bluuebunny/crossref_metadata_2025 huggingface dataset:
Equity for Children in the United States
Authors: Meek Shantel , Catherine Evandra , Boykin Xigrid Soto- , Blevins Darielle
Published: April 2024

All children deserve access to the conditions and opportunities needed to thrive, including unbiased accessible healthcare and high-quality learning opportunities; safe, toxin-free communities and stable housing; access to nutritious meals; and secure, warm, available, and loving caregivers. Historic and contemporary injustices in US society have created inequities in opportunity and access to resources for Black, Latine, Asian, American Indian and Alaska Native, and other children of color, children with disabilities, children in poverty, and other marginalized children; these have contributed to stark disparities across child development outcomes. This Element overviews inequities in economic, educational, and health systems through historical and contemporary perspectives and describes how these inequities impact children and families. Solutions to address these inequities are considered for a fairer US society, starting with its youngest residents, where all families have what they need to thrive. This title is also available as Open Access on Cambridge Core.
A Convergence Science Approach to Understanding the Changing Arctic
Authors: Ivanov Valeriy Y. , Ungar Peter S. , Ziker John P. , Abdulmanova Svetlana , Celis Gerardo , Dixon Andrew , Ehrich Dorothee , Fufachev Ivan , Gilg Olivier , Heskel Mary , Liu Desheng , Macias‐Fauria Marc , Mazepa Valeriy , Mertens Karl , Orekhov Pavel , Peterson Alexandria , Pokrovskaya Olga , Sheshukov Aleksey , Sokolov Aleksandr , Sokolova Natalia , Spiegel Marcus , Sponheimer Matt , Stammler Florian , Taylor Tyeen , Terekhina Alexandra , Valdayskikh Victor , Volkovitskiy Alexander , Wang Jingfeng , Zhou Wenbo
Published: April 2024

Science, engineering, and society increasingly require integrative thinking about emerging problems in complex systems, a notion referred to as convergence science. Due to the concurrent pressures of two main stressors—rapid climate change and industrialization, Arctic research demands such a paradigm of scientific inquiry. This perspective represents a synthesis of a vision for its application in Arctic system studies, developed by a group of disciplinary experts consisting of social and earth system scientists, ecologists, and engineers. Our objective is to demonstrate how convergence research questions can be developed via a holistic view of system interactions that are then parsed into material links and concrete inquiries of disciplinary and interdisciplinary nature. We illustrate the application of the convergence science paradigm to several forms of Arctic stressors using the Yamal Peninsula of the Russian Arctic as a representative natural laboratory with a biogeographic gradient from the forest‐tundra ecotone to the high Arctic.
Phenology of Photosynthesis in Winter‐Dormant Temperate and Boreal Forests: Long‐Term Observations From Flux Towers and Quantitative Evaluation of Phenology Models
Authors: Bowling David R. , Schädel Christina , Smith Kenneth R. , Richardson Andrew D. , Bahn Michael , Arain M. Altaf , Varlagin Andrej , Ouimette Andrew P. , Frank John M. , Barr Alan G. , Mammarella Ivan , Šigut Ladislav , Foord Vanessa , Burns Sean P. , Montagnani Leonardo , Litvak Marcy E. , Munger J. William , Ikawa Hiroki , Hollinger David Y. , Blanken Peter D. , Ueyama Masahito , Matteucci Giorgio , Bernhofer Christian , Bohrer Gil , Iwata Hiroki , Ibrom Andreas , Pilegaard Kim , Spittlehouse David L. , Kobayashi Hideki , Desai Ankur R. , Staebler Ralf M. , Black T. Andrew
Published: April 2024

We examined the seasonality of photosynthesis in 46 evergreen needleleaf (evergreen needleleaf forests (ENF)) and deciduous broadleaf (deciduous broadleaf forests (DBF)) forests across North America and Eurasia. We quantified the onset and end (StartGPP and EndGPP) of photosynthesis in spring and autumn based on the response of net ecosystem exchange of CO2 to sunlight. To test the hypothesis that snowmelt is required for photosynthesis to begin, these were compared with end of snowmelt derived from soil temperature. ENF forests achieved 10% of summer photosynthetic capacity ∼3 weeks before end of snowmelt, while DBF forests achieved that capacity ∼4 weeks afterward. DBF forests increased photosynthetic capacity in spring faster (1.95% d−1) than ENF (1.10% d−1), and their active season length (EndGPP–StartGPP) was ∼50 days shorter. We hypothesized that warming has influenced timing of the photosynthesis season. We found minimal evidence for long‐term change in StartGPP, EndGPP, or air temperature, but their interannual anomalies were significantly correlated. Warmer weather was associated with earlier StartGPP (1.3–2.5 days °C−1) or later EndGPP (1.5–1.8 days °C−1, depending on forest type and month). Finally, we tested whether existing phenological models could predict StartGPP and EndGPP. For ENF forests, air temperature‐ and daylength‐based models provided best predictions for StartGPP, while a chilling‐degree‐day model was best for EndGPP. The root mean square errors (RMSE) between predicted and observed StartGPP and EndGPP were 11.7 and 11.3 days, respectively. For DBF forests, temperature‐ and daylength‐based models yielded the best results (RMSE 6.3 and 10.5 days).
Revisiting the Ionospheric Disturbances Over Low Latitude Region of China During Super Typhoon Hato
Authors: Li Ke , Zhang Donghe , Zeng Yi , Tian Yaoyu , Dai Guofeng , Liu Zhizhao , Yang Guanglin , Sun Shuji , Li Guozhu , Hao Yongqiang , Xiao Zuo
Published: April 2024

The ionosphere exhibits complex variations due to the influences from above and below. To distinguish the source of ionospheric disturbances is important for understanding the variation process and the coupling mechanism among different regions. Using the ionospheric total electron content (TEC) derived from Global Navigation Satellite System observations, the ionospheric disturbances during the super typhoon Hato in 2017 that was accompanied by a weak geomagnetic storm are revisited, including the ionospheric deviation and traveling ionospheric disturbances (TIDs). It is found that the ionospheric TEC in the low‐latitude region of China experienced a significant enhancement (200% compared to the quiet geomagnetic day) on Hato landing day. This enhancement covers the northern and southern equatorial ionization anomaly (EIA) region from 80°E to 180°E. Considering the geomagnetic condition, the hmF2 and the O/N2 ratio in thermosphere, it is concluded that this enhancement is not related to the typhoon, but to the coinciding weak geomagnetic storm. Additionally, several medium‐scale TIDs are verified from differential TEC data in China low latitude region during Hato period. Most of them occur after sunset and their propagating direction is southwest that often occur in East‐Asian sector in summer months, which are not related to the typhoon. While a few TIDs with concentric wavefront (Concentric TIDs) are also observed on the day before Hato landfall that should be excited in the deep convective region of the typhoon. Because the ionosphere is affected by disturbances both from above and below, it should be careful to determine the source of the ionospheric disturbances.
Multi‐Segment Earthquake Clustering as Inferred From 36Cl Exposure Dating, the Bet Kerem Fault System, Northern Israel
Authors: Dawood R. , Matmon A. , Benedetti L. ,   ASTER Team, Siman‐Tov S.
Published: April 2024

Recovering the seismic history of multiple segments within a fault system provides a spatiotemporal framework for the fault activity across the system. This kind of data is essential for improving our understanding of how faults interact during earthquake cycles and how they are distributed within a fault system. Bedrock fault scarps, reaching up to 10‐m height, are abundant across the Bet Kerem fault system, Galilee, northern Israel. Using the 36Cl exposure dating method, we recovered the last 30 ka scarp exhumation history of three fault segments from the Bet Kerem fault system. Results indicate that the three faults were active simultaneously in at least three distinguished activity periods, during which a minimum of 1.2 m of surface rupturing occurred in each period. The synchronized activity and total surface rupture at each activity period suggest that the three dated segments were ruptured simultaneously by the same earthquake. That is, a multi‐segment rupture earthquake and that each activity period included a cluster of at least two large multi‐segment earthquakes. The results also indicate a recurrence interval between clusters of 3.5–4.5 ka and the existence of a seismic super cycle with a recurrence interval of about 13 ka.
SWOL2023: Report of Space Weather Observations Throughout Latinoamerica: Filling the Southern Gaps
Authors: Natali M. Paula , Meza Amalia M. , Robinson Robert , Janches Diego , Berger Thomas , Dasso Sergio , De Nardin Clezio , Colazo Marcelo
Published: April 2024

The “Space Weather Observations throughout Latinoamerica: Filling the Southern gaps” Workshop took place in Ushuaia, Argentina, from 2 to 4 October 2023. This event was exclusively dedicated to Space Weather (SWx), gathering leading international academic and governmental agencies focused on the subject. The meeting addressed the field of SWx from three perspectives: driving phenomena occurring in the solar atmosphere, evolution in the interplanetary environment, and interaction with the Earth. In addition, emphasis was placed on identifying key research directions in solar and space physics that warrant development in Argentina and across the region in the forthcoming years. The workshop also focused on the current observational infrastructure that supports SWx studies, and how to improve and develop it through strategic international partnerships, stressing on the need for real‐time data. The conference fostered discussion among different partners involved in SWx studies, that is, researchers and potential space weather service providers, and the need to include in this debate potential users of space weather services.
The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma—a randomized, open-label phase III trial of the European mantle cell lymphoma network
Authors: Fischer Luca , Jiang Linmiao , Dürig Jan , Schmidt Christian , Stilgenbauer Stephan , Bouabdallah Krimo , Solal-Celigny Philippe , Scholz Christian W. , Feugier Pierre , de Wit Maike , Trappe Ralf Ulrich , Hallek Michael , Graeven Ullrich , Hänel Mathias , Hoffmann Martin , Delwail Vincent , Macro Margaret , Greiner Jochen , Giagounidis Aristoteles A. N. , Dargel Beate , Durot Eric , Foussard Charles , Silkenstedt Elisabeth , Weigert Oliver , Pott Christiane , Klapper Wolfram , Hiddemann Wolfgang , Unterhalt Michael , Hoster Eva , Ribrag Vincent , Dreyling Martin
Published: April 2024

The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47–1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29–0.79) and without previous ASCT (aHR 0.52, 0.28–0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.
Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1
Authors: Li Xian , Xu Mengxin , Yang Jingyi , Zhou Li , Liu Lin , Li Min , Wang Shasha , Liu Mei-Qin , Huang Zhixiang , Zhang Zhen , Liu Shuning , Hu Yunqi , Lin Haofeng , Liu Bowen , Sun Ying , Wu Qingguo , Shi Zheng-Li , Lan Ke , Chen Yu , Yan Huimin , Chen Yao-Qing
Published: April 2024

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.
The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms
Authors: Chang Chao-Hui , Liu Feng , Militi Stefania , Hester Svenja , Nibhani Reshma , Deng Siwei , Dunford James , Rendek Aniko , Soonawalla Zahir , Fischer Roman , Oppermann Udo , Pauklin Siim
Published: April 2024

The lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways and cell-autonomous transcriptional machinery orchestrate the stem cell-like characteristics of CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins of CSCs in pancreatic cancer. We uncover that the cell-autonomous E2F1/4-pRb/RBL2 axis balances non-cell-autonomous signalling in healthy ductal cells but becomes deregulated upon KRAS mutation. E2F1 and E2F4 induce whereas pRb/RBL2 reduce WNT ligand expression (e.g. WNT7A, WNT7B, WNT10A, WNT4) thereby regulating self-renewal, chemoresistance and invasiveness of CSCs in both PDAC and breast cancer, and fibroblast proliferation. Screening for epigenetic enzymes identifies GCN5 as a regulator of CSCs that deposits H3K9ac onto WNT promoters and enhancers. Collectively, paracrine signalling pathways are controlled by the E2F-GCN5-RB axis in diverse cancers and this could be a therapeutic target for eliminating CSCs.
Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform
Authors: Esmaeili Anvar Nazanin , Lin Chenchu , Ma Xingdi , Wilson Lori L. , Steger Ryan , Sangree Annabel K. , Colic Medina , Wang Sidney H. , Doench John G. , Hart Traver
Published: April 2024

Genetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale. Here, we identify background-independent paralog synthetic lethals from previous CRISPR genetic interaction screens, and find that the Cas12a platform provides superior sensitivity and assay replicability. We develop the in4mer Cas12a platform that uses arrays of four independent guide RNAs targeting the same or different genes. We construct a genome-scale library, Inzolia, that is ~30% smaller than a typical CRISPR/Cas9 library while also targeting ~4000 paralog pairs. Screens in cancer cells demonstrate discrimination of core and context-dependent essential genes similar to that of CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes. Importantly, the in4mer platform offers a fivefold reduction in library size compared to other genetic interaction methods, substantially reducing the cost and effort required for these assays.
Revealing hidden spin polarization in centrosymmetric van der Waals materials on ultrafast timescales
Authors: Arnoldi B. , Zachritz S. L. , Hedwig S. , Aeschlimann M. , Monti O. L. A. , Stadtmüller B.
Published: April 2024

One of the key challenges for spintronic and quantum technologies is to achieve active control of the spin angular momentum of electrons in nanoscale materials on ultrafast, femtosecond timescales. While conventional ferromagnetic materials and materials supporting spin texture suffer both from conceptional limitations in miniaturization and inefficiency of optical and electronic manipulation, non-magnetic centrosymmetric layered materials with hidden spin polarization may offer an alternative pathway to manipulate the spin degree of freedom by external stimuli. Here we demonstrate an approach for generating transient spin polarization on a femtosecond timescale in the otherwise spin-unpolarized band structure of the centrosymmetric 2H-stacked group VI transition metal dichalcogenide WSe2. Using ultrafast optical excitation of a fullerene layer grown on top of WSe2, we trigger an ultrafast interlayer electron transfer from the fullerene layer into the WSe2 crystal. The resulting transient charging of the C60/WSe2 interface leads to a substantial interfacial electric field that by means of spin-layer-valley locking ultimately creates ultrafast spin polarization without the need of an external magnetic field. Our findings open a novel pathway for true optical engineering of spin functionalities such as the sub-picosecond generation and manipulation of ultrafast spin currents in 2D heterostructures.
Mechanism of DNA unwinding by MCM8-9 in complex with HROB
Authors: Acharya Ananya , Bret Hélène , Huang Jen-Wei , Mütze Martin , Göse Martin , Kissling Vera Maria , Seidel Ralf , Ciccia Alberto , Guérois Raphaël , Cejka Petr
Published: April 2024

HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.
A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
Authors: Ascheid David , Baumann Magdalena , Pinnecker Jürgen , Friedrich Mike , Szi-Marton Daniel , Medved Cornelia , Bundalo Maja , Ortmann Vanessa , Öztürk Asli , Nandigama Rajender , Hemmen Katherina , Ergün Süleymann , Zernecke Alma , Hirth Matthias , Heinze Katrin G. , Henke Erik
Published: April 2024

Targeting the supportive tumor microenvironment (TME) is an approach of high interest in cancer drug development. However, assessing TME-targeted drug candidates presents a unique set of challenges. We develop a comprehensive screening platform that allows monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumor spheroids (VTSs). The confrontation of four human-derived cell populations makes it possible to recreate and study complex changes in TME composition and cell-cell interaction. The platform is modular and adaptable for tumor entity or genetic manipulation. Treatment effects are recorded by light sheet fluorescence microscopy and translated by an advanced image analysis routine in processable multi-parametric datasets. The system proved to be robust, with strong interassay reliability. We demonstrate the platform’s utility for evaluating TME-targeted antifibrotic and antiangiogenic drugs side-by-side. The platform’s output enabled the differential evaluation of even closely related drug candidates according to projected therapeutic needs.
Association between vitamin C in serum and trouble sleeping based on NHANES 2017–2018
Authors: Wang Shihong , Lai Fengxia , Zhao Le , Zhou Jiyu , Kong Danli , Yu Haibing , Ding Yuanlin
Published: April 2024

Vitamin C is an important micronutrient for human. Association between vitamin C and trouble sleeping was less studied. Therefore, the purpose of this study was to investigate the possible link between vitamin C in serum and trouble sleeping. The cross-sectional data was derived from the National Health and Nutrition Examination Survey (NHANES, 2017–2018). Trouble sleeping was measured by asking participants: “Have you ever told doctor had trouble sleeping”. Responses to this question was “yes” or “no”. vitamin C in serum was obtained by measuring the serum samples. We used multivariable binary logistic regressions to examine the possible link between vitamin C in serum and trouble sleeping, and then a subgroup analysis was performed. Moreover, the non-linear relationship between vitamin C in serum and trouble sleeping was further detected using a restricted cubic spline (RCS) model. A total of 3227 participants were included in the study. After adjusting all potential confounders, the results of multivariable logistic regression showed the significant negative association between vitamin C in serum and trouble sleeping(OR = 0.816; 95% CI:0.669 ~ 0.995). The significant inverse association was also found in female(OR = 0.713; 95% CI:0.546 ~ 0.931), age ≤ 65 years(OR = 0.773; 95% CI:0.600 ~ 0.996), and in participants with high cholesterol level(OR = 0.738; 95% CI:0.548 ~ 0.994). In addition, the RCS model demonstrated the significant non-linear relationship between vitamin C in serum and trouble sleeping (P value of nonlinear = 0.010). Our study demonstrates the significant negative association between vitamin C in serum and trouble sleeping.
Integrating physical experiments with computational fluid dynamics to transform mosque minarets into efficient solar chimneys
Authors: Awad Hesham H. , Desouki Mahmoud
Published: April 2024

This study explores the potential of repurposing mosque minarets as solar chimneys in hot arid regions to facilitate natural ventilation and diminish the reliance on energy-intensive cooling systems. Originating as a means to call the faithful to prayer, minarets have become iconic landmarks within Islamic cities. This research focuses on Cairo, Egypt, as a representative hot arid environment. The paper traces the evolution of the minaret, underscoring the variations in form that influence the experimental design. The investigation proceeded in two stages: the construction of physical mosque models with variably positioned minarets for laboratory testing, ensuring standardized measurements, followed by computational fluid dynamics (CFD) simulations for comparison. Findings indicate that mosque minarets can be effectively adapted for passive ventilation, with their performance significantly influenced by orientation and placement. This study concludes that traditional mosque minarets offer a viable, sustainable option for passive cooling in hot climates.
Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress
Authors: de Oliveira-Júnior Benedito Alves , Marques Danilo Benette , Rossignoli Matheus Teixeira , Prizon Tamiris , Leite João Pereira , Ruggiero Rafael Naime
Published: April 2024

Clinical depression is characterized by multiple concurrent symptoms, manifesting as a complex heterogeneous condition. Although some well-established classical behavioral assessments are widespread in rodent models, it remains uncertain whether rats also display stress-induced depression-related phenotypes in a multidimensional manner, i.e., simultaneous alterations in multiple behavioral tests. Here, we investigated multivariate patterns and profiles of depression-related behavioral traits in male Wistar rats subjected to inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests and ethological characterization. We observed generalized stronger intra-test but weaker inter-test correlations. However, feature clustering of behavioral measures successfully delineated variables linked to resilience and susceptibility to stress. Accordingly, a noteworthy covariation pattern emerged, characterized by increased open field locomotion, reduced time in the elevated plus maze open arms, lower sucrose preference, and increased shuttle box escape failures that consistently differentiated IS from NS. Surprisingly there is little contribution from forced swim. In addition, individual clustering revealed a diversity of behavioral profiles, naturally separating NS and IS, including subpopulations entirely characterized by resilience or susceptibility. In conclusion, our study elucidates intricate relationships among classical depression-related behavioral measures, highlighting multidimensional individual variability. Our work emphasizes the importance of a multivariate framework for behavioral assessment in animal models to understand stress-related neuropsychiatric disorders.
Potential probiotic Lactobacillus delbrueckii subsp. lactis KUMS-Y33 suppresses adipogenesis and promotes osteogenesis in human adipose-derived mesenchymal stem cell
Authors: Goudarzi Farjam , Kiani Amir , Nami Yousef , Shahmohammadi Azin , Mohammadalipour Adel , Karami Afshin , Haghshenas Babak
Published: April 2024

Today, probiotics are considered to be living microorganisms whose consumption has a certain number of beneficial effects on the consumer. The present study aimed to investigate the effect of a new probiotic extract (Lactobacillus delbrueckii subsp. lactis KUMS Y33) on the differentiation process of human adipose-derived stem cells (hADSCs) into adipocytes and osteocytes and, as a result, clarify its role in the prevention and treatment of bone age disease. Several bacteria were isolated from traditional yogurt. They were evaluated to characterize the probiotic’s activity. Then, the isolated hADSCs were treated with the probiotic extract, and then osteogenesis and adipogenesis were induced. To evaluate the differentiation process, oil red O and alizarin red staining, a triglyceride content assay, an alkaline phosphatase (ALP) activity assay, as well as real-time PCR and western blot analysis of osteocyte- and adipocyte-specific genes, were performed. Ultimately, the new strain was sequenced and registered on NBCI. In the probiotic-treated group, the triglyceride content and the gene expression and protein levels of C/EBP-α and PPAR-γ2 (adipocyte-specific markers) were significantly decreased compared to the control group (P < 0.05), indicating an inhibited adipogenesis process. Furthermore, the probiotic extract caused a significant increase in the ALP activity, the expression levels of RUNX2 and osteocalcin, and the protein levels of collagen I and FGF-23 (osteocyte-specific markers) in comparison to the control group (P < 0.05), indicating an enhanced osteogenesis process. According to the results of the present study, the probiotic extract inhibits adipogenesis and significantly increases osteogenesis, suggesting a positive role in the prevention and treatment of osteoporosis and opening a new aspect for future in-vivo study.
Investigating the factors affecting farmers’ intention to adopt contract farming
Authors: Khalili Fatemeh , Choobchian Shahla , Abbasi Enayat
Published: April 2024

Agricultural endeavors, especially in developing nations, entail inherent risks. Amidst challenges related to capital and agricultural marketing, contract farming emerges as a highly effective strategy. It not only facilitates capital accumulation but also ensures consistent product sales, establishes fair pricing, and contributes to the overall balanced development of the agricultural sector. This concern has been a longstanding global consideration, with Iran now addressing it. Recognizing the paramount importance of implementing contemporary agricultural methodologies, including contract farming, this research systematically investigates factors influencing farmers’ intentions in Iran. A survey methodology is employed for systematic information collection from a statistical population of 98,777 farmers in rural Markazi Province, Iran. Using the Karjesi and Morgan table for sample size determination, a representative subset of 383 farmers is selected through stratified random sampling, ensuring proportional assignment within strata. A researcher-made questionnaire, validated by expert panels and confirmed for reliability through Cronbach’s alpha coefficient, serves as the research instrument. Data analysis was conducted using SPSS 27, and structural equation modeling was performed with SmartPLS4. The findings reveal that trust (0.528), awareness (0.332), and attitude (0.168), exert the most substantial causal influence on farmers’ intention to embrace contract farming. Consequently, the research findings offer practical recommendations for the adoption of contract farming, providing valuable insights to policymakers and stakeholders for implementing targeted interventions aimed at boosting farmers’ willingness to participate in contractual agreements.
Genetic polymorphisms and clinical parameters associated with renal toxicity in Thai hematologic malignancy patients receiving high dose methotrexate
Authors: Pitakkitnukun Palada , Pongpitakmetha Thanakit , Suttichet Thitima Benjachat , Sukkummee Warumphon , Chariyavilaskul Pajaree , Polprasert Chantana
Published: April 2024

High-dose methotrexate (HD-MTX) is a widely used chemotherapy regimen for hematologic malignancies such as lymphomas and acute lymphoblastic leukemia, but its use can lead to adverse effects, including acute kidney injury (AKI), impaired liver function, and mucositis, causing extended hospital stays and delayed subsequent chemotherapy. Our study aimed to investigate the predictive factors for renal toxicities associated with HD-MTX in Thai patients undergoing treatment for hematologic malignancies. We enrolled 80 patients who underwent MTX-containing regimens, analyzing 132 chemotherapy cycles. The most common disease was primary central nervous system lymphoma (33%). Genetic polymorphisms were examined using the MassARRAY® system, identifying 42 polymorphisms in 25 genes. Serum creatinine and MTX levels were measured 24 and 48 h after MTX administration. For the primary outcome, we found that the allele A of MTRR rs1801394 was significantly related to renal toxicity (odds ratio 2.084 (1.001–4.301), p-value 0.047). Patients who exceeded the MTX threshold levels at 24 h after the dose had a significantly higher risk of renal toxicity (OR (95%CI) = 6.818 (2.350–19.782), p < 0.001). Multivariate logistic regression analysis with a generalized estimated equation revealed hypertension and age as independent predictors of increased MTX levels at 24 h after the given dose.
Investigation of temperature effects on wide steel box girder of suspension bridge based on long-term monitoring data
Authors: Wang Yanru , Zhang Guoliang , Wang Hui , Liu Lang , Wang Xu , Zheng Shuqin , Huang Jin , Fu Bin , Zhou Lei
Published: April 2024

The time-varying temperature distributions on bridge structures may remarkably change structural performance, which may result in differential strain/stress responses on structural members compared with the design conditions. Therefore, it is crucial to have a comprehensive understanding of temperature distributions and its effects on bridges. In this study, taking advantage of structural health monitoring technology, 1-year field monitoring data collected from a long-span suspension bridge were used to investigate the temperature distributions and their effects on the steel box girder. Specifically, the distributions and probability statistics of temperatures on the top and bottom plates were firstly analyzed. Based on which, the transverse and vertical temperature differences on the box girder were further examined, moreover, the representative values of temperature differences for various return periods were calculated by exceedance probability method. At end, a temperature prediction method was proposed to simulated the temperature field distributions during bridge life cycle, to provide substantial temperature data for estimating future operation condition. The results of this study were beneficial to structural evaluation of in-service bridges to ensure their serviceability and integrity in the life cycle.
Application of ultrasound to monitor in vivo residual bone movement within transtibial prosthetic sockets
Authors: Jonkergouw Niels , Prins Maarten R. , Donse Daniël , van der Wurff Peter , van Dieën Jaap H. , Buis Arjan , Houdijk Han
Published: April 2024

Transtibial prosthetic users do often struggle to achieve an optimal prosthetic fit, leading to residual limb pain and stump-socket instability. Prosthetists face challenges in objectively assessing the impact of prosthetic adjustments on residual limb loading. Understanding the mechanical behaviour of the pseudo-joint formed by the residual bone and prosthesis may facilitate prosthetic adjustments and achieving optimal fit. This study aimed to assess the feasibility of using B-mode ultrasound to monitor in vivo residual bone movement within a transtibial prosthetic socket during different stepping tasks. Five transtibial prosthesis users participated, and ultrasound images were captured using a Samsung HM70A system during five dynamic conditions. Bone movement relative to the socket was quantified by tracking the bone contour using Adobe After-Effect. During the study a methodological adjustment was made to improve data quality, and the first two participants were excluded from analysis. The remaining three participants exhibited consistent range of motion, with a signal to noise ratio ranging from 1.12 to 2.59. Medial–lateral and anterior–posterior absolute range of motion varied between 0.03 to 0.88 cm and 0.14 to 0.87 cm, respectively. This study demonstrated that it is feasible to use B-mode ultrasound to monitor in vivo residual bone movement inside an intact prosthetic socket during stepping tasks.
Establishment and preliminary evaluation of CT-based classification for distal radius fracture
Authors: Zhang Jun , Yao Xiaoke , Song Yanan , Yin Peng
Published: April 2024

Establish a new classification system of distal radius fracture based on computed tomographic (CT), and evaluate its reliability and reproducibility preliminarily, and provide a new theoretical reference for clinicians to use the clinical classification system. The imaging data and clinical data of 204 inpatients with distal radius fracture during 6 years from January 1, 2014 to January 1, 2019 in orthopaedic department were analyzed retrospectively and classified based on CT. Three observers evaluated the image data of 48 randomly selected cases based on CT at different time nodes of T1 and T2. Cohen's kappa was used to calculate the consistency. At the last follow-up, patients' Disabilities of the Arm, Shoulder and Hand (DASH), Patient Rated Wrist Evaluation (PRWE), and VAS scores were collected. Among 204 cases, there were 12 cases of type 1, including 6 cases of type 1-D, 4 cases of type 1-V and 2 cases of type 1-R. There were 6 cases of type 2, including 2 cases of type 2-DV, 2 cases of type 2-DR and 2 cases of type 2-VR. There were 186 cases of type 3, including 32 cases of type 3–0, 127 cases of type 3–1 and 27 cases of type 3–2. There was no significant difference in DASH, PRWE and VAS scores among all types (P > 0.05). The results of interobserver reproducibility were kappa = 0.985, ICC = 0.984 in the first evaluation, kappa = 0.986, ICC = 0.986 in the second evaluation. The results of intraobserver reproducibility were O1 = 0.991, O2 = 0.991, O3 = 0.989 respectively. The new classification system of distal radius fracture based on CT has theoretical and practical significance for incision selection, fracture reduction and internal fixation. 123 classification system is clear, comprehensive, easy to understand and remember. Moreover, it has higher interobserver reliability and intraobserver reproducibility than other systems reported at present.
Advanced humidity sensing properties of CuO ceramics
Authors: Sreejivungsa Kaniknun , Thanamoon Noppakorn , Phromviyo Nutthakritta , Jarernboon Wirat , Takesada Masaki , Thongbai Prasit
Published: April 2024

This research explores the capacitive humidity sensing properties of CuO ceramic, selected for its simplicity as an oxide and ease of fabrication, in addition to its remarkable dielectric properties. The CuO sample was fabricated by sintering at 980 °C for 5 h. A microstructure with a relative density of 88.9% was obtained. X-ray diffraction confirmed the formation of a pure CuO phase. Broadband dielectric spectroscopy revealed that the observed giant dielectric properties at room temperature (RT) were attributed to extrinsic effects, including the internal barrier layer capacitor and sample-electrode contact effects. A key focus of this study was to examine the giant dielectric properties of CuO ceramic as a function of relative humidity (RH) at RT and frequencies of 102 and 103 Hz. It was observed that the capacitance of CuO continuously increased with rising RH levels, ranging from 30 to 95%. Notably, the maximum hysteresis errors were constrained to 2.3 and 3.3% at 102 and 103 Hz, respectively. Additionally, the CuO ceramic demonstrated very fast response and recovery times, approximately 2.8 and 0.95 min, respectively. The repeatability of the humidity response of the capacitance was also established. Overall, this research highlights the high potential of CuO as a giant dielectric material for application in humidity sensors.
Efficient diagnosis of psoriasis and lichen planus cutaneous diseases using deep learning approach
Authors: Eskandari Arshia , Sharbatdar Mahkame
Published: April 2024

The tendency of skin diseases to manifest in a unique and yet similar appearance, absence of enough competent dermatologists, and urgency of diagnosis and classification on time and accurately, makes the need of machine aided diagnosis blatant. This study is conducted with the purpose of broadening the research in skin disease diagnosis with computer by traversing the capabilities of deep Learning algorithms to classify two skin diseases noticeably close in appearance, Psoriasis and Lichen Planus. The resemblance between these two skin diseases is striking, often resulting in their classification within the same category. Despite this, there is a dearth of research focusing specifically on these diseases. A customized 50 layers ResNet-50 architecture of convolutional neural network is used and the results are validated through fivefold cross-validation, threefold cross-validation, and random split. By utilizing advanced data augmentation and class balancing techniques, the diversity of the dataset has increased, and the dataset imbalance has been minimized. ResNet-50 has achieved an accuracy of 89.07%, sensitivity of 86.46%, and specificity of 86.02%. With their promising results, these algorithms make the potential of machine aided diagnosis clear. Deep Learning algorithms could provide assistance to physicians and dermatologists by classification of skin diseases, with similar appearance, in real-time.
Sphingosine-1-phosphate receptor 1/5 selective agonist alleviates ocular vascular pathologies
Authors: Nakamura Shinsuke , Yamamoto Rie , Matsuda Takaya , Yasuda Hiroto , Nishinaka Anri , Takahashi Kei , Inoue Yuki , Kuromitsu Sadao , Shimazawa Masamitsu , Goto Masahide , Narumiya Shuh , Hara Hideaki
Published: April 2024

Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.
Surface roughness prediction of AISI D2 tool steel during powder mixed EDM using supervised machine learning
Authors: Kaigude Amreeta R. , Khedkar Nitin K. , Jatti Vijaykumar S. , Salunkhe Sachin , Cep Robert , Nasr Emad Abouel
Published: April 2024

Surface integrity is one of the key elements used to judge the quality of machined surfaces, and surface roughness is one such quality parameter that determines the pass level of the machined product. In the present study, AISI D2 steel was machined with electric discharge at different process parameters using Jatropha and EDM oil. Titanium dioxide (TiO2) nanopowder was added to the dielectric to improve surface integrity. Experiments were performed using the one variable at a time (OVAT) approach for EDM oil and Jatropha oil as dielectric media. From the experimental results, it was observed that response trends of surface roughness (SR) using Jatropha oil are similar to those of commercially available EDM oil, which proves that Jatropha oil is a technically and operationally feasible dielectric and can be efficiently replaced as dielectric fluid in the EDM process. The lowest value of S.R. (i.e., 4.5 microns) for EDM and Jatropha oil was achieved at current = 9 A, Ton = 30 μs, Toff = 12 μs, and Gap voltage = 50 V. As the values of current and pulse on time increase, the S.R. also increases. Current and pulse-on-time were the most significant parameters affecting S.R. Machine learning methods like linear regression, decision trees, and random forests were used to predict the surface roughness. Random forest modeling is highly accurate, with an R2 value of 0.89 and an MSE of 1.36% among all methods. Random forest models have better predictive capabilities and may be one of the best options for modeling complex EDM processes.
Behaviour, use and safety aspects of astatine-211 solvated in chloroform after dry distillation recovery
Authors: Aneheim Emma , Hansson Ellinor , Timperanza Chiara , Jensen Holger , Lindegren Sture
Published: April 2024

Targeted alpha therapy of disseminated cancer is an emerging technique where astatine-211 is one of the most promising candidate nuclides. Astatine-211 can be produced in medium energy cyclotrons by alpha particle bombardment of natural bismuth. The produced astatine is then commonly recovered from the irradiated solid target material through dry distillation. The dry distillation process often includes elution and solvation of condensed astatine with chloroform, forming Chloroform Eluate. In this work the handling and safe use of the high activity concentration Chloroform Eluate has been investigated. Correctly performed, evaporation of Chloroform Eluate results in a dry residue with complete recovery of the astatine. The dry residue can then serve as a versatile starting material, using appropriate oxidizing or reducing conditions, for subsequent downstream chemistry. However, it has been found that when evaporating the Chloroform Eluate, astatine can be volatilized if continuing the process beyond the point of dryness. This behavior is more pronounced when the Chloroform Eluate has received a higher absorbed dose. Upon water phase contact of the Chloroform Eluate, a major part of the astatine activity becomes water soluble, leaving the organic phase. A behavior which is also dependent on dose to the solvent.
Effectiveness of DialBetesPlus, a self-management support system for diabetic kidney disease: Randomized controlled trial
Authors: Waki Kayo , Nara Mitsuhiko , Enomoto Syunpei , Mieno Makiko , Kanda Eiichiro , Sankoda Akiko , Kawai Yuki , Miyake Kana , Wakui Hiromichi , Tsurutani Yuya , Hirawa Nobuhito , Yamakawa Tadashi , Komiya Shiro , Isogawa Akihiro , Satoh Shinobu , Minami Taichi , Iwamoto Tamio , Takano Tatsuro , Terauchi Yasuo , Tamura Kouichi , Yamauchi Toshimasa , Nangaku Masaomi , Kashihara Naoki , Ohe Kazuhiko
Published: April 2024

We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group’s change (P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage (P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: −32.3% [95% CI: −49.2%, −9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.