bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Ground Reaction Forces, Foot Positions and Type of Clubs Used in Golf: A Systematic Review and Meta-Analysis
Authors: You Xinci , Xu Yining , Liang Minjun , Baker Julien S. , Gu Yaodong
Published: June 2023

Background: Despite the growing interest in golf, the impact of motion control strategy on golf performance may be uncertain. A network meta-analysis was conducted to investigate the relationships between ground reaction force (GRF), foot positions, and club types in golf and determine whether different clubs have a different impact when swinging. Methods: Three databases were searched from the time of inception to March 2023. Eligibility criteria included studies that provided data using a driver to swing and compared outcomes to control data. Results: Searches yielded 6527 studies. Seven studies met the selection criteria (n = 422 participants). The results showed that an iron 6 is the best when considering the trail foot vertical ground reaction force (TVGRF), trail foot anteroposterior ground reaction force (TAGRF), and lead foot vertical ground reaction force (LVGRF). The pitching wedge was the best in the lead foot mediolateral ground reaction force (LMGRF) and lead foot anteroposterior ground reaction force (LAGRF). Iron 7 was the best in the trail foot mediolateral ground reaction force (TMGRF), and the lead foot was larger than the trail foot to the vertical GRF. Discussion: The study found that clubs may influence a player’s posture and swing power because golf clubs are available in various lengths and shapes. The lead foot generates a larger GRF than the trail foot; three-dimensional GRFs differ among golf clubs. When a golfer aims to maximize the distance of their drives, they must generate relatively more resultant horizontal reaction force (RFH). Golfers often use different clubs to achieve optimal performance on the course by controlling their motion. However, there needs to be a focus on the quality of the included studies because the sample size was too small, increasing the risk of bias associated with the results.
Comparative Analysis of Machine Learning Models for Predicting Crack Propagation under Coupled Load and Temperature
Authors: Omar Intisar , Khan Muhammad , Starr Andrew
Published: June 2023

Crack propagation in materials is a complex phenomenon that is influenced by various factors, including dynamic load and temperature. In this study, we investigated the performance of different machine learning models for predicting crack propagation in three types of materials: composite, metal, and polymer. For composite materials, we used Random Forest Regressor, Support Vector Regression, and Gradient Boosting Regressor models, while for polymer and metal materials, we used Ridge, Lasso, and K-Nearest Neighbors models. We trained and tested these models using experimental data obtained from crack propagation tests performed under varying load and temperature conditions. We evaluated the performance of each model using the mean squared error (MSE) metric. Our results showed that the best-performing model for composite materials was Gradient Boosting Regressor, while for polymer and metal materials, Ridge and K-Nearest Neighbors models outperformed the other models. We also validated the models using additional experimental data and found that they could accurately predict crack propagation in all three materials with high accuracy. The study’s findings provide valuable insights into crack propagation behavior in different materials and offer practical applications in the design, construction, maintenance, and inspection of structures. By leveraging this knowledge, engineers and designers can make informed decisions to enhance the strength, reliability, and durability of structures, ensuring their long-term performance and safety.
Safety and Stability Analysis of Demolition and Reconstruction of Existing Railway Bridge Piers and Caps
Authors: Pan Pengxu , Chen Wei , Wu Pei
Published: June 2023

The process of bridge reconstruction often involves the demolition and reconstruction of bridge piers and caps, while most of the construction methods used in the previous bridge reconstruction projects changed the bridge-bearing positions. In this paper, an in situ replacement scheme of bridge piers and caps is proposed, which can maintain the existing stress state of the bridge without changing the bearing position. In order to figure out the safety and stability of the in situ replacement scheme of existing railway bridges, a steel support system model for the removal and reconstruction of the bridge piers and caps is established by ABAQUS, according to a domestic railway bridge reconstruction project, and verified by field measurement test. Based on the model, the stress and deformation of the steel support system under a trainload are analyzed, as well as those of the bearing foundation and the superstructure. The results show that the steel support system and steel pipe piles located directly below the line carrying the trainload are subjected to the greatest stress and deformation. While under various load conditions, the stress and deformation of the main components in the steel support system of the in situ replacement scheme meet the design requirements, and the structure is safe under a trainload. In addition, guided by the numerical calculation results, the implementation scheme, existing problems, and solutions of the project are introduced in detail, which can provide a reference for similar projects.
Use of Underwater-Image Color to Determine Suspended-Sediment Concentrations Transported to Coastal Regions
Authors: Kang Woochul , Lee Kyungsu , Kim Seongyun
Published: June 2023

The amount of suspended sediment transported from rivers to the ocean fluctuates over time, with a substantial increase occurring during storm events. This surge in sediment poses numerous challenges to coastal areas, highlighting the importance of accurately assessing the sediment load to address these issues. In this study, we developed and experimentally verified a novel method for suspended-sediment-discharge quantification in estuaries and coasts using underwater imaging. Specifically, red clay samples with different particle sizes were introduced into separate tanks containing clean water. After adequate mixing, the concentration, particle size, turbidity, and water quality were measured and analyzed using LISST-200x and EXO2 Multiparameter Sonde sensors. To maintain constant lighting conditions, a camera box was created for filming. Based on the experimental results, a turbidity–concentration relationship formula was derived. The proposed regression equation revealed that the relationship between the turbidity and estimated suspended-sediment concentration was significantly affected by the particle size, and the prediction results were underestimated under high-concentration conditions. Using blue, green, and gray band values, a multiple regression model for estimating suspended-sediment concentrations was developed; its predictions were better than those obtained from the turbidity–concentration relationship. Following efficiency improvements through additional approaches considering underwater-image filming conditions and characteristics of actual streams, estuaries, and coasts, this method could be developed into an easily usable technique for sediment-discharge estimation, helping address sediment-related issues in estuaries and coastal regions.
Single Nucleotide Polymorphisms of FAM13A Gene in Chronic Obstructive Pulmonary Disease—A Case Control Study in Vietnam
Authors: Pham Khanh Hoang , Tran Nhung Thi Cam , Tran Hung Do , Ngo Toan Hoang , Tran Van De , Ly Hung Huynh Vinh , Pham Nga Thi Ngoc , Nguyen Thang , Nguyen Binh Huy , Nguyen Kien Trung
Published: June 2023

Background: In 2018, GOLD addressed the issues of genotypes associated with risk factors for COPD. The genome-wide association study (GWAS) demonstrated an association between COPD and several genetic variants of single nucleotide polymorphisms (SNPs) of the FAM13A gene with the risk of COPD. Objective: To study the single nucleotide polymorphisms rs2869967 and rs17014601 of the FAM13A gene in chronic obstructive pulmonary disease. Subjects and research methods: 80 subjects diagnosed with COPD and 80 subjects determined not to have COPD according to GOLD 2020 criteria; the subjects were clinically examined, interviewed, and identified as possessing single nucleotide polymorphisms using the sanger sequencing method on whole blood samples. Results: The male/female ratio of the patient group and the control group was 79/1 and 39/1, respectively. The percentages of C and T alleles of rs2869967 in COPD patients were 50.6% and 49.4%, respectively. The percentages of C and T alleles of rs17014601 in COPD patients were 31.9% and 68.1%, respectively. At rs17014601, the ratio values of alleles T and C in the disease group and the control group were markedly different, making them statistically reliable (p = 0.031). The rate of CT genotype in the group of patients was considerably higher than that of the control group. The TT homozygous genotype had a lower risk of COPD compared with the other genotypes in the dominant model (ORTT/(CC + CT) = 0.441; CI95% = 0.233–0.833); this difference was statistically significant (p = 0.012). Conclusions: With rs17014601, it is characteristic that the frequency of the T allele appears more than the C allele, and the CT heterozygous phenotype accounts for the highest proportion in rs17014601 and rs2869967 recorded in COPD patients. There is an association between the genetic variant of the SNP FAM13A-rs17014601 and the risk of COPD.
Sensitivity of Vegetation Productivity to Extreme Droughts across the Yunnan Plateau, China
Authors: Lin Chen , He Yunling , Wang Zhenyan
Published: June 2023

Extreme drought has negative impacts on the health of vegetation and the stability of ecosystems. In this study, the CASA model was employed to estimate the net primary productivity of vegetation over the Yunnan Plateau. The time-lag effects on vegetation were observed within a 0–6 month period of extreme droughts using the Pearson correlation coefficient. The resistance of vegetation during extreme droughts was quantified, and the recovery capability of vegetation following these events was analyzed using the ARIMA model. Moreover, the study investigated the response of vegetation to extreme droughts across diverse altitudinal gradients. The results showed that: (1) This round of extreme drought led to a decrease in the NPP of vegetation in the Yunnan Plateau. (2) Vegetation exhibits a 1–3-month lag period in response to extreme drought, with forests showing slower responses than grasslands and shrubs and higher resistance to the drought. Except for agricultural vegetation, most other vegetation types are able to recover their productivity within a year. (3) Vegetation above 3000 m is less susceptible to the impacts of extreme drought. With increasing elevation, forests exhibit an earlier lag period in response to extreme drought and an increase in resistance, but lower elevation vegetation demonstrates better recovery from extreme drought events. Shrub vegetation shows the highest resistance at elevations between 3000–4000 m, and shrubs at middle to high elevations have better recovery capacity than those at low elevations. Grassland vegetation exhibits increased resistance to extreme drought with higher elevation and shows better recovery. Agricultural vegetation demonstrates higher resistance at middle to high elevations, with no significant elevation differences in recovery capacity. Extreme drought events not only have a lag effect on the vegetation ecosystem, but also affect its stability and resilience to future drought events. To adapt to climate change, future research should emphasize the role of small-scale climate in vegetation’s response to drought.
Tuning Monte Carlo Models to Reproduce Cosmic Radiation Interacting with the Earth’s Atmosphere
Authors: Ajaz Muhammad , Haj Ismail Abd , Waqas Muhammad , Shehzadi Ramoona , Asghar Ishrat , Younis Hannan , Mian Mateen Ullah , AbdelKader Atef , Adil Khan Muhammad , Safeen Kashif
Published: June 2023

In this work, we performed a comparative study between HIJING, Sibyll, and QGSJET model-based event generators. Such Monte Carlo (MC) models are used to simulate the interaction and propagation of high-energy cosmic radiation (e.g., coming from the sun) with the Earth’s atmosphere. The global event observables selected for the study were the transverse momentum (pT) spectra and rapidity density distributions of strange particles (KS0, Λ, and Ξ−). This study was performed in the STAR and CMS fiducial phase spaces by simulating the strange particles in pp collisions at s = 200 GeV, 900 GeV, and 7 TeV, and the simulations were then compared to the experimental measurements. It was observed that none of the discussed model-based event generators ultimately predicted the experimental results, except QGSJET, which generally agrees reasonably with the data. However, QGSJET does not produce Ξ particles; therefore, it does not provide any predictions for Ξ. The other two models reproduced the data only in a limited rapidity or transverse momentum region while mainly underpredicting the data in the rest of the areas. These cosmic radiation simulation models are capable of covering the mid-rapidity regions of density distributions. Utilizing model-based observations, some fundamental parameters can be re-tuned and extrapolations to the highest energies can be investigated. Furthermore, these observations can provide valuable insights that could potentially constrain and improve perturbative- and non-perturbative-based QCD event generators, thereby facilitating a better understanding of the underlying physics.
ENSO Forcing of Rainfall Erosivity in the Wuding River Basin
Authors: Zhao Jing , Zhao Jiayang , Huang Qiang
Published: June 2023

Rainfall erosivity (RE) is an important indicator of the ability of rainfall to cause soil erosion and is linked to ENSO through the transport of rainfall. Accurate assessment of RE and improved understanding of RE are essential for soil erosion prediction, optimization of soil and water conservation measures, and ecological management and restoration. Therefore, the Wuding River Basin, a typical ecologically fragile area, is selected as the research area. The erosivity model based on daily rainfall was first used to calculate RE, and the temporal and periodic characteristics of RE are studied. Then the effects of the Southern Oscillation Index (SOI), the Surface Temperature of the Central East Equatorial Pacific Ocean (SST), and the Multivariate ENSO Index (MEI) on RE are explored by using cross wavelet technique. Results indicated that: (1) the concentration of rainfall leads to the largest RE values in summer compared with other seasons, accumulating about 69% of the annual RE; (2) The overall trend of increasing RE in the Wuding River basin is not significant, but shows an abrupt change in 2015; (3) the influence of the SOI and SST indices of ENSO events on RE is significant, which is shown to be a statistically significant correlation (95% confidence level), indicating that ENSO has a strong influence on the changing pattern of RE. These findings are helpful in predicting soil erosion and are significant for developing further erosion control measures.
Outdoor Thermal Environment Regulation of Urban Green and Blue Infrastructure on Various Types of Pedestrian Walkways
Authors: Pan Haonan , Luo Yihan , Zeng Liyue , Shi Yurong , Hang Jian , Zhang Xuelin , Hua Jiajia , Zhao Bo , Gu Zhongli , Buccolieri Riccardo
Published: June 2023

Urban green and blue infrastructure (GBI) is effective in urban heat mitigation. However, the diurnal variations in the thermal regulation of GBI on different types of urban pedestrian walkways in the subtropical humid climate zone are unclear. Based on traverse measurements in January 2022, this study investigates how outdoor air temperature (Ta) and wet-bulb temperature (Tw) at the pedestrian level are affected by various urban morphology and GBI characteristics in the central urbanized area of Guangzhou (China). Six building-related, three vegetation-related, and three water-related parameters were applied in the analyses. Results show that green infrastructure (GI) has the strongest cooling effect (Pearson’s coefficient r = −0.33~−0.54) on Ta on cloudy evenings and the weakest cooling effect (r = −0.22~−0.32) on clear evenings. Blue infrastructure (BI) exhibits the highest correlations with the cooling effect for Ta on clear afternoons (r = −0.35~−0.51) and weaker, but more consistent, correlations throughout cloudy days (r = −0.23~−0.43). Strong correlations between GI and Tw cooling are observed in the morning and evening on clear days (r = −0.13~−0.48), while BI exhibits the strongest correlation with Tw cooling on clear afternoons (r = −0.13~−0.37). In addition, both GI and BI show a greater cooling effect on both Ta and Tw in low-rise areas compared to high-rise areas. Compared to the individual GI or BI, the integrated GBI has a higher cooling intensity for both Ta and Tw in high-rise areas. However, the cooling potential of integrated GBI is slightly lower for both Ta and Tw during noon and afternoon in low-rise areas. The findings of this study give insights into urban GBI planning and design of specific urban microclimate regulation strategies.
Impacts of the Surface Potential Vorticity Circulation over the Tibetan Plateau on the East Asian Monsoon in July
Authors: Liu Yimin , Luan Lulu , Wu Guoxiong , Ma Tingting
Published: June 2023

Based on the definition of potential vorticity substance (W) and its equation, an index “iPV” representing the leading mode of the surface potential vorticity circulation (PVC) over the Tibetan Plateau is defined to characterize the orographic potential vorticity (PV) forcing on the atmospheric general circulation. The relationships between the iPV index and the East Asian monsoon in July, as well as the Silk Road pattern in Eurasia, are investigated on an interannual time scale. Results show that the iPV in July is closely related to the interannual variability of the East Asian monsoon. Corresponding to the positive phase of iPV with negative (positive) PVC over the north (south) of the plateau, strong positive PV anomalies and westerly flows develop in the troposphere over the plateau. Consequently, in the downstream region, the zonal PV advection increases with height just above the Jianghuai Meiyu front, which is conducive to the generation of upward movement. Over the East Asian area, the upper troposphere is controlled by the eastward shifted South Asian High. In the lower troposphere, the southwesterly flow anomaly on the northwestern side of the strengthened western Pacific subtropical high transports abundant water vapor to the north, forming a convergence in the Jianghuai area, leading to the formation of large-scale precipitation along the Meiyu front. Results from partial correlation analysis also demonstrate that the link between the variability of the East Asian monsoon in July and the plateau PV forcing is affected very little by the Silk Road pattern, whereas the plateau PV forcing plays a key “bridging” role in the influence of the Silk Road pattern on the East Asian monsoon.
In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders
Authors: Sierra-Delgado Julieth Andrea , Sinha-Ray Shrestha , Kaleem Abuzar , Ganjibakhsh Meysam , Parvate Mohini , Powers Samantha , Zhang Xiaojin , Likhite Shibi , Meyer Kathrin
Published: June 2023

Spinal Muscular Atrophy (SMA) is the leading genetic cause of infant mortality. The most common form of SMA is caused by mutations in the SMN1 gene, located on 5q (SMA). On the other hand, mutations in IGHMBP2 lead to a large disease spectrum with no clear genotype–phenotype correlation, which includes Spinal Muscular Atrophy with Muscular Distress type 1 (SMARD1), an extremely rare form of SMA, and Charcot–Marie–Tooth 2S (CMT2S). We optimized a patient-derived in vitro model system that allows us to expand research on disease pathogenesis and gene function, as well as test the response to the AAV gene therapies we have translated to the clinic. We generated and characterized induced neurons (iN) from SMA and SMARD1/CMT2S patient cell lines. After establishing the lines, we treated the generated neurons with AAV9-mediated gene therapy (AAV9.SMN (Zolgensma) for SMA and AAV9.IGHMBP2 for IGHMBP2 disorders (NCT05152823)) to evaluate the response to treatment. The iNs of both diseases show a characteristic short neurite length and defects in neuronal conversion, which have been reported in the literature before with iPSC modeling. SMA iNs respond to treatment with AAV9.SMN in vitro, showing a partial rescue of the morphology phenotype. For SMARD1/CMT2S iNs, we were able to observe an improvement in the neurite length of neurons after the restoration of IGHMBP2 in all disease cell lines, albeit to a variable extent, with some lines showing better responses to treatment than others. Moreover, this protocol allowed us to classify a variant of uncertain significance on IGHMBP2 on a suspected SMARD1/CMT2S patient. This study will further the understanding of SMA, and SMARD1/CMT2S disease in particular, in the context of variable patient mutations, and might further the development of new treatments, which are urgently needed.
Resting Heart Rate Affects Heart Response to Cold-Water Face Immersion Associated with Apnea
Authors: Malinowski Krzysztof S. , Wierzba Tomasz H. , Neary J. Patrick , Winklewski Paweł J. , Wszędybył-Winklewska Magdalena
Published: June 2023

The regular cardiac response to immersion of the face in cold water is reduction in heart rate (HR). The highly individualized and unpredictable course of the cardiodepressive response prompted us to investigate the relationship between the cardiac response to face immersion and the resting HR. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20–27 years) and a BMI of 21.49 kg/m2 (16.60–28.98). The face-immersion test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in cold water (8–10 °C) for as long as possible. Measurements included determination of minimum, average, and maximum HR at rest and minimum and maximum HR during the cold-water face-immersion test. The results indicate a strong relationship between the cardiodepressive reaction of the immersion of the face and the minimum HR before the test, as well as a relationship between the maximum HR during the test and the maximum HR at rest. The results also indicate a strong influence of neurogenic HR regulation on the described relationships. The parameters of the basal HR can, therefore, be used as prognostic indicators of the course of the cardiac response of the immersion test.
OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1
Authors: Lee Yuri , Piao Hai-long , Kim Jongchan
Published: June 2023

The Wnt signaling pathway plays a critical role in regulating normal cellular processes, including proliferation, differentiation, and apoptosis. Dysregulation of Wnt signaling has been implicated in various human diseases, including cancer. β-catenin and LEF1 are key mediators of Wnt signaling, and their dysregulation is a hallmark of many cancer types. In this study, we aimed to identify the deubiquitinases (DUBs) that regulate the Wnt signaling pathway through the essential component LEF1. Screening candidate DUBs from the human DUB library, we discovered that OTUD7B interacts with LEF1 and activates Wnt signaling. OTUD7B and LEF1 interact with each other through the UBA and HMG domains, respectively. Furthermore, OTUD7B promotes the nuclear localization of LEF1, leading to an increased interaction with β-catenin in the nucleus while not noticeably affecting ubiquitination on LEF1. Using qPCR array analysis, we found that OTUD7B overexpression leads to an upregulation of 75% of the tested Wnt target genes compared to the control. These findings suggest that OTUD7B may serve as a potential therapeutic target in human diseases, including cancers where Wnt signaling is frequently dysregulated.
Research on Walking Gait Planning and Simulation of a Novel Hybrid Biped Robot
Authors: Sun Peng , Gu Yunfei , Mao Haoyu , Chen Zhao , Li Yanbiao
Published: June 2023

A kinematics analysis of a new hybrid mechanical leg suitable for bipedal robots was carried out and the gait of the robot walking on flat ground was planned. Firstly, the kinematics of the hybrid mechanical leg were analyzed and the applicable relevant models were established. Secondly, based on the preliminary motion requirements, the inverted pendulum model was used to divide the robot walking into three stages for gait planning: mid-step, start and stop. In the three stages of robot walking, the forward and lateral robot centroid motion trajectories and the swinging leg joint trajectories were calculated. Finally, dynamic simulation software was used to simulate the virtual prototype of the robot, achieving its stable walking on flat ground in the virtual environment, and verifying the feasibility of the mechanism design and gait planning. This study provides a reference for the gait planning of hybrid mechanical legged bipedal robots and lays the foundation for further research on the robots involved in this thesis.
Effect of Platelet-Rich Plasma Addition on the Chemical Properties and Biological Activity of Calcium Sulfate Hemihydrate Bone Cement
Authors: Liu Jingyu , Wang Yifan , Liang Yanqin , Zhu Shengli , Jiang Hui , Wu Shuilin , Ge Xiang , Li Zhaoyang
Published: June 2023

Currently, platelet-rich plasma (PRP) is an attractive additive for bone repair materials. PRP could enhance the osteoconductive and osteoinductive of bone cement, as well as modulate the degradation rate of calcium sulfate hemihydrate (CSH). The focus of this study was to investigate the effect of different PRP ratios (P1: 20 vol%, P2: 40 vol%, and P3: 60 vol%) on the chemical properties and biological activity of bone cement. The injectability and compressive strength of the experimental group were significantly higher than those of the control. On the other hand, the addition of PRP decreased the crystal size of CSH and prolonged the degradation time. More importantly, the cell proliferation of L929 and MC3T3-E1 cells was promoted. Furthermore, qRT-PCR, alizarin red staining, and western blot analyses showed that the expressions of osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) genes and β-catenin protein were up-regulated, and mineralization of extracellular matrix was enhanced. Overall, this study provided insight into how to improve the biological activity of bone cement through PRP incorporation.
Highly Conserved Microchromosomal Organization in Passeriformes Birds Revealed via BAC-FISH Analysis
Authors: de Souza Marcelo Santos , Barcellos Suziane Alves , Tura Victoria , Bobrowski Vera Lúcia , Garnero Analía Del Valle , Gunski Ricardo José , Griffin Darren K. , Kretschmer Rafael
Published: June 2023

Passeriformes birds are widely recognized for their remarkable diversity, with over 5700 species described so far. Like most bird species, they possess a karyotype characteristic of modern birds, which includes a bimodal karyotype consisting of a few pairs of macrochromosomes and many pairs of microchromosomes. Although the karyotype is typically 2n = 80, the diploid number can atypically vary greatly, ranging from 56 to approximately 100 chromosomes. In this study, we aimed to understand the extent of conservation of the karyotype’s organizational structure within four species of this group using Bacterial Artificial Chromosomes via Fluorescence In Situ Hybridization (BAC-FISH) with microchromosome probes from Chicken (Gallus gallus) or Zebra Finch (Taeniopygia guttata) per microchromosomes (GGA10-28, except GGA16). By examining the chromosome complement of four passerine species—the Streaked Flycatcher (Myiodynastes maculatus), Shiny Cowbird (Molothrus bonariensis), Southern House Wren (Troglodytes aedon), and Double-collared Seedeater (Sporophila caerulescens)—we discovered a new chromosome number for Southern House Wren. Through FISH experiments, we were able to observe the same pattern of microchromosome organization as in the common ancestor of birds. As a result, we propose a new diploid number for Southern House Wren and confirm the conservation status of microchromosome organization, which may confer evolutionary advantages to this group.
A Weakly Supervised Deep Learning Model and Human–Machine Fusion for Accurate Grading of Renal Cell Carcinoma from Histopathology Slides
Authors: Zheng Qingyuan , Yang Rui , Xu Huazhen , Fan Junjie , Jiao Panpan , Ni Xinmiao , Yuan Jingping , Wang Lei , Chen Zhiyuan , Liu Xiuheng
Published: June 2023

(1) Background: The Fuhrman grading (FG) system is widely used in the management of clear cell renal cell carcinoma (ccRCC). However, it is affected by observer variability and irreproducibility in clinical practice. We aimed to use a deep learning multi-class model called SSL-CLAM to assist in diagnosing the FG status of ccRCC patients using digitized whole slide images (WSIs). (2) Methods: We recruited 504 eligible ccRCC patients from The Cancer Genome Atlas (TCGA) cohort and obtained 708 hematoxylin and eosin-stained WSIs for the development and internal validation of the SSL-CLAM model. Additionally, we obtained 445 WSIs from 188 ccRCC eligible patients in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort as an independent external validation set. A human–machine fusion approach was used to validate the added value of the SSL-CLAM model for pathologists. (3) Results: The SSL-CLAM model successfully diagnosed the five FG statuses (Grade-0, 1, 2, 3, and 4) of ccRCC, and achieved AUCs of 0.917 and 0.887 on the internal and external validation sets, respectively, outperforming a junior pathologist. For the normal/tumor classification (Grade-0, Grade-1/2/3/4) task, the SSL-CLAM model yielded AUCs close to 1 on both the internal and external validation sets. The SSL-CLAM model achieved a better performance for the two-tiered FG (Grade-0, Grade-1/2, and Grade-3/4) task, with AUCs of 0.936 and 0.915 on the internal and external validation sets, respectively. The human–machine diagnostic performance was superior to that of the SSL-CLAM model, showing promising prospects. In addition, the high-attention regions of the SSL-CLAM model showed that with an increasing FG status, the cell nuclei in the tumor region become larger, with irregular contours and increased cellular pleomorphism. (4) Conclusions: Our findings support the feasibility of using deep learning and human–machine fusion methods for FG classification on WSIs from ccRCC patients, which may assist pathologists in making diagnostic decisions.
Cognitive Aging in Older Breast Cancer Survivors
Authors: Root James C. , Li Yuelin , Schofield Elizabeth , Orlow Irene , Ryan Elizabeth , Traina Tiffany , Patel Sunita K. , Ahles Tim A.
Published: June 2023

Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two–five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 to 89 years utilizing cross-sectional cognitive performance data as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5- to 15-year survivors (N = 328) and non-cancer controls (N = 158) were assessed at enrollment and at 8, 16, and 24 months with standard neuropsychological tests and comprehensive geriatric assessment. Results: A cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower overall than controls in learning and memory (LM). Younger survivors, i.e., those under 75 years of age, exhibited lower performance in both LM and attention, and processing speed and executive function (APE), compared to controls, with no differences being observed between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Cognitive differences between the survivors and controls for the LM and APE domains were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.
pCR and 2-Year Disease-Free Survival: A Combination of the Two Endpoints as a New Classification for Locally Advanced Rectal Cancer Patients—An Updated Pooled Analysis of Eleven International Randomized Trials
Authors: Gambacorta Maria Antonietta , Chiloiro Giuditta , Masciocchi Carlotta , Mariani Silvia , Romano Angela , Gonnelli Alessandra , Gerard Jean-Pierre , Ngan Samuel , Rödel Claus , Bujko Krzysztof , Glynne-Jones Robert , van Soest Johan , Dekker Andre , Damiani Andrea , Valentini Vincenzo
Published: June 2023

LARC is managed by multimodal treatments whose intensity can be highly modulated. In this context, we need surrogate endpoints to help predict long-term outcomes and better personalize treatments. A previous study identified 2yDFS as a stronger predictor of OS than pCR in LARC patients undergoing neoadjuvant RT. The aim of this pooled analysis was to assess the role of pCR and 2yDFS as surrogate endpoints for OS in a larger cohort. The pooled and subgroup analyses were performed on large rectal cancer randomized trial cohorts who received long-course RT. Our analysis focused on the evaluation of OS in relation to the pCR and 2-year disease status. A total of 4600 patients were analyzed. Four groups were identified according to intermediate outcomes: 12% had both pCR and 2yDFS (the better); 67% achieved 2yDFS but not pCR (the good); 1% had pCR but not 2yDFS; and 20% had neither pCR nor 2yDFS (the bad). The pCR and 2yDFS were favorably associated with OS in the univariate analysis, and 2yDFS maintained a statistically significant association in the multivariate analysis independently of the pCR status. The combination of the pCR and 2yDFS results in a strong predictor of OS, whereas failure to achieve 2yDFS carries a poor prognosis regardless of the pCR status. This new stratification of LARC patients could help design predictive models where the combination of 2yDFS and pCR should be employed as the primary outcome.
TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
Authors: Zhao Davidson , Zarif Mojgan , Zhou Qianghua , Capo-Chichi José-Mario , Schuh Andre , Minden Mark D. , Atenafu Eshetu G. , Kumar Rajat , Chang Hong
Published: June 2023

TP53 mutations are associated with extremely poor outcomes in acute myeloid leukemia (AML). The outcomes of patients with TP53-mutated (TP53MUT) AML after different frontline treatment modalities are not well established. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for AML; however, long-term outcomes among patients with TP53MUT AML after allo-HCT are dismal, and the benefit of allo-HCT remains controversial. We sought to evaluate the outcomes of patients with TP53MUT AML after treatment with different frontline induction therapies and allo-HCT. A total of 113 patients with TP53MUT AML were retrospectively evaluated. Patients with TP53MUT AML who received intensive or azacitidine-venetoclax induction had higher complete remission rates compared to patients treated with other hypomethylating-agent-based induction regimens. However, OS and EFS were not significantly different among the induction regimen groups. Allo-HCT was associated with improved OS and EFS among patients with TP53MUT AML; however, allo-HCT was not significantly associated with improved OS or EFS in time-dependent or landmark analysis. While the outcomes of all patients were generally poor irrespective of therapeutic strategy, transplanted patients with lower TP53MUT variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher TP53 VAF. Our study provides further evidence that the current standards of care for AML confer limited therapeutic benefit to patients with TP53 mutations.
Maintaining Engagement in Adults with Neurofibromatosis Type 1 to Use the iCanCope Mobile Application (iCanCope-NF)
Authors: Buono Frank D. , Larkin Kaitlyn , Pham Quynh , De Sousa Diane , Zempsky William T. , Lalloo Chitra , Stinson Jennifer N.
Published: June 2023

Introduction: Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic condition in which chronic pain is a predominant issue. Given the rarity of the disease, there are limited psychosocial treatments for individuals with NF1 suffering with chronic pain. Using mobile applications can facilitate psychosocial treatments; however, there are consistent issues with engagement. Utilizing a mixed methodology, the current study evaluated the customized iCanCope mobile application for NF1 on increasing engagement through the usage of contingency management. Methods: A mixed methods study from a subset of data coming from a randomized clinical trial that occurred from January 2021 to August 2022 was undertaken. Two groups (iCC and iCC + CM) were exposed to the customized iCanCope mobile application in which engagement data were captured in real-time with daily check-ins for interference, sleep, mood, physical activity, energy levels, goal setting, and accessing article content (coping strategies). Additionally, semi-structured interviews were conducted to gain insight into the participants’ experience at the end of the trial. Results: Adults (N = 72) were recruited via NF patient advocacy groups. Significant differences were noted between the groups in total articles read (p = 0.002), goals achieved (p = 0.017), and goals created (p = 008). Additionally, there were significant differences observed between user-generated goals and those that were app recommended (p < 0.001). Both groups qualitatively reported positive feedback on the customized mobile application, indicating that continued usage and engagement of the mobile application were acceptable. Conclusions: Employing customized mobile applications for adults with NF1 along with contingency management can leverage self-managed pain treatments while providing auxiliary resources to this population.
Clinical Utility of Optical Genome Mapping and 523-Gene Next Generation Sequencing Panel for Comprehensive Evaluation of Myeloid Cancers
Authors: Sahajpal Nikhil Shri , Mondal Ashis K. , Singh Harmanpreet , Vashisht Ashutosh , Ananth Sudha , Saul Daniel , Hastie Alex R. , Hilton Benjamin , DuPont Barbara R. , Savage Natasha M. , Kota Vamsi , Chaubey Alka , Cortes Jorge E. , Kolhe Ravindra
Published: June 2023

The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping/fluorescent in situ hybridization (FISH) (cytogenetic analysis) and targeted gene panels (usually ≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Despite this combinatorial approach, ~50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the molecular etiology of many myeloid tumors. In this study, we evaluated the performance and clinical utility of combinatorial use of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 30 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel had an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Importantly, the IPSS-R cytogenetic risk group changed from very good/good to very poor in 22% of MDS (2/9) cases based on comprehensive profiling (karyotyping, FISH, and 54-gene panel vs. OGM and 523-gene panel), while additionally identifying six compound heterozygous events of potential clinical relevance in six cases (6/30, 20%). This cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers demonstrated increased yield of actionable targets that can potentially result in improved clinical outcomes.
Association between MGMT Enhancer Methylation and MGMT Promoter Methylation, MGMT Protein Expression, and Overall Survival in Glioblastoma
Authors: Zappe Katja , Pühringer Katharina , Pflug Simon , Berger Daniel , Böhm Andreas , Spiegl-Kreinecker Sabine , Cichna-Markl Margit
Published: June 2023

The repair protein O6-methylguanine-DNA methyltransferase (MGMT) is regulated epigenetically, mainly by the methylation of the MGMT promoter. MGMT promoter methylation status has emerged as a prognostic and predictive biomarker for patients with newly diagnosed glioblastoma (GBM). However, a strong negative correlation between MGMT promoter methylation and MGMT protein expression cannot be applied as a rule for all GBM patients. In order to investigate if the DNA methylation status of MGMT enhancers is associated with MGMT promoter methylation, MGMT expression, and the overall survival (OS) of GBM patients, we established assays based on high-resolution melting analysis and pyrosequencing for one intragenic and three intergenic MGMT enhancers. For CpGs in an enhancer located 560 kb upstream of the MGMT promoter, we found a significant negative correlation between the methylation status and MGMT protein levels of GBM samples expressing MGMT. The methylation status of CpGs in the intragenic enhancer (hs696) was strongly negatively correlated with MGMT promoter methylation and was significantly higher in MGMT-expressing GBM samples than in MGMT-non-expressing GBM samples. Moreover, low methylation of CpGs 01–03 and CpGs 09–13 was associated with the longer OS of the GBM patients. Our findings indicate an association between MGMT enhancer methylation and MGMT promoter methylation, MGMT protein expression, and/or OS.
SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells
Authors: Li Yu-He , Sun Chia-Cheng , Chen Po-Ming , Chen Hsin-Hung
Published: June 2023

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.
Mesoporous Silica-Based Catalysts for Biodiesel Production: A Review
Authors: Fatimah Is , Fadillah Ganjar , Sagadevan Suresh , Oh Won-Chun , Ameta Keshav Lalit
Published: June 2023

High demand for energy consumption forced the exploration of renewable energy resources, and in this context, biodiesel has received intensive attention. The process of biodiesel production itself needs to be optimized in order to make it an eco-friendly and high-performance energy resource. Within this scheme, development of low-cost and reusable heterogeneous catalysts has received much attention. Mesoporous silica materials with the characteristics of having a high surface area and being modifiable, tunable, and chemical/thermally stable have emerged as potential solid support of powerful catalysts in biodiesel production. This review highlights the latest updates on mesoporous silica modifications including acidic, basic, enzyme, and bifunctional catalysts derived from varied functionalization. In addition, the future outlook for progression is also discussed in detail.
The Role of Mesenchymal Stromal Cells and Their Products in the Treatment of Injured Spinal Cords
Authors: Slovinska Lucia , Harvanova Denisa
Published: June 2023

Spinal cord injury (SCI) is a destructive condition that results in lasting neurological damage resulting in disruption of the connection between the central nervous system and the rest of the body. Currently, there are several approaches in the treatment of a damaged spinal cord; however, none of the methods allow the patient to return to the original full-featured state of life before the injury. Cell transplantation therapies show great potential in the treatment of damaged spinal cords. The most examined type of cells used in SCI research are mesenchymal stromal cells (MSCs). These cells are at the center of interest of scientists because of their unique properties. MSCs regenerate the injured tissue in two ways: (i) they are able to differentiate into some types of cells and so can replace the cells of injured tissue and (ii) they regenerate tissue through their powerful known paracrine effect. This review presents information about SCI and the treatments usually used, aiming at cell therapy using MSCs and their products, among which active biomolecules and extracellular vesicles predominate.
Report on Existing Fireproof Construction Guidelines for Dwellings against Wildfires
Authors: Cantor Pedro , Bicelli António Renato , de Assis Ellon Bernardes , Arruda Mário Rui , Branco Fernando
Published: June 2023

This work presents a state-of-the-art review of existing fireproof construction guidelines for dwellings against wildfires. The most important wildfire-proof construction guidelines and codes for dwellings are presented, and these are later associated with existing fire engineering chapters associated with building codes. It was concluded that the variability in this subject is very high, and the approach to classifying the thermal effects in construction still lags behind scientific consensus. Moreover, the constructive requirements depend severally on the country’s building code when assessing the fireproof requirements for wildfire. Moreover, the thermal actions of wildfires in dwellings are presented and compared with classical ISO-834 standard fire curves, in which the maximum equivalent fire exposure time can range from 2 to 4 h depending on the country’s code. The key contributions of this work consist of (i) thoroughly disseminating codes and guidelines to promote scientific discussion in order to advance the wildfire fireproof standards dedicated to WUI; (ii) emphasizing the void in current codes in order to promote conversation between future researchers.