bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of porous beta-cyclodextrin functionalized PVDF/Fe–MOF mixed matrix membrane for enhanced ciprofloxacin removal
Authors: Njaramba Lewis Kamande , Yoon Yeomin , Park Chang Min
Published: March 2024

Herein, we demonstrate the synthesis of beta-cyclodextrin (β–CD) functionalized polyvinylidene fluoride (PVDF) and iron-based metal-organic framework (Fe–MOF) mixed matrix membrane (MMM) for the enhanced removal of ciprofloxacin (CIP) from water. The membranes were prepared using the phase inversion technique with PVDF as the polymer matrix, Fe–MOF as the filler, and polyvinylpyrrolidone (PVP) as the porogen. The optimized MMM with 7% wt. Fe–MOF exhibited excellent performance with 87.6% removal efficiency. Moreover, the maximum adsorption capacity was 6.43 mg g–1. The β–CD functionalization improved the MMM hydrophilicity exhibited by the water contact angle (WCA) analysis (WCA = 55°). Furthermore, excellent adsorption performance can be attributed to the large Fe–MOF specific surface area (682.5 m2 g–1), the high porosity (77%), and the average pore diameter (395 nm) of the membrane. The inclusion of PVP (1% wt.) enhanced the porous nature of the MMM and, consequently, the adsorption performance for CIP. Notably, the hydrophilic and macroporous membrane showed good reusability with over 70% removal efficiency after five sequential adsorption–desorption cycles. The insights from this study suggest that the PMC–7 membrane can be an excellent candidate for the remediation of organic contaminants from aquatic environments.
Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury
Authors: Vlasschaert Caitlyn , Robinson-Cohen Cassianne , Chen Jianchun , Akwo Elvis , Parker Alyssa C. , Silver Samuel A. , Bhatraju Pavan K. , Poisner Hannah , Cao Shirong , Jiang Ming , Wang Yinqiu , Niu Aolei , Siew Edward , Van Amburg Joseph C. , Kramer Holly J. , Kottgen Anna , Franceschini Nora , Psaty Bruce M. , Tracy Russell P. , Alonso Alvaro , Arking Dan E. , Coresh Josef , Ballantyne Christie M. , Boerwinkle Eric , Grams Morgan , Zhang Ming-Zhi , Kestenbaum Bryan , Lanktree Matthew B. , Rauh Michael J. , Harris Raymond C. , Bick Alexander G.
Published: March 2024

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-DNMT3A-CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2-CHIP and Jak2V617F-CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.
Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial
Authors: Brown Christine E. , Hibbard Jonathan C. , Alizadeh Darya , Blanchard M. Suzette , Natri Heini M. , Wang Dongrui , Ostberg Julie R. , Aguilar Brenda , Wagner Jamie R. , Paul Jinny A. , Starr Renate , Wong Robyn A. , Chen Wuyang , Shulkin Noah , Aftabizadeh Maryam , Filippov Aleksandr , Chaudhry Ammar , Ressler Julie A. , Kilpatrick Julie , Myers-McNamara Paige , Chen Mike , Wang Leo D. , Rockne Russell C. , Georges Joseph , Portnow Jana , Barish Michael E. , D’Apuzzo Massimo , Banovich Nicholas E. , Forman Stephen J. , Badie Behnam
Published: March 2024

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 106 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362.
PEARL-Neuro Database: EEG, fMRI, health and lifestyle data of middle-aged people at risk of dementia
Authors: Dzianok Patrycja , Kublik Ewa
Published: March 2024

Interdisciplinary approaches are needed to understand the relationship between genetic factors and brain structure and function. Here we describe a database that includes genetic data on apolipoprotein E (APOE) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes, both of which are known to increase the risk of late-onset Alzheimer's disease, paired with psychometric (memory, intelligence, mood, personality, stress coping strategies), basic demographic and health data on a cohort of 192 healthy middle-aged (50–63) individuals. Part of the database (~79 participants) also includes blood tests (blood counts, lipid profile, HSV virus) and functional neuroimaging data (EEG/fMRI) recorded with a resting-state protocol (eyes open and eyes closed) and two cognitive tasks (multi-source interference task, MSIT; and Sternberg's memory task). The data were validated and showed overall good quality. This open-science dataset is well suited not only for research relating to susceptibility to Alzheimer's disease but also for more general questions on brain aging or can be used as part of meta-analytical multi-disciplinary projects.
Successful topical treatment of human biofilms using multiple antibiotic elution from a collagen-rich hydrogel
Authors: Sharma Ayushi D. , Jarman Evan H. , Kuppalli Krutika , Murphy Matthew J. , Longaker Michael T. , Gurtner Geoffrey , Fox Paige M.
Published: March 2024

Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1–2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient’s wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient’s microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.
Bi-stability in femtosecond laser ablation by MHz bursts
Authors: Žemaitis Andrius , Gaidys Mantas , Gečys Paulius , Gedvilas Mindaugas
Published: March 2024

In this work, a bi-stable behavior of laser ablation efficiency and quality was controlled by fluence and burst length. The plasma shielding of incoming laser radiation caused sudden jumps with a significant decrease in ablation efficiency for every even number of pulses in the burst. The attenuation of incoming laser radiation by plasma created by the previous pulse was incorporated into the toy model of burst ablation efficiency. The mathematical recurrence relation has been derived for the first time, binding ablation efficiency for the next pulse with the efficiency of the previous pulse, which predicts bi-stability, as well as sudden jumps occurring in ablation efficiency depending on the number of pulses in burst with the response to changes of the control parameter of peak laser fluence in the pulse. The modeling results using new recurrence relation showed stable and bi-stable ablation efficiency depending on burst fluence and the number of pulses, which agreed well with experimental data. The extremely efficient laser ablation has been achieved by optimizing the shielding effect using three pulses in the burst.
Brain tumour microstructure is associated with post-surgical cognition
Authors: Aznarez-Sanado Maite , Romero-Garcia Rafael , Li Chao , Morris Rob C. , Price Stephen J. , Manly Thomas , Santarius Thomas , Erez Yaara , Hart Michael G. , Suckling John
Published: March 2024

Brain tumour microstructure is potentially predictive of changes following treatment to cognitive functions subserved by the functional networks in which they are embedded. To test this hypothesis, intra-tumoural microstructure was quantified from diffusion-weighted MRI to identify which tumour subregions (if any) had a greater impact on participants’ cognitive recovery after surgical resection. Additionally, we studied the role of tumour microstructure in the functional interaction between the tumour and the rest of the brain. Sixteen patients (22–56 years, 7 females) with brain tumours located in or near speech-eloquent areas of the brain were included in the analyses. Two different approaches were adopted for tumour segmentation from a multishell diffusion MRI acquisition: the first used a two-dimensional four group partition of feature space, whilst the second used data-driven clustering with Gaussian mixture modelling. For each approach, we assessed the capability of tumour microstructure to predict participants’ cognitive outcomes after surgery and the strength of association between the BOLD signal of individual tumour subregions and the global BOLD signal. With both methodologies, the volumes of partially overlapped subregions within the tumour significantly predicted cognitive decline in verbal skills after surgery. We also found that these particular subregions were among those that showed greater functional interaction with the unaffected cortex. Our results indicate that tumour microstructure measured by MRI multishell diffusion is associated with cognitive recovery after surgery.
Observational retrospective clinical study on clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia in Chinese pediatric cases
Authors: Li Peng , Wang Wei , Zhang Xianhui , Pan Jie , Gong Lina
Published: March 2024

This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.
Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration
Authors: Tao Shigui , Tao Kunlin , Cai Xiaoyong
Published: March 2024

Pyruvate dehydrogenase kinases (PDKs) play a key role in glucose metabolism by exerting negative regulation over pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibition of PDKs holds the potential to enhance PDC activity, prompting cells to adopt a more aerobic metabolic profile. Consequently, PDKs emerge as promising targets for condition rooted in metabolic dysregulation, including malignance and diabetes. However, a comprehensive exploration of the distinct contribution of various PDK family members, particularly PDK3, across diverse tumor types remain incomplete. This study undertakes a systematic investigation of PDK family expression patterns, forging association with clinical parameters, using data from the TCGA and GTEx datasets. Survival analysis of PDKs is executed through both Kaplan–Meier analysis and COX regression analysis. Furthermore, the extent of immune infiltration is assessed by leveraging the CIBERSORT algorithm. Our study uncovers pronounced genetic heterogeneity among PDK family members, coupled with discernible clinical characteristic. Significantly, the study establishes the potential utility of PDK family genes as prognostic indicators and as predictors of therapeutic response. Additionally, our study sheds light on the immune infiltration profile of PDK family. The results showed the intimate involvement of these genes in immune-related metrics, including immune scoring, immune subtypes, tumor-infiltrating lymphocytes, and immune checkpoints expression. In sum, the findings of this study offer insightful strategies to guide the therapeutic direction, aiming at leveraging the impact of PDK family genes in cancer treatment.
Comprehensive study on in vitro propagation of some imported peach rootstocks: in vitro explant surface sterilization and bud proliferation
Authors: Eliwa Galal I. , El-Dengawy El-Refaey F. , Gawish Mohamed S. , Yamany Mona M.
Published: March 2024

The present study was conducted in the Laboratory of Tissue Culture, Horticulture Department, Faculty of Agriculture, Damietta University, Egypt. The objective of this study was to establish a micropropagation protocol suitable for three imported peach rootstocks: Okinawa (P. persica), Nemared (P. persica × P. davidiana) × P. persica), and Garnem (P. dulcis × P. persica) in vitro. The results showed that soaking the explants in sodium hypochlorite (NaOCl) at 20% for 15 min produced the highest responsiveness (82.81%), survival (96.61%), with the lowest mortality (3.14%) and contamination (0.24%). Explants of the Garnem genotype had the best response (89.12%), survival (90.62%), lowest mortality (0.00%), and highest contamination (9.37%) when compared to the other genotypes. In comparison with axillary buds, the shoot tip displayed the highest responsiveness, survival, and death (100, 87.40, and 12.59%, respectively), as well as the least significant contamination (0.00%). Additionally, the percentages of responsive, survived, dead, and contaminated explants at the various collection dates varied significantly. The 6-benzylaminopurine (BAP) concentrations used (3 to 5.0 mg/L) demonstrated similar behavior in terms of in vitro proliferation, with rates of 3.77 to 6.11, 4.33 to 8.88, and 3.33 to 7.44 shoot numbers per explant for the Okinawa, Nemared, and Garnem peach rootstocks, respectively, indicating that the number of shoot proliferations is genotype-dependent. Additionally, using 5.0 mg/L BAP in combination with 0.2 mg/L IBA significantly increased average shoot proliferation (96.29%), number of shoots per explant (7.48), and average leaf number/explant (16.33) compared to the other treatments. Based on these results, adventitious bud development was enhanced during in vitro multiplication of the Okinawa, Nemared, and Garnem peach rootstocks by the synergistic interaction of indole-butyric acid (IBA) and 6-benzylaminopurine (BAP).
Experimental and numerical analysis of flow through a natural rough fracture subject to normal loading
Authors: Trinchero Paolo , Zou Liangchao , de La Iglesia Miquel , Iraola Aitor , Bruines Patrick , Deissmann Guido
Published: March 2024

Fractured crystalline rocks have been chosen or are under consideration by several countries as host rock formations for deep geological repositories for spent nuclear fuel. In such geological formations, flow and solute transport are mostly controlled by a network of connected natural fractures, each of them being characterised by internal heterogeneity, also denoted as roughness. Fractures are, in turn, subject to variable load caused by various factors, such as the presence of thick ice sheets formed during glaciation periods. Understanding how coupled hydro-mechanical (HM) processes affect flow and transport at the scale of a single natural fracture is crucial for a robust parameterisation of large-scale discrete fracture network models, which are not only used for nuclear waste disposal applications but are also of interest to problems related to geothermics, oil and gas production or groundwater remediation. In this work, we analyse and model an HM experiment carried out in a single natural fracture and use the results of both, the experimental and the modelling work, to get insights into fundamental questions such as the applicability of local cubic law or the effect of normal load on channeling. The initial fracture aperture was obtained from laser scanning of the two fracture surfaces and an equivalent initial aperture was then defined by moving the two fracture surfaces together and comparing the results obtained using a Navier–Stokes based computational fluid dynamics (CFD) model with the experimental flowrate obtained for unloaded conditions. The mechanical effect of the different loading stages was simulated using a high-resolution contact model. The different computed fracture apertures were then used to run groundwater flow simulations using a modified Reynolds equation. The results show that, without correction, local cubic law largely overestimates flowrates. Instead, we show that by explicitly acknowledging the difference between the mechanical aperture and the hydraulic aperture and setting the latter equal to 1/5 of the former, cubic law provides a very reasonable approximation of the experimental flowrates over the entire loading cycle. A positive correlation between fluid flow channeling and normal load is also found.
Biosynthesis of copper nanoparticles using Alstonia scholaris leaves and its antimicrobial studies
Authors: Labaran Ahmad Nasir , Zango Zakariyya Uba , Tailor Giriraj , Alsadig Ahmed , Usman Fahad , Mukhtar Muhammad Tukur , Garba Alhassan Muhammad , Alhathlool Raed , Ibnaouf Khalid Hassan , Aldaghri Osamah A.
Published: March 2024

The utilization of plants for the production of metallic nanoparticles is gaining significant attention in research. In this study, we conducted phytochemical screening of Alstonia scholaris (A. scholaris) leaves extracts using various solvents, including chloroform, ethyl acetate, n-hexane, methanol, and water. Our findings revealed higher proportions of flavonoids and alkaloids in both solvents compared to other phytochemical species. In the methanol, extract proteins, anthraquinone and reducing sugar were not detected. On the other hand, the aqueous extract demonstrated the presence of amino acids, reducing sugar, phenolic compounds, anthraquinone, and saponins. Notably, ethyl acetate and chloroform extracts displayed the highest levels of bioactive compounds among all solvents. Intrigued by these results, we proceeded to investigate the antibacterial properties of the leaf extracts against two major bacterial strains, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). All extracts exhibited significant zones of inhibition against both bacterial isolates, with S. aureus showing higher susceptibility compared to E. coli. Notably, the methanol extract displayed the most potent I hibitory effect against all organisms. Inspired by the bioactivity of the methanol extract, we employed it as a plant-based material for the green synthesis of copper nanoparticles (Cu-NPs). The synthesized Cu-NPs were characterized using Fourier infrared spectroscopy (FT-IR), UV–visible spectroscopic analysis, and scanning electron microscopy (SEM). The observed color changes confirmed the successful formation of Cu-NPs, while the FTIR analysis matched previously reported peaks, further verifying the synthesis. The SEM micrographs indicated the irregular shapes of the surface particles. From the result obtained by energy dispersive X-ray spectroscopic analysis, Cu has the highest relative abundance of 67.41 wt%. Confirming the purity of the Cu-NPs colloid. These findings contribute to the growing field of eco-friendly nanotechnology and emphasize the significance of plant-mediated approaches in nanomaterial synthesis and biomedical applications.
Study of the intestinal microbiota composition and the effect of treatment with intensive chemotherapy in patients recovered from acute leukemia
Authors: Vázquez Xenia , Lumbreras-Iglesias Pilar , Rodicio M. Rosario , Fernández Javier , Bernal Teresa , Moreno Ainhoa Fernández , de Ugarriza Paula López , Fernández-Verdugo Ana , Margolles Abelardo , Sabater Carlos
Published: March 2024

A dataset comprising metagenomes of outpatients (n = 28) with acute leukemia (AL) and healthy controls (n = 14) was analysed to investigate the associations between gut microbiota composition and metabolic activity and AL. According to the results obtained, no significant differences in the microbial diversity between AL outpatients and healthy controls were found. However, significant differences in the abundance of specific microbial clades of healthy controls and AL outpatients were found. We found some differences at taxa level. The relative abundance of Enterobacteriaceae, Prevotellaceae and Rikenellaceae was increased in AL outpatients, while Bacteirodaceae, Bifidobacteriaceae and Lachnospiraceae was decreased. Interestingly, the abundances of several taxa including Bacteroides and Faecalibacterium species showed variations based on recovery time from the last cycle of chemotherapy. Functional annotation of metagenome-assembled genomes (MAGs) revealed the presence of functional domains corresponding to therapeutic enzymes including l-asparaginase in a wide range of genera including Prevotella, Ruminococcus, Faecalibacterium, Alistipes, Akkermansia. Metabolic network modelling revealed potential symbiotic relationships between Veillonella parvula and Levyella massiliensis and several species found in the microbiota of AL outpatients. These results may contribute to develop strategies for the recovery of microbiota composition profiles in the treatment of patients with AL.
Time to death and its determinants of under-five children in rural Ethiopia by using shared frailty
Authors: Yemane Getahun Dejene , Tareke Abiyu Abadi , Zakaria Hamdi Fekredin , Takele Bayley Adane , Jemal Sebwedin Surur
Published: March 2024

Under-five (U5M) is one of the most significant and sensitive measures of the community's health. Children who live in rural areas are more likely than those who live in urban areas to die before the age of five. Therefore, the study aimed to assess the Survival status of under-five mortality and its determinants in rural Ethiopia. The 2019 Ethiopia Mini Demographic and Health Survey was used in this study as a secondary source (EMDHS). A total of 4426 weighted under-five children were included in the study. To determine survival time and identify predictors of death among children under the age of five, the Cox's gamma shared frailty model and the Kaplan Meier model, respectively, were used. An adjusted Hazard Ratio (AHR) along with a 95% Confidence Interval (CI) were used to measure the size and direction of the association. The Study showed that in rural Ethiopia, 6.03% of children died before celebrating their first birthday. The median age of under-five mortality in rural Ethiopia was estimated to be 29 Months. The hazard of death among under-five children and those who had given birth to two children in the last five years was 4.99 times less likely to be at risk of dying than those who had given birth to one Child in the previous five years (AHR 4.99, 95% CI 2.97, 8.83). The Study Concluded that under-five mortality remained high in rural Ethiopia. In the final model, the Age of Mothers, Sex of Household, Breastfeeding, Types of Birth, Sex of Child, Educational Level of Mothers, Wealth Index, Child ever born, Marital Status, and Water Source were significant predictors of under-five mortality. Twins and children who are not breastfed should receive additional attention, along with improving water resources for households and mothers income.
Evolutionary law and regulatory technology of roof migration on gob-side entry retaining
Authors: Zhang Li-Xin , Yi Li , Gang Li , Liu Guang-Chao , Deng Ze-Hui , Mi Jia-Le
Published: March 2024

In order to study the evolutionary law of roof migration on Gob-Side Entry Retaining, this paper takes the gob-side entry retaining in the comprehensive mining face of the Ningtiaota coal mine as the engineering background, and analyzes the evolutionary law of the overlying rock layer on the roof at different locations during the roadway stay and the stress distribution around the roadway through numerical simulation software, which shows that there is a concentration of stress inside the Flexible formwork concrete wall, and therefore the maximum settlement of the roof on the side of Flexible formwork concrete wall is 35.35 mm, due to the existence of “arch-shaped” decompression area from the working face. Therefore, the maximum settlement of the roof slab on the side of flexible formwork concrete wall was 35.35 mm. Due to the existence of “arch-shaped” decompression area on the roof and floor of roadway, the settlement of the roof slab on both sides of the roadway gradually increased when it was from − 20 to 10 m away from the working face, and the central position had the following pattern of firstly decreasing and then gradually increasing, and then exceeding the top of the roadway. After decreasing and then gradually increasing, after 10 m ahead of the working face, the two sides of the roadway roof subsidence law and the central part of the roadway to maintain the same; the use of cutting the top of the flexible mold concrete wall support technology as a means of controlling the top of the roof along the empty roadway subsidence, the analysis shows that the roof after roof cutting of the amount of subsidence have been reduced, the maximum difference in the rate of change of the displacement is 0.011%, and the maximum difference in the amount of subsidence of 4.98 mm; through the field monitoring data analysis of the pressure of mining The peak value of the influence curve of the working face is located at 19 m of the working face, 9 m of the lagging working face and 19 m of the roadway outside the working face are less affected by the additional mining stress field, comparing the fracture brokenness of the roadway roof before and after the roof cutting, the fracture area in the uncut section is much larger than that in the section of the roof cutting.
X-ray dark-field computed tomography for monitoring of tissue freezing
Authors: John Dominik , Gottwald Wolfgang , Berthe Daniel , Wirtensohn Sami , Hickler Julia , Heck Lisa , Herzen Julia
Published: March 2024

Accurately monitoring the extent of freezing in biological tissue is an important requirement for cryoablation, a minimally invasive cancer treatment that induces cell death by freezing tissue with a cryoprobe. During the procedure, monitoring is required to avoid unnecessary harm to the surrounding healthy tissue and to ensure the tumor is properly encapsulated. One commonly used monitoring method is attenuation-based computed tomography (CT), which visualizes the ice ball by utilizing its hypoattenuating properties compared to unfrozen tissue. However, the contrast between frozen and unfrozen tissue remains low. In a proof-of-principle experiment, we show that the contrast between frozen and unfrozen parts of a porcine phantom mimicking breast tissue can be greatly enhanced by acquiring X-ray dark-field images that capture the increasing small-angle scattering caused by the ice crystals formed during the procedure. Our results show that, compared to X-ray attenuation, the frozen region is detected significantly better in dark-field radiographs and CT scans of the phantom. These findings demonstrate that X-ray dark-field imaging could be a potential candidate for improved monitoring of cryoablation procedures.
Dumbbell shaped structure loaded modified circular ring resonator based perfect metamaterial absorber for S, X and Ku band microwave sensing applications
Authors: Rabbani Md. Golam , Islam Mohammad Tariqul , Moniruzzaman Md. , Alamri Saeed , Rahman Abdullah Al Mahfazur , Moubark Asraf Mohamed , Islam Md. Shabiul , Soliman Mohamed S.
Published: March 2024

In this paper, a new metamaterial absorber (MMA) is presented that exhibits peak absorptions at 3.26 GHz, 11.6 GHz, and 17.13 GHz within S, X, and Ku bands. The unit cell of the proposed MMA is constructed on an FR4 substrate having an electrical dimension of 0.144λ × 0.144λ, where wavelength, λ is calculated at the lowest absorption frequency. The unique structural design of the unit cell consists of two concentric copper rings with which dumbbell-shaped structures are attached. The rotating symmetrical structural design of this MMA provides around 93.8%, 96.47%, and 99.95% peak absorptance in the mentioned frequencies, which is invariable with the change of incident angle as well as polarization angle. The metamaterial properties of the proposed absorber are studied along with the surface current analysis. The MMA shows single negative behaviour and it also exhibits high-quality factors (Q factor) of 21.73, 41.42, and 51.90 at maximum absorptance frequencies. The MMA is analysed by it's equivalent circuit to understand the resonance phenomenon, which is verified through simulation in Advanced Design Systems (ADS) software. The testing is done on the developed prototype of the proposed MMA. Measurement results are in close proximity to the simulation results. Due to its high Q factor, high EMR, and insensitivity to polarization and angle of incidence, it can be utilized as a part of miniaturized microwave device. In addition, the proposed MMA can exhibit high sensing performance and flexibility to differentiate different oils in S, X, and Ku bands.
Optimization of induction and hairy root culture establishment in two mullein species, Verbascum erianthum and Verbascum stachydiforme
Authors: Amini Soniya , Fattahi Mohammad , Nazemiyeh Hossein
Published: March 2024

The genus Verbascum, belonging to the family Scrophulariaceae, has a significant center of diversity in Iran. Two of its species, V. erianthum and V. stachydiforme, originate in the Iranian-Turanian region, but no studies have been conducted on the induction of their hairy roots. This genus is a valuable source of biologically active compounds such as iridoid glycosides and flavonoids. Hairy root culture is a suitable technique for the production and accumulation of secondary metabolites. Three different studies were conducted to optimize the induction and establishment of hairy roots. In the first experiment, the influence of explant type (leaf and hypocotyl), six infection methods, and co-culture time (48 and 72 h) on the efficiency of hairy root induction was investigated. The results showed that the highest hairy root induction (68.18%) was observed in the leaf explants inoculated by direct infection with three wounds within 72 h co-culture time. In the second experiment, the effect of four Agrobacterium rhizogenes strains (ATCC 15834, A4, A7, and A13) and leaf age (14, 21, and 28 days) on transformation efficiency and some morphological traits examined in both species were studied. The high transformation efficiency of hairy root (80.55%) was detected in the 21-day-old leaf explant of V. erianthum species that was inoculated with the A13 strain. The transformed hairy root colons were confirmed by PCR using rolB gene-specific primers. To optimize hairy root growth and avoid tissue browning, hairy roots were cultured in various media containing different antioxidants and improver agents (including ascorbic acid, citric acid, and NAA). The results showed that the highest fresh growth index (20.42) and the lowest tissue browning (9%) as well as total phenol (8.51 mg GA/g DW), and total flavonoid content (4.42 mg QUE/g DW) were obtained in medium B5 with 1.5 mg/l NAA.
Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis
Authors: She Xianhua , Yin Donghong , Guo Qian , Tang Yang , Wang Shuyun , Wang Xuyan
Published: March 2024

To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45–64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65–74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events.
A long-read sequencing strategy with overlapping linkers on adjacent fragments (OLAF-Seq) for targeted resequencing and enrichment
Authors: Uppuluri Lahari , Shi Christina Huan , Varapula Dharma , Young Eleanor , Ehrlich Rachel L. , Wang Yilin , Piazza Danielle , Mell Joshua Chang , Yip Kevin Y. , Xiao Ming
Published: March 2024

In this report, we present OLAF-Seq, a novel strategy to construct a long-read sequencing library such that adjacent fragments are linked with end-terminal duplications. We use the CRISPR-Cas9 nickase enzyme and a pool of multiple sgRNAs to perform non-random fragmentation of targeted long DNA molecules (> 300kb) into smaller library-sized fragments (about 20 kbp) in a manner so as to retain physical linkage information (up to 1000 bp) between adjacent fragments. DNA molecules targeted for fragmentation are preferentially ligated with adaptors for sequencing, so this method can enrich targeted regions while taking advantage of the long-read sequencing platforms. This enables the sequencing of target regions with significantly lower total coverage, and the genome sequence within linker regions provides information for assembly and phasing. We demonstrated the validity and efficacy of the method first using phage and then by sequencing a panel of 100 full-length cancer-related genes (including both exons and introns) in the human genome. When the designed linkers contained heterozygous genetic variants, long haplotypes could be established. This sequencing strategy can be readily applied in both PacBio and Oxford Nanopore platforms for both long and short genes with an easy protocol. This economically viable approach is useful for targeted enrichment of hundreds of target genomic regions and where long no-gap contigs need deep sequencing.
Correlative single-cell hard X-ray computed tomography and X-ray fluorescence imaging
Authors: Lin Zihan , Zhang Xiao , Nandi Purbasha , Lin Yuewei , Wang Liguo , Chu Yong S. , Paape Timothy , Yang Yang , Xiao Xianghui , Liu Qun
Published: March 2024

X-ray computed tomography (XCT) and X-ray fluorescence (XRF) imaging are two non-invasive imaging techniques to study cellular structures and chemical element distributions, respectively. However, correlative X-ray computed tomography and fluorescence imaging for the same cell have yet to be routinely realized due to challenges in sample preparation and X-ray radiation damage. Here we report an integrated experimental and computational workflow for achieving correlative multi-modality X-ray imaging of a single cell. The method consists of the preparation of radiation-resistant single-cell samples using live-cell imaging-assisted chemical fixation and freeze-drying procedures, targeting and labeling cells for correlative XCT and XRF measurement, and computational reconstruction of the correlative and multi-modality images. With XCT, cellular structures including the overall structure and intracellular organelles are visualized, while XRF imaging reveals the distribution of multiple chemical elements within the same cell. Our correlative method demonstrates the feasibility and broad applicability of using X-rays to understand cellular structures and the roles of chemical elements and related proteins in signaling and other biological processes.
Repeat DNA methylation is modulated by adherens junction signaling
Authors: Brenner Lisa-Marie , Meyer Florian , Yang Haiqian , Köhler Anja R. , Bashtrykov Pavel , Guo Ming , Jeltsch Albert , Lungu Cristiana , Olayioye Monilola A.
Published: March 2024

Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA methylation is highly abundant at repetitive elements, but its investigation in live cells has been complicated by methodological challenges. Utilizing a CRISPR/dCas9 biosensor that reads DNA methylation of human α-satellite repeats in live cells, we here uncover a signaling pathway linking the chromatin and transcriptional state of repetitive elements to epithelial adherens junction integrity. Specifically, we find that in confluent breast epithelial cell monolayers, α-satellite repeat methylation is reduced by comparison to low density cultures. This is coupled with increased transcriptional activity at repeats. Through comprehensive perturbation experiments, we identify the junctional protein E-cadherin, which links to the actin cytoskeleton, as a central molecular player for signal relay into the nucleus. Furthermore, we find that this pathway is impaired in cancer cells that lack E-cadherin and are not contact-inhibited. This suggests that the molecular connection between cell density and repetitive element methylation could play a role in the maintenance of epithelial tissue homeostasis.
Shaped liquid drops generate MeV temperature electron beams with millijoule class laser
Authors: Mondal Angana , Sabui Ratul , Tata Sheroy , Trines R. M. G. M. , Rahul S. V. , Li Feiyu , Sarkar Soubhik , Trickey William , Kumar Rakesh Y. , Rajak Debobrata , Pasley John , Sheng Zhengming , Jha Jagannath , Anand M. , Gopal Ram , Robinson A. P. L. , Krishnamurthy M.
Published: March 2024

MeV temperature electrons are typically generated at laser intensities of 1018 W cm−2. Their generation at non-relativistic intensities (~1016 W cm−2) with high repetition rate lasers is cardinal for the realization of compact, ultra-fast electron sources. Here we report a technique of dynamic target structuring of micro-droplets using a 1 kHz, 25 fs, millijoule class laser, that uses two collinear laser pulses; the first to create a concave surface in the liquid drop and the second, to dynamically-drive electrostatic plasma waves that accelerate electrons to MeV energies. The acceleration mechanism, identified as two plasmon decay instability, is shown to generate two beams of electrons with hot electron temperature components of 200 keV and 1 MeV, respectively, at an intensity of 4 × 1016 Wcm−2, only. The electron beams are demonstrated to be ideal for single shot high resolution (tens of μm) electron radiography.
Taming cyclo-pentazolate anions with a hydrogen-bonded organic framework
Authors: Xu Yuangang , Zhou Jianxin , Li Xinyi , Hou Tianyang , Xu Ze , Wang Pengcheng , Lu Ming
Published: March 2024

Because of its high energy, aromaticity, and carbon- and hydrogen-free structure, the cyclo-pentazolate anion (c-N5-) has attracted increased attention as a potential polynitrogen structural unit for the research of next-generation high energy density materials. However, the poor thermal stability of c-N5--based compounds has become an important factor restricting their development. Here, we show that a hydrogen-bonded organic framework (HOF) self-assembles with and stabilizes c-N5-, with c-N5- situated in the pores of the resulting framework through the formation of symmetrical c-N5- hydrogen bonds as the main stabilizing factors. These factors result in an onset decomposition temperature of 153 °C for the c-N5-@HOF portion, which exceeds the thermal stabilities generally observed for c-N5--based derivatives of below 135 °C. We envisage that further c-N5--based materials with enhanced stabilities and better performance will be developed in the future.
Mendelian randomization study of the relationship between blood and urine biomarkers and schizophrenia in the UK Biobank cohort
Authors: Cheng Bolun , Bai Yunfeng , Liu Li , Meng Peilin , Cheng Shiqiang , Yang Xuena , Pan Chuyu , Wei Wenming , Liu Huan , Jia Yumeng , Wen Yan , Zhang Feng
Published: March 2024

Background

The identification of suitable biomarkers is of crucial clinical importance for the early diagnosis of treatment-resistant schizophrenia (TRS). This study aims to comprehensively analyze the association between TRS and blood and urine biomarkers.

Methods

Candidate TRS-related single nucleotide polymorphisms (SNPs) were obtained from a recent genome-wide association study. The UK Biobank cohort, comprising 376,807 subjects with blood and urine biomarker testing data, was used to calculate the polygenic risk score (PRS) for TRS. Pearson correlation analyses were performed to evaluate the correlation between TRS PRS and each of the biomarkers, using calculated TRS PRS as the instrumental variables. Bidirectional two-sample Mendelian randomization (MR) was used to assess potential causal associations between candidate biomarkers with TRS.

Results

Here we identify a significant association between TRS PRS and phosphate (r = 0.007, P = 1.96 × 10−4). Sex subgroup analyses identify seven and three candidate biomarkers associated with TRS PRS in male and female participants, respectively. For example, total protein and phosphate for males, creatinine and phosphate for females. Bidirectional two-sample MR analyses indicate that TRS is negatively associated with cholesterol (estimate = −0.363, P  = 0.008). Conversely, TRS is positively associated with total protein (estimate = 0.137, P  = 0.027), mean corpuscular volume (estimate = 0.032, P  = 2.25 × 10−5), and mean corpuscular hemoglobin (estimate = 0.018, P  = 0.007).

Conclusions

Our findings provide insights into the roles of blood and urine biomarkers in the early detection and treatment of TRS.