bluuebunny/crossref_metadata_2025 huggingface dataset:
Step‐By‐Step Procedure to Identify Previously Unknown Compounds by LC‐QTOF‐MS Exemplified by an Intoxication With the Methaqualone Analog SL‐164
Authors: Fels Helena , Franz Simon , Dame Torsten , Skopp Gisela , Musshoff Frank
Published: September 2024

In September 2019, a 22‐year‐old man with a history of drug abuse presented to the hospital with altered mental status. Due to a suspected drug overdose, a blood sample taken on admission and a urine sample collected 30 h thereafter were submitted to our laboratory to test for illegal drugs, pharmaceutical substances, and designer drugs. During the routine toxicological analysis of the serum sample, morphine and phenobarbital were identified by liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Additionally, two compounds showing identical accurate masses and isotope ratios as the designer benzodiazepine diclazepam and the benzodiazepine lormetazepam were found. However, retention times differed significantly from the expected values, and the acquired MS/MS spectra did not match the library entries of the two compounds, indicating the presence of two previously unknown substances. After further investigation, SL‐164 (5‐chloro‐3‐(4‐chloro‐2‐methylphenyl)‐2‐methyl‐4(3H)‐quinazolinone), a methaqualone analog, which has recently emerged on the research chemical market, and its hydroxy metabolite were tentatively identified by accurate mass, isotope matching, and plausible fragmentation. However, for unequivocal confirmation and quantification, a reference standard is required. As no reference material was available by the end of 2019, SL‐164 was obtained from an online shop, and its identity and purity (97.8%) were confirmed by nuclear magnetic resonance spectroscopy. The subsequent quantitative analysis revealed a concentration of 390 ng/mL SL‐164 in serum. In the urine sample, the parent compound was not detected, but three suspected monohydroxylated metabolites were found. This example shows that LC‐QTOF‐MS is a powerful approach for the (tentative) identification of unknown compounds in biological matrices.
Effects of functional composition on plant competitors, stress‐tolerators, ruderals ecological strategies in forest communities across different climatic zones
Authors: Han Xin , Yao Jie , Wang Ruixue , Xu Yue , Huang Jihong , Ding Yi , Zang Runguo
Published: September 2024

Ecological strategies identified by plant functional traits are valuable descriptors for understanding species, populations, communities, and ecosystems in response to environmental conditions. Ecological strategies, in conjunction with the functional structure of plant communities, serve as crucial tools for investigating complex relationships among the environment, vegetation, and ecosystem functions. However, it remains unclear whether the functional structure (specifically, community‐weighted mean [CWM] traits) accurately reflects the optimal ecological strategies in forest communities. Here, we gathered seven functional traits for each species from four distinct forest vegetation types across four climatic zones, including leaf area (LA), specific leaf area (SLA), leaf dry matter content (LDMC), leaf phosphorus concentration (LPC), leaf nitrogen concentration (LNC), wood density (WD) and maximum plant height (H). We based on CSR (Competitors, Stress‐tolerators, Ruderals) theory and “StrateFy” ordination method utilizing LA, LDMC and SLA to position them within CSR triangle and categorize them into four ecological strategy groups: Competitive, Stress‐tolerant, Intermediate, and Ruderal ecological strategy groups (C‐group, S‐group, Int‐group, and R‐group). We then determined the proportion of species in each group. Subsequently, we calculated the CWM trait values for the remaining four functional traits: WD (CWM‐WD), LPC (CWM‐LPC), LNC (CWM‐LNC) and H (CWM‐H). Non‐metric multidimensional scaling and hierarchical partitioning revealed that CWM‐WD, CWM‐LPC, CWM‐LNC and CWM‐H significantly influenced the ecological strategies of forest communities. The synergistic interaction of CWM‐WD and CWM‐LPC had the most significant impact on ecological strategies within forest communities. Notably, CWM‐WD emerged as the most crucial single CWM trait for explaining variation in ecological strategies within forest communities. In conclusion, our study demonstrates that CWM traits effectively reflect optimal CSR ecological strategies in forest communities across different climatic zones, with CWM‐WD serving as a preferred indicator. This can improve our critical insights into key ecological processes in forest communities using trait‐based approach.
Nanoencapsulation of wheat germ oil with chitosan‐nettle seed gum‐ovalbumin: Preparation, optimization, and characterization
Authors: Kutlu Gözde , Akman Perihan Kubra , Erol Kübra Feyza , Bozkurt Fatih , Tornuk Fatih
Published: September 2024

This study was aimed to optimize nanoencapsulation conditions of ovalbumin (OV)‐nettle seed gum (NSG)‐chitosan (CS), ONC‐based nanocarriers, using response surface methodology (RSM). Then, wheat germ oil (WGO) was encapsulated in optimized ONC nanocarriers, and WGO‐loaded nanocarriers were characterized for their encapsulation efficiency, zeta potential, average particle size, emulsion stability, thermal, structural, micromorphological, rheological, and cytotoxic properties. The results showed that NSG‐CS amount of 30 mL, OV amount of 20 mL, and pH of 3 gave the maximum zeta potential and minimum average particle size based on the predicted conditions for the production of ONC nanocarriers by RSM. Encapsulation efficiencies of WGO‐loaded nanoparticles (WGONs) containing different ratios of WGO (2.5% to 4.5%, v:w) ranged from 48.66% to 71.91%. According to rheological properties, both the solutions of ONC complex and WGONs exhibited Newtonian flow behavior. The FT‐IR spectra exhibited changes in the peaks associated with amino and carboxyl groups following the encapsulation of WGO, suggesting the successful completion of the encapsulation process. SEM images revealed that the addition of WGO into the capsule resulted in the formation of rough particles. The cytotoxicity tests demonstrated that concentrations of WGO, CS, NSG, OV, WGO, ONC, and WGON up to 10 mg mL–1 did not significantly reduce the viability of L‐929 human fibroblast cell lines, indicating their nontoxicity toward healthy cells. In conclusion, this study suggested the successful encapsulation of WGO within ONC carriers at the nanoscale, achieving high encapsulation efficiency and favorable properties to enhance their uses for different purposes.

Practical Application: Wheat germ, an important by‐product of wheat milling industry, contains considerable amounts of oil which possesses many beneficial components like tocopherol, vitamin B, phytosterols, and policosanols. These compounds have potential health benefits such as supporting exercise performance, cardiovascular health, and reducing the risk of overweight/obesity. Therefore, this underutilized oil needs to be introduced to the food/nutraceutical industry more extensively. However, the susceptibility of wheat germ oil (WGO) to oxidation and its short shelf‐life limit its further use. Encapsulation technology can be employed to protect the WGO, extend its shelf‐life, and improve its stability. Response surface methodology (RSM) is also a versatile way to determine the optimal conditions for encapsulation, resulting in the formation of stable nanocapsules containing WGO. The resulting nanocapsules effectively release the active ingredients of WGO, protecting them from oxidation and making them highly suitable for use as functional food ingredients or in pharmaceutical products with promising potential.
Integrating computational thinking practices into early childhood education in culturally responsive ways: Insights from research–practice partnership
Authors: Hubelbank Jeanne , Dubosarsky Mia , Kayumova Shakhnoza , Davis Tiffany , Sann Nea , Fortin Shawn , Smith Gillian
Published: September 2024

The study examines the research–practice partnership (RPP) model aimed at co‐constructing and integrating computational thinking (CT) in culturally responsive (CR) ways within early childhood and elementary (PreK‐5) classrooms, focusing on teachers' RPP experiences. Recent research underlines the importance of integrating CT in early childhood and elementary education, demonstrating that culturally, linguistically, and developmentally responsive computational activities in PreK‐5 settings are key to such efforts. However, there is a gap in research regarding effective professional development models that would prepare early childhood teachers in terms of both disciplinary ideas and practices of CT, as well as attending to cultural, linguistic, and developmental differences in young children in asset‐based ways. Our research contributes to this body of knowledge by examining how RPP can be a model for teacher learning in which teachers, administrators, and researchers can co‐develop knowledge and confidence in integrating CT into the PreK‐5 teaching curriculum and practices in CR ways. The study outlines the collaborative development of processes and frameworks co‐constructed by the RPP educators, as well as teacher‐developed curricular materials and lesson plans integrating CT in CR ways. Findings include teachers' experience of these lessons and teacher insights about the support needed to incorporate CT and CR practices into their existing curricula. The study concludes by highlighting the potential challenges and opportunities inherent in such endeavors, thereby contributing to the broader discourse on supporting CT integration into early childhood classrooms in CR ways.
An assessment of future climatic and anthropogenic impacts on the hydrological system of a semi‐arid catchment
Authors: Nune Rajesh , Western Andrew W. , George Biju A. , Gummadi Sridhar , Pasupuleti Srinivas , Ragab Ragab , Dixit Sreenath
Published: September 2024

Climate and catchment characteristics, particularly land and water use and management, may vary according to the population growth rate, future food habits and water demands. Three climate simulations corresponding to the Intergovernmental Panel on Climate Change, Special Report on Emissions Scenarios (A1B) were downscaled using the ‘Providing Regional Climates for Impact Studies’ (PRECIS) for the period 1961–2098, and bias correction was performed using the quantile mapping (QM) method. A semi‐distributed integrated model (Modified Soil and Water Assessment Tool, SWAT) was used to predict the impacts of dynamic changes in catchment characteristics in the Himayat Sagar (HS) catchment and the effects of future climate change on future streamflow and groundwater storage. Simulations predicted that if this trend continues in the future, future climate and anthropogenic changes will lead to a more than 50% reduction in streamflow and a 50% increase in actual evaporation in the HS catchment. This would reduce groundwater storage to a depth of 15 m compared to current conditions, and by the end of the century, there would be no contribution from the base flow to the streamflow. Overall, unless current policies are modified to stabilize land and water management practices, anthropogenic changes will have greater importance than climate change.
Improved understanding of soil water content at field capacity and estimates from pedotransfer functions
Authors: Andabili Samira Jaefarzade , Rasoulzadeh Ali , Moghadam Javad Ramezani , Pollacco Joseph Alexander Paul , Fernández‐Gálvez Jesús
Published: September 2024

The soil water content at field capacity, θFC, is a fundamental variable for irrigation and agriculture. This study determines the optimal tension (−33 or −10 kPa) of deriving θFC which best matches the in situ field measurements following the Veihmeyer procedure. The Veihmeyer method refers to a profile water status for which there is a negligible drainage rate of bare soil without evaporation. In addition, we derive a set of linear and nonlinear pedotransfer functions (PTFs) which estimate θFC. θFC was measured in 69 plots in north‐western Iran, which has a cold semi‐arid climate. The soil properties used for developing PTFs include texture, bulk density, and organic matter. The results show that θFC cannot be derived at a fixed tension. We therefore developed PTFs with satisfactory performance in reproducing in situ measured θFC. The findings show that PTFs developed at a fixed tension consistently underestimate θFC derived in situ. It was also speculated that tension less than −10 kPa could yield improved predictions of in situ θFC.
Pathogenicity and transcriptomic resolution in dengue virus serotype 1 infected AGB6 mouse model
Authors: Yu Ning , Chen Shigang , Liu Yumeng , Wang Peng , Wang Longlong , Hu Ningning , Zhang He , Li Xiao , Lu Huijun , Jin Ningyi
Published: September 2024

Dengue viruses are the causative agents of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, which are mainly transmitted by Aedes aegypti and Aedes albopictus mosquitoes, and cost billions of dollars annually in patient treatment and mosquito control. Progress in understanding DENV pathogenesis and developing effective treatments has been hampered by the lack of a suitable small pathological animal model. Until now, the candidate vaccine, antibody, and drug for DENV have not been effectively evaluated. Here, we analyzed the pathogenicity of DENV‐1 in type Ⅰ and type Ⅱ interferon receptor‐deficient mice (AGB6) by intraperitoneal inoculation. Infected mice showed such neurological symptoms as opisthotonus, hunching, ataxia, and paralysis of one or both hind limbs. Viremia can be detected 3 days after infection. It was found that 6.98 × 103 PFU or higher dose induce 100% mortality. To determine the cause of lethality in mice, heart, liver, spleen, lung, kidney, intestinal, and brain tissues were collected from AGB6 mice (at an attack dose of 6.98 × 103 PFU) for RNA quantification, and it was found that the viral load in brain tissues peaked at moribund states (14 dpi) and that the viral loads in the other tissues and organs decreased over time. Significant histopathologic changes were observed in brain tissue (hippocampal region and cerebral cortex). Hematological analysis showed hemorrhage and hemoconcentration in infected mice. DENV‐1 can be isolated from the brain tissue of infected mice. Subsequently, brain tissue transcriptome sequencing was performed to assess host response characteristics in infected AGB6 mice. Transcriptional patterns in brain tissue suggest that aberrant expression of pro‐inflammatory cytokines induces antiviral responses and tissue damage. Screening of hub genes and their characterization by qPCR and ELISA, it was hypothesized that IL‐6 and IFN‐γ might be the key factors in dengue virus‐induced inflammatory response. Therefore, this study provides an opportunity to decipher certain aspects of dengue pathogenesis further and provides a new platform for drug, antibody, and vaccine testing.
Spectral Ultrasound Combined With Clinical Pathological Parameters in Prediction of Axillary Lymph Node Metastasis in Breast Cancer
Authors: Sun Pengfei , Han Jiaqi , Li Min , Wang Zhixiang , Guo Ruifang , Zhang Yanning , Qian Linxue , Ma Jianguo , Hu Xiangdong
Published: September 2024

Objectives

To explore the clinical value of the nomogram based on spectral Doppler ultrasound combined with clinical pathological parameter in predicting axillary lymph node metastasis in breast cancer.

Methods

We prospectively gathered clinicopathologic and ultrasonic data from 240 patients confirmed breast cancer. The risk factors of axillary lymph node metastasis were analyzed by univariate and multivariate logistic regression, and the prediction model was established. The model calibration, predictive ability, and diagnostic efficiency in the training set and the testing set were analyzed by receiver operating characteristic curve and calibration curve analysis, respectively.

Results

Univariate analysis showed that lymph node metastasis was related with tumor size, Ki‐67, axillary ultrasound, ultrasound spectral quantitative parameter, internal echo, and calcification (P < .05). Multivariate logistic regression analysis showed that the Ki‐67, axillary ultrasound, quantitative parameter (the mean of the mid‐band fit in tumor and posterior tumor) were independent risk factors of axillary lymph node metastasis (P < .05). The models developed using Ki‐67, axillary ultrasound, and quantitative parameters for predicting axillary lymph node metastasis demonstrated an area under the receiver operating characteristic curve of 0.83. Additionally, the prediction model exhibited outstanding predictability for axillary lymph node metastasis, as evidenced by a Harrell C‐index of 0.83 (95% confidence interval 0.73–0.93).

Conclusion

Axillary ultrasound combined with Ki‐67 and spectral ultrasound parameters has the potential to predict axillary lymph node metastasis in breast cancer, which is superior to axillary ultrasound alone.
Sub‐Nyquist wideband spectrum sensing for multicarrier wireless applications
Authors: Rao T. J. V. Subrahmanyeswara , Aswini T. V. N. L. , Sharma Purnima K. , Sharma Dinesh
Published: September 2024

The incredible growth of wireless technologies has led to an increase in demand of spectral resources for various communication systems. The allocated spectrum for GSM is insufficient to support applications that operate at high data rates (e.g., multimedia applications or 5G mobile communications). Orthogonal frequency division multiplexing (OFDM) and generalized frequency division multiplexing (GFDM) are the recent technologies with high data rates for multimedia applications and mobile communications. These are the perfect candidates for wireless applications and 5G technologies. In this paper, an in‐depth study was presented where the multicarrier models of orthogonal frequency‐division multiplexing (OFDM) and GFDM are integrated with a sub‐Nyquist sampling architecture. The primary focus is to evaluate and compare their spectrum sensing performance. Also analyzed the performance of both OFDM and GFDM under sub‐Nyquist sampling framework and measured the bit error rate (BER) as a function of the received signal‐to‐noise ratio (SNR).
Geographical Differences in the Perspective of Osteoarthritis Care Management: A Cross‐Sectional Study in Italy, Sweden and Russia
Authors: Battista Simone , Recenti Filippo , Giardulli Benedetto , Testa Marco , Pchelnikova Polina , Ndosi Mwidimi , Dell’Isola Andrea
Published: September 2024

Background

This study aimed to explore the awareness, experiences, and beliefs of individuals with osteoarthritis (OA) regarding their healthcare management, along with assessing their overall satisfaction levels.

Methods

A cross‐sectional online survey was conducted in Italy, Sweden, and Russia, rigorously developed based on OA international guidelines in collaboration with healthcare professionals and individuals with OA. Participants over 40 years of age with self‐reported hip and/or knee OA were eligible. The analytical framework included descriptive analysis (assessment of awareness levels for ‘recommended’, ‘optional’, and ‘not recommended’ treatments), analysis of suggested treatments and taken treatments, exploration of beliefs, barriers and satisfaction analysis (0–100 scale).

Results

A total of 401 participants (mean age: 59.7, 78.3% female, 28% Italian, 49% Swedish, 23% Russian) contributed to the study. In Sweden, 57%–72% accurately identified recommended treatments, while in Russia, the range was 34%–91%, and in Italy, it was 35%–73%. The predominant suggested and taken treatments were oral anti‐inflammatory drugs in Italy (87/81%) and Russia (97/97%) and specific exercise in Sweden (84/79%). Notably, only Sweden reached a consensus on the effectiveness of exercise for everyone, while Russia and Italy insisted on radiographic findings as a prerequisite for exercise. Mean satisfaction levels were 59.7 (Italy), 47.4 (Sweden), and 35.2 (Russia).

Conclusions

This study uncovered variations in awareness, treatment preferences, and beliefs among the three countries, underscoring the necessity for tailored education on OA management that accounts for regional differences across Europe.
Investigation of Novel 2‐(Chloromethyl)‐5‐(3, 5‐Disubstituted‐1H‐Indol‐2‐yl)‐1,3,4‐Oxadiazole Derivatives as In Vitro, and In Silico Bioactivity Potential: Anti‐inflammatory, Anti‐TB and Antioxidant Activities Study
Authors: Harish Kumar K. , Sridhar B. T. , Karunakar Prashantha , Nagesh G. Y. , Gupta Nidhi , Jisha S. P. , Basavarajaiah S. M.
Published: September 2024

A series of novel 2‐(chloromethyl)‐5‐(3, 5‐disubstituted‐1H‐indol‐2‐yl)‐1,3,4‐oxadiazole (3 a–h) derivatives have been synthesized as potential COX inhibitors, anti‐TB, and anti‐oxidant activities. The structures were confirmed by IR, NMR (1H and 13C) mass spectral techniques. The physicochemical properties, ADME, and drug‐likeness profile for the synthesized compounds were evaluated by SwissADME. Based on our interest in indole chemistry and SAR study, foresaid indole compounds were examined for in vitro COX inhibitory activity, anti‐TB, and antioxidant activities. The physicochemical and ADME studies were disclosed for newly synthesized compounds. The compounds 3 a,3 b and 3 c recognized outstanding COX‐II inhibitions with IC50 values of 0.28, 0.24, and 0.45 μM compared to standard drugs. The compounds 3 a,and3 b showed outstanding anti‐TB activity with MIC value 0.78 μg/mL. The compounds 3 a,3 b, and 3 c attested outstanding antioxidant activity at 10 μg/ml with a rate of inhibition of 66.52 %, 68.25 %, and 65.95 % respectively. Finally, the molecular docking studies carried out with cyclooxygenase‐2 (PDB ID: 6COX), M. tuberculosis enoyl reductase (INHA) complexed with 1‐cyclohexyl‐N‐(3,5‐dichlorophenyl)‐5‐oxopyrrolidine‐3‐carboxamide (PDB ID: 4TZK), and cytochrome c peroxidase (PDB ID: 2X08), for all the newly synthesized derivatives. Finally, selected compounds were taken for their molecular dynamic studies.
Synthesis of Dendritic Polymer for Hydrogen Peroxide Production and Organic Pollutants Degradation Under Visible Light Conditions
Authors: Jin M. Z. , Li J. , Song D. , Jing F. F. , Lu W. W. , He X. Y. , Wang T. , Yu R. T.
Published: September 2024

A process for photocatalytically synthesizing hydrogen peroxide while simultaneously degrading organic pollutants is of interest. In this study, a dendritic nanopolymer was synthesized and utilized as a photocatalyst for the production of hydrogen peroxide, which was then used in tandem with the degradation of Tetracycline (TC) and Rhodamine B (Rh B) organic pollutants under a 36 W incandescent bulb. The yield of H2O2 was measured at 8.4 mg g−1 h−1, with photocatalytic degradation rates of 93.90 % for Rh B and 72.92 % for TC. The degradation kinetics of TC and Rh B by the dendritic polymer were found to follow pseudo‐first‐order kinetics, and a higher affinity for degradation was observed for Rh B. The photocatalytic degradation mechanism of TC in a Fenton‐like system was attributed to an oxidation system involving hydrogen peroxide and ferrous ions.
Rethinking Models of DNA Organization in Micrometer‐Sized Chromosomes from the Perspective of the Nanoproperties of Chromatin Favoring a Multilayer Structure
Authors: Daban Joan‐Ramon
Published: September 2024

The long genomic DNA molecules in eukaryotes are fragile and prone to entanglement, and must be tightly folded to fit into the micrometric dimensions of mitotic chromosomes. Histones transform the monotonous linear structure of double‐helical DNA into a chromatin filament formed by many nucleosomes. A physically consistent model for the packaging of the chromatin filament must be compatible with all the constraints imposed by the structural properties of chromosomes. It has to be compatible with 1) the high concentration of DNA and the elongated cylindrical shape of chromosomes and 2) the known self‐associative properties of chromatin, and also with 3) an effective protection of chromosomal DNA from topological entanglement and mechanical breakage. The multilayer chromosome model, in which a repetitive weak interaction between nucleosomes at the nanoscale produces the stacking of many chromatin layers, is compatible with all these constraints. The self‐organization of the multilayer structure of the whole chromosome is consistent with current knowledge of the self‐assembly of micrometric structures from different repetitive building blocks. The multilayer model justifies the geometry of chromosome bands and translocations, and is compatible with feasible physical mechanisms for the control of gene expression, and for DNA replication, repair, and segregation to daughter cells.
Effect of interfacial properties between polyethylene and polyvinyl alcohol fiber/cement matrix on properties of mortar and ECC
Authors: Fan Qichang , Zheng Yuanyuan , He Chunhui , Meng Dan , Guo Qun , Liu Yiming
Published: September 2024

To explore the influence of the interface properties between fiber/cement matrix on the performance of fiber‐modified cement‐based composite. Polyethylene (PE) and polyvinyl alcohol fiber (PVA) are brought in the cement‐based materials to prepare mortar and Engineered Cementitious Composite (ECC) samples. The mortar's mechanical, and ECC's tensile capacity, four‐point bending and porosity were tested to verify the interface's influence on samples' performance. Furthermore, the water contact angle was used to analyze the wettability of the fiber, and a scanning electron microscope (SEM) was used to observe the fiber/matrix interface on the microscopic scale. Molecular dynamics simulation was performed to calculate the interfacial paraments from an atomic scale. The results shows that fiber increases the toughness of the mortar and improved its flexural strength. Through SEM, it was found that PVA fiber can form tight adsorption with the hydration matrix. While there are many apparent cracks and pores at the PE/matrix interface, the poor bonding destroys the matrix's structure and reduces its compressive strength. By analyzing the performance of ECC samples, it was known that PVA‐ECC's strain rate can reach 5.73%, while PE‐ECC is 4.20%. PE fiber has higher mechanical strength and can bear more loads, it helps PE‐ECC to obtain a greater modulus of rapture. Nuclear magnetic resonance results showed that the porosity of PVA‐ECC is lower than PE‐ECC. The ability of PE‐ECC to resist external interference is weak, and the interface of PE/matrix is easily damaged. Molecule dynamics simulation results indicated the adsorption energy between PVA/CSH is 6.17 times that of PE/CSH. The PVA/C‐S‐H interface tends to form CaO and H‐bonds to strengthen the bonding, the bonding has limited the movement of atoms and making the PVA chains tightly adsorbed on the CSH surface. While the adsorption between PE and CSH is weak, the PE will detach from the CSH surface and form aggregates. Moreover, PVA and water molecules form a stable hydrogen bond network to promote the hydration production grows on the surface of PVA fiber. However, PE fiber is complex enough to adsorb water molecules and hardly encourage the development of pores at the interface. By analyzing the properties of the interface between different fibers and cement matrix can provide insights for strengthening the interface properties of fiber cement matrix, and then improve the properties of fiber cement‐based composites.
Integrative analysis of bulk and single‐cell RNA sequencing reveals sphingolipid metabolism and immune landscape in clear cell renal cell carcinoma
Authors: Xie Dongdong , Han Zhitao , Wang Yu , Shi Haoyu , Wu Xiang , Wu Jiaqing , Dai Yingbo
Published: September 2024

Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive behavior and complex molecular heterogeneity, posing significant challenges for treatment and prognostication. This study offers a comprehensive analysis of ccRCC by leveraging both bulk and single‐cell RNA sequencing data, with a specific aim to unravel the complexities of sphingolipid metabolism and the intricate dynamics within the tumor microenvironment (TME). By examining ccRCC samples sourced from public databases, our investigation delves deep into the genetic and transcriptomic landscape of this cancer type. Employing advanced analytical techniques, we have identified pivotal patterns in gene expression and cellular heterogeneity, with a special focus on the roles and interactions of various immune cells within the TME. Significantly, our research has unearthed insights into the dynamics of sphingolipid metabolism in ccRCC, shedding light on its potential implications for tumor progression and strategies for immune evasion. A novel aspect of this study is the development of a risk score model designed to enhance prognostic predictions for ccRCC patients, which is currently pending external validation to ascertain its clinical utility. Despite its contributions, the study is mindful of its limitations, including a reliance on observational data from public sources and a primary focus on RNA sequencing data, which may constrain the depth and generalizability of the findings. The study does not encompass critical aspects, such as protein expression, posttranslational modifications, and comprehensive metabolic profiles. Moreover, its retrospective design underscores the necessity for future prospective studies to solidify these preliminary conclusions. Our findings illuminate the intricate interplay between genetic alterations, sphingolipid metabolism, and immune responses in ccRCC. This research not only enhances our understanding of the molecular foundations of ccRCC but also paves the way for the development of targeted therapies and personalized treatment modalities. The study underlines the importance of cautious interpretation of results and champions ongoing research using diverse methodologies to thoroughly comprehend and effectively combat this formidable cancer type.
Correlation of greyzone fibrosis compared to troponin T and late gadolinium enhancement with survival and ejection fraction in patients after acute myocardial infarction
Authors: Schmitt Ramona , Staats Clara , Kaier Klaus , Ahlgrim Christoph , Hein Manuel , Brado Johannes , Steinhoff Philipp , Billig Hannah , Soschynski Martin , Krauss Tobias , Schlett Christopher L. , Westermann Dirk , Neumann Franz-Josef , Ruile Philipp , Breitbart Philipp
Published: September 2024

Aims

To quantify greyzone fibrosis (GZF) in patients after acute myocardial infarction (MI) and to evaluate its correlation with MI-free survival and improvements in left ventricular ejection fraction (LVEF) compared with the established risk factors high-sensitivity cardiac troponin T (hs-cTnT) and Late Gadolinium Enhancement (LGE).

Methods and results

The study involved 176 patients who experienced acute MI and underwent cardiac magnetic resonance (CMR) prior to hospital discharge, followed by a second CMR on average six months later. LGE was quantified in both examinations, a separate analysis of the GZF was conducted only in the follow-up CMR after resolution of the initial infarct edema. LVEF was measured in both CMR. hs-cTnT levels were assessed at hospital admission, as well as 8, 16, 24, 48 and 72 h after coronary intervention. Telephone follow-ups were conducted annually for up to 8 years. LGE measurements showed better correlation with MI-free survival (Harrell’s C of 0.711 of LGE mass) compared to GZF (0.579 of GZF mass). Additionally, hs-cTnT outperformed GZF (Harrell’s C of 0.645). As an univariable predictor for MI-free survival, only hs-cTnT reached significance (p < 0.05). With regard to improvements in ejection fraction, both hs-cTnT and LGE measurements showed acceptable correlation with improvement in ejection fraction (p < 0.05), while GZF measurements showed no correlation (p > 0.5).

Conclusions

In CMR, the assessment of GZF demonstrated inferior p correlation compared to hs-cTnT and LGE in patients after acute MI with respect to the endpoint of MI-free survival. Furthermore, GZF showed no correlation with the improvement of LVEF.

Graphical abstract
Signed Barcodes for Multi-parameter Persistence via Rank Decompositions and Rank-Exact Resolutions
Authors: Botnan Magnus Bakke , Oppermann Steffen , Oudot Steve
Published: September 2024

In this paper, we introduce the signed barcode, a new visual representation of the global structure of the rank invariant of a multi-parameter persistence module or, more generally, of a poset representation. Like its unsigned counterpart in one-parameter persistence, the signed barcode decomposes the rank invariant as a $${\mathbb {Z}}$$
Z
-linear combination of rank invariants of indicator modules supported on segments in the poset. We develop the theory behind these decompositions, both for the usual rank invariant and for its generalizations, showing under what conditions they exist and are unique. We also show that, like its unsigned counterpart, the signed barcode reflects in part the algebraic structure of the module: specifically, it derives from the terms in the minimal rank-exact resolution of the module, i.e., its minimal projective resolution relative to the class of short exact sequences on which the rank invariant is additive. To complete the picture, we show some experimental results that illustrate the contribution of the signed barcode in the exploration of multi-parameter persistence modules.
Helicobacter pylori in oral cavity: current knowledge
Authors: Costa Liana Cristina Melo Carneiro , Carvalho Maria das Graças , Vale Filipa F. , Marques Andreia T. , Rasmussen Lucas Trevizani , Chen Tsute , Barros-Pinheiro Melina
Published: September 2024

The oral cavity may play a role as a reservoir and in the transmission and colonization of Helicobacter pylori. The route of transmission for H. pylori is not fully understood. The prevalence of this pathogen varies globally, affecting half of the world’s population, predominantly in developing countries. Here, we review the prevalence of H. pylori in the oral cavity, the characteristics that facilitate its colonization and dynamics in the oral microbiome, the heterogeneity and diversity of virulence of among strains, and noninvasive techniques for H. pylori detection in oral samples. The prevalence of H. pylori in the oral cavity varies greatly, being influenced by the characteristics of the population, regions where samples are collected in the oral cavity, and variations in detection methods. Although there is no direct association between the presence of H. pylori in oral samples and stomach infection, positive cases for gastric H. pylori frequently exhibit a higher prevalence of the bacterium in the oral cavity, suggesting that the stomach may not be the sole reservoir of H. pylori. In the oral cavity, H. pylori can cause microbiome imbalance and remodeling of the oral ecosystem. Detection of H. pylori in the oral cavity by a noninvasive method may provide a more accessible diagnostic tool as well as help prevent transmission and gastric re-colonization. Further research into this bacterium in the oral cavity will offer insights into the treatment of H. pylori infection, potentially developing new clinical approaches.
Mitigating inter-story drift concentration in seismic-resistant self-centering braced frames by using strong backup systems
Authors: Huang Jiahao , Zhu Songye
Published: September 2024

Seismic-resistant self-centering concentrically braced frames (SC-CBFs) are susceptible to the concentration of inter-story drifts during earthquakes owing to the relatively low energy dissipation ability of braces. To address this limitation, this study proposed a novel solution by designing a strong backup (SB) system to mitigate inter-story deformation concentration in “weak” stories. The proposed SB system consisting of truss members can be attached to the existing SC-CBF through pin connections, forming a system, termed strong backup SC-CBF (SC-CBF-SB), to promote a more uniform distribution of inter-story drifts along the height of the frame and mitigate the weak story behavior. A six-story chevron-braced frame is adopted to investigate the seismic performance of SC-CBF and SC-CBF-SB. Finite element models of SC-CBF and SC-CBF-SB are built. The mechanical characteristics and dynamic responses of the SC-CBF-SB are examined. To comprehensively evaluate the performance of both SC-CBF and SC-CBF-SB, static pushover analyses and nonlinear time-history analyses are conducted. Additionally, incremental dynamic analysis (IDA) is performed to evaluate the responses (particularly drift concentration) of both frame types subjected to increasing seismic intensity levels. Numerical results show that the maximum value of the drift concentration factor (DCF) is around 1.3 and 1.8 for SC-CBF-SB and SC-CBF, respectively, indicating that SC-CBF-SB can effectively mitigate inter-story drift concentration of SC-CBF. Meanwhile, the proposed SB system has a minimal negative impact on the favorable SC ability of the frame.
Systematic design approach for tailored air intake manifolds
Authors: Fiorineschi Lorenzo , Generini Giulio , Rotini Federico , Andreini Antonio
Published: September 2024

The work described in this paper aims to present a systematic approach for efficiently exploiting Computational Fluid Dynamics (CFD) simulations in early conceptual design phases. More specifically, the proposed procedure strives to use simplified CFD models with a limited amount of computational resources. It is then expected to better support preliminary evaluations of the fluid dynamic efficiency of early ideas, as well as to support idea generation. The proposed approach is focused on the conceptual design phase, intended here as the design stage where new ideas about forms and geometries for the fluid volume are generated. A systematic and iterative procedure has been devised and constitutes the core of the approach, which has been applied to a real case study, involving both industrial and academic staff. Five different concepts have been proposed and then evaluated from a manufacturing point of view by the industrial staff, who identified a preferred solution, which has been further developed and then verified through an additional simulation. The results show that by using the proposed systematic procedure, it has been possible to prevent the firm from developing a non-optimal solution, previously hypothesized by following a simple intuitive path based on precedent experiences. This work shows that the adoption of systematic design approaches integrated with modern tools like CFD can actually be a valid support also for SMEs.
Violence and Abuse Towards Grandparent Kinship Carers in Informal Kinship Care Context
Authors: Bentum Hajara , Banham Vicki , Adusei-Asante Kwadwo
Published: September 2024

Violence and abuse by grandchildren towards their grandparent kinship carers is an important but under-researched issue. Research evidence on the perceived legitimacy of aged-related myths, beliefs, and witchcraft accusations against older people, especially grandparents, in Ghana and Africa suggest that violence and abuse against grandparent kinship carers could be common. This study explored the types of violence or abuse experienced by grandparent kinship carers, and the meanings grandparents associate with the abuse. Thirty-one grandparents were recruited from four communities in Ghana following a horizontal network sampling approach and interviewed using a qualitative in-depth narrative storytelling strategy. Analysis of the narratives revealed three common types of abuse experienced by the grandparent kinship carers which were perpetrated by children living under their care: (1) insults and verbal abuse, (2) stealing and financial exploitation, and (3) physical threats. However, the grandparents rationalised and justified the abusive behaviours by attributing them to factors within the children’s eco-system, such as friends and household members. The findings highlighted three crucial interrelated factors that underlie these incidents of violence including cultural beliefs around witchcraft, family structural dynamics, and grandparents’ attitudes towards violence. Practical recommendations, including the development of a community normative change program, have been proposed to address violence by grandchildren towards grandparent kinship carers in Ghana.
Mindfulness for test anxiety and negative self-evaluation in high school
Authors: Dundas Ingrid , Nygård Inghild
Published: September 2024

There is growing evidence that mindfulness-based interventions reduce test anxiety in university-level students, but less is known about high school students. Adolescence is a time of frequent testing, identity concerns, and increases in self-conscious emotions. We hypothesized that test anxiety would be associated with negative self-referential thinking (negative self-thinking, study 1) and that Mindfulness-based Stress Reduction (MBSR) would reduce test anxiety, negative self-thinking, and self-judgment (study 2). 455 high school students (M age = 17.1 years (SD = 1.07), 43.2% female) reported their test anxiety and negative self-thinking in a cross-sectional study (study 1) and 33 high school students (mean age = 17.5 years (SD = 1.60, 88% female) reported measures at the pre-, post, and one-year follow-up during an 8-week MBSR course (study 2). Test anxiety was positively related to negative self-thinking (study 1). Test anxiety and self-judgment were reduced after participating in MBSR and remained low one year after (study 2). Negative self-thinking was not reduced during the intervention. MBSR seems promising in reducing test anxiety and self-judgment in adolescents and might increase awareness of negative self-thinking, perhaps also reducing the impact of such thoughts by encouraging observation of the thoughts as “events in the mind” rather than facts. Mindfulness training seems promising for reducing test anxiety in high school, but results need to be replicated in larger samples with a control group.
Future Shorelines: A Living Shoreline Site Selection and Design Decision Support Tool that Incorporates Future Conditions Induced by Sea Level Rise
Authors: Parkinson Randall W. , Juhasz Levente , Xu Jinwen , Fu Zhaohui Jennifer
Published: September 2024

Most living shoreline site selection and design decision support tools are based upon existing environmental conditions. We developed a web-based, geospatial tool called Future Shorelines that integrates high-resolution landscape elevation data and a matrix of locally derived NOAA Interagency Sea Level Rise Scenarios to characterize future conditions of submergence and shoreline translation induced by sea level rise. Once the practitioner selects a location of interest, sea level rise scenario (e.g., high), and target year (e.g., 2050), the tool will generate plan view and cross-sectional informational graphics specific to their choices. This information can then be paired with other menu options, like parcel ownership, to facilitate the planning and construction of nature-based shoreline stabilization solutions that (1) are located where opportunities for horizontal migration are optimized, (2) remain accessible for monitoring and maintenance, and (3) perform as intended over the design life of the installation. The tool’s menu options and the user interface were informed by project partner input solicited during numerous workshops convened over the duration of the 2-year project. This coproduction created a product that was familiar to the end user and therefore increased the likelihood that it would be utilized by them during the planning and design of living shoreline projects. Although developed for use in the Indian River Lagoon, located along the east-central Florida coast, it can be seamlessly replicated for application in other coastal regions of the USA where the requisite data are available.
Accelerated Approval for Cancer Drugs in the United States and the Clinical Evidence Required for Conversion to Regular Approval
Authors: Kato Satoshi , Ono Shunsuke
Published: September 2024

Purpose

Oncology products often leverage accelerated approval program to seek earlier launches in the United States. Little is known about how the Food and Drug Administration (FDA) has been balancing evidence and access, and the factors that may characterize post-accelerated approval requirements. The present study aimed to obtain insights on how accelerated approval is determined by investigating the balance between pre-accelerated approval and supplemental clinical evidence required for future regular approval.

Methods

The product properties, pre-accelerated approval evidence, rationale, post-accelerated approval requirements, and prior regulatory designations for oncology accelerated approvals were summarized based on public databases. Regression analyses were performed to investigate factors that may have been associated with the post-accelerated approval requirements.

Results

Hundred fifty-seven accelerated approvals were granted between 1992 and 2021. An increase in the number of pre-accelerated approval trials by one trial resulted in a 20% decrease in supplemental trials. The endpoint for the post-accelerated approval trial tended to be more robust when products were indicated for common cancers, while less robust when products had been used to treat fewer subjects, when products were indicated for respiratory and skin cancers, or when less malignant cancers were targeted.

Conclusions

Accelerated approvals for oncology products were often based on the response rate of a noncomparative trial. However, considerable variation was observed in the post-accelerated approval requirements. Factors such as the quality and quantity of pre-accelerated approval evidence, regulatory designations, and operational feasibility may have been considered when determining the accelerated approvals and post-accelerated approval requirements.
Revealing Roadblocks: Determinants Influencing Diagnostic Delays in Geriatric Cancer Patients – A Case Series Analysis at a Tertiary Cancer Center
Authors: Gupta Nidhi , Yadav Dev Kumar , Yadav Arun Kumar , Pandey Vinay Kumar , Singh Virendra
Published: September 2024

Background

This study delves into the critical issues related to delay in diagnosis and associated factors surrounding cancer care in the elderly, particularly focusing on the Indian demographic. The research approved by an institutional ethics committee, involved analyzing patient records and conducting interviews at a hospital to understand the time taken for cancer diagnosis and initiation of treatment in older patients.

Method and Result

A total of 80 study participants with histologically confirmed cancers were included in this study. The majority of patients belonged to the 65–75 years age group (n = 62, 77.5%). Only 18 (22.5%) were in the age group of 76–85 years. Of the total patients, the disease was confined to the primary site in 45 (56.2%) and it had nodal spread or metastasized in 35 (43.7%) at the time of first diagnosis. After treatment completion, during the first month of follow-up, 2 cases of gastrointestinal cancer died, and 1 case of genitourinary and other cancers died. During the second month of follow-up, 3 cases of gastrointestinal cancer died, 4 cases of genitourinary cancer died, and 2 cases of other cancers died. During the sixth month of follow-up, 2 cases of head & neck and genitourinary cancer died, and 5 cases of gastrointestinal and other cancers died.

Conclusion

The study highlights the need for increased awareness of delays in diagnosis and treatment of cancer in the geriatric age group and government intervention in the form of setting up geriatric cancer units to provide affordable cancer treatment aiming to improve the quality of life survival rates in this vulnerable population.