bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards an Effective Architectural Form: The Composition of Squareness and Roundness Based on Scale Proportion—Evidence from the Yingxian Wooden Pagoda
Authors: Shi Lu , Chen Xu , Xu Yuqian , Gao Xing , Lai Jialong , Wang Shusheng
Published: May 2024

Investigating the mathematical and geometric principles embedded in ancient classic architecture is a significant tradition in the history of architectural development. Drawing inspiration from the modular design and creative ideology based on the geometric proportions of squareness and roundness in ancient Chinese architecture, we propose a new mode of squareness and roundness composition based on scale proportion specifically for the design of multi-story buildings. Taking Yingxian Wooden Pagoda as the case study, we not only re-evaluate the modular system and proportional rules followed in the design of the entire pagoda, but also reveal the technical approaches and geometric rules for effectively controlling the form of multi-story buildings. In particular, the mode of squareness and roundness composition based on scale proportion, utilizing a modular grid combined with squareness and roundness drawings as decision-making tools, can control the scale and proportion of buildings across different design dimensions and organically coordinate the design of multi-story buildings’ plans and elevations. Thus, it can achieve an effective balance of multi-story architectural forms. This study has potential applications in the creation of traditional multi-story buildings and heritage restoration projects, and offers valuable insights for future research on ancient multi-story buildings.
Clinical Characteristics, Patterns of Care, and Treatment Outcomes of Radiation-Associated Sarcomas
Authors: Raj Rohit , Kim Han Gil , Xu Menglin , Roach Tyler , Liebner David , Konieczkowski David , Tinoco Gabriel
Published: May 2024

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases.
Conventional versus Hepatic Arteriography and C-Arm CT-Guided Ablation of Liver Tumors (HepACAGA): A Comparative Analysis
Authors: Wijnen Niek , Bruijnen Rutger C. G. , Vonken Evert-Jan P. A. , de Jong Hugo W. A. M. , de Bruijne Joep , Bol Guus M. , Hagendoorn Jeroen , Intven Martijn P. W. , Smits Maarten L. J.
Published: May 2024

Purpose: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic–arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation. Materials and Methods: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate. Results: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique (p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041). Conclusions: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications.
Efficacy of Cytoreductive Surgery (CRS) + HIPEC in Gastric Cancer with Peritoneal Metastasis: Systematic Review and Meta-Analysis
Authors: Langellotti Lodovica , Fiorillo Claudio , D’Annibale Giorgio , Panza Edoardo , Pacelli Fabio , Alfieri Sergio , Di Giorgio Andrea , Santullo Francesco
Published: May 2024

Background: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. Methods: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Results: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8–28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9–8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (−1.8954 (95% CI: −2.5761 to −1.2146; p < 0.001). Conclusions: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.
Keratin-Positive Giant Cell-Rich Tumor: A Review and Update
Authors: Nishio Jun , Nakayama Shizuhide , Koga Kaori , Aoki Mikiko
Published: May 2024

Keratin-positive giant cell-rich tumor (KPGCT) is an extremely rare and recently described mesenchymal neoplasm that occurs in both soft tissue and bone, frequently found in young women. It has locally recurrent potential if incompletely excised but low risk for metastasis. KPGCT is histologically similar to conventional giant cell tumors of soft tissue but shows the presence of keratin-positive mononuclear cells. Interestingly, KPGCT also shares some morphological features with xanthogranulomatous epithelial tumors. These two tumors have recently been shown to harbor an HMGA2–NCOR2 fusion, arguing in favor of a single entity. Surgery is the treatment of choice for localized KPGCT. Therapeutic options for advanced or metastatic disease are unknown. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology, and treatment of KPGCT. In addition, we will discuss the differential diagnosis of this emerging entity.
Glucose Isomerization to Fructose Catalyzed by MgZr Mixed Oxides in Aqueous Solution
Authors: Zuo Xiongxiong , Tang Xing
Published: May 2024

The catalytic isomerization of glucose to fructose plays a pivotal role in the application of biomass as a feedstock for chemicals. Herein, we propose a facile solid-state-grinding strategy to construct ZrO2/MgO mixed oxides, which offered an excellent fructose yield of over 34.55% and a high selectivity of 80.52% (80 °C, 2 h). The co-mingling of amphiphilic ZrO2 with MgO improved the unfavorable moderate/strongly basic site distribution on MgO, which can prohibit the side reactions during the reaction and enhance the fructose selectivity. Based on the catalyst characterizations, MgO was deposited on the ZrO2 surface by plugging the pores, and the addition of ZrO2 lessened the quantity of strongly basic sites of MgO. Additionally, the presence of ZrO2 largely enhanced the catalyst stability in comparison with pure MgO by recycling experiments.
Early Childhood Development Is Not Enough: In Defense of Children with Developmental Delays and Disabilities and Their Right to Family-Centered Early Childhood Intervention (In the Global South)
Authors: Störbeck Claudine
Published: May 2024

The international recognition of the critical importance of the early childhood phase has been firmly established through decades of rigorous research, evidence-based practices, and undeniable evidence of the returns on investment made during this formative period. Consequently, early childhood development has emerged as a top priority on both national and international agendas. This momentum reached a pinnacle in 2015 with the unanimous adoption of the 17 Sustainable Development Goals (SDGs) by the United Nations, which placed a particular emphasis on children under the age of five within the education-focused SDG 4, notably target 4.2, centered on ensuring that all girls and boys are ready for primary education through the provision of accessible “quality early childhood development, care and pre-primary education”. However, the Global South reflects the glaring omission of addressing the needs of children at risk of poor development due to disabilities. This paper underscores the imperative for specialized early childhood intervention tailored to young children with disabilities and their families, commencing as early as possible following birth. It advocates for Early Childhood Intervention (ECI) as a service distinct from general Early Childhood Development (ECD), emphasizing the crucial role of families as active partners from the outset. Furthermore, the paper strengthens the case for Family-Centered Early Childhood Intervention (Fc-ECI) through the integration of evidence-based practices and an in-depth description of one such program in South Africa with specific reference to deaf and hard-of-hearing infants and their families. This model will be guided by core concepts outlined in WHO and UNICEF Early Childhood Intervention frameworks. Through this exploration, the paper aims to shed light on the urgent need for inclusive approaches to early childhood development, particularly for children with disabilities, and to advocate for the adoption of Family-Centered Early Childhood Intervention as a cornerstone of global efforts to ensure the holistic well-being and development of all children.
Plastid Phylogenetics, Biogeography, and Character Evolution of the Chinese Endemic Genus Sinojackia Hu
Authors: Jian Xing , Wang Yuliang , Li Qiang , Miao Yongmei
Published: May 2024

Sinojackia Hu. comprises five to eight Chinese endemic species with high ornamental and medicinal value. However, the generic limits, interspecific relationships and evolutionary history of the genus remain unresolved. In this study, we newly sequenced three plastomes of S. oblongicarpa and compared them with those of the other congeneric species to explore the taxonomic delimitation of the species and the evolutionary history of the genus. The plastome structure of Sinojackia species was extremely conserved in terms of number of genes, sequence length, and GC content. The codon usage patterns revealed that natural selection may be the main factor shaping codon usage bias. Our phylogenetic tree shows that Sinojackia is monophyletic and can be divided into two clades. Sinojackia oblongicarpa as a distinct species is supported for it is distantly related to S. sarcocarpa. The evolutionary analysis of morphological features indicates that the woody mesocarp is an ancestral feature. Sinojackia originated in central Southeast China during the early Miocene. In this period, it experienced elevated diversification and migrated from central Southeast China to the Hunan Province and the Sichuan Province with the development of the Asian monsoon and East Asian flora. Glacial–interglacial interactions with the monsoon climate may provide favorable expansion conditions for Sinojackia on a small scale.
A Comprehensive Review of Existing and Pending University Campus Microgrids
Authors: Alhawsawi Edrees Yahya , Salhein Khaled , Zohdy Mohamed A.
Published: May 2024

Over the past few decades, many universities have turned to using microgrid systems because of their dependability, security, flexibility, and less reliance on the primary grid. Microgrids on campuses face challenges in the instability of power production due to meteorological conditions, as the output of renewable sources such as solar and wind power relies entirely on the weather and determining the optimal size of microgrids. Therefore, this paper comprehensively reviews the university campuses’ microgrids. Some renewable energy sources, such as geothermal (GE), wind turbine (WT), and photovoltaic (PV), are compared in terms of installation costs, availability, weather conditions, efficiency, environmental impact, and maintenance. Furthermore, a description of microgrid systems and their components, including distributed generation (DG), energy storage system (ESS), and microgrid load, is presented. As a result, the most common optimization models for analyzing the performance of campus microgrids are discussed. Hybrid microgrid system configurations are introduced and compared to find the optimal configuration in terms of energy production and flexibility. Therefore, configuration A (Hybrid PV- grid-connected) is the most common configuration compared to the others due to its simplicity and free-charge operation.
Selection of an Optimal Frequency for Offshore Wind Farms
Authors: An Byeonghyeon , Che Junsoo , Kim Taehun , Park Taesik
Published: May 2024

Offshore wind power has attracted significant attention due to its high potential, capability for large-scale farms, and high capacity factor. However, it faces high investment costs and issues with subsea power transmission. Conventional high-voltage AC (HVAC) methods are limited by charging current, while high-voltage DC (HVDC) methods suffer from the high cost of power conversion stations. The low-frequency AC (LFAC) method mitigates the charging current through low-frequency operation and can reduce power conversion station costs. This paper aims to identify the economically optimal frequency by comparing the investment costs of LFAC systems at various frequencies. The components of LFAC, including transformers, offshore platforms, and cables, exhibit frequency-dependent characteristics. Lower frequencies result in an increased size and volume of transformers, leading to higher investment costs for offshore platforms. In contrast, cable charging currents and losses are proportional to frequency, causing the total cost to reach a minimum at a specific frequency. To determine the optimal frequency, simulations of investment costs for varying capacities and distances were conducted.
Yarrowia lipolytica Yeast: A Treasure Trove of Enzymes for Biocatalytic Applications—A Review
Authors: Zieniuk Bartłomiej , Jasińska Karina , Wierzchowska Katarzyna , Uğur Şuheda , Fabiszewska Agata
Published: May 2024

Yarrowia lipolytica is a robust yeast species that has gained significant attention as a biofactory for various biotechnological applications and undoubtedly can be referred to as a hidden treasure trove due to boasting a diverse array of enzymes with wide-ranging applications in multiple industries, including biofuel production, food processing, biotechnology, and pharmaceuticals. As the biotechnology field continues to expand, Y. lipolytica is poised to play a pivotal role in developing eco-friendly and economically viable bioprocesses. Its versatility and potential for large-scale production make it a promising candidate for sustainably addressing various societal and industrial needs. The current review article aimed to highlight the diverse enzymatic capabilities of Y. lipolytica and provide a detailed analysis of its relevance in biocatalysis, including the use of whole-cell catalysts and isolated enzymes. The review focused on wild-type yeast strains and their species-dependant properties and selected relevant examples of Y. lipolytica used as a host organism for overexpressing some enzymes. Furthermore, the application of Y. lipolytica’s potential in enantiomers resolution, lipids processing, and biodiesel synthesis, as well as the synthesis of polymers or esterification of different substrates for upgrading biologically active compounds, was discussed.
New Solutions in Single-Cell Protein Production from Methane: Construction of Glycogen-Deficient Mutants of Methylococcus capsulatus MIR
Authors: But Sergey Y. , Suleimanov Ruslan Z. , Oshkin Igor Y. , Rozova Olga N. , Mustakhimov Ildar I. , Pimenov Nikolai V. , Dedysh Svetlana N. , Khmelenina Valentina N.
Published: May 2024

The biotechnology of converting methane to single-cell protein (SCP) implies using fast-growing thermotolerant aerobic methanotrophic bacteria. Among the latter, members of the genus Methylococcus received significant research attention and are used in operating commercial plants. Methylococcus capsulatus MIR is a recently discovered member of this genus with the potential to be used for the purpose of SCP production. Like other Methylococcus species, this bacterium stores carbon and energy in the form of glycogen, particularly when grown under nitrogen-limiting conditions. The genome of strain MIR encodes two glycogen synthases, GlgA1 and GlgA2, which are only moderately related to each other. To obtain glycogen-free cell biomass of this methanotroph, glycogen synthase mutants, ΔglgA1, ΔglgA2, and ΔglgA1ΔglgA2, were constructed. The mutant lacking both glycogen synthases exhibited a glycogen-deficient phenotype, whereas the intracellular glycogen content was not reduced in strains defective in either GlgA1 or GlgA2, thus suggesting functional redundancy of these enzymes. Inactivation of the glk gene encoding glucokinase also resulted in a sharp decrease in glycogen content and accumulation of free glucose in cells. Wild-type strain MIR and the mutant strain ΔglgA1ΔglgA2 were also grown in a bioreactor operated in batch and continuous modes. Cell biomass of ΔglgA1ΔglgA2 mutant obtained during batch cultivation displayed high protein content (71% of dry cell weight (DCW) compared to 54% DCW in wild-type strain) as well as a strong reduction in glycogen content (10.8 mg/g DCW compared to 187.5 mg/g DCW in wild-type strain). The difference in protein and glycogen contents in biomass of these strains produced during continuous cultivation was less pronounced, yet biomass characteristics relevant to SCP production were slightly better for ΔglgA1ΔglgA2 mutant. Genome analysis revealed the presence of glgA1-like genes in all methanotrophs of the Gammaproteobacteria and Verrucomicrobia, while only a very few methanotrophic representatives of the Alphaproteobacteria possessed these determinants of glycogen biosynthesis. The glgA2-like genes were present only in genomes of gammaproteobacterial methanotrophs with predominantly halo- and thermotolerant phenotypes. The role of glycogen in terms of energy reserve is discussed.
A Review of Weak Gel Fracturing Fluids for Deep Shale Gas Reservoirs
Authors: Yang Shichu , Yu Weichu , Zhao Mingwei , Ding Fei , Zhang Ying
Published: May 2024

Low-viscosity slickwater fracturing fluids are a crucial technology for the commercial development of shallow shale gas. However, in deep shale gas formations with high pressure, a higher sand concentration is required to support fractures. Linear gel fracturing fluids and crosslinked gel fracturing fluids have a strong sand-carrying capacity, but the drag reduction effect is poor, and it needs to be pre-prepared to decrease the fracturing cost. Slick water fracturing fluids have a strong drag reduction effect and low cost, but their sand-carrying capacity is poor and the fracturing fluid sand ratio is low. The research and development of viscous slick water fracturing fluids solves this problem. It can be switched on-line between a low-viscosity slick water fracturing fluid and high-viscosity weak gel fracturing fluid, which significantly reduces the cost of single-well fracturing. A polyacrylamide drag reducer is the core additive of slick water fracturing fluids. By adjusting its concentration, the control of the on-line viscosity of fracturing fluid can be realized, that is, ‘low viscosity for drag reduction, high viscosity for sand-carrying’. Therefore, this article introduces the research and application status of a linear gel fracturing fluid, crosslinked gel fracturing fluid, and slick water fracturing fluid for deep shale gas reservoirs, and focuses on the research status of a viscous slick water fracturing fluid and viscosity-controllable polyacrylamide drag reducer, with the aim of providing valuable insights for the research on water-based fracturing fluids in the stimulation of deep shale gas reservoirs.
Making the Memory Book: War-Time Loss and Memorialization through Ephemera
Authors: Scates Bruce
Published: May 2024

This article explores the way a family fashioned a memorial to a son ‘taken by the war’. It focuses on the Robert’s collection in Melbourne, Australia’s largest bound collection of war time ephemera, and the making of what was called ‘Frank’s Memory Book’. It argues that families asserted ownership over their dead, crafting different modes of memorialization to authorized modes of remembrance, considers the way communities of mourners were brought together and highlights tensions between private loss and public memory. The making of ephemera is examined at length as is the part material culture plays in libraries and archives.
Morphological and Molecular Analysis Identified a Subspecies of Crassostrea ariakensis (Fujita, 1913) along the Coast of Asia
Authors: Chen Ya , Li Cui , Lu Ruijing , Wang Haiyan
Published: May 2024

Crassostrea ariakensis (Fujita, 1913) is one of the most important economic and ecological oysters that is naturally distributed along the coast of Asia, separated by the Yangtze River estuary. They are usually compared as different populations, while there is no consensus on whether C. ariakensis in northern and southern areas should be considered as two species or subspecies. Here, we analyzed morphological characteristics, COI, 16s rRNA, mitogenome sequences, and species delimitation analysis (ASAP and PTP) to resolve the intraspecific taxonomic status of the C. ariakensis. Phylogenetic and ASAP analysis highlight that C. ariakensis was divided into N-type and S-type. PTP was unable to differentiate between the two types of C. ariakensis. The divergence time of N-type and S-type C. ariakinsis is estimated to be 1.6 Mya, using the relaxed uncorrelated lognormal clock method. Additionally, significant morphological differences exist between the two groups in terms of the adductor muscle scar color. Despite these differences, the COI (0.6%) and 16S rRNA (0.6%) genetic distance differences between N-type and S-type C. ariakensis has not yet reached the interspecific level. These results suggest that N-type and S-type C. ariakensis should be treated as different subspecies and renamed as C. ariakensis ariakensis subsp. nov and C. ariakensis meridioyangtzensis subsp. nov.
Spatial Interaction Analysis of Infectious Disease Import and Export between Regions
Authors: Lyu Mingdong , Liu Kuofu , Hall Randolph W.
Published: May 2024

Human travel plays a crucial role in the spread of infectious disease between regions. Travel of infected individuals from one region to another can transport a virus to places that were previously unaffected or may accelerate the spread of disease in places where the disease is not yet well established. We develop and apply models and metrics to analyze the role of inter-regional travel relative to the spread of disease, drawing from data on COVID-19 in the United States. To better understand how transportation affects disease transmission, we established a multi-regional time-varying compartmental disease model with spatial interaction. The compartmental model was integrated with statistical estimates of travel between regions. From the integrated model, we derived a transmission import index to assess the risk of COVID-19 transmission between states. Based on the index, we determined states with high risk for disease spreading to other states at the scale of months, and we analyzed how the index changed over time during 2020. Our model provides a tool for policymakers to evaluate the influence of travel between regions on disease transmission in support of strategies for epidemic control.
Exploring the Relationship of Anxiety and Depressive Symptoms and Impulsiveness with the Quality of Life of Older Patients with Cardiovascular Disease: A Cross-Sectional Study
Authors: Pietrabissa Giada , Marchesi Gloria , Gondoni Luca Alessandro , Castelnuovo Gianluca
Published: May 2024

Background: This study aimed to evaluate the relationship of selected clinical (i.e., body mass index, BMI) and psychological factors (i.e., anxiety, depression, and impulsiveness) with the quality of life (QoL) of elderly patients with cardiovascular disease (CVD) in a single clinical center in Italy. Methods: A total of 238 patients of older age (≥65 years) with CVD who voluntarily attended a single clinical center for weight loss and cardiac rehabilitation were sequentially recruited and tested upon admission to the hospital based on pre-established inclusion criteria. Results: The findings indicated that anxiety and depressive symptoms were moderately associated with lower QoL. Additionally, there were noteworthy but minor negative connections between impulsivity and QoL. Furthermore, BMI was inversely associated with the perceived QoL of the participants, and when incorporated into the regression analysis, BMI alone significantly accounted for 11.8% of the variability in QoL. This percentage increased to 18.4% with the inclusion of impulsiveness in the model and further to 34.3% with the addition of anxiety and depressive symptoms. However, after introducing anxiety and depression, the association between impulsivity and QoL ceased to be statistically significant. Conclusions: Integrating the routine assessment and treatment of psychological factors into the care of older patients with CVD is important for optimizing their overall health outcomes and improving their QoL.
Environmental Determinants of Post-Discharge Acute Respiratory Illness among Preterm Infants with Bronchopulmonary Dysplasia
Authors: Szeto Jonathan J. , Radack Joshua K. , DeMauro Sara B. , Jensen Erik A. , Gibbs Kathleen , Novick Nicolas P. , Scott Kristan A. , Murosko Daria C. , Burris Heather H. , Nelin Timothy D.
Published: May 2024

Objective: To analyze the association of components of the Centers for Disease Control and Prevention (CDC) Environmental Justice Index (EJI) with respiratory health outcomes among infants with bronchopulmonary dysplasia (BPD) within one year after discharge from the neonatal intensive care unit. Methods: This was a retrospective cohort study of a cohort of preterm infants with BPD. Multivariable logistic regression models estimated associations of EJI and its components with medically attended acute respiratory illness, defined as an ED visit or inpatient readmission, within one year of discharge from the neonatal intensive care unit. A mediation analysis was conducted to evaluate how environmental injustice may contribute to racial disparities in acute respiratory illness. Results: Greater EJI was associated with an increased risk of medically attended respiratory illness (per EJI standard deviation increment, aOR 1.38, 95% CI: 1.12–1.69). Of the index’s components, the Environmental Burden Module’s Air pollution domain had the greatest association (aOR 1.44, 95% CI: 1.44–2.61). With respect to individual indicators within the EJI, Diesel Particulate Matter (DSLPM) and Air Toxic Cancer Risk (ATCR) demonstrated the strongest relationship (aOR 2.06, 95% CI: 1.57–2.71 and aOR 2.10, 95% CI: 1.59–2.78, respectively). Among non-Hispanic Black infants, 63% experienced a medically attended acute respiratory illness as compared to 18% of non-Hispanic White infants. DSLPM mediated 39% of the Black–White disparity in medically attended acute respiratory illness (p = 0.004). Conclusions: Environmental exposures, particularly air pollution, are associated with post-discharge respiratory health outcomes among preterm infants with BPD after adjusting for clinical, demographic, and social vulnerability risk factors. Certain types of air pollutants, namely, DSLPM, are more greatly associated with acute respiratory illness. Environmental exposures may contribute to racial disparities in medically attended acute respiratory illness among infants with BPD.
LPA3 Receptor Phosphorylation Sites: Roles in Signaling and Internalization
Authors: Solís K. Helivier , Romero-Ávila M. Teresa , Rincón-Heredia Ruth , García-Sáinz J. Adolfo
Published: May 2024

Lysophosphatidic acid (LPA) type 3 (LPA3) receptor mutants were generated in which the sites detected phosphorylated were substituted by non-phosphorylatable amino acids. Substitutions were made in the intracellular loop 3 (IL3 mutant), the carboxyl terminus (Ctail), and both domains (IL3/Ctail). The wild-type (WT) receptor and the mutants were expressed in T-REx HEK293 cells, and the consequences of the substitutions were analyzed employing different functional parameters. Agonist- and LPA-mediated receptor phosphorylation was diminished in the IL3 and Ctail mutants and essentially abolished in the IL3/Ctail mutant, confirming that the main phosphorylation sites are present in both domains and their role in receptor phosphorylation eliminated by substitution and distributed in both domains. The WT and mutant receptors increased intracellular calcium and ERK 1/2 phosphorylation in response to LPA and PMA. The agonist, Ki16425, diminished baseline intracellular calcium, which suggests some receptor endogenous activity. Similarly, baseline ERK1/2 phosphorylation was diminished by Ki16425. An increase in baseline ERK phosphorylation was detected in the IL3/Ctail mutant. LPA and PMA-induced receptor interaction with β-arrestin 2 and LPA3 internalization were severely diminished in cells expressing the mutants. Mutant-expressing cells also exhibit increased baseline proliferation and response to different stimuli, which were inhibited by the antagonist Ki16425, suggesting a role of LPA receptors in this process. Migration in response to different attractants was markedly increased in the Ctail mutant, which the Ki16425 antagonist also attenuated. Our data experimentally show that receptor phosphorylation in the distinct domains is relevant for LPA3 receptor function
The Impact of the IL-10 Gene Polymorphism on mRNA Expression and IL-10 Serum Concentration in Polish Lupus Patients
Authors: Żak-Gołąb Agnieszka , Cieślik Paweł , Siekiera Urszula , Kuśmierz Dariusz , Hrycek Antoni , Holecki Michał
Published: May 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against a lot of nuclear components. Despite many studies on the genetic background of this disease, the pathogenesis remains unclear. The aim of the study is to comprehensively evaluate the polymorphism of the IL-10 promoter gene, its mRNA expression, and the serum IL-10 concentration of SLE female patients and females age-matched controls. Analyzing the association between the level of the tested cytokine and the polymorphism genotype-1082; -819; -592, we found statistically higher serum IL-10 levels in SLE patients compared to in healthy controls (11.9 ± 2.2 pg/mL vs. 9.4 ± 1.7 pg/mL, accordingly; p < 0.0001). We did not find statistically significant differences in the gene polymorphism of IL-10 among SLE patients and controls. The most significant observation derived from our study is that IL-10 mRNA transcripts are upregulated in SLE patients compared to in healthy controls (p < 0.0001). According to our results, the presence of the IL-10 genetic polymorphism has no clinical significance for the development of SLE, and subsequent differences in mRNA and IL-10 concentration results from the influence of other factors which should be the subject of further research.
Genome-Wide Identification and Expression Analysis of ent-kaurene synthase-like Gene Family Associated with Abiotic Stress in Rice
Authors: Teng Yantong , Wang Yingwei , Zhang Yutong , Xie Qinyu , Zeng Qinzong , Cai Maohong , Chen Tao
Published: May 2024

Rice (Oryza sativa) is one of the most important crops for humans. The homologs of ent-kaurene synthase (KS) in rice, which are responsible for the biosynthesis of gibberellins and various phytoalexins, are identified by their distinct biochemical functions. However, the KS-Like (KSL) family’s potential functions related to hormone and abiotic stress in rice remain uncertain. Here, we identified the KSL family of 19 species by domain analysis and grouped 97 KSL family proteins into three categories. Collinearity analysis of KSLs among Poaceae indicated that the KSL gene may independently evolve and OsKSL1 and OsKSL4 likely play a significant role in the evolutionary process. Tissue expression analysis showed that two-thirds of OsKSLs were expressed in various tissues, whereas OsKSL3 and OsKSL5 were specifically expressed in the root and OsKSL4 in the leaf. Based on the fact that OsKSL2 participates in the biosynthesis of gibberellins and promoter analysis, we detected the gene expression profiles of OsKSLs under hormone treatments (GA, PAC, and ABA) and abiotic stresses (darkness and submergence). The qRT-PCR results demonstrated that OsKSL1, OsKSL3, and OsKSL4 responded to all of the treatments, meaning that these three genes can be candidate genes for abiotic stress. Our results provide new insights into the function of the KSL family in rice growth and resistance to abiotic stress.
Fatty Acids and Their Lipogenic Enzymes in Anorexia Nervosa Clinical Subtypes
Authors: Nguyen Nhien , Woodside D. Blake , Lam Eileen , Quehenberger Oswald , German J. Bruce , Shih Pei-an Betty
Published: May 2024

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.
Isolation and Characterization of Cell-Free DNA from Cerebral Organoids
Authors: Silver Brian B. , Brooks Ashley , Gerrish Kevin , Tokar Erik J.
Published: May 2024

Early detection of neurological conditions is critical for timely diagnosis and treatment. Identifying cellular-level changes is essential for implementing therapeutic interventions prior to symptomatic disease onset. However, monitoring brain tissue directly through biopsies is invasive and poses a high risk. Bodily fluids such as blood or cerebrospinal fluid contain information in many forms, including proteins and nucleic acids. In particular, cell-free DNA (cfDNA) has potential as a versatile neurological biomarker. Yet, our knowledge of cfDNA released by brain tissue and how cfDNA changes in response to deleterious events within the brain is incomplete. Mapping changes in cfDNA to specific cellular events is difficult in vivo, wherein many tissues contribute to circulating cfDNA. Organoids are tractable systems for examining specific changes consistently in a human background. However, few studies have investigated cfDNA released from organoids. Here, we examined cfDNA isolated from cerebral organoids. We found that cerebral organoids release quantities of cfDNA sufficient for downstream analysis with droplet-digital PCR and whole-genome sequencing. Further, gene ontology analysis of genes aligning with sequenced cfDNA fragments revealed associations with terms related to neurodevelopment and autism spectrum disorder. We conclude that cerebral organoids hold promise as tools for the discovery of cfDNA biomarkers related to neurodevelopmental and neurological disorders.
The Development of a One-Step RT-qPCR for the Detection and Quantification of Viable Forms of Trypanosoma cruzi in Açai Samples from Areas at Risk of Chagas Disease through Oral Transmission
Authors: Faier-Pereira Amanda , Finamore-Araujo Paula , Brito Carlos Ramon do Nascimento , Peres Eldrinei Gomes , de Lima Yamaguchi Klenicy Kazumy , de Castro Daniele Pereira , Moreira Otacilio C.
Published: May 2024

Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites’ viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.
Genome Variability in Artificial Allopolyploid Hybrids of Avena sativa L. and Avena macrostachya Balansa ex Coss. et Durieu Based on Marker Sequences of Satellite DNA and the ITS1–5.8S rDNA Region
Authors: Amosova Alexandra V. , Gnutikov Alexander A. , Rodionov Alexander V. , Loskutov Igor G. , Nosov Nikolai N. , Yurkevich Olga Yu. , Samatadze Tatiana E. , Zoshchuk Svyatoslav A. , Muravenko Olga V.
Published: May 2024

Artificial hybrids between cultivated Avena species and wild Avena macrostachya that possess genes for resistance to biotic and abiotic stresses can be important for oat breeding. For the first time, a comprehensive study of genomes of artificial fertile hybrids Avena sativa × Avena macrostachya and their parental species was carried out based on the chromosome FISH mapping of satellite DNA sequences (satDNAs) and also analysis of intragenomic polymorphism in the 18S–ITS1–5.8S rDNA region, using NGS data. Chromosome distribution patterns of marker satDNAs allowed us to identify all chromosomes in the studied karyotypes, determine their subgenomic affiliation, and detect several chromosome rearrangements. Based on the obtained cytogenomic data, we revealed differences between two A. macrostachya subgenomes and demonstrated that only one of them was inherited in the studied octoploid hybrids. Ribotype analyses showed that the second major ribotype of A. macrostachya was species-specific and was not represented in rDNA pools of the octoploids, which could be related to the allopolyploid origin of this species. Our results indicate that the use of marker satDNAs in cytogenomic studies can provide important data on genomic relationships within Avena allopolyploid species and hybrids, and also expand the potential for interspecific crosses for breeding.
Structure-Based De Novo Design for the Discovery of Miniprotein Inhibitors Targeting Oncogenic Mutant BRAF
Authors: Ham Jae Min , Kim Myeongbin , Kim Taeho , Ryu Seong Eon , Park Hwangseo
Published: May 2024

Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for anticancer drug discovery due to oncogenic mutations that lead to pathway hyperactivation. Despite the discovery of several small-molecule BRAF kinase inhibitors targeting oncogenic mutants, their clinical utility has been limited by challenges such as off-target effects and suboptimal pharmacological properties. This study focuses on identifying miniprotein inhibitors for the oncogenic V600E mutant BRAF, leveraging their potential as versatile drug candidates. Using a structure-based de novo design approach based on binding affinity to V600E mutant BRAF and hydration energy, 39 candidate miniprotein inhibitors comprising three helices and 69 amino acids were generated from the substructure of the endogenous ligand protein (14-3-3). Through in vitro binding and kinase inhibition assays, two miniproteins (63 and 76) were discovered as novel inhibitors of V600E mutant BRAF with low-micromolar activity, with miniprotein 76 demonstrating a specific impediment to MEK1 phosphorylation in mammalian cells. These findings highlight miniprotein 76 as a potential lead compound for developing new cancer therapeutics, and the structural features contributing to its biochemical potency against V600E mutant BRAF are discussed in detail.
Synthesis of Novel 3-Deoxy-3-thio Derivatives of d-Glucosamine and Their Application as Ligands for the Enantioselective Addition of Diethylzinc to Benzaldehyde
Authors: Hakim Yusuf Zaim , Bauer Tomasz
Published: May 2024

A series of novel thio-derivatives of d-glucosamine has been synthesized using double inversion procedures at the C3 atom. New compounds were applied as ligands for the diethylzinc addition to benzaldehyde and the products of the addition were obtained with a low to good enantiomeric ratio. The direction and the level of the asymmetric induction were highly dependent on the type of protecting groups on the nitrogen and sulfur atoms.
Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder
Authors: Chien Wei-Hsien , Chen Chia-Hsiang , Cheng Min-Chih , Wu Yu-Yu , Gau Susan Shur-Fen
Published: May 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.