bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of immunomodulation therapy in immunocompromised patients with severe Covid-19 and high oxygen requirement
Authors: Goldstein Avigayil , Neuberger Ami , Darawsha Yazeed Qassem , Hussein Khetam , Shafat Tali , Grupel Daniel , strahilevitz Jacob , Israel Sarah , Weil Ariel , Ben-Ami Ronen , Elbaz Meital , Najjar-Debbiny Ronza , Bishara Jihad , Shlomai Amir , Landes Michal
Published: August 2023

Background & Objective: Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease. However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce. We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients.
Design and Participants: A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30- and 60-days mortality, super-infection and thromboembolic events.
Key Results: Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p=1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p=0.84) or thromboembolic events (8.3% vs 3.1%, p=0.39).
Conclusions: In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.
The effect of Whey protein and MBP (milk basic protein) on bone health parameters: A systematic review and meta-analysis of randomized clinical trials
Authors: Khodadadi Fatemeh , Morvaridzadeh Mojghan , Khodadadi Hashem , Parnian-khajehdizaj Nazila , Pizarro Ana Beatriz , lamir Amir Rashid
Published: August 2023

Background and Aims:
A major public health concern worldwide, osteoporosis causes an increased risk of bone fractures and a decrease in bone mineral density (BMD). The present systematic review and meta-analysis aimed to determine the effect of whey protein and MBP (milk basic protein) on bone health parameters.
Methods
We performed a systematic review and meta-analysis of randomized clinical trial (RCT) studies. The online databases of PubMed, Scopus, Web of Science, and Google Scholar was searched up to 30 July 2022, using controlled terms (e.g. MESH) and text words for milk protein or whey and bone-health outcomes, including lumbar-BMD, hip-BMD, Urinary N-terminal telopeptides of type I collagen (NTx) serum C-terminal telopeptides of type I collagen (CTx), Osteocalcin, and IGF levels.
Results
Outcomes were pooled as standard mean difference (SMD) and 95% confidence interval (CI) in a Random-effect meta-analysis model. Nine RCTs met the eligibility criteria and were selected for the final analyses. The analysis indicated a significant decrease in NTx [SMD: -0.89 nmol/mmol, CI: -1.69 to -0.10%, P = 0.028] following supplementation with MBP compared to the placebo group. Also, whey supplementation resulted in a significant increase in IGF [SMD: 3.55 nmol/l, 95% CI: 3.12 to 3.98%, P = 0.001, \({I}^{2}\) = 58.1%, p = 0.092]. However, there were no significant mean differences in lumbar-BMD, hip-BMD, serum CTx and Osteocalcin between the two groups.
Conclusions
Whey or MBP supplementation may reduce NTx and increase IGF, particularly when adults are supplemented for 12 weeks or longer, however findings on lumbar-BMD, hip-BMD, serum CTx and Osteocalcin are inconclusive.
The Impact of Ecological Nano-Calcium from Eggshells as an Alternative Calcium Source on Calcium Nutrition and Oxidative Stress Mechanisms in Lettuce Grown Under Saline and Boron Toxic Conditions
Authors: Sahin Ozge , Yagcioglu Kıymet Deniz , kadioglu Yusuf Kagan , Gunes Aydin
Published: August 2023

Nano-fertilizers with higher efficacy compared to conventional fertilizers can provide advantage for plant cultivation in both productive and problematic soils. Therefore, this study aimed to determine the effect of nano-calcium (nano-Ca) on lettuce plants grown in saline-boron (B) toxic soil. Nano-calcium fertilizer was prepared from eggshells. Functional and structural properties of nano-Ca was determined by Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) before plant experiment. The treatments was; control, 40 mM NaCl and 20 mg kg− 1 B (NaCl + B), and 40 mM NaCl and 20 mg kg− 1 B with 4 mM Nano-Ca (NaCl + B + nano-Ca). The nano-Ca significantly increased the dry weight and calcium (Ca) concentration of lettuce plants under saline-B toxic conditions. Although there was a decrease in the concentrations of sodium, chloride, and B with nano-Ca application, it was not statistically significant. Due to salinity and B toxicity, the level of malondialdehyde (MDA) as a measure of lipid peroxidation and hydrogen peroxide (H2O2) concentration decreased significantly with nano-Ca application. The catalase activity (CAT) increased with nano-Ca application, while the ascorbate peroxidase (APX) activity decreased, and there was no significant change in superoxide dismutase activity (SOD). The results obtained from the study indicate that nano-Ca plays a protective role for lettuce plants grown saline-B toxic conditions.
Effect of vacancy defects on thermal transport properties of tungsten nitride compounds on divertor surface in ITER
Authors: Pan Bicai , Yu Pengfei
Published: August 2023

In Tokomak, tungsten nitrides (WNx) films that form on the surface of the divertor are a byproduct of the nitrogen seeding system. The impact of their thermal transport properties is an important issue. Leveraging density functional theory calculations along with the Kubo-Greenwood method, we investigate how vacancy defects influence the electrical conductivity and thermal conductivity of h-W2N1, β-W1N1, and h-W2N3, respectively. Our findings suggest that both nitrogen vacancy and tungsten vacancy defects can suppress the electrical and thermal conductivities of h-W2N1 and β-W1N1 to some extent, with the tungsten vacancy having a more considerable effect than the nitrogen vacancy. Conversely, for h-W2N3, both types of vacancy defects can enhance its electrical and thermal conductivities. Furthermore, we reveal that the fluctuation in the electrical conductivity of the three WNx compounds correlates with the changes in the density of states at the fermi energy level induced by the vacancies for each system. The insights gleaned from our findings are beneficial for the assessment and comprehension of the thermal conductivity performance of WNx films on the divertor surface.
Creep behavior of dry and saturated medium-grain sandstone and its relationship with short-term mechanical properties
Authors: Gu Qingheng , Tan Yunliang , Zhao Guangming , Meng Xiangrui , Cheng Xiang
Published: August 2023

With the continuous exploitation of coal and the increase of abandoned goafs under weakly cemented aquifer strata in Western China, the study of the time dependent mechanical properties of the unique weakly cemented medium-grain sandstone, which is susceptible to water, is imminent. In this paper, creep mechanical properties of dry and saturated medium-grain sandstone, which represent two limit states affected by water, were studied and compared. The results showed that water greatly weakens the compressive resistance of medium-grained sandstone, but balances the volumetric compressive deformation by filling in the internal defects of rock samples with different confining pressures. The rock showed a state of volume expansion except for the first or second loading stage. Compared with short-term compressive strength, the turning point of saturated rock from viscoelasticity to viscoplasticity is earlier than that of dry rock. The short-term elastic modulus has a negative exponential relationship with deviating stress, and creep rate has a positive exponential relationship with deviating stress. Based on Burges model with exponential damage variables, the method of obtaining creep model parameters by short-term mechanical parameters of rocks was introduced, and the linear relationship between elastic modulus of medium-grained sandstone and parameters of Burgers model with damage was found. This conclusion will enrich the framework of the above-mentioned methods for obtaining time-dependent properties.
The pathogenic role of Succinate-SUCNR1: A critical function that induces renal fibrosis via infiltration of M2 macrophage
Authors: Pu Min , Zhang Jing , Hong Fuyan , Wang Yan , Zhang Chengwei , Zeng Yongcheng , Fang Zhenzhen , Qi Weiwei , Yang Xia , Gao Guoquan , Zhou Ti
Published: August 2023

Background
Renal fibrosis is a major determinant of progressive loss of kidney function in chronic kidney disease (CKD), and alternatively activated M2 macrophages play an essential role in the progression. Serum succinate level is consistently elevated in diabetes and obesity, and diabetes and obesity are critical causes of CKD, but whether elevated succinate can mediate M2 polarization of macrophages and contribute to renal interstitial fibrosis is undetermined.
Methods
Male C57/BL6 mice were fed with special water (supplement with 4% succinate) for 12 weeks to evaluate the effects on renal interstitial fibrosis, and depletion of macrophages by clodronate liposomes was adopted to validate the importance of macrophages in vivo. We further used RAW 264.7 and NRK-49F cells to explore the underlying molecular mechanisms.
Results
Succinate caused renal interstitial macrophage infiltration, activation of profibrotic M2 phenotype, upregulation of profibrotic factors, and interstitial fibrosis. Treatment of clodronate liposomes markedly depleted macrophages and prevented the succinate-induced increase in profibrotic factors and fibrosis. Mechanically, succinate promoted CTGF transcription via triggering SUCNR1-p-Akt/p-GSK3β/β-catenin signaling, which was inhibited by SUCNR1 siRNA. The knockdown of succinate receptor (SUCNR1) or pretreatment of anti-CTGF(connective tissue growth factor) antibody suppressed the stimulating effects of succinate on RAW 264.7 and NRK-49F cells.
Conclusions
The causative effects of succinate on renal interstitial fibrosis were mediated by the activation of profibrotic M2 macrophages, and succinate-SUCNR1 was involved in activating p-Akt/p-GSK3β/β-catenin, CTGF expression and the crosstalk between the macrophages and fibroblasts. Our findings provide a promising strategy for preventing metabolic CKD progress by promoting urine succinate excretion and/or employing selective antagonists for SUCNR1.
Identification of abnormal closed-loop pathways in patients with MRI-negative drug-resistant epilepsy
Authors: Bu Jinxin , Yin Hangxing , Ren Nanxiao , Zhu Haitao , Wang Yonglu , Wei Ran , Zhang Rui , Zhang Shugang
Published: August 2023

To identify abnormal changes in closed-loop pathways among magnetic resonance imaging-negative drug-resistant epilepsy (MRI−-DRE) patients and to examine the associations of these abnormalities with emotional and cognitive impairments. A total of 26 patients with MRI−-DRE and 26 healthy controls (HCs) were included in this study. Causal brain networks and temporal-lag brain networks were constructed from rs-fMRI data, and the Johnson algorithm was used to identify stable closed-loop pathways. Abnormal closed-loop pathways in the MRI−-DRE group were identified by comparison with HCs, and associations with indicators of cognitive and emotional impairments were examined using Pearson correlation analysis. The results reveal that the abnormal stable closed-loop pathways were distributed across frontal, parietal, and occipital lobes, and included altered FC values both within and between cerebral hemispheres. Four abnormal closed-loop pathways in the occipital lobe were associated with emotional and cognitive impairments. These abnormalities may serve as biomarkers for diagnosis and guidance of individualized treatments for MRI−-DRE.
Mechanism study of flow characteristics of molten pool and keyhole dynamic behavior of K-TIG welding
Authors: Cui Shuwan , Dai Penghui , Ma Rong , Xu Lei , Pang Shuwen , Tian Fuyuan , Yu Yunhe
Published: August 2023

The stability and reliability of K-TIG welding depend on the flow characteristics of molten pool and the dynamic behavior of keyhole. In order to explain the variation mechanism between the flow behavior of liquid metal and the dynamic behavior of the keyhole while taking electromagnetic force, surface tension, buoyancy, etc. into consideration, this work developed a mathematical model of K-TIG welding. The simulation results of the keyhole exit were compared with images of the keyhole exit taken by the high-speed CCD camera and the keyhole exit characteristics parameters, and the deviation of keyhole outlet parameters XL and YL under each group of process parameters were less than 0.2 mm, and the deviation of SA was less than 0.4 mm2. The flow trend of molten metal in keyhole formation was mainly from the center of keyhole to the surrounding of the keyhole under the consideration of electromagnetic force, surface tension, etc. The trend of melt pool distribution decreased along the perimeter of the keyhole and the thickness of the workpiece, and the overall flow field was stepped. Moreover, the keyhole exit was in a dynamic equilibrium state under the action of gravity, surface tension and arc pressure. The reduction in welding speed accelerated the formation of the keyhole exit and increased the maximum flow velocity of molten metal under the influence of Marangoni forces.
WITHDRAWN: Normal Weight Obesity and Normal Weight Central Obesity is Associated with Geriatric Syndromes in Hospitalized Older Adults
Authors: Nascimento Stephany Beatriz do , Santos Roana Carolina Bezerra dos , Santos Letícia Sabino , Mendes Taynara de Sousa Rego , Pereira Jarson Pedro da Costa , LEMOS MARIA CONCEIÇÃO CHAVES , PINHO CLAUDIA PORTO SABINO
Published: August 2023

Purpose. To evaluate the prevalence of Normal Weight Obesity (NWO) and Normal Weight Central Obesity (NWCO) and its associated factors in hospitalized older adults.
Methods. This is a cross-sectional study involving older patients at a University Hospital in Northeastern of Brazil. The NWO was determined by the coexistence of normal BMI (18.5 – 25kg/m2) and high fat percentage (>33.5% for men and >42.8% for women). The NWCO was determined by the coexistence of normal BMI and a very increased waist circumference (> 102cm for men and > 88cm for women). Demographic data, clinical, geriatric, behavior and nutritional aspects were also collected.
Results. The prevalence of NWO was 8% and NWCO was 7.4%. NWO was associated to weight loss (p=0.006), calf circumference (p<0.001), low muscle mass (p<0.001) and sarcopenia (p<0.001). The frequency of NWCO was higher in women (p<0.001), also in those who presented weight loss (p=0.04), in patients with lower calf circumference (p<0.001), low muscle mass (p<0.001), low muscle strength (p=0,018), in sarcopenic (p<0.001), in fragile (p=0.049) and those with functional dependency (p=0,004).
Conclusion. The risk factors associated with NWO were weight loss >5%, low muscle mass and sarcopenia. The risk factors to NWCO were sex (women), weight loss > 5%, functional dependency, low muscle mass, low muscle strength, sarcopenia and frailty.
Sentiment Analysis Using Multinomial LR-LSTM Model
Authors: Rani Seema , Boora Jaibhagwan , Kumar Sanjeev , Chaba Yogesh , Godara Sunila , Noliya Amandeep , Sindhu Sumit
Published: August 2023

Sentiment analysis (SA) refers to a technique utilized to ascertain the emotional state conveyed in information or text. It involves categorizing the text into three classes: positive, negative, or neutral. For instance, when someone says "the aqi of the city is good," they are expressing a positive opinion about the aqi of a specific place, while the statement "the aqi is bad" reflects the opposite. The introduction of social media increased the amount of content on the internet of sentiment data. Users on various social media platforms have been able to offer their opinions on various products, services, etc. These opinions are often expressed on social media in the form of movie reviews, product reviews, user comments, posts, etc. In light of this context, one of the captivating research areas in Natural Language Processing (NLP) is Twitter sentiment analysis. The paper proposes a stacked Multinomial-LR-LSTM model for the classification of tweets into three classes. Tweets are re-annotated using Text Blob. Twitter Sentiment dataset was used for experiments with accuracy of 97%.
A Study to Explore the Substance Basis and Mechanism of Action of the Potential Intestinal-Hepatic-Brain Toxicity of Densefruit Pittany Root-Bark Based on Toxicological Evidence Chain (TEC)
Authors: Xu Xiaomin , Sun Huijuan , Wang Yu , Chen Pingping , Hu Wenkai , Wo Jiameixue , Jia Suxia , Liu Sujie , Lu Fang , Liu Shumin
Published: August 2023

Background Densefruit pittany root-bark is derived from the dried root bark of rutaceae Baixian, a traditional Chinese medicine widely used to treat eczema, psoriasis, and other skin diseases in China. However, in recent years, there have been an increasing number of reports about its negative effects. The potential toxic components and targets of densefruit pittany root-bark intestinal-liver-brain toxicity were screened in this study using pharmacochemistry and network drug/toxicology, molecular docking and molecular dynamics simulation, and were verified by evidence of adverse outcome (AOE).Methods HPLC was used to characterise the densefruit pittany root-bark.TCMSP, TCM-ID, TCM@Taiwan, and CTD databases are used to filter Densefruit pittany root-bark. PharmMapper, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases were used to predict the targets of Dense Fruit Root-Bark-induced intestinal-liver-brain tissue damage, and the intersecting targets were chosen for PPI protein interaction analysis, KEGG pathway analysis, and GO enrichment analysis. To depict the core regulatory network, a "drug-compound-toxic target-pathway" map was created using Cytoscape software. The binding affinity and reliability were investigated using molecular docking and molecular dynamics simulation. Finally, HPLC, HE staining, immunohistochemistry, and WB were used to confirm AOE.Results Three compounds in densefruit pittany root-bark were tested, and 125 targets were found to be related to the intestinal-liver-brain toxicity caused by Dense fruit pittance root-bark. The primary targets, according to PPI network analysis, were AKT1, JUN, RELA, SRC, and TP53.Furthermore, GO/KEGG enrichment analysis revealed that densefruit pittany root-bark may modulate Lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the TNF signalling pathway to cause intestinal-liver-brain tissue injury. According to the "herb-compound-toxic target-pathway-organ damage" network, dictamine, obakunone, and fraxinone may be therapeutic or main toxic compounds. Molecular docking and molecular dynamics simulation results show that the core compound has a high affinity for the target.Conclusion This study clarified the mechanism of densefruit pittany root-bark-induced intestinal-liver-brain toxicity, which was the first study on the toxicity of densefruit pittany root-bark based on the concept of TEC, and provided a reference for future research on the toxicity mechanism of densefruit pittany root-bark. However, further experimental validation is required before using densefruit pittany root-bark in clinical practise.
Chromosomal Microarray Analysis for Prenatal Diagnosis of Uniparental Disomy: A Retrospective Study
Authors: xu chenxia , Li Miaoyuan , Gu Tiancai , Xie Fenghua , Zhang Yanfang , Wang Degang , Peng Jianming
Published: August 2023

Background: Chromosomal microarray analysis (CMA) is a valuable tool in prenatal diagnosis for detecting chromosome uniparental disomy (UPD). This retrospective study examines fetuses undergoing invasive prenatal diagnosis through Affymetrix CytoScan 750K array analysis. We evaluated both chromosome G-banding karyotyping data and CMA results from 2007 cases subjected to amniocentesis.
Results: The detection rate of regions of homozygosity (ROH) ≥10 Mb was 1.8% (33/2007), with chromosome 11 being the most frequently implicated (17.1%, 6/33). CMA successfully identified three cases of UPD stemming from imprinted genes.
Conclusion: The combination of karyotyping and CMA can provide a more accurate prenatal genetic diagnosis. CMA proves effective in identifying ROH and in averting the birth of children afflicted with imprinting diseases.
Seasonal distribution, source identification, health and eco-toxicological risk assessment of PAHs in water and sediment from the Danube River in Hungary
Authors: Grmasha Ruqayah Ali , Stenger-Kovács Csilla , Al-sareji Osamah J. , Al-Juboori Raed A. , Meiczinger Mónika , Andredaki Manolia , Idowu Ibijoke A. , Hashim Khalid S.
Published: August 2023

The Danube is one of the largest transboundary rivers word-wide, having several tributaries. The discharges from industrial activities and wastewater treatment facilities affect the river's aquatic environment. These discharges pose a serious risk to aquatic life by degrading the water and sediment quality. Therefore, 16 Polycyclic Aromatic Hydrocarbons (PAHs) compounds in six different locations were examined along the river over 12 months to investigate the temporal and special variations of the compounds in water and sediment. The findings highlighted a broad variance range in PAHs concentration in water within a year, ranging from 224.85 ng/L in summer to 365.87 ng/L in winter, whereas PAHs in sediment samples recorded values ranging from 316.72 ng/g in dry weight in summer to 422.98 ng/g in dry weight in winter. The overall results indicate that the putative anthropogenic sources of PAHs were of pyrolytic and pyrogenic origin; with pyrogenic sources being more prominent. Generally, except for Acenaphthylene and Fluorene concentrations, the eco-toxicological concerns for the aquatic environment of the Danube River do not pose a significant threat. In addition, the combined impact of the 16 PAHs pollutants in sediments suggests a low chance for negative biological impacts and low ecological risk. The total ILCR for both children and adults is more than 1/104 in all seasons, with the highest values recorded in spring followed by winter time, which becomes a matter of urgency.
Stick Roller: A Case Study on Efficiently Learning Precise Tactile Dynamics for In-hand Manipulation
Authors: Du Yipai , Wang Michael Yu , Lian Wenzhao , She Yu
Published: August 2023

In-hand manipulation is challenging in robotics due to the intricate contact dynamics and high degrees of control freedom. Precise manipulation with high accuracy often requires tactile perception, which adds further complexity to the system. This paper addresses these challenges in perception and control and proposes a framework for learning high-resolution tactile dynamics on real hardware that is feasible and scalable. Specifically, we use a case study on manipulating a small stick using the Allegro hand equipped with the Digit vision-based tactile sensor to demonstrate the framework's effectiveness. The framework includes an action space reduction module, tactile perception module, and learning with uncertainty module, all designed to operate in low data regimes. With minimal manually collected data, our learned contact dynamics model achieves grasp stability, sub-millimeter precision, and zero-shot generalizability across novel objects. The proposed framework demonstrates promising results for enabling precise in-hand manipulation with tactile feedback on real hardware.
Cell structure of epiphytic orchids’ root cortex and exodermis shape fungal colonization
Authors: Bibikov Nikita , Voronina Elena , Eskov Alen , Ignatov Mikhael
Published: August 2023

Epiphytic orchids unlike terrestrial species possess water storage elements as an adaptation to dry habitats. Two types of structures are present in roots and thus involved in interaction with mycorrhizal fungi that obligately colonize roots. Lignified water storage cells (WSC) are situated in cortex and perform the function of water storage. Among lignified exodermis cells thin-walled passage cells (PC) are present. These elements are necessary for water exchange between cortex and the environment. In this study we measure colonization rate of water storage cells and passage cells and discuss how these two functions interact in orchid root. We show that water storage cells may be colonized but less favorably than thin-walled cortex cells and support exiting data that passage cells are the only way for fungal hyphae to pass through exodermis. This evidence provokes discussion on water uptake and mycorrhiza of epiphytic orchids.
Simultaneous multiple target detection platform based on vertical flow immunoassay
Authors: Yong Taek , Kim Dami , Kim Sanghyo
Published: August 2023

In general, vertical flow assay (VFA) has a disadvantage of requiring a complex analysis process that involves manually injecting various reagents (target analyte, washing buffer, detection conjugate, etc.) sequentially. However, in this study, we have developed an innovative paper-based VFA device that replaces the complex analysis process with one-step and enables the detection of multiple targets. The fabrication process of the multi-target detection VFA device is as follows: preparation and pre-treatment of the strip materials, design of strip cartridge, design of the multiple detection VFA device, optimization experiments for strip sample flow rates, determination of device analysis time, determination of device limit of detection (LOD), multiple target signal uniformity experiment, IgG and CRP antigen-antibody multiple detection experiment, and data extraction and analysis method. The use of paper-based materials enables the device to be produced at cost-effective, and cartridge production allowed for uniform array formation. IgG and CRP are used to evaluate the performance of the device as common biomarkers. To validate multiple target detection capability of the VFA device proposed in this study, two types of antigens-antibodies (Human IgG and Human CRP) were employed. In conclusion, the VFA device proposed in this study consists of a one-step analysis process, and it has been confirmed that it can detect multiple targets simultaneously.
Loss of CYP2D6 sensitizes hepatocellular carcinomas and neuroblastomas to talazoparib
Authors: Sjöblom Tobias , Zhang Xiaonan , Rameika Natallia , Zhong Lei , Rendo Verónica , Kundu Snehangshu , Nuciforo Sandro , Dupuis Jordan , Azhar Muhammad Al , Tsiara Ioanna , Seeburger Pauline , Nassralla Shahed Al , Ljungström Viktor , Svensson Richard , Stoimenov Ivaylo , Artursson Per , Heim Markus , Globisch Daniel
Published: August 2023

Cancers often have reduced allelic diversity because of loss of heterozygosity (LOH). Therefore, tumors arising in patients heterozygous for a functional and a loss-of-functon(LoF) allele may lose the functional allele, rendering them sensitive to allele-specific therapies. To discover such alleles, we mined the 1000 Genomes dataset for SNVs causing protein truncation through base substitution, indels or splice site disruptions, resulting in 60 LoF variants in 60 genes. The LoF splice site variant rs3892097 in CYP2D6 was selected as it resides in a genomic region undergoing LOH in different tumor types, is highly polymorphic with over 135 allelic variants, and metabolizes ~25% of clinically used drugs. We generated cell systems and screened anticancer agents in clinical use or in clinical trials for differential toxicity, and Talazoparib and MK-8776 were shown to exhibit consistent cytotoxicity against hepatocellular carcinoma and MYCN-amplified neuroblastoma cells with low CYP2D6 activity in 2D and 3D culture. Moreover, Talazoparib displayed CYP2D6 genotype dependent effects on primary hepatocellular carcinoma organoids. These findings support a new therapeutic strategy targeting LoF variants of drug-metabolizing enzymes, enabling anticancer drug selection for precision medicine.
Some New Properties of Hyperbolic K-fibonacci and K-lucas octonions
Authors: Godase A. D.
Published: August 2023

The aim of this paper is to establish some novel identities for hyperbolic k-Fibonacci octonions and k-Lucas octonions. We prove these properties using the identities of k-Fibonacci and k-Lucas numbers, which we determined previously. Mathematics Subject Classification (2010). Primary 11B39; Secondary 11B37, 11B52.
Multimodal Imaging of Retinal Toxicity in a Patient Taking Axitinib
Authors: Çomçalı Sebile , Coşkun Çiğdem , Çavdarlı Cemal , Alp Mehmet Numan
Published: August 2023

Background: Axitinib is a selective inhibitor of vascular endothelial growth factor receptors.
Case presentation: A forty-five years old female presented with blurred vision who had been taking 7 mg of Axitinib bid for 5 months. Initial best corrected visual acuity (BCVA) was 20/32 at the right and counting fingers at the left eye. Funduscopic examination revealed bilaterally widespread intraretinal hemorrhages, cotton-wool spots, and hard exudates with a star-like appearance at the macula. The optical coherence tomography revealed central macular edema. There was hyperreflective edema in the inner layers, exudates in the middle retinal layers and subfoveal subretinal fluid. Fundus fluorescein angiography revealed localized ischaemic findings in the early phase and multifocal perivascular ink-blot fluorescein leakage in the middle and late phases.
Conclusions: Axitinib treatment was discontinued immediately, and at the 3-month of follow-up, the macular edema and fundus findings improved with final BCVA 20/20 at the right, and 20/32 at the left eye.
Contribution of 18F-FDG PET/MR Imaging in Detection of Peritoneal Carcinomatosis in Patients with Ovarian Cancer
Authors: Baltacioglu Muhammet Halil , Soydal Cigdem , Araz Mine , Oz Digdem Kuru , Taskin Salih , Kucuk Nuriye Ozlem , Erden Gul Ayse , Elhan Atilla Halil
Published: August 2023

Purpose: Presence of peritoneal metastasis in ovarian cancer is one of the most important factors affecting the prognosis of the disease. In this study, it was aimed to compare the diagnostic performances of 18F-FDG PET/CT and 18F-FDG PET/MR imaging for the detection of peritoneal recurrence in patients with ovarian cancer.
Material-Methods: 66 images of 45 patients with ovarian cancer who had elevated serum Ca-125 levels at post-operative follow-up and were referred to 18F-FDG PET/CT for restaging of disease were prospectively recruited in the study. All patients underwent whole body 18F-FDG PET/CT followed by whole abdomen PET/MRI. The peritoneal carcinomatosis index (PCI) was calculated for each patient in both imaging modalities. PET/CT and PET/MRI were evaluated for the presence and localization of peritoneal recurrences for each modality.
Results: In study-based analysis; PET/MRI was positive in 49 studies (74%), while PET/CT was positive in 34 studies (51%) (p=0.001). The total number of regions with peritoneal uptake was 144 in PET/CT and 243 in PET/MRI (p<0.001). The median PCI was 1.5 in PET/CT and 4 in PET/MRI (p<0.001). In the evaluation of liver-spleen capsule metastases, the detection rate was 17/66 (26%) for PET/CT and 30/66 (45%) for PET/MRI (p=0.008). Distant organ metastases were detected on PET/MR in 3 studies where PET/CT was negative. In our study, additional findings obtained from PET/MRI changed the treatment strategy in 15 patients.
Conclusion: Peritoneal metastasis detection rate is higher in PET/MRI than PET/CT in patients with recurrent ovarian cancer with elevated Ca-125 levels. In addition, PET/MRI is useful in the evaluation of the liver-spleen capsule metastases. PET/MRI findings can help to selection of appropriate treatment strategy in recurrent ovarian cancer patients.
Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K
Authors: Miyahara Yuka , Hu Chen , Moriyama Masafumi , Mochizuki Keita , Kaneko Naoki , Haque Rafiul ASM , Chinju Akira , Kai Kazuki , Sakamoto Mizuki , Kakizoe-Ishiguro Noriko , Yamauchi Masaki , Ogata Kenichi , Kiyoshima Tamotsu , Kawano Shintaro , Nakamura Seiji
Published: August 2023

Oral lichen planus (OLP) is a chronic inflammatory disease associated with T cell infiltration. The crosstalk between oral epithelium and mucosal T cells was considered to play an important role in the pathogenesis of OLP. Here, we selectively extracted the normal and lesional epithelium (LE) of buccal mucosa specimens from three patients with OLP by laser capture microdissection due to identify the pathogenic factors. Cathepsin K (CTSK) was identified as one of common upregulated genes in the LE by DNA microarray. Immunohistochemically, CTSK was distinctly detected in and around the LE, while it was rarely seen in the NE. Recent studies showed that CTSK enhanced Toll-like receptor 9 (TLR9) signaling in antigen-presenting cells, leading to Th17 cell differentiation. TLR9 expression mainly co-localized with CD123+ plasmacytoid dendritic cells (pDCs). The number of RORγt-positive cells correlated with that of CTSK-positive cells in OLP tissues. CD123+ pDCs induced the production of Th17-related cytokines (IL-6, IL-23, and TGF-β) upon stimulation with TLR9 agonist CpG DNA. Moreover, single cell RNA-sequencing analysis revealed that TLR9-positive pDCs enhanced in genes associated with Th17 cell differentiation in comparison with TLR9-negative pDCs. CTSK may induce Th17-related production of CD123+ pDCs via TLR9 signaling to promote the pathogenesis of OLP.
An Extended Sparse Model for Blind Image Deburring
Authors: Ge Xianyu , Liu Jing , Hu Dandan , Tan Jieqing
Published: August 2023

Blind image deburring is a classical ill-posed problem that usually requires constraints on the clean image, the blur kernel, and noise to make it well-posed. Recently, a simple yet effective sparse norm le is proposed, which adds two widely-adopted sparse norms, i.e., l0 and l1. By using le to regularize the gradients of the clean image, and l2 + ∇le as the noise fitting function, an enhanced sparse model for blind image deburring is established and achieves surprisingly attractive results. In this paper, inspired by the facts that the gradients of a natural image tend to obey a heavy-tailed distribution, and the noise exhibits spatial random-ness, we propose a more flexible model called the extended sparse model which can take the enhanced sparse model as a special case. Specifically, for the image gradients, we suggest a improved sparse norm lP , which is developed from l0 and lp(0 < p ≤ 1). Furthermore, we constrain the second-order derivative of noise to boost the percentage of high-frequencies in the fidelity such that the recovery focuses more on high-frequencies that are erased in the blurry image. Based on the half-quadratic splitting method and a variant of the generalized iterated shrinkage algorithm (GISA), we provide an effective optimization scheme for the overall model. Extensive evaluations of benchmark datasets and real images indicate the superiority of the proposed method against state-of-the-art deburring algorithms.
Comparison of daily 400 and 600 units of vitamin D in prevention of osteopenia of prematurity in infants with gestational age of less than and equal to 32 weeks
Authors: Barekatain Behzad , Hamidipour Shima , Badiei Zohreh , Farghadani Maryam
Published: August 2023

Background
Use of vitamin D in premature infants is one of the important preventive factors for Osteopenia of prematurity but there are conflicting results on the appropriate doses, so this study aimed to compare the dose of 400 and 600 units vitamin D in the prevention of osteopenia of prematurity in infants with gestational age ≤ 32 weeks.
Methods
This clinical trial study was conducted on 108 premature infants divided into two groups of 54 with gestational age of ≤ 32 weeks born between 2020-2021 in Shahid Beheshti and Al-Zahrai hospitals in Isfahan. In the first group, daily vitamin D was 400 units from the 7th day of birth, and in the second group, it was 600 units. At the age of 5 weeks, levels of calcium, phosphorus, alkaline phosphatase and vitamin D were evaluated. If the alkaline phosphatase level was above 1000, the wrist radiography was requested.
Also, the baby was examined for clinical symptoms of rickets at the age of 5 weeks. The data were analyzed by SPSS software version 26 and P-value<0.05 was considered significant.
Results
In the present study, there was no significant difference between the level of alkaline phosphatase in the two groups (p=0.596), but the level of vitamin D was significantly higher in 600 units group (p<0.001). The level of calcium was higher in 400 units group, but this difference was slightly significant (p=0.062). The level of phosphorus in 600 units group was higher than the 400 units, and the difference was slightly significant (P=0.062).
Conclusion
The present study showed that daily 600 and 400 units of vitamin D in infants with gestational age of ≤ 32 weeks had no effect on the incidence of clinical symptoms and radiological findings of rickets at the age of 5 weeks.
Seismic Risk Assessment of Vertical Geometric Irregular Buildings
Authors: Netke Bhushan , Bhosale Avdhoot
Published: August 2023

Historically, construction predominantly comprised conventional rectangular structures. However, modern construction has expanded to encompass organic designs, prompting a demand for seismic assessment techniques for irregular buildings. Analysing these structures poses intricate challenges, requiring innovative resolutions from structural engineers. This paper concentrates on enhancing the structural stability of vertical geometric irregular buildings. It continues by conducting a comparative analysis of diverse vertical geometric irregular buildings using pushover curves and performing seismic risk assessments. The study offers engineers and practitioners valuable insights to ascertain irregularities critical for ensuring structural stability. Ultimately, the research delves into studying the earthquake response of such irregular buildings in seismic zone 5, a high-risk area. This pursuit aligns with the broader goal of fortifying these structures against seismic forces through meticulous examination and comprehension of their behaviour.
Inhibition of granule cell dispersion and seizure development by AAV1-AEG-1 administration in a mouse model of TLE
Authors: Kim Sang Ryong , Leem Eunju , Kim Sehwan , Sharma Chanchal , Nam Youngpyo , Kim Tae Yeon , Shin Minsang , Lee Seok-Geun , Kim Jaekwang
Published: August 2023

Although granule cell dispersion (GCD) in the hippocampus is known to be an important feature associated with epileptic seizures in temporal lobe epilepsy (TLE), the endogenous molecules that regulate GCD remain elusive. Here, we have identified that the expression of astrocyte elevated gene-1 (AEG-1) is upregulated in the dentate gyrus (DG) of a kainic acid (KA)-induced mouse model of TLE. We further demonstrated that AEG-1 upregulation by adeno-associated virus 1 (AAV1) delivery in the DG induced anticonvulsant activities such as the delay of seizure onset and inhibition of spontaneous recurrent seizures (SRS) through GCD suppression in the mouse model of TLE, while the inhibition of AEG-1 expression increased susceptibility to seizures. Thus, the present observations suggest that AEG-1 is a novel regulator of GCD formation and seizure development associated with TLE, and the induction of AEG-1 in the DG may have therapeutic potential against epilepsy.
Association between invasively measured central aortic pulse pressure and diameter of ascending aorta
Authors: Kim Hack-Lyoung , Joh Hyun Sung , Lim Woo-Hyun , Seo Jae-Bin , Kim Sang-Hyun , Zo Joo-Hee , Kim Myung-A
Published: August 2023

No study has investigated the relationship between arterial stiffness and aortic root geometry using invasive hemodynamic measurement. Thus, this study was aimed to assess the relationship between invasively measured aortic pulse pressure (aPP), a reliable indicator of aortic stiffness, and the diameter of ascending aorta (AoD). We analyzed 665 subjects (64.3 ± 11.0 years; 34.6% female) who underwent elective invasive coronary angiography (ICA) for the evaluation of coronary artery disease (CAD). Transthoracic echocardiography was performed on the same day, and AoD was measured at the level of 1 cm above the sinotubular junction at the end-diastole. Body surface area (BSA)-adjusted AD (AoD/BSA) was used for the analysis. A pig-tail catheter was used to measure aortic pressures at a level approximately 3 cm above the aortic valve just before ICA. aPP was calculated as the difference between systolic and diastolic pressures of the aorta. In multiple linear regression analyses, aPP (β = 0.259; P < 0.001) were found to be significantly correlated with AoD/BSA even after controlling for potential confounders. This correlation power was stronger than aortic systolic pressure (β = 0.189; P < 0.001) and brachial pulse pressure (β = 0.091; P = 0.018) at the same multivariable analyses. In conclusion, our study demonstrated a significant association between invasively measured aPP and AoD/BSA, providing stronger evidence for the link between central aortic stiffness and aortic root geometry.
Experimental assessment of bond behavior of HPC of beam column joint under static load
Authors: Lande Abhijeet Chandrakant , M.Awati Mahesh , Patil Vidya Malgonda
Published: August 2023

An experimental examination of high-performance column compression behaviour (HPC) under static loads is presented in this research. High performance concrete strength, amount and reinforcing space, connection, and yield strength of all materials are among the test variables. The loaded column is distinguished by the pre-cover opening caused by the split plate generated between the cover and the core. Twelve beam column joints specimens are built according to current practice by high performance with different grades and forms and tested under static loads to determine the common concrete effect of in place of traditional concrete at the joint location. The testing results indicate that high performance concrete specimens are more effective in T section than reference concrete specimens in L section. The software's response is appropriate. According to the experimental investigation's findings, the joint region's HPC and reinforcing components interact effectively. Thoroughly investigated the bond strength, crack initiation and propagation, load transfer mechanisms, and overall ductility. These results offer a greater comprehension of the role that HPC plays in the structural integrity of beam-column joints and the ways in which its characteristics affect how well the joint functions under static loading circumstances.
Experimental investigation of reinforced concrete beam behavior under pure torsion and bending and microstructure characteristics
Authors: Patane Atul , Vesmawala Gaurang
Published: August 2023

The present research paper presents the results of an experimental examination of the load behavior and microstructure property analysis of reinforced concrete beams. In addition, the mix design process involves a number of trials to determine the cement, fine aggregate, and coarse aggregate physical characteristics. Experimentally determined values are used in determining the mix design for M20 grade concrete. Eight different beams are produced from the same M20 concrete mixture. These beams range in length from 2100 mm to 2100 mm and have a width of 150 mm and a depth of 250 mm. The beam has 12 mm diameter longitudinal reinforcement at the bottom and 10 mm diameter reinforcement at the top. The employed stirrups have a diameter of 8 mm, a distance between each stirrup of 100 mm, and a distance between each support of 40 mm for a total length of 150 mm. All eight test beams are subjected to a wide range of loading conditions and BFRP wrapping combinations. The cracking load, ultimate load, twist angle and deflection are investigated for all the beams. It is observed that A6 beam combination is a good alternative over the beam with conventional reinforcement. It significantly enhanced the structural performance in all directions.
Construction and Control Tools in Karbandi Construction Technology
Authors: Ainechi shahrzad , Valibeig Nima
Published: August 2023

The design and construction of karbandies from the beginning of the drawing of the plans to the stage of the construction of the domical vault always requires a careful review and control of the construction process. Several control and construction tools are currently used in the same traditional method in the construction of Karbandi elements, however, these tools have not yet been investigated in detail and no sufficient data are available in this field. Knowledge of construction manner and arrangement of karbandi elements and control methods in construction might result in the identification of solutions for restoration and maintenance of such traditional structures. Karbandi control and construction tools have not been specifically studied so far and insufficient information is available. Understanding how the components are built and assembled and how they are controlled during karbandi construction can help identify ways to maintain and repair these traditional structures. This paper aims to clarify the construction and control tools in karbandi construction technology, especially in the rectangular base, based on the teachings of traditional masters and by examining real examples. For this purpose, information was first extracted through library studies, field observations, and direct interviews with master builders and architectural conservators, and then the geometrical system of the samples was constructed by 3D modeling software. The result of the research shows that the construction of the karbandi by traditional architects is the same in general, but differs in detail. The construction differences are discussed in terms of how the bricks are arranged, the fillers and the centering, how the centering is constructed, the size of the base, and so on. These various factors are at the discretion of the architect, making decisions about the details of these features. Also, during the construction of the karbandi, the control of the horizontal and vertical alignment of the centering and components by the control tools is very effective in increasing the accuracy of the execution.