant wavelengths can be controlled independently by changing the geometry of the perturbations. Furthermore, a chirality-switchable metasurface is demonstrated taking advantage of the sensitivity of quasi-BICs to the variation of out-of-plane symmetry caused by changing refractive index of surroundings. The proposed chiral metasurface could find potential applications in nonlinear optics, sensing, imaging and near-to-eye displays.
Accessing the topological Mott insulator in cold atom quantum simulators with realistic Rydberg dressing
Authors: Cardarelli Lorenzo , Julià-Farré Sergi , Lewenstein Maciej , Dauphin Alexandre , Müller Markus
Published: February 2023

The interplay between many-body interactions and the kinetic energy gives rise to rich phase diagrams hosting, among others, interaction-induced topological phases. These phases are characterized by both a local order parameter and a global topological invariant, and can exhibit exotic ground states such as self-trapped polarons and interaction-induced edge states. In this work, we investigate a realistic scenario for the quantum simulation of such systems using cold Rydberg-dressed atoms in optical lattices. We consider spinless fermions on a checkerboard lattice, interacting via the tunable-range effective potential induced by the Rydberg dressing. We perform a detailed analysis of the phase diagram at half- and incommensurate fillings, in the mean-field approximation. We furthermore study the stability of the phases with respect to temperature within the mean-field approximation and with respect to quantum fluctuations using the density matrix renormalization group method. Finally, we propose an implementation protocol, and in particular identify attainable regimes of experimental parameters in which the topological properties of the model become accessible. Our work thereby opens a realistic pathway to the outstanding experimental observation of this predicted phase in state-of-the-art cold atom quantum simulators.
Importin α/β promote Kif18B microtubule association and enhance microtubule destabilization activity
Authors: Shrestha Sanjay , Ems-McClung Stephanie C. , Hazelbaker Mark A. , Yount Amber L. , Shaw Sidney L. , Walczak Claire E.
Published: February 2023

The critical regions of interaction between the Kif18B tail and its binding partners, importin α/β and EB1, are defined, and it is shown how these interactions control Kif18B function in cells and activity in vitro. A new mechanism is uncovered by which the spatial activity of Kif18B is controlled through the RanGTP pathway.
BioID2 screening identifies KIAA1671 as an EPS8 proximal factor that marks sites of microvillus growth
Authors: Gaeta Isabella M. , Tyska Matthew J.
Published: February 2023

Brush-border microvilli are defining structural features of epithelial apical surfaces. We used biotin proximity labeling with EPS8 as an anchor and identified the uncharacterized protein KIAA1671 as a new component of the brush border involved in the biogenesis of microvilli.
MSGCL: inferring miRNA–disease associations based on multi-view self-supervised graph structure contrastive learning
Authors: Ruan Xinru , Jiang Changzhi , Lin Peixuan , Lin Yuan , Liu Juan , Huang Shaohui , Liu Xiangrong
Published: February 2023

Potential miRNA–disease associations (MDA) play an important role in the discovery of complex human disease etiology. Therefore, MDA prediction is an attractive research topic in the field of biomedical machine learning. Recently, several models have been proposed for this task, but their performance limited by over-reliance on relevant network information with noisy graph structure connections. However, the application of self-supervised graph structure learning to MDA tasks remains unexplored. Our study is the first to use multi-view self-supervised contrastive learning (MSGCL) for MDA prediction. Specifically, we generated a learner view without association labels of miRNAs and diseases as input, and utilized the known association network to generate an anchor view that provides guiding signals for the learner view. The graph structure was optimized by designing a contrastive loss to maximize the consistency between the anchor and learner views. Our model is similar to a pre-trained model that continuously optimizes upstream tasks for high-quality association graph topology, thereby enhancing the latent representation of association predictions. The experimental results show that our proposed method outperforms state-of-the-art methods by 2.79$\%$ and 3.20$\%$ in area under the receiver operating characteristic curve (AUC) and area under the precision/recall curve (AUPR), respectively.
Persistent Tor-algebra for protein–protein interaction analysis
Authors: Liu Xiang , Feng Huitao , Lü Zhi , Xia Kelin
Published: February 2023

Protein–protein interactions (PPIs) play crucial roles in almost all biological processes from cell-signaling and membrane transport to metabolism and immune systems. Efficient characterization of PPIs at the molecular level is key to the fundamental understanding of PPI mechanisms. Even with the gigantic amount of PPI models from graphs, networks, geometry and topology, it remains as a great challenge to design functional models that efficiently characterize the complicated multiphysical information within PPIs. Here we propose persistent Tor-algebra (PTA) model for a unified algebraic representation of the multiphysical interactions. Mathematically, our PTA is inherently algebraic data analysis. In our PTA model, protein structures and interactions are described as a series of face rings and Tor modules, from which PTA model is developed. The multiphysical information within/between biomolecules are implicitly characterized by PTA and further represented as PTA barcodes. To test our PTA models, we consider PTA-based ensemble learning for PPI binding affinity prediction. The two most commonly used datasets, i.e. SKEMPI and AB-Bind, are employed. It has been found that our model outperforms all the existing models as far as we know. Mathematically, our PTA model provides a highly efficient way for the characterization of molecular structures and interactions.
MDBuilder: a PyMOL plugin for the preparation of molecular dynamics simulations
Authors: Liu Hui , Jin Ye , Ding Hanjing
Published: February 2023

The preprocessed initial files that feed the molecular dynamics (MD) simulation packages dramatically influence the outcome of the simulations. However, the popular MD simulation packages depend, to a great extent, on the user’s experience in the preparation of MD simulation systems. In this work, we present an easy-to-use tool called MDBuilder, a PyMOL plugin that assists researchers in building the starting structures for multiple popular MD simulation packages. MDBuilder is not only designed to assist MD beginners to overcome the steep learning curve by providing a menu-oriented, point-and-click user graphic interface (GUI), but also to provide an alternative way to prepare the input files for some highly scalable CHARMM force field-based MD simulation packages. The platform-independent GUI is implemented as a PyMOL plugin using the Python language, and it has been tested on Windows and Linux platforms. The source code and documentation of MDBuilder can be downloaded freely from https://github.com/HuiLiuCode/MDBuilder under the GNU General Public License.
polishCLR: A Nextflow Workflow for Polishing PacBio CLR Genome Assemblies
Authors: Chang Jennifer , Stahlke Amanda R , Chudalayandi Sivanandan , Rosen Benjamin D , Childers Anna K , Severin Andrew J
Published: February 2023

Long-read sequencing has revolutionized genome assembly, yielding highly contiguous, chromosome-level contigs. However, assemblies from some third generation long read technologies, such as Pacific Biosciences (PacBio) continuous long reads (CLR), have a high error rate. Such errors can be corrected with short reads through a process called polishing. Although best practices for polishing non-model de novo genome assemblies were recently described by the Vertebrate Genome Project (VGP) Assembly community, there is a need for a publicly available, reproducible workflow that can be easily implemented and run on a conventional high performance computing environment. Here, we describe polishCLR (https://github.com/isugifNF/polishCLR), a reproducible Nextflow workflow that implements best practices for polishing assemblies made from CLR data. PolishCLR can be initiated from several input options that extend best practices to suboptimal cases. It also provides re-entry points throughout several key processes, including identifying duplicate haplotypes in purge_dups, allowing a break for scaffolding if data are available, and throughout multiple rounds of polishing and evaluation with Arrow and FreeBayes. PolishCLR is containerized and publicly available for the greater assembly community as a tool to complete assemblies from existing, error-prone long-read data.
Why and how do consumers use dietary supplements? A systematic review and thematic analysis
Authors: Wang Yun , Neilson Leighann C , Ji Shaobo
Published: February 2023

Using the input-process-output (IPO) model as an organizing framework, this paper provides an overview of the literature on multiple dimensions of dietary supplement (DS) consumption. Based on a systematic review of 174 studies from different disciplines over two decades, we pinpointed the key topics that have been examined in this growing body of literature and identified the major themes within DS consumption. Moreover, we integrated the major themes in inputs, processes, and outputs to develop a comprehensive understanding of individuals’ DS consumption behaviors, motivations, and social mechanisms underlying such behaviors. This research has implications for health consumption and promotion research. We identified DS consumption as a social–cultural process in which individuals practice lifelong self-learning and socialization activities through which lay health knowledge may be developed. Accordingly, their DS use motives may be related to health improvement or not (e.g. identity expressions), which are formed during interactions with various stakeholders in the health marketplace. When confronting the contemporary health promotion culture and self-care paradigm, it is important for researchers to deepen our knowledge of consumers’ motives for DS consumption and the underlying social mechanisms to aid consumers’ health consumption decisions and guide the multiple stakeholders in the health marketplace.
Rare genetic variants underlie outlying levels of DNA methylation and gene-expression
Authors: Chundru V Kartik , Marioni Riccardo E , Prendergast James G D , Lin Tian , Beveridge Allan J , Martin Nicholas G , Montgomery Grant W , Hume David A , Deary Ian J , Visscher Peter M , Wray Naomi R , McRae Allan F
Published: February 2023

Testing the effect of rare variants on phenotypic variation is difficult due to the need for extremely large cohorts to identify associated variants given expected effect sizes. An alternative approach is to investigate the effect of rare genetic variants on DNA methylation (DNAm) as effect sizes are expected to be larger for molecular traits compared with complex traits. Here, we investigate DNAm in healthy ageing populations—the Lothian Birth Cohorts of 1921 and 1936—and identify both transient and stable outlying DNAm levels across the genome. We find an enrichment of rare genetic single nucleotide polymorphisms (SNPs) within 1 kb of DNAm sites in individuals with stable outlying DNAm, implying genetic control of this extreme variation. Using a family-based cohort, the Brisbane Systems Genetics Study, we observed increased sharing of DNAm outliers among more closely related individuals, consistent with these outliers being driven by rare genetic variation. We demonstrated that outlying DNAm levels have a functional consequence on gene expression levels, with extreme levels of DNAm being associated with gene expression levels toward the tails of the population distribution. This study demonstrates the role of rare SNPs in the phenotypic variation of DNAm and the effect of extreme levels of DNAm on gene expression.
Safety Analysis of Preoperative Anti-TNF-α Therapy in Pediatric IBD After Intestinal Resection: A Systematic Review and Meta-analysis
Authors: Bajzát Dorina , Kéri Adrienn F , Imrei Marcell , Kói Tamás , Párniczky Andrea , Hegyi Péter , Kovács Kinga , Váncsa Szilárd , Müller Katalin Eszter
Published: February 2023

Background

Biological agents have transformed the management of inflammatory bowel disease (IBD). However, intestinal resection is still unavoidable in complicated IBD. It is still under debate whether antitumor necrosis factor (TNF)-α is related to higher postoperative complications in children with IBD. Therefore, we aimed to analyze data on preoperative anti-TNF-α and postoperative complications in pediatric IBD.

Methods

We conducted a systematic literature search in 4 databases for studies that compared the incidence of postoperative complications between children with IBD who received anti-TNF-α treatment within 12 weeks prior to intestinal resection and who did not receive anti-TNF-α before the operation. To analyze this question, pooled odds ratios (ORs) were calculated with 95% confidence intervals (CIs). Odds ratios higher than 1 mean higher complication rate among children treated with preoperative anti-TNF-α, whereas an OR lower than 1 means lower complication rate. The I² value was calculated to measure the strength of the between-study heterogeneity, where a smaller percentage means the lower heterogeneity.

Results

We found 8 eligible articles with 526 pediatric patients with IBD. The primary outcome was the overall complication. The pooled OR of overall complications was 1.38 (95% CI, 0.10-18.76; P = .65; I2 = 34%) in contrast, the OR of infectious and noninfectious complications were 0.59 (95% CI, 0.21-1.69; P = .16; I2 = 0%) and 0.48 (95% CI, 0.18-1.25; p = .09; I2 = 0%), although both showed a nonsignificant result.

Conclusion

There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection. However, the evidence is low due to the low number of studies investigating this question.
Legal Mobilisations, Trade Unions and Radical Social Change: A Case Study of the IWGB
Authors: Adams Zoe
Published: February 2023

In recent years, a number of new style trade unions have emerged which are said to exhibit a more ‘radical’ orientation to social change than more ‘traditional’ trade unions. This has raised questions as to the significance of the willingness of these new style trade unions to mobilise the law in pursuit of that change, and in particular, to engage in so-called ‘strategic litigation’. Through a case study of some of the legal mobilisations of one of the more well-known new style trade unions in the UK, the Independent Workers of Great Britain union (IWGB), drawing on insights from the literature on legal mobilisation, and supplementing this with insights from the Marxist theory of the legal form, this paper will highlight the distinctiveness of these new style trade unions and explain the basis of their radical potential, before showing how that potential is limited, or negated, by the particular way in which they engage with law in practice. The paper will conclude with some observation as to what a more radical orientation to the law might look like for social organisations and trade unions in practice.
Discovery and Genetic Characterization of Single Cohort Adult Colonies With Male Aggregations, and Preliminary Evidence for Lekking in a Malagasy Kite Spider (Isoxya, Gasteracanthinae)
Authors: Agnarsson Ingi , Starrett James , Babbitz Zachary , Bond Jason E , Gregorič Matjaž , Christian Raberahona Onjaherizo , Williams Steven , Kuntner Matjaž
Published: February 2023

Spiders are notoriously solitary and cannibalistic, with instances of colonial or social lifestyles in only about 50-60, or ~0.1% of 50,000 described species. Population analyses indicate that most colonies consist of multiple cohorts formed by close relatives. Territorial social spiders facultatively form colonies by interlinking individual webs, but further cooperation is infrequent, and only among juveniles or (rarely) females. In spiders therefore, aggregations of males outside of the male-male competition context has been unknown. Here, we report on a discovery of a kite spider from Madagascar that exhibits unique colonies. We found colonies of the newly described araneid Isoxya manangonan. sp. formed by up to 41 interconnected, single-cohort adult female webs with up to 38 adult males aggregating on a central, single, nonsticky line. With males resting tightly together, we found no evidence for male-male aggression. Genetic analyses from RAD sequencing suggest that most colonies consist of unrelated individuals. Furthermore, genetic variability of males was somewhat less than that of females. Single cohort colonies made up purely of adults, and peaceful male aggregations, have not previously been observed in spiders. Although direct behavioral observations are preliminary, we speculate based on the available evidence that these colonies may represent a novel and first case of lekking in spiders.
Effects of five carbohydrate sources on cat diet digestibility, postprandial glucose, insulin response, and gut microbiomes
Authors: Zhang Shu , Ren Yang , Huang Yuqin , Wang Yingchun , Dang Han , Shan Tizhong
Published: February 2023

Cat obesity has become a serious problem that affects cats’ lives and welfare. Knowing how to control obesity in pet cats and its mechanism is urgently needed. Here, by feeding 30 cats different diets for 28 d, we explored the effects of 5 cat foods with potato, sweet potato, cassava, rice, and wheat as the main carbohydrate sources on the glycolipid metabolism of pet cats. The results showed that dietary carbohydrate sources did not affect the normal growth performance and stool scores of cats. Notably, we found that the starch gelatinization degree of sweet potato and cassava cat food were higher than those of other groups, while the rice diets had the highest digestibility, but the difference was not significant (P > 0.05). Furthermore, cats fed cassava diets had lower postprandial glucose responses. The mean glucose value, maximum glucose value, AUC0–360 min, AUC≤30 min, and AUC≥30 min in the cassava group were lower than those in other dietary groups (P > 0.05). In addition, we found that the carbohydrate source had a minimal effect on serum biochemical immune indices, but the blood lipid indices, such as TG, TC, HDL, and LDL of cats fed the cassava diet were maintained at a low level compared with other groups (P > 0.05). In addition, diets with different carbohydrate sources affect the gut microbial composition, and sweet potato and cassava diets tend to increase the diversity of gut microbiota with a higher Shannon index and Simpson index. The abundance of Fusobacterium, Veillonella, and Actinobacillus was significantly higher in sweet potato diet-fed cats (P < 0.05), while the abundance of Delftia, Shinella, Rothia, and Hydrogenophage was highest in cassava diet-fed cats (P < 0.05). Collectively, this study revealed that cassava and sweet potato diets have a better effect on feeding value, controlling blood glucose and blood lipids, and improving the intestinal flora of pet cats, which is worth developing dietary formulations to alleviate pet obesity.
Of mice, or men: TLR4 signaling in HIV pathogenesis
Authors: Acosta Reyes , Claiborne Daniel T
Published: February 2023

A murine Tlr4null humanized mouse model offers a new tool to study mechanisms by which microbial translocation affects adaptive immune function and exacerbates HIV-1 pathogenesis.
Insecticide Resistance Status ofAedes albopictus(Diptera:Culicidae) Populations from Cuba
Authors: Piedra Luis Augusto , Rodriguez Maria Magdalena , Lopez Isabel , Ruiz Armando , Martinez Liss Claudia , Garcia Israel , Rey Jorge , Bisset Juan Andres
Published: February 2023

Aedes albopictus (Skuse, 1894) is one of the major vectors for arboviruses such as dengue, Zika, and chikungunya. Originally from Southeast Asia, this species has spread to Africa, Europe, and the Americas, including Cuba. This spread has been favored by its great adaptability to variable temperatures and to the resistance of its eggs to desiccation. Chemical control of mosquitoes is an essential alternative to stop arbovirus transmission, but insecticide resistance status of the Cuban Ae. albopictus populations is unknown. For this study, Ae. albopictus larvae and adults were collected from two municipalities in Havana, Cuba in 2019. Adult bioassays for deltamethrin, cypermethrin, lambda-cyhalothrin, chlorpyrifos, propoxur, and bendiocarb susceptibility were conducted according to CDC methodology. Larval bioassays for temephos susceptibility were performed following WHO protocols. Resistance profiles for α and β-esterases, glutathione S-transferase (GST), and multifunction oxidases (MFO) pathways were constructed and analyzed. Resistance to temephos and deltamethrin was detected in Mulgoba and Plaza field populations, but resistance to lambda-cyhalothrin was only found in the Plaza colony. Plaza colony exhibited a higher expression level to all four metabolic enzymes and α-esterases and GTS were over-expressed in Mulgoba. The development of insecticide resistance in Cuban Ae. albopictus populations makes it imperative that we develop integrated control strategies to minimize the development of resistance and provide effective vector control that prevents the onset of arbovirus epidemics.
Human papillomavirus–associated cancer incidence by disaggregated Asian American, Native Hawaiian, and other Pacific Islander ethnicity
Authors: Shing Jaimie Z , Corbin Jereme , Kreimer Aimée R , Carvajal Loretto J , Taparra Kekoa , Shiels Meredith S , Vo Jacqueline B
Published: February 2023

Background

Asian Americans and Native Hawaiians and other Pacific Islanders have suboptimal human papillomavirus (HPV) vaccination and cancer screening rates. Asian Americans and NHPIs are often aggregated, masking disparities characterized by varying colonization and immigration patterns and cultural and religious beliefs between populations and ethnicities. We examined the incidence of HPV-associated cancers across disaggregated Asian American and NHPI ethnicities.

Methods

Using the Surveillance, Epidemiology, and End Results Detailed Asian/Pacific Islander database, we calculated 1990 to 2014 sex-specific, age-standardized HPV-associated cancer incidence of cervical carcinoma, oropharyngeal squamous cell carcinoma (SCC), vulvar SCC, vaginal SCC, anal SCC, and penile SCC by ethnicity: Asian Indian and Pakistani, Chinese, Filipino, Japanese, Kampuchean, Korean, Laotian, Native Hawaiian, other Pacific Islander, and Vietnamese. Trends by calendar period (1990 to 1996, 1997 to 2002, 2003 to 2008, 2009 to 2014) were estimated using Joinpoint regression.

Results

The most common HPV-associated cancer was cervical carcinoma in women and oropharyngeal SCC in men. During 1990 to 2014, cervical carcinoma incidence per 100 000 ranged from 4.5 (Asian Indian and Pakistani) to 20.7 (Laotian). Cervical carcinoma incidence only statistically significantly declined for Asian Indian and Pakistani, Filipino, Korean, Laotian, and Vietnamese women (range = 19.9% to 44.1% decline per period). Among men, oropharyngeal SCC incidence per 100 000 ranged from 1.1 (Chinese) to 5.1 (Native Hawaiian). Oropharyngeal SCC incidence only statistically significantly increased (31.0% increase per period) for Japanese men. Heterogeneity across ethnicities were observed for other cancer sites.

Conclusions

HPV-associated cancer incidence varied widely between Asian Americans and NHPIs and by ethnicity, underscoring the need for improved data capture of ethnic groups in research and more tailored interventions to better address health disparities between Asian American and NHPI populations.
A rare case of survival after traumatic blunt ventricular rupture
Authors: Yang Ryan , Van Gent Michael , Clements Thomas , Cotton Bryan , Wandling Michael
Published: February 2023

A male in his 40s presented to the trauma center via air ambulance after colliding with a cement wall at highway speeds. Cross-sectional imaging revealed a right ventricular pseudoaneurysm, confirmed by echocardiography. He was taken emergently to the operating room where he was found to have a pericardial laceration, hemopericardium and a right ventricular rupture, which was primarily repaired. Postoperatively, the patient was transferred to intensive care and after 34 days in the hospital was ultimately discharged home.
Cell Survival Enabled by Leakage of a Labile Metabolic Intermediate
Authors: Medina-Carmona Encarnación , Gutierrez-Rus Luis I , Manssour-Triedo Fadia , Newton Matilda S , Gamiz-Arco Gloria , Mota Antonio J , Reiné Pablo , Cuerva Juan Manuel , Ortega-Muñoz Mariano , Andrés-León Eduardo , Ortega-Roldan Jose Luis , Seelig Burckhard , Ibarra-Molero Beatriz , Sanchez-Ruiz Jose M
Published: February 2023

Many metabolites are generated in one step of a biochemical pathway and consumed in a subsequent step. Such metabolic intermediates are often reactive molecules which, if allowed to freely diffuse in the intracellular milieu, could lead to undesirable side reactions and even become toxic to the cell. Therefore, metabolic intermediates are often protected as protein-bound species and directly transferred between enzyme active sites in multi-functional enzymes, multi-enzyme complexes, and metabolons. Sequestration of reactive metabolic intermediates thus contributes to metabolic efficiency. It is not known, however, whether this evolutionary adaptation can be relaxed in response to challenges to organismal survival. Here, we report evolutionary repair experiments on Escherichia coli cells in which an enzyme crucial for the biosynthesis of proline has been deleted. The deletion makes cells unable to grow in a culture medium lacking proline. Remarkably, however, cell growth is efficiently restored by many single mutations (12 at least) in the gene of glutamine synthetase. The mutations cause the leakage to the intracellular milieu of a highly reactive phosphorylated intermediate common to the biosynthetic pathways of glutamine and proline. This intermediate is generally assumed to exist only as a protein-bound species. Nevertheless, its diffusion upon mutation-induced leakage enables a new route to proline biosynthesis. Our results support that leakage of sequestered metabolic intermediates can readily occur and contribute to organismal adaptation in some scenarios. Enhanced availability of reactive molecules may enable the generation of new biochemical pathways and the potential of mutation-induced leakage in metabolic engineering is noted.
Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients
Authors: He Yi , Jin Ying , Xue Hen , Liu Runhan , Zhang Mengyu , Liao Ruoxi , Chen Maoli , Zhou Xueli , He Xueqin , Qin Min , Li Kuo , Zou Huiqun , Gan Ying , Wang Zhenlei , Zheng Li , Zhong Hui , Fu Ping
Published: February 2023

Background

There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF.

Methods

This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association Class II–IV HF. The concentrations of valsartan, sacubitril and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF).

Results

Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50 mg twice daily (BID), 100 mg once daily and 100 mg BID. The plasma maximum drug concentrations in the 100 mg BID group were 1995 ± 1499 ng/mL for valsartan, 171 ± 148 ng/mL for sacubitril and 13 686 ± 7418 ng/mL for LBQ657. The 24-h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25 ± 10.32 mmHg and 10.10 ± 8.00 mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00–18 198.00) from baseline, while LVEF increased by 5.00 (–0.25 to 9.25) from baseline after SV treatment.

Conclusions

PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100 mg BID SV is safe and effective in patients with PD with complications of hypertension or HF.
Programming the lifestyles of engineered bacteria for cancer therapy
Authors: Fu Shengwei , Zhang Rongrong , Gao Yanmei , Xiong Jiarui , Li Ye , Pu Lu , Xia Aiguo , Jin Fan
Published: February 2023

Bacteria can be genetically engineered to act as therapeutic delivery vehicles in the treatment of tumors, killing cancer cells or activating the immune system. This is known as bacteria-mediated cancer therapy (BMCT). Tumor invasion, colonization and tumor regression are major biological events, which are directly associated with antitumor effects and are uncontrollable due to the influence of tumor microenvironments during the BMCT process. Here, we developed a genetic circuit for dynamically programming bacterial lifestyles (planktonic, biofilm or lysis), to precisely manipulate the process of bacterial adhesion, colonization and drug release in the BMCT process, via hierarchical modulation of the lighting power density of near-infrared (NIR) light. The deep tissue penetration of NIR offers us a modality for spatio-temporal and non-invasive control of bacterial genetic circuits in vivo. By combining computational modeling with a high-throughput characterization device, we optimized the genetic circuits in engineered bacteria to program the process of bacterial lifestyle transitions by altering the illumination scheme of NIR. Our results showed that programming intratumoral bacterial lifestyle transitions allows precise control of multiple key steps throughout the BMCT process and therapeutic efficacy can be greatly improved by controlling the localization and dosage of therapeutic agents via optimizing the illumination scheme.
Pressure-induced superconductivity at 32 K in MoB2
Authors: Pei Cuiying , Zhang Jianfeng , Wang Qi , Zhao Yi , Gao Lingling , Gong Chunsheng , Tian Shangjie , Luo Ruitao , Li Mingtao , Yang Wenge , Lu Zhong-Yi , Lei Hechang , Liu Kai , Qi Yanpeng
Published: February 2023

Since the discovery of superconductivity in MgB2 (Tc ∼ 39 K), the search for superconductivity in related materials with similar structures or ingredients has never stopped. Although about 100 binary borides have been explored, only a few of them show superconductivity with relatively low Tc. In this work, we report the discovery of superconductivity up to 32 K, which is the highest Tc in transition-metal borides, in MoB2 under pressure. The Tc of MoB2 in the α phase can be well explained by theoretical calculations in the framework of electron-phonon coupling. Furthermore, the coupling between the d electrons of Mo and the out-of-plane Mo-phonon modes are the main driving force of the 32 K superconductivity of MoB2. Our study sheds light on the exploration of high-Tc superconductors in transition metal borides.
Androstadienone modulates human aggression in a sex-dependent manner
Authors: Wu Yin , Wei Ran , Nan Yu , Hu Yang , Ye Yuting
Published: February 2023

Chemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.
Amino acid digestibility and nitrogen-corrected true metabolizable energy of mildly cooked human-grade vegan dog foods using the precision-fed cecectomized and conventional rooster assays
Authors: Roberts Leah J , Oba Patricia M , Utterback Pamela L , Parsons Carl M , Swanson Kelly S
Published: February 2023

The pet food market is constantly changing and adapting to meet the needs and desires of pets and their owners. One trend that has been growing in popularity lately is the feeding of fresh, human-grade foods. Human-grade pet foods contain ingredients that have all been stored, handled, processed, and transported in a manner that complies with regulations set for human food production. While most human-grade pet foods are based on animal-derived ingredients, vegan options also exist. To our knowledge, no in vivo studies have been conducted to analyze the performance of human-grade vegan diets. Therefore, the objective of this study was to investigate the amino acid (AA) digestibility and nitrogen-corrected true metabolizable energy (TMEn) of mildly cooked human-grade vegan dog foods using precision-fed cecectomized rooster and conventional rooster assays. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets (Bramble Cowbell diet (BC); Bramble roost diet (BR)), while the third was a chicken-based extruded dog diet (chicken and brown rice recipe diet (CT)). Prior to the rooster assays, both mildly cooked diets were lyophilized, and then all three diets were ground. Diets were fed to cecectomized roosters to determine AA digestibility, while conventional roosters were used to determine TMEn. All data were analyzed using the mixed models procedure of SAS (version 9.4). The majority of indispensable and dispensable AA across all diets had digestibilities higher than 80%, with a few exceptions (BC: histidine, lysine, threonine, and valine; BR: histidine). The only difference in indispensable AA digestibility among diets was observed with tryptophan, with its digestibility being higher (P = 0.0163) in CT than in BC. TMEn values were higher (P = 0.006) in BC and BR (4.55 and 4.66 kcal/g dry matter, respectively) than that in CT (3.99 kcal/g dry matter). The TMEn/GE was also higher (P = 0.0193) in BR than in CT. Metabolizable energy (ME) estimates using Atwater factors accurately estimated the energy content of CT, but modified Atwater factors and the predictive equations for ME recommended by the National Research Council underestimated energy content. All calculations underestimated the measured TMEn values of BC and BR, with Atwater factors being the closest. Although testing in dogs is required, these data suggest that mildly cooked human-grade vegan dog diets are well-digested. Moreover, TMEn data suggest that existing methods and equations underestimate the ME of the mildly cooked human-grade vegan foods tested.
Towards research-based organizational structures in mathematics tutoring centres
Authors: Byerley Cameron , Johns Carolyn , Moore-Russo Deborah , Rickard Brian , James Carolyn , Mills Melissa , Mammo Behailu , Oien Janet , Burks Linda , Heasom William , Ferreira Melissa , Farthing Cynthia , Moritz Daniel
Published: February 2023

Undergraduate mathematics tutoring centres are prevalent in many countries; however, there is limited research-based evidence on effective organizational structures for these centres. In this study, we consider two research questions. First, how can the quantitative and qualitative data from 10 mathematics tutoring centres be organized for research purposes? Second, what hypotheses do expert mathematics tutoring centre leaders generate about characteristics of effective centres given data from a sample of ten centres? We collected quantitative data from over 26,000 students taking mathematics courses at ten institutions. Data collected included college entrance exam scores, high school grade point average, number of student visits to the centre per eligible student and course letter grade. We used exploratory data analysis to look for relationships between visits to the tutoring centre, student grades and other variables. Qualitative centre characteristics that were considered include: specialist–generalist tutoring system, tutoring capacity, physical layout, relationships between tutors and mathematics instructors and extent of tutor training. We used the Delphi process to generate testable hypotheses from the data, such as the following: (1) The more courses a tutor is responsible for tutoring the more likely it is that the tutor will struggle to answer student questions, when the difficulty level of the courses is roughly the same. (2) Centres with more specialized tutor models have more visits per student than centres with generalized tutor models. The preceding two hypotheses, along with the other generated hypotheses, have been identified by the experts participating in this study as plausible based on professional experience, exploratory data analysis and inferences based on prior research on tutoring. This study has not rigorously shown the validity of these hypotheses; rather it lays the groundwork for future investigations to determine what combination of features characterize an effective tutoring centre.
Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic*
Authors: Anesi George L. , Andrews Adair , Bai He (Julia) , Bhatraju Pavan K. , Brett-Major David M. , Broadhurst M. Jana , Campbell Elizabeth Salvagio , Cobb J. Perren , Gonzalez Martin , Homami Sonya , Hypes Cameron D. , Irwin Amy , Kratochvil Christopher J. , Krolikowski Kelsey , Kumar Vishakha K. , Landsittel Douglas P. , Lee Richard A. , Liebler Janice M. , Lutrick Karen , Marts Lucian T. , Mosier Jarrod M. , Mukherjee Vikramjit , Postelnicu Radu , Rodina Valentina , Segal Leopoldo N. , Sevransky Jonathan E. , Spainhour Christine , Srivastava Avantika , Uyeki Timothy M. , Wurfel Mark M. , Wyles David , Evans Laura ,   for the Severe Acute Respiratory Infection-Preparedness (SARI-PREP) Study Group
Published: February 2023

OBJECTIVES:

The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity.

DESIGN:

Prospective weekly hospital stress survey, November 2020–June 2022.

SETTING:

Society of Critical Care Medicine’s Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study.

SUBJECTS:

Thirteen hospitals across seven U.S. health systems.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82;p< 0.0001) but only moderately correlated with ED stress (ρ = 0.52;p< 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5–12%), 7% (3–10%), and 4% (2–6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9–14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6–14 wk] after local case peak;p= 0.59) while the resolution of ED stress (median 6 wk [5–6 wk] after local case peak;p= 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge.

CONCLUSIONS:

During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.
Aberrant fucosylation sustains the NOTCH and EGFR/NF-κB pathways and has a prognostic value in human intrahepatic cholangiocarcinoma
Authors: Ament Cindy E. , Steinmann Sara , Evert Katja , Pes Giovanni M. , Ribback Silvia , Gigante Isabella , Pizzuto Elena , Banales Jesus M. , Rodrigues Pedro M. , Olaizola Paula , Wang Haichuan , Giannelli Gianluigi , Chen Xin , Evert Matthias , Calvisi Diego F.
Published: February 2023

Background and Aims:

Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy, with increasing incidence worldwide and limited therapeutic options. Aberrant protein glycosylation is a hallmark of cancer. Here, we thoroughly investigated the possible involvement of fucosylation in cholangiocarcinogenesis.

Approach and Results:

We discovered that the levels of global fucosylation and members of the fucosylation pathway are ubiquitously upregulated in human iCCA tissues compared to nontumorous surrounding livers and normal biliary cells. In addition, total fucosylation levels correlate with poor patients’ prognosis. Furthermore, fucosylation inhibition following 6-alkynylfucose (6AF) administration triggered a dose-dependent decrease in the proliferation and migration of iCCA cell lines. Notably, adding fucose to the cell medium annulled these effects. At the molecular level, 6AF administration or small interfering RNA-mediated silencing of GDP-L-fucose synthetase (FX) and the GDP-fucose transmembrane transporter (SLC35C1), both pivotal players of cellular fucosylation, decreased NOTCH activity, NOTCH1/Jagged1 interaction, NOTCH receptors, and related target genes in iCCA cell lines. In the same cells, EGFR, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and Bcl-xL protein levels diminished, whereas IκBα (a critical cellular NF-κB inhibitor) increased after FX/SLC35C1 knockdown or 6AF administration. In the chick chorioallantoic membrane assay, 6AF treatment profoundly suppresses the growth of iCCA cells.

Conclusions:

Elevated global fucosylation characterizes human iCCA, contributing to cell growth and migration through the upregulation of the NOTCH and EGFR/NF-κB pathways. Thus, aberrant fucosylation is a novel pathogenetic player and a potential therapeutic target for human iCCA.