bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, synthesis, and biological evaluation of furan‐bearing pyrazolo[3,4‐b]pyridines as novel inhibitors of CDK2 and P53–MDM2 protein–protein interaction
Authors: Ezzat Manal Abdel Fattah , Elmasry Ghada F. , El‐Mageed Menna M. A. Abd , Fouad Marwa A. , Abdel‐Aziz Hatem A. , Elewa Safaa I.
Published: May 2023

The novel series of furan‐bearing pyrazolo[3,4‐b]pyridines were designed as cyclin‐dependent kinase 2 (CDK2) inhibitors and as p53–murine double minute 2 (MDM2) inhibitors. The newly synthesized compounds were screened for their antiproliferative activity toward hepatocellular carcinoma (HepG2) and breast cancer (MCF7) cell lines. The most active compounds on both cell lines were additionally evaluated for their in vitro CDK2 inhibitory activity. Compounds 7b and 12f displayed enhanced activity (half‐maximal inhibitory concentration [IC50] = 0.46 and 0.27 µM, respectively) in comparison to the standard roscovitine (IC50 = 1.41 ± 0.03 µM), in addition to, cell cycle arrest at S phase and G1/S transition phase in MCF7 cells treated with both compounds, respectively. Moreover, the most active spiro‐oxindole derivative against MCF7 cell line, 16a, exhibited enhanced inhibitory activity against p53–MDM2 interaction in vitro (IC50 = 3.09 ± 0.12 µM) compared to nutlin, and increased the levels of both p53 and p21 by nearly fourfold in comparison to the negative control. Molecular docking studies demonstrated the plausible interaction patterns of the most potent derivatives 17b and 12f in the CDK2 binding pocket and the spiro‐oxindole 16a with p53–MDM2 complex, respectively. Consequently, the new chemotypes 7b, 12f, and 16a can be presented as promising antitumor hits for further studies and optimization.
Behavioral and neurostructural correlates of childhood physical violence victimization: Interaction with family functioning
Authors: Delaney Scott W. , Cortes Hidalgo Andrea P. , White Tonya , Haneuse Sebastien , Ressler Kerry J. , Tiemeier Henning , Kubzansky Laura D.
Published: May 2023

Violence victimization may cause child behavior problems and neurostructural differences associated with them. Healthy family environments may buffer these effects, but neural pathways explaining these associations remain inadequately understood. We used data from 3154 children (x̅age = 10.1) to test whether healthy family functioning moderated possible associations between violence victimization, behavior problems, and amygdala volume (a threat‐responsive brain region). Researchers collected data on childhood violence victimization, family functioning (McMaster Family Assessment Device, range 0–3, higher scores indicate healthier functioning), and behavior problems (Achenbach Child Behavior Checklist [CBCL] total problem score, range 0–117), and they scanned children with magnetic resonance imaging. We standardized amygdala volumes and fit confounder‐adjusted models with “victimization × family functioning” interaction terms. Family functioning moderated associations between victimization, behavior problems, and amygdala volume. Among lower functioning families (functioning score = 1.0), victimization was associated with a 26.1 (95% confidence interval [CI]: 9.9, 42.4) unit higher CBCL behavior problem score, yet victimized children from higher functioning families (score = 3.0) exhibited no such association. Unexpectedly, victimization was associated with higher standardized amygdala volume among lower functioning families (ŷ = 0.5; 95% CI: 0.1, 1.0) but lower volume among higher functioning families (ŷ = −0.4; 95% CI: −0.7, −0.2). Thus, healthy family environments may mitigate some neurobehavioral effects of childhood victimization.
Staying Involved in Disability Services
Authors: Lyerly Eric
Published: May 2023

Louise Bedrossian, Ed.S., L.P.C., a former Director of the Disability Resource Center at Clayton State University in Georgia, explains how to stay involved in disability services after retiring or transitioning to another field. Louise also provides consulting and private coaching and counseling. Email her at louisebedrossian@clayton.edu.
Postpartum cessation of urban space use by a female baboon living at the edge of the City of Cape Town
Authors: Bracken Anna M. , Christensen Charlotte , O'Riain M. Justin , Fürtbauer Ines , King Andrew J.
Published: May 2023

Species with slow life history strategies that invest in few offspring with extended parental care need to adapt their behavior to cope with anthropogenic changes that occur within their lifetime. Here we show that a female chacma baboon (Papio ursinus) that commonly ranges within urban space in the City of Cape Town, South Africa, stops using urban space after giving birth. This change of space use occurs without any significant change in daily distance traveled or social interactions that would be expected with general risk‐sensitive behavior after birth. Instead, we suggest this change occurs because of the specific and greater risks the baboons experience within the urban space compared to natural space, and because leaving the troop (to enter urban space) may increase infanticide risk. This case study can inform methods used to manage the baboons' urban space use in Cape Town and provides insight into how life history events alter individuals' use of anthropogenic environments.
Environmental DNA extraction method from water for a high and consistent DNA yield
Authors: Fukuzawa Takashi , Shirakura Hiromi , Nishizawa Naofumi , Nagata Hisao , Kameda Yuichi , Doi Hideyuki
Published: May 2023

Environmental DNA (eDNA) measurements have been widely applied in the biomonitoring of organisms. However, different DNA extraction methods may cause changes in yield and consistency, resulting in an inaccurate estimation of eDNA, especially when quantitative measurements are performed. This study focused on evaluating the effects of DNA extraction methods on the magnitude and consistency of fish DNA yield from water samples. Samples were collected periodically over a year from river and lake water systems, and reference eDNA was spiked into them. The spiked samples were extracted using three methods: using lysis buffer for blood and cells (AL method) with the DNeasy Blood and Tissue Kit (Qiagen), using lysis buffer for tissue (ATL method), and the microfluidic‐channel method (BC method). DNA yields were compared by determining the copy number using qPCR. The ATL method showed better stability and a higher yield than the AL method. In addition, despite being comparatively simple, the BC method performed extractions stably and at relatively high yields. Based on the long‐term evaluation of eDNA measurements using various methods, we showed that differences in DNA extraction methods may alter DNA yield and stability.
Oleic acid‐rich waste fleshing oil as a secondary carbon source for the synthesis of sophorolipids
Authors: Velappan Brindha , Nagarajan Vedaraman , Narayana Murthy Venkatesh , Arumugam Sivasamy , Kandukalpatti Chinnaraj Velappan
Published: May 2023

Biosurfactants are nontoxic, renewable, and environmentally benign; and have excellent emulsification and antibacterial properties. Oleic acid‐rich oils have a crucial role as a hydrophobic substrate in the biological production of sophorolipids (SL). The major purpose of this study is to identify a low‐cost oleic acid‐rich hydrophobic substrate that may be used as a secondary carbon source in the synthesis of SL by Starmerella bombicola (S. bombicola). Thus, the biosynthesis of SL was investigated utilizing a variety of edible and nonedible oils rich in oleic acid, which acts as a precursor. Characterization of SL generated from different oils using FT‐IR and NMR indicated the presence of both lactonic and acidic SL. SL production was greatest with secondary carbon sources, with 38.9, 27.57, and 19 g/L, respectively, in the order olive oil > sunflower oil > fleshing oil. Surprisingly, the cost analysis for fleshing oil synthesis indicated that it was the lowest at 0.43 INR/g, followed by sunflower oil at 0.52 INR/g and olive oil at 1.71 INR/g. Our findings indicate that fleshing oil is a potential secondary carbon source with significant SL yield as well as environmental and economic benefits.
A Framework for Algae Modeling in Regulatory Risk Assessment
Authors: Rendal Cecilie , Witt Johannes , Preuss Thomas G. , Ashauer Roman
Published: May 2023

The use of toxicokinetic–toxicodynamic (TKTD) modeling in regulatory risk assessment of plant protection products is increasingly popular, especially since the 2018 European Food Safety Authority (EFSA) opinion on TKTD modeling announced that several established models are ready for use in risk assessment. With careful adherence to the guidelines laid out by EFSA, we present a stepwise approach to validation and use of the Simple Algae Model Extended (SAM-X) for regulatory submission in Tier 2C. We demonstrate how the use of moving time windows across time-variable exposure profiles can generate thousands of virtual laboratory mimic simulations that seamlessly predict the effects of time-variable exposures across a full exposure profile while maintaining the laboratory conditions of the standard Organisation for Economic Co-operation and Development (OECD) growth inhibition test. Thus, every virtual laboratory test has a duration of 72 h, with OECD medium and constant light and temperature conditions. The only deviation from the standard test setup is the replacement of constant exposure conditions for time-variable concentrations. The present study demonstrates that for simulation of 72-h toxicity tests, the nutrient dynamics in the SAM-X model are not required, and we propose the alternative use of a simplified model version. For risk assessment, in accordance with the EFSA guidelines we use a median exposure profile of 10 as a threshold, meaning that if a time window within the exposure profile causes 50% growth inhibition when magnified by a factor of 10, the threshold will have been exceeded. We present a simplified example for chlorotoluron and isoproturon. The present case study brings to life our proposed framework for TKTD modeling of algae to establish whether a given exposure can be considered to be of low risk. Environ Toxicol Chem 2023;42:1823–1838. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Jump Power Predicts Fracture Risk in Older Adults Independent of Sarcopenia and FRAX
Authors: Hong Namki , Burm Seung Won , Kim Hyeon Chang , Kim Chang Oh , Rhee Yumie
Published: May 2023

Low countermovement jump power is associated with prevalent fracture, osteoporosis, and sarcopenia in older adults. However, whether jump power predicts incident fracture risk remains uninvestigated. Data of 1366 older adults in a prospective community cohort were analyzed. Jump power was measured using a computerized ground force plate system. Fracture events were ascertained by follow‐up interview and linkage to the national claim database (median follow‐up 6.4 years). Participants were divided into normal and low jump power groups using a predetermined threshold (women <19.0 W/kg; men <23.8 W/kg; or unable to jump). Among the study participants (mean age 71.6 years, women 66.3%), low jump power was associated with a higher risk of fracture (hazard ratio [HR] = 2.16 versus normal jump power, p < 0.001), which remained robust (adjusted HR = 1.45, p = 0.035) after adjustment for fracture risk assessment tool (FRAX) major osteoporotic fracture (MOF) probability with bone mineral density (BMD) and Asian Working Group for Sarcopenia (AWGS) 2019 sarcopenia definition. In the AWGS no sarcopenia group, participants with low jump power had a significantly higher risk of fracture than those with normal jump power (12.5% versus 6.7%; HR = 1.93, p = 0.013), comparable to that of possible sarcopenia without low jump power (12.0%). Possible sarcopenia group with low jump power had a similar risk of fracture (19.3%) to sarcopenia group (20.8%). When the definition of sarcopenia was modified with jump power measurement (step‐up approach: no sarcopenia to possible sarcopenia; possible sarcopenia to sarcopenia when low jump power present), jump power–modified sarcopenia improved sensitivity (18%–39.3%) to classify individuals who sustained MOF during follow‐up to high risk compared with AWGS 2019 sarcopenia, while maintaining positive predictive value (22.3%–20.6%). In summary, jump power predicted fracture risk in community‐dwelling older adults independently of sarcopenia and FRAX MOF probabilities, suggesting potential contribution of complex motor function measurement in fracture risk assessment. © 2023 American Society for Bone and Mineral Research (ASBMR).
Selinexor: Targeting a novel pathway in multiple myeloma
Authors: Mo Clifton C. , Yee Andrew J. , Midha Shonali , Hartley‐Brown Monique A. , Nadeem Omar , O'Donnell Elizabeth K. , Bianchi Giada , Sperling Adam S. , Laubach Jacob P. , Richardson Paul G.
Published: May 2023

Selinexor is an orally bioavailable selective inhibitor of nuclear export compound that inhibits exportin‐1 (XPO1), a novel therapeutic target that is overexpressed in multiple myeloma (MM) and is responsible for the transport of ∼220 nuclear proteins to the cytoplasm, including tumour suppressor proteins. Inhibition of this process has demonstrated substantial antimyeloma activity in preclinical studies, both alone and in combination with established MM therapeutics. Based on a clinical trial programme encompassing multiple combination regimens, selinexor‐based therapy has been approved for the treatment of relapsed/refractory MM (RRMM), with selinexor‐dexamethasone approved in the later‐relapse setting for penta‐refractory patients and selinexor‐bortezomib‐dexamethasone approved for patients who have received ≥1 prior therapy. Here, we provide a comprehensive review of the clinical data on selinexor‐based regimens, including recent updates from the 2022 American Society of Hematology annual meeting, and summarise ongoing studies of this novel targeted agent in newly diagnosed MM and RRMM.
Reception of experimental pedagogy and psychology in Chile. Analysis of the intellectual influences of Wilhelm Mann, 1904–1915
Authors: Millán Juan David , Salas Gonzalo
Published: May 2023

This article provides a detailed analysis of the intellectual research project of Wilhelm Mann, one of the pioneers of experimental and educational psychology in Chile. Mann's work has been the object of so little analysis that his intellectual influences and networks are not clearly known. We analyzed 338 intratext citations from 22 works by Wilhelm Mann published during the period 1904–1915. As a result, we obtained a mapping of his cooperation networks and used a quantitative approach to study the authors who most influenced his career, among whom were William Stern, Herbert Spencer, Wilhelm Wundt, Alfred Binet, and Ernst Meumann. Mann was closely connected to the international and contemporary advances and discussions of his time, despite the lack of infrastructure and difficulties in communication. Mann was the first psychologist to develop a long‐term project in Chile that aimed to measure the individualities of Chilean students and their intellectual development.
Amidate ion‐mediated intramolecular ring transformation of 2‐pyrones to 2‐pyridones
Authors: Kumar Rajan , Kumari Neha , Kaur Harpreet , Bal Chandralata , Sharon Ashoke
Published: May 2023

Herein, we report a new and cost‐effective methodology for synthesizing N‐substituted 2‐pyridone‐3‐carboxylic acids (2) from 2‐pyrone‐3‐carboxamides (1) with a good yield at room temperature. The notable feature of this reaction is the promotion of amidate ion formation mediated by NaH to initiate intramolecular ring transformation. In addition to ring transformation, simultaneous decarboxylation and substitution under the metal‐free condition in one pot have been achieved to yield N‐substituted 2‐pyridones (3) from 1.
Multiparametric Quantitative MRI of Peripheral Nerves in the Leg: A Reliability Study
Authors: Chen Yongsheng , Baraz Jacob , Xuan Stephanie Yan , Yang Xue , Castoro Ryan , Xuan Yang , Roth Alison R. , Dortch Richard D. , Li Jun
Published: May 2023

Background

Patients with polyneuropathies typically have demyelination and/or axonal degeneration in peripheral nerves. Currently, there is a lack of imaging biomarkers to track the changes in these pathologies.

Purpose

To develop and evaluate the reliability of a multiparametric quantitative magnetic resonance imaging (qMRI) method of peripheral nerves in the leg.

Study Type

Prospective.

Subjects

Seventeen healthy volunteers (36.2 ± 13.8 years old, 9 males) with 10 of them scanned twice for test–retest.

Field Strength/Sequence

3 T, three‐dimensional gradient echo and diffusion tensor imaging.

Assessment

A qMRI protocol and processing pipeline was established for quantifying the following nerve parameters that are sensitive to myelin and axonal pathologies: magnetization transfer (MT) ratio (MTR), MT saturation index (MTsat), T2*, T1, proton density (PD), fractional anisotropy (FA), and mean/axial/radial diffusivities (MD, AD, and RD). The qMRI protocol also measures the volume of nerve fascicles (fVOL) and the fat fraction (FF) of muscles.

Statistical Tests

The intersession reproducibility and inter‐rater reliability of each qMRI parameter were assessed by Bland–Altman analysis and intraclass correlation coefficient (ICC). Pairwise Pearson correlation analyses were performed to investigate the intrinsic association between qMRI parameters. Distal‐to‐proximal variations were evaluated by paired t‐tests with Bonferroni‐Holm multiple comparison corrections. P < 0.05 was considered statistically significant.

Results

The MTR, MTsat, T2*, T1, PD, FA, AD, and fVOL of the sciatic and tibial nerves, and the FF of leg muscles, had an overall good‐to‐excellent test–retest agreement (ICC varying from 0.78 to 0.99). All the qMRI parameters had good‐to‐excellent inter‐rater reliability (ICC > 0.80). The data demonstrated a pattern of distal‐to‐proximal changes of an increased nerve MTsat and FA, and a decreased nerve T1, PD, MD, and RD, as well as a significantly increased muscle FF.

Data Conclusion

The proposed multiparametric qMRI method of the peripheral nerves is highly reproducible and provided healthy control data which will be used in developing monitoring biomarkers in patients with polyneuropathies.

Level of Evidence

1

Technical Efficacy

Stage 2
The merit of the North Sea‐Caspian pattern in explaining climate variability in the Euro‐Mediterranean region
Authors: Çağlar Ferat , Yetemen Omer , Chun Kwok Pan , Sen Omer Lutfi
Published: May 2023

Teleconnection patterns are one of the key features to understanding high‐frequency natural climate variability. The North Sea‐Caspian Pattern (NCP) was identified as a middle tropospheric dipole and its hydroclimatological implications have been substantially restricted to the Eastern Mediterranean region. Thus, the hydroclimatological influences of the NCP in the Euro‐Mediterranean region were investigated via a comparative approach with dominant tropospheric teleconnections in the Eurasian region and synoptic features such as ridge‐trough positioning and strength. By using high‐resolution ERA5 reanalysis data, cross‐correlations between indexes, anticorrelations at 500 hPa and composite anomaly maps for seasonally representative months were produced to understand the working mechanism of the NCP. Comparisons included the East Atlantic/Western Russian (EAWR) pattern, a rotated principal component analysis (RPCA) variant of NCP which utilizes pole‐based representation. Analysis revealed that the NCP was correlated well with the Mediterranean trough displacement and with the strength of the East Asian trough. Climate anomalies indicated by the NCP were greater and more spatially consistent compared to other teleconnections. The NCP also showed higher contrasts of temperature and precipitation than the EAWR based on the composite anomaly maps. In conclusion, the NCP explained climate variability in all seasons linking remote centres of action within Eurasia's east and west extremes.
Managerial competencies: A comparative study of US‐India employer's needs
Authors: Agnihotri Amit , Misra Rajnish Kumar
Published: May 2023

COVID‐19 pandemic brought novel challenges for society and businesses. Along with psychological impact on humans, COVID‐19 led to significant changes in business processes. Managerial competencies, which positively impact performance of both the employees and businesses, are influenced by changing social and business context. In this milieu, there is a call for research to understand the impact of recent changes on managerial competencies to make them future‐ready. Further, in light of prior studies that present opposing findings, a related question worth exploring is—does the importance of managerial competencies differ across countries? By answering these questions, key competencies, that can boost both employee performance and business profitability, can be assessed and nurtured for a positive global impact.

This paper presents theoretical background, methodology, findings and implications from a two‐part study that was conducted to answer above questions. Phase 1, which included literature review, analysis of US Government's O*NET database and expert validation, yielded a unique 9 × 51 Managerial Competencies Framework. Using quantitative methodology, that involved primary survey of Indian experts and hypothesis testing on matching data‐sets, Phase 2 of this cross‐country study reports a broad agreement amongst US and Indian experts on the importance of key managerial competencies. Study offers many theoretical and practical implications, along with directions for future research.
Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study
Authors: Howell Rebecca , Johnson Christopher , Allen Jacqui , Altaye Mekibib , Amin Milan , Bayan Semirra , Belafsky Peter , Cervenka Brian , Desilva Brad , Dion Gregory R. , Ekbom Dale , Friedman Aaron , Fritz Mark , Giliberto John Paul , Guardiani Elizabeth , Kasperbauer Jan , Kim Brandon , Krekeler Brittany N. , Kuhn Maggie , Kwak Paul , Ma Yue , Madden Lyndsay L. , Matrka Laura , Mayerhoff Ross , McKeon Mallory , Piraka Cyrus , Rosen Clark A. , Tabangin Meredith , Wahab Shaun A. , Wilson Keith , Wright Carter , Young VyVy N. , Postma Gregory ,   Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative
Published: May 2023

Objective

To compare improvement in patient‐reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD).

Methodology

Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10‐item Eating Assessment Tool (EAT‐10) pre‐ and post‐procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t‐test, Wilcoxon rank sum test or chi‐square test, as appropriate.

Results

One hundred and forty‐seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT‐10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT‐10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow‐up was 86 and 97.5 days, respectively.

Conclusion

Both endoscopic and open surgical management of ZD provide significant improvement in patient‐reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group.

Level of Evidence

3 Laryngoscope, 134:97–102, 2024
Development of a new multiplex quantitative PCR for the detection of Glaesserella parasuis, Mycoplasma hyorhinis, and Mycoplasma hyosynoviae
Authors: Scherrer Simone , Schmitt Sarah , Rademacher Fenja , Kuhnert Peter , Ghielmetti Giovanni , Peterhans Sophie , Stephan Roger
Published: May 2023

Glaesserella parasuis, Mycoplasma hyorhinis, and Mycoplasma hyosynoviae are important porcine pathogens responsible for polyserositis, polyarthritis, meningitis, pneumonia, and septicemia causing significant economic losses in the swine industry. A new multiplex quantitative polymerase chain reaction (qPCR) was designed on one hand for the detection of G. parasuis and the virulence marker vtaA to distinguish between highly virulent and non‐virulent strains. On the other hand, fluorescent probes were established for the detection and identification of both M. hyorhinis and M. hyosynoviae targeting 16S ribosomal RNA genes. The development of the qPCR was based on reference strains of 15 known serovars of G. parasuis, as well as on the type strains M. hyorhinis ATCC 17981T and M. hyosynoviae NCTC 10167T. The new qPCR was further evaluated using 21 G. parasuis, 26 M. hyorhinis, and 3 M. hyosynoviae field isolates. Moreover, a pilot study including different clinical specimens of 42 diseased pigs was performed. The specificity of the assay was 100% without cross‐reactivity or detection of other bacterial swine pathogens. The sensitivity of the new qPCR was demonstrated to be between 11–180 genome equivalents (GE) of DNA for M. hyosynoviae and M. hyorhinis, and 140–1200 GE for G. parasuis and vtaA. The cut‐off threshold cycle was found to be at 35. The developed sensitive and specific qPCR assay has the potential to become a useful molecular tool, which could be implemented in veterinary diagnostic laboratories for the detection and identification of G. parasuis, its virulence marker vtaA, M. hyorhinis, and M. hyosynoviae.
SUMO1 degrader induces ER stress and ROS accumulation through deSUMOylation of TCF4 and inhibition of its transcription of StarD7 in colon cancer
Authors: Zhao Yin Quan , Jin Hong Ri , Kim Daeho , Jung Sung Han , Liu Sheng , Wan Jun , Lo Ho‐Yin , Fu Xue Qi , Wang Quan , Hao Chunhai , Bellail Anita C.
Published: May 2023

Small molecule degraders of small ubiquitin‐related modifier 1 (SUMO1) induce SUMO1 degradation in colon cancer cells and inhibits the cancer cell growth; however, it is unclear how SUMO1 degradation leads to the anticancer activity of the degraders. Genome‐wide CRISPR‐Cas9 knockout screen has identified StAR‐related lipid transfer domain containing 7 (StarD7) as a critical gene for the degrader's anticancer activity. Here, we show that both StarD7 mRNA and protein are overexpressed in human colon cancer and its knockout significantly reduces colon cancer cell growth and xenograft progression. The treatment with the SUMO1 degrader lead compound HB007 reduces StarD7 mRNA and protein levels and increases endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production in colon cancer cells and three‐dimensional (3D) organoids. The study further provides a novel mechanism of the compound anticancer activity that SUMO1 degrader‐induced decrease of StarD7 occur through degradation of SUMO1, deSUMOylation and degradation of T cell‐specific transcription 4 (TCF4) and thereby inhibition of its transcription of StarD7 in colon cancer cells, 3D organoids and patient‐derived xenografts (PDX).
Development of a mid‐infrared early fire detection system based on dual optical path nonresonant photoacoustic cell
Authors: Lu Yang , Li Yafei , Song Fang , Zhang Yu , Li Xiuying , Zheng Chuantao , Wang Yiding
Published: May 2023

A mid‐infrared carbon dioxide (CO2) sensor system was developed for early fire detection based on photoacoustic spectroscopy. A miniaturized nonresonant photoacoustic gas cell was optimized by means of finite element method (FEM). A cylindrical cell was optimized with a radius of 12.7 mm and a length of 32 mm. An approximately proportional relationship between the optical path length and the amplitude of the photoacoustic signal was observed by theoretical analysis. The optimal modulation frequency was determined to be 44 Hz. A dual optical path was adopted to gain a low limit of detection (LoD) and a high sensitivity. The amplitude of the photoacoustic signal was increased by 1.8 times compared to single optical path. The LoD of the sensor system was measured to be 4.1 ppmv at an averaging time of 84 s.
Thermoporoelastic response of a semi‐permeable wellbore subjected to convective cooling and non‐hydrostatic in situ stresses
Authors: Fan Zhiqiang , Zhang Chongyuan , Wang Dayong , Li Shiyang , Zhao Jiamin , Wu Ziyan
Published: May 2023

Existing models of wellbore stability idealize the borehole wall as either a perfectly permeable or an entirely impermeable surface. The widespread observation that a shale borehole allows solvent molecules to pass through but impedes solutes suggests that the borehole wall should be regarded as a non‐ideal semi‐permeable medium. To address the magnitude and rate of fluid penetration into the formation when a semi‐permeable wellbore is exposed to a non‐isothermal drilling fluid quantitatively, this work develops analytical solutions for a semi‐permeable borehole undergoing convective cooling and far‐field non‐hydrostatic in situ stresses in the framework of fully coupled thermoporoelasticity. Integral transform and load decomposition techniques are employed to facilitate the derivation of analytical solutions. The results show that, in contrast to the permeable or impermeable borehole models, the semi‐permeable model predicts significantly different stress and pore pressure fields. The transient evolution of temperature, pore pressure, and stresses is predominantly governed by two non‐dimensional numbers: the Biot number Bi and a newly identified number πf that characterizes the capability of shale to transport fluid across the solid‐fluid interface.
Urinary flow through urethras with a rough lumen
Authors: Yang Patricia J. , Chen Tony G. , Bracher Sarah B. , Hui Aaron , Hu David L.
Published: May 2023

Aims

This study investigates how lumen roughness and urethral length influence urinary flow speed.

Methods

We used micro‐computed tomography scans to measure the lumen roughness and dimensions for rabbits, cats, and pigs. We designed and fabricated three‐dimensional‐printed urethra mimics of varying roughness and length to perform flow experiments. We also developed a corresponding mathematical model to rationalize the observed flow speed.

Results

We update the previously reported relationship between body mass and urethra length and diameter, now including 41 measurements for urethra length and 10 measurements for diameter. We report the relationship between lumen diameter and roughness as a function of position down the urethra for rabbits, cats, and pigs. The time course of urinary speed from our mimics is reported, as well as the average speed as a function of urethra length.

Conclusions

Based on the behavior of our mimics, we conclude that the lumen roughness in mammals reduces flow speed by up to 25% compared to smooth urethras. Urine flows fastest when the urethra length exceeds 25 times its diameter. Longer urethras do not drain faster due to viscous effects counteracting the additional gravitational head. However, flows with our urethra mimics are still 6 times faster than those observed in nature, suggesting that further work is needed to understand flow resistance in the urethra.
Anthropometric Determinants of Autonomic Control in Obstructive Sleep Apnea: A Large‐Scale Study
Authors: Zhu Yaxin , Liu Yupu , Xu Huajun , Zhao Xiaolong , Li Xinyi , Huang Weijun , Zhang Xiaoman , Zhu Huaming , Qian Di , Yi Hongliang , Guan Jian , Yin Shankai
Published: May 2023

Objective

Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness.

Study Design

Cross‐sectional study.

Setting

Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017.

Methods

Total of 2134 subjects (503 non‐OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5‐minute wakefulness period and analyzed by using time‐domain method and frequency‐domain method. Multiple step‐wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated.

Results

Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (β = −.116, p < .001) and high‐frequency power (β = −.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed.

Conclusion

Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.
Study on durability of transverse shear properties for novel carbon/glass hybrid fiber‐reinforced polymer bars in simulated concrete environments
Authors: Zhang Yu , Gao Danying , Yang Lin , Fang Dong , Pang Yuyang , Gu Zhiqiang
Published: May 2023

Durability on the transverse shear properties of hybrid fiber‐reinforced polymer (HFRP) bar may control the cross‐sectional load‐bearing capacity and failure mode of the HFRP bar reinforced concrete members due to its strength degradation with time. Herein, the degradation of novel carbon/glass (C/G)‐HFRP bars were accelerated in simulated concrete environments at 60°C to investigate the effects of fiber volume fraction and distribution pattern, matrix resin volume fraction, exposure environment, and period on their transverse shear properties. The results displayed that the transverse shear strength of the samples reduced by 15%, 20%, and 8% after exposure to the simulated ordinary concrete, seawater sea‐sand concrete environments, and tap water for 6 months, respectively. The inward diffusion of water molecules and free hydroxyl ions caused the hydrolysis of matrix resin, etching of glass fiber and debonding of fiber/matrix interface, which were the incentives of the degradation of C/G‐HFRP bars. The increase of matrix resin volume fraction and the application of a waterproof coating were recommended to alleviate the degradation of fibrous composites in concrete environments. Finally, two prediction models were proposed to determine the transverse shear strength of HFRP bar before and after exposure to different harsh environments, respectively. The comparisons indicated that the predicted values were coincided with the experimental results.
Construction of a monoclonal antibody against glabridin (2G4) and development of an enzyme‐linked immunosorbent assay
Authors: Krittanai Supaluk , Choonong Rattanathorn , Butdapheng Khunkhang , Jabsanthia Jakkrit , Sakamoto Seiichi , Putalun Waraporn
Published: May 2023

Introduction

Glabridin is a unique isoflavonoid found only in Glycyrrhiza glabra L. The pharmacological effects of glabridin are well established, especially for beauty‐ and wellness‐related uses, such as antioxidant, anti‐inflammatory, ultraviolet (UV) protection, and skin‐lightening effects. Therefore, glabridin is often found in commercial products such as creams, lotions, and dietary supplements.

Objective

This study aimed to develop an enzyme‐linked immunosorbent assay (ELISA) using a glabridin‐specific antibody.

Method

Immunogen conjugation of glabridin‐bovine serum albumin was performed via the Mannich reaction, and the resulting conjugates were injected into BALB/c mice. Subsequently, hybridomas were produced. An ELISA method for glabridin determination was developed and validated.

Result

A highly specific antibody against glabridin was produced using clone 2G4. The assay range for the determination of glabridin was 0.28–7.02 μg/ml, with a detection limit of 0.16 μg/ml. The validation parameters in terms of accuracy and precision met the acceptable criteria. Standard curves of glabridin in various matrices were compared to evaluate the matrix effect on human serum using ELISA. Standard curves of the human serum and water matrix were obtained in the same manner, and the measurement range was 0.41–10.57 μg/ml.

Conclusion

The developed ELISA method was used to quantify glabridin in plant materials and products with high sensitivity and specificity, and has potential applications in quantifying compounds in plant‐derived products and human serum samples.
National markets in a world of global platform giants: The persistence of Russian domestic competitors
Authors: Kontareva Alina , Kenney Martin
Published: May 2023

US platform companies have dominated the global platform economy. Drawing on archival research, interviews, and company reports, we explore the reasons that Russia was able to develop platform companies that survived the entry of US firms. The chaotic post‐Soviet society paradoxically provided a sheltered environment within which domestic companies could build sufficient competence to maintain their domestic market position. As first movers, Russian companies created and leveraged within‐country network effects based on social, cultural, and physical affinities with their user base. This made it difficult for US platforms to overwhelm domestic companies. After 2008, the Russian government's position regarding the internet changed, and it began to selectively shield domestic leaders by preventing acquisitions by foreign companies and requiring the preloading of domestic applications on devices. Our Russian case study is instructive for other countries that want to remain open but, at the same time, build domestic platform companies.
Safe prescribing for refugees and asylum seekers
Authors: Rowlands Sophie
Published: May 2023

Prescribing safely for refugees and asylum seekers presents a unique set of challenges. This article discusses some of the issues that need to be addressed, including removing barriers to medicine access and ensuring continuity of care, and outlines the work of the Refugee and Asylum Seeker Service at the Alliance for Better Care.
Summary of the third annual HQIP CVDPREVENT audit report
Authors: Chaplin Steve
Published: May 2023

The Healthcare Quality Improvement Partnership (HQIP) CVDPREVENT audit was set up to monitor and support improvements in cardiovascular disease prevention in primary care in England. This article summarises the findings of its third annual audit report, which includes data up to March 2022.
Achieving sustainable development through economic growth, energy consumption, and agricultural productivity in China
Authors: Xia Ruoxuan , Long Zhuoming , Xing Licong , Khan Yousaf Ali
Published: May 2023

Large amount of carbon emission is the main hazard to environment and human health. The aim of this research is to investigate the impact of economic growth, forest zone, agricultural productivity, and energy consumption on environmental pollution in China using time series data from 1980 to 2020. The underline research utilized dynamic ordinary least‐squares (DOLS) method, Johansen and Engle–Granger cointegration tests, and the autoregressive‐distributed lag (ARDL) technique to analyze the varying data set. To compare findings, fully modified ordinary least squares (FMOLS) and canonical cointegrating regression (CCR) estimators are estimated. Energy use and population raise CO2 emissions with 1% economic development. Long‐term CO2 emissions may be reduced by 1% agriculture production and forestry zone growth. The Granger causality test showed causation between all variables. Results reveal that China might achieve sustainable development goals by cutting down CO2 emissions and mitigate global climate change. The underline research presents policy recommendations for attaining environmental sustainability in China through green investment by reducing carbon emissions. These policies highlight promoting use of renewable energy, financing green technological progression in agricultural productivity, and the ecological feasibility of China's forests.
Textures of value: Tactility, experience, and exclusion in the cashmere commodity chain
Authors: Graber Kathryn E.
Published: May 2023

Cashmere provides an ideal material for examining how humans co‐opt tangible and intangible qualities into their ascription of value. The fiber's relative worth lies at the intersection of its tangible qualities (e.g., softness, lightness, strength) and intangible qualities (e.g., rarity, history, authenticity, sustainability). Mediating the relationship between those qualities are actors with very different stakes: the families of Mongolian herders who comb goats together each spring, the brokers and buyers who weigh it and feel it to adjudicate it for fashion houses, and the advertisers and marketers who decide what is desirable in global markets of end consumers. This article examines three nodes in the production and circulation of Mongolian cashmere to show how different forms of value—economic, social, linguistic, moral—accrue to material goods and travel, or not, from one context to another. I focus on interactions as moments of qualic evaluation. Here embodied, tactile experiences of qualia—which might seem to be immune to perceptual difference and “outside culture”—in fact differ. The example shows how valuation in a transnational commodity chain depends on both exploiting semiotic gaps in the chain and nonetheless meeting a threshold of commensurability, neither of which is divorceable from physicality.
The robustness of reinforced concrete tied arch bridges: A case study
Authors: Formisano Antonio , Felitti Matteo , Oliveto Francesco , Mendicino Lorenzo
Published: May 2023

The robustness of a structural systems is understood as their ability to prevent or reduce the consequences of a local (exceptional and/or extreme) event. The current work aims to address the issues related to the evaluation of robustness of structures with incorporated damage. The case study of an existing reinforced concrete arch bridge is investigated in terms of robustness considering the variation of both the cracking state from concrete spalling and the corrosion of reinforcement bars. The damage variation related to these different matters is assessed both in terms of intensity and occurrence in the various structural elements of the bridge. Finally, the structural robustness index is estimated through push‐down analysis to make an overall assessment of the bridge behavior.
Metakaolin‐based geopolymer concretes for nuclear protection: On the perspective of physicochemical, durability, and microstructure
Authors: Bayrak Barış , Kaplan Gökhan , Öz Ali , Kavaz Esra , Çelebi Oğuzhan , Alcan Haluk Görkem , Mohabbi Mehrzad , Aydın Abdulkadir Cüneyt
Published: May 2023

As a striking contribution of metakaolin to geopolymer concretes, the varying contents of metakaolin with quartz powder are included the mixtures with ground granulated blast furnace slag, and quartz sand to observe the mechanical, physical, transport, microstructure, and nuclear protection parameters of the samples, within this study. The geopolymer concrete samples are tested for the mechanical transport and physical properties depending on the curing time, curing temperature, and the raw/by‐product material type. The results show that the samples containing the most metakaolin performed well with a 24‐h compressive strength of 131.78 MPa. Increasing the curing temperature and curing time affected both mechanical, physical and transport properties. In addition, the microstructure of the samples was analyzed by scanning electron microscopy, x‐ray diffraction, and Fourier transform infrared spectroscopy. Moreover, the effect of increasing metakaolin reinforcement on the nuclear protection capacity of the produced geopolymer concretes with experimental gamma transmission and neutron dose measurements was investigated. The M3 sample with high content of both metakaolin and granulated blast‐furnace slag showed the highest resistance to gamma photons in the energy range of 0.081–0.383 MeV. The produced geopolymer samples absorbed almost 40% of the fast neutrons with 4.5 MeV energy. Neutron removal cross sections of the produced geopolymer concretes are in the range of 0.0952–0.0949 cm−1 and are larger than those of B4C, graphite, and boric acid. The findings of this study revealed that the addition of metakaolin improved the mechanical, nuclear shielding and structural properties of geopolymer concretes.
Arch Action Model for the structural assessment of existing prestressed concrete bridges
Authors: Gleich Philipp , Maurer Reinhard
Published: May 2023

Structural assessments of existing older prestressed concrete bridges according to the currently applicable standards and guidelines in Germany generally reveal significant deficiencies in shear reinforcement. Large‐scale tests within the scope of research activities commissioned by the Federal Highway Research Institute (BASt) were carried out at TU Dortmund University to analyze the shear load‐bearing behavior of continuous prestressed concrete beams in more detail. The Arch Action Model (AAM) was derived from the Simplified Arch Action Model (SAAM) to provide a possible analysis method for determining shear contribution from concrete. Thus, the shear capacity of prestressed beams can be determined in a more realistic manner than using the truss model underlying the current state of standardization. The paper at hand provides information and explanations about the SAAM and AAM with regard to their application to real‐world structures for structural bridge assessments.