bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of stabilizing materials on soil Cd bioavailability, uptake, transport, and rice growth
Authors: Xu Meizhen , Luo Fei , Tu Feng , Rukh Gul , Ye Zhengqian , Ruan Zhongqiang , Liu Dan
Published: November 2022

Cadmium, a widespread toxic heavy metal in farmland soils, is harmful to human health. A field experiment was conducted to investigate the effects of biochar and biochar-based fertilizers on soil pH, organic matter, and available Cd, as well as rice Cd uptake and translocation. The results showed that rice biomass was significantly increased after both the application of biochar and high rate of biochar-based fertilizers at the tillering stage. The biomass and plant height of rice were improved at filling and maturity stages. Soil pH was significantly increased with the application of biochar but not with the biochar-based fertilizer. The amendments of biochar and biochar-based fertilizers had no significant (p < 0.05) influence on soil organic matter content. The concentration of available Cd in soil and the concentration of Cd in rice were decreased with the application of different amounts of biochar and biochar-based fertilizers in the mature stage. However, this effect was much greater under biochar amendment. Compared to the control, the concentration of available Cd in soil was reduced by 33.09% with the low application rate of biochar, while that was reduced by 18.06% with the high application rate of biochar. The lowest bioaccumulation factor was due to the high concentration of biochar and biochar-based fertilizers. It is concluded that biochar and biochar-based fertilizers particularly at a high addition rate are appropriate for decreasing Cd mobility and improve soil quality for contaminated paddy soils. The study showed a method for the safe production of rice in Cd-polluted farmlands by using a high application rate of biochar or carbon-based fertilizers.
A novel heterozygous SIX1 missense mutation resulted in non-syndromic unilateral hearing loss
Authors: Li Ang , Liu Siwen , Zhang Peng , Hu Xintong , Li Guiying , Gu Weiyue , Jiang Yanfang
Published: November 2022

Familial non-syndromic unilateral hearing loss (NS-UHL) is rare and its genetic etiology has not been clearly elucidated. This study aimed to identify the genetic cause of NS-UHL in a three-generation Chinese family. Detailed medical history consultation and clinical examination were conducted. Further, whole-exome sequencing (WES) was performed to identify the genetic etiology of the proband, and the variant was verified by Sanger sequencing. A novel missense mutation, c.533G>C (p.Arg178Thr), in the SIX homeobox 1 gene (SIX1) was identified in four patients and co-segregated with NS-UHL in a three-generation Chinese family as a dominant trait. Using bioinformatics analyses, we show that this novel mutation is pathogenic and affects the structure of SIX1 protein. These data suggest that mutations in SIX1 gene are associated with NS-UHL. Our study added the NS-UHL phenotype associated with SIX1, and thereby improving the genetic counseling provided to individuals with SIX1 mutations.
Mutational analysis of ribosomal proteins in a cohort of pediatric patients with T-cell acute lymphoblastic leukemia reveals Q123R, a novel mutation in RPL10
Authors: Bacci Lorenza , Indio Valentina , Rambaldelli Guglielmo , Bugarin Cristina , Magliocchetti Franco , Del Rio Alberto , Pollutri Daniela , Melchionda Fraia , Pession Andrea , Lanciotti Marina , Dufour Carlo , Gaipa Giuseppe , Montanaro Lorenzo , Penzo Marianna
Published: November 2022

T-cell acute lymphoblastic leukemia (T-ALL) is a subtype of ALL involving the malignant expansion of T-cell progenitors. It is driven by a number of different possible genetic lesions, including mutations in genes encoding for ribosomal proteins (RPs). These are structural constituents of ribosomes, ubiquitous effectors of protein synthesis. Albeit the R98S mutation in RPL10, recurring with a higher frequency among RP mutations, has been extensively studied, less is known about the contribution of mutations occurring in other RPs. Alterations affecting translational machinery may not be well tolerated by cells, and there may be a selective pressure that determines the emergence of mutations with a compensatory effect. To explore this hypothesis, we sequenced the exomes of a cohort of 37 pediatric patients affected by T-ALL, and analyzed them to explore the co-occurrence of mutations in genes involved in ribosome biogenesis (including RPs) and translational control, and in known T-ALL driver genes. We found that some of the mutations in these sub-classes of genes tend to cluster together in different patients, indicating that their co-occurrence may confer some kind of advantage to leukemia cells. In addition, our sequencing highlighted the presence of a novel mutation in RPL10, namely the Q123R, which we found associated with a defect in protein synthesis. Our findings indicate that genetic alterations involving ribosome biogenesis and translational control should be carefully considered in the context of precision medicine in T-ALL.
CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil
Authors: Nasiri Fatemeh , Kazemi Mehrasa , Mirarefin Seyed Mohamad Javad , Mahboubi Kancha Maral , Ahmadi Najafabadi Milad , Salem Faeze , Dashti Shokoohi Setareh , Evazi Bakhshi Sahar , Safarzadeh Kozani Pouya , Safarzadeh Kozani Pooria
Published: November 2022

Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body’s immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.
CPUE retrieval from spaceborne lidar data: A case study in the Atlantic bigeye tuna fishing area and Antarctica fishing area
Authors: Zhong Chunyi , Chen Peng , Zhang Zhenhua , Sun Miao , Xie Congshuang
Published: November 2022

The measurement of Catch Per Unit Effort (CPUE) supports the assessment of status and trends by managers. This proportion of total catch to the harvesting effort estimates the abundance of fishery resources. Marine environmental data obtained by satellite remote sensing are essential in fishing efficiency estimation or CPUE standardization. Currently, remote sensing chlorophyll data used for fisheries resource assessment are mainly from passive ocean color remote sensing. However, high-resolution data are not available at night or in high-latitude areas such as polar regions due to insufficient solar light, clouds, and other factors. In this paper, a CPUE inversion method based on spaceborne lidar data is proposed, which is still feasible for polar regions and at nighttime. First, Atlantic bigeye tuna CPUE was modeled using Cloud aerosol lidar and infrared pathfinder satellite observations (CALIPSO) lidar-retrieved chlorophyll data in combination with sea surface temperature data. The Generalized Linear Model (GLM), Artificial Neural Network (ANN) and Support Vector Machine Methods (SVM) were used for modeling, and the three methods were compared and validated. The results showed that the correlation between predicted CPUE and nominal CPUE was higher for the ANN method, with an R2of 0.34, while the R2was 0.08 and 0.22 for GLM and SVM, respectively. Then, chlorophyll data in the polar regions were derived using CALIPSO diurnal data, and an ANN was used for Antarctic krill. The inversion result performed well, and it showed that the R2of the predicted CPUE to nominal CPUE was 0.92. Preliminary results suggest that (1) nighttime measurements can increase the understanding of the diurnal variability of the upper ocean; (2) CALIPSO measurements in polar regions fill the gap of passive measurements; and (3) comparison with field data shows that ANN-based lidar products perform well, and a neural network approach based on CALIPSO lidar data can be used to simulate CPUE inversions in polar regions.
Analysis of the marine resource environmental carrying capacity in Zhejiang Province based on the Pressure-Support and Destructiveness-Resilience and Degradation-Promotion (PS-DR-DP) model
Authors: Ying Chao , Yang Yunze , Liu Yongchao
Published: November 2022

Introduction

Large-scale and high-intensity marine resource exploitation activities have brought irreversible influences on the marine resource environment and ecosystem. As an important index to evaluate the state of marine development, the marine resource environmental carrying capacity (MRECC) is vital to the sustainable development of the sea areas.

Methods

In this study, an evaluation index system was established based on the PS-DR-DP (Pressure and Support-Destructiveness and Resilience- Degradation and Promotion) theoretical model. The MRECC in Zhejiang Province from 2004 to 2018 was evaluated through the categorical arrangement polygon representation. Moreover, the coordination degree of the MRECC system was analyzed by using the coupling harmonious degree model.

Results and Discussion

Results demonstrated the following from 2004 to 2018: 1) The MRECC level in Zhejiang Province increased firstly, then decreased slightly, and finally presented a slow increasing trend. 2) The mean contributions of the acting forces in the MRECC system in Zhejiang Province fluctuate between 0.64 and 0.68. It was in the high-speed unsteady growth and tended to be the ideal carrying state. The positive force tends to increase, while the negative force is generally stable or only slightly increased except for the degradation force. 3) The coupling degree and degree of coupling coordination of the acting force subsystems in the marine resource environmental system in Zhejiang Province presented a rising trend. The coupling degree ranged between 0.50 and 0.80 except for those in 2004, 2006, and 2007. The acting force subsystems in the marine resource environmental system in Zhejiang Province were generally running-in during the study period. The coupling degree type changed from mild imbalance to moderate coordination.
Depth-related patterns and regional diversity of free-living nematodes in the deep-sea Southwestern Gulf of Mexico
Authors: Armenteros Maickel , Quintanar-Retama Octavio , Gracia Adolfo
Published: November 2022

Diversity of free-living marine nematode assemblages in the Southwestern Gulf of Mexico (SW GoM) is scarcely studied. Here, we aimed (1) to analyze the influence of a water depth gradient on the species richness, feeding type and taxonomic composition of assemblages; and (2) to document the regional diversity of free-living nematodes in the SW GoM. We sampled 63 sites along a water depth gradient from 186 to 3774 m during four oceanographic cruises. We found clear variations along the depth gradient of bottom water (temperature, salinity, and dissolved oxygen) and sediment variables (grain size and organic content). We identified 1881 nematodes belonging to 108 genera, 33 families, ten orders, and two classes. The abundance and species richness decreased with water depth. However, the expected number of species for a same level of abundance did not change along the depth gradient likely because the scarcity of food was compensated by reduced environmental stress (e.g., higher oxygen content and physical stability). Microbial sucker was the most abundant feeding type indicating the important role of sediment bacteria in the nematode’s diet. Species composition varied along the depth gradient with dominance in the upper slope sites of species of Comesomatidae tolerant to reduced sediments (e.g., Dorylaimopsis sp., Sabatieria spp., and Setosabatieria hilarula). Many congeneric species typical of deep sea were restricted to the deepest sites such as Acantholaimus spp., Ledovitia spp., Desmoscolex spp., and Halalaimus spp. The nematode regional diversity of SW GoM was 154 species, but the Chao 1 estimator indicated a richness of about 194 species and a highest limit of 246 species. The accumulation curves of richness were non-asymptotic suggesting a substantial fraction of undiscovered richness. Our study increased the free-living nematode fauna of GoM in 144 species (76%) respect to Hope’s list (2009). The large diversity of nematodes stands out the necessity of further studies to unravel the environmental drivers of α- and β-diversities and highlights the potential of this taxon for monitoring the deep sea of the Gulf of Mexico.
MsmR1, a global transcription factor, regulates polymyxin synthesis and carbohydrate metabolism in Paenibacillus polymyxa SC2
Authors: Zhao Dongying , Li Hui , Cui Yanru , Tang Shengyue , Wang Chengqiang , Du Binghai , Ding Yanqin
Published: November 2022

The multiple-sugar metabolism regulator (MsmR), a transcription factor belonging to the AraC/XylS family, participates in polysaccharide metabolism and virulence. However, the transcriptional regulatory mechanisms of MsmR1 in Paenibacillus polymyxa remain unclear. In this study, knocking out msmR1 was found to reduce polymyxin synthesis by the SC2-M1 strain. Chromatin immunoprecipitation assay with sequencing (ChIP-seq) revealed that most enriched pathway was that of carbohydrate metabolism. Additionally, electromobility shift assays (EMSA) confirmed the direct interaction between MsmR1 and the promoter regions of oppC3, sucA, sdr3, pepF, yycN, PPSC2_23180, pppL, and ydfp. MsmR1 stimulates polymyxin biosynthesis by directly binding to the promoter regions of oppC3 and sdr3, while also directly regulating sucA and influencing the citrate cycle (TCA cycle). In addition, MsmR1 directly activates pepF and was beneficial for spore and biofilm formation. These results indicated that MsmR1 could regulate carbohydrate and amino acid metabolism, and indirectly affect biological processes such as polymyxin synthesis, biofilm formation, and motility. Moreover, MsmR1 could be autoregulated. Hence, this study expand the current knowledge of MsmR1 and will be beneficial for the application of P. polymyxa SC2 in the biological control against the certain pathogens in pepper.
Mr.Vc v2: An updated version of database with increased data of transcriptome and experimental validated interactions
Authors: Zhang Zhiyuan , Chen Guozhong , Hussain Wajid , Qin Zixin , Liu Juntong , Su Yang , Zhang Hao , Ye Mingquan
Published: November 2022

Mr.Vc is a database of curated Vibrio cholerae transcriptome data and annotated information. The main objective is to facilitate the accessibility and reusability of the rapidly growing Vibrio cholerae omics data and relevant annotation. To achieve these goals, we performed manual curation on the transcriptome data and organized the datasets in an experiment-centric manner. We collected unknown operons annotated through text-mining analysis that would provide more clues about how Vibrio cholerae modulates gene regulation. Meanwhile, to understand the relationship between genes or experiments, we performed gene co-expression analysis and experiment-experiment correlation analysis. In additional, functional module named “Interactions” which dedicates to collecting experimentally validated interactions about Vibrio cholerae from public databases, MEDLINE documents and literature in life science journals. To date, Mr.Vc v2, which is significantly increased from the previous version, contains 107 microarray experiments, 106 RNA-seq experiments, and 3 Tn-seq projects, covering 56,839 entries of DEGs (Differentially Expressed Genes) from transcriptomes and 7,463 related genes from Tn-seq, respectively. and a total of 270,129 gene co-expression entries and 11,990 entries of experiment-experiment correlation was obtained, in total 1,316 entries of interactions were collected, including 496 protein-chemical signaling molecule interactions, 472 protein–protein interactions, 306 TF (Transcription Factor)-gene interactions and 42 Vibrio cholerae-virus interactions, most of which obtained from 402 literature through text-mining analysis. To make the information easier to access, Mr.Vc v2 is equipped with a search widget, enabling users to query what they are interested in. Mr.Vc v2 is freely available at http://mrvcv2.biownmc.info.
Gut microbiota alterations may increase the risk of prescription opioid use, but not vice versa: A two-sample bi-directional Mendelian randomization study
Authors: Lin Liling , Lin Jianwei , Qiu Junxiong , Wei Feng , Bai Xiaohui , Ma Weiying , Zeng Jingxian , Lin Daowei
Published: November 2022

Introduction

Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.

Methods

A two-sample bi-directional Mendelian randomization was conducted to assess the potential associations between gut microbiota and POU/MCP using summary level Genome-wide association studies (GWASs) that were based on predominantly European ancestry.

Results

Potential causal effects were identified between seven host genetic-driven traits of gut microbiota on POU, including Adlercreutzia, Allisonella, Dialister, Anaerofilum, Anaerostipes, ChristensenellaceaeR.7group, and LachnospiraceaeNC2004group at the genus level (p < 0.05) by the Inverse-variance weighted method, with significant causal effects of ChristensenellaceaeR.7group and Allisonella on POU (p < 0.025). A total of five genetically greater abundance of gut microbiota traits were identified to be possibly related to the level of MCP (p < 0.05), including genus ErysipelotrichaceaeUCG003, family Clostridiaceae1, order Gastranaerophilales, order Actinomycetales, and family Actinomycetaceae. In the other direction, no clear evidence was found to support a significant causal relationship between POU and gut microbiota, as well as MCP and gut microbiota. In addition, evidence was also provided for the relationship between triacylglycerols and diacylglycerol elevation, and an increased risk of POU and MCP. No evidence was found across various sensitivity analyses, including reverse causality, pleiotropy, and heterogeneity.

Conclusion

The findings from this study provide robust evidence that gut microbiota alterations may be a risk of POU/MCP, but not vice versa.
Review of Generative Adversarial Networks in mono- and cross-modal biomedical image registration
Authors: Han Tingting , Wu Jun , Luo Wenting , Wang Huiming , Jin Zhe , Qu Lei
Published: November 2022

Biomedical image registration refers to aligning corresponding anatomical structures among different images, which is critical to many tasks, such as brain atlas building, tumor growth monitoring, and image fusion-based medical diagnosis. However, high-throughput biomedical image registration remains challenging due to inherent variations in the intensity, texture, and anatomy resulting from different imaging modalities, different sample preparation methods, or different developmental stages of the imaged subject. Recently, Generative Adversarial Networks (GAN) have attracted increasing interest in both mono- and cross-modal biomedical image registrations due to their special ability to eliminate the modal variance and their adversarial training strategy. This paper provides a comprehensive survey of the GAN-based mono- and cross-modal biomedical image registration methods. According to the different implementation strategies, we organize the GAN-based mono- and cross-modal biomedical image registration methods into four categories: modality translation, symmetric learning, adversarial strategies, and joint training. The key concepts, the main contributions, and the advantages and disadvantages of the different strategies are summarized and discussed. Finally, we analyze the statistics of all the cited works from different points of view and reveal future trends for GAN-based biomedical image registration studies.
Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies
Authors: Ma Lirong , Zhang Zhuoran , Li Liyang , Zhang Lijie , Lin Zhijuan , Qin Hao
Published: November 2022

Background

Bacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.

Materials and methods

We searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.

Results

A total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P < 0.001). In subgroup analyses, positive associations were also found in studies that were: conducted in black women (OR, 1.56; 95% CI, 0.98–2.48; P = 0.060), focused on the first trimester of pregnancy (OR, 2.22; 95% CI, 1.35–3.64; P = 0.002), of high quality (OR, 3.05; 95% CI, 1.26–7.41; P = 0.014), and adjusted for confounders (OR, 1.28; 95% CI, 1.06–1.55; P = 0.012). Sensitivity analysis reported that BV risk during pregnancy resulting from vitamin D deficiency increased by 157% (OR, 2.57; 95% CI, 1.50–4.42; P = 0.001) when removing the first two high-weight studies. Publication bias was observed using Egger’s test (t = 3.43, P = 0.005) and a visual funnel plot.

Conclusion

This meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.
The role of reinforcement learning and value-based decision-making frameworks in understanding food choice and eating behaviors
Authors: Pearce Alaina L. , Fuchs Bari A. , Keller Kathleen L.
Published: November 2022

The obesogenic food environment includes easy access to highly-palatable, energy-dense, “ultra-processed” foods that are heavily marketed to consumers; therefore, it is critical to understand the neurocognitive processes the underlie overeating in response to environmental food-cues (e.g., food images, food branding/advertisements). Eating habits are learned through reinforcement, which is the process through which environmental food cues become valued and influence behavior. This process is supported by multiple behavioral control systems (e.g., Pavlovian, Habitual, Goal-Directed). Therefore, using neurocognitive frameworks for reinforcement learning and value-based decision-making can improve our understanding of food-choice and eating behaviors. Specifically, the role of reinforcement learning in eating behaviors was considered using the frameworks of (1) Sign-versus Goal-Tracking Phenotypes; (2) Model-Free versus Model-Based; and (3) the Utility or Value-Based Model. The sign-and goal-tracking phenotypes may contribute a mechanistic insight on the role of food-cue incentive salience in two prevailing models of overconsumption–the Extended Behavioral Susceptibility Theory and the Reactivity to Embedded Food Cues in Advertising Model. Similarly, the model-free versus model-based framework may contribute insight to the Extended Behavioral Susceptibility Theory and the Healthy Food Promotion Model. Finally, the value-based model provides a framework for understanding how all three learning systems are integrated to influence food choice. Together, these frameworks can provide mechanistic insight to existing models of food choice and overconsumption and may contribute to the development of future prevention and treatment efforts.
Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV
Authors: Klausen Uffe , Grauslund Jacob Handlos , Jørgensen Nicolai Grønne Dahlager , Ahmad Shamaila Munir , Jonassen Merete , Weis-Banke Stine Emilie , Martinenaite Evelina , Pedersen Lone Bredo , Lisle Thomas Landkildehus , Gang Anne Ortved , Enggaard Lisbeth , Hansen Morten , Holmström Morten Orebo , Met Özcan , Svane Inge Marie , Niemann Carsten Utoft , Pedersen Lars Møller , Andersen Mads Hald
Published: November 2022

Chronic lymphocytic leukemia (CLL) patients with unmutated immunoglobulin heavy chain (IgHV) are at risk of early disease progression compared to patients with mutated IgHV. As a preventive strategy, we treated 19 previously untreated CLL patients with unmutated IgHV in a phase 1/2 trial (clinicaltrials.gov, NCT03939234) exploring the efficacy and toxicity of a therapeutic cancer vaccine containing peptides derived from programmed death ligand 1 (PD-L1) and ligand 2 (PD-L2), hoping to restore immunological control of the disease. According to the International Workshop on Chronic lymphocytic Leukemia (iwCLL) response criteria, no patients obtained a response; however, during follow-up, one patient had complete normalization of the peripheral lymphocyte count and remained in biochemical remission after a follow-up time of 15 months. At the end of treatment, one patient had progressed, and 17 patients had stable disease. During follow-up with a median time of 23.5 months since inclusion, seven patients had progressed, and eight patients had stable disease. The median time to first treatment (TTFT) from diagnosis was 90.3 months with a median follow-up time of 50.1 months. This apparent favorable outcome in TTFT needs to be investigated in a randomized setting, as our population may have been biased. More than 80% of patients obtained vaccine-specific immune responses, confirming the immunogenicity of the vaccine. The vaccine was generally well tolerated with only grade I–II adverse events. Although there were some signs of clinical effects, the vaccine seems to be insufficient as monotherapy in CLL, possibly due to a high tumor burden. The efficacy of the vaccine should preferably be tested in combination with novel targeted therapies or as a consolidating treatment.
Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic Rag2-null rat model of glioblastoma
Authors: Jackson Luke R. , Masi Megan R. , Selman Bryce M. , Sandusky George E. , Zarrinmayeh Hamideh , Das Sudip K. , Maharjan Surendra , Wang Nian , Zheng Qi-Huang , Pollok Karen E. , Snyder Scott E. , Sun Phillip Zhe , Hutchins Gary D. , Butch Elizabeth R. , Veronesi Michael C.
Published: November 2022

Many drugs that show potential in animal models of glioblastoma (GBM) fail to translate to the clinic, contributing to a paucity of new therapeutic options. In addition, animal model development often includes histologic assessment, but multiparametric/multimodality imaging is rarely included despite increasing utilization in patient cancer management. This study developed an intracranial recurrent, drug-resistant, human-derived glioblastoma tumor in Sprague–Dawley Rag2-Rag2tm1Hera knockout rat and was characterized both histologically and using multiparametric/multimodality neuroimaging. Hybrid 18F-fluoroethyltyrosine positron emission tomography and magnetic resonance imaging, including chemical exchange saturation transfer (18F-FET PET/CEST MRI), was performed for full tumor viability determination and characterization. Histological analysis demonstrated human-like GBM features of the intracranially implanted tumor, with rapid tumor cell proliferation (Ki67 positivity: 30.5 ± 7.8%) and neovascular heterogeneity (von Willebrand factor VIII:1.8 to 5.0% positivity). Early serial MRI followed by simultaneous 18F-FET PET/CEST MRI demonstrated consistent, predictable tumor growth, with exponential tumor growth most evident between days 35 and 49 post-implantation. In a second, larger cohort of rats, 18F-FET PET/CEST MRI was performed in mature tumors (day 49 post-implantation) for biomarker determination, followed by evaluation of single and combination therapy as part of the model development and validation. The mean percentage of the injected dose per mL of 18F-FET PET correlated with the mean %CEST (r = 0.67, P < 0.05), but there was also a qualitative difference in hot spot location within the tumor, indicating complementary information regarding the tumor cell demand for amino acids and tumor intracellular mobile phase protein levels. Finally, the use of this glioblastoma animal model for therapy assessment was validated by its increased overall survival after treatment with combination therapy (temozolomide and idasanutlin) (P < 0.001). Our findings hold promise for a more accurate tumor viability determination and novel therapy assessment in vivo in a recently developed, reproducible, intracranial, PDX GBM.
Secondary preventing effect of lung cancer in non-high-risk population: A retrospective investigation of opportunistic screening with low-dose computed tomography in Wuhan
Authors: Zhou Zhiqiang , Qiu Chun , Liu Shangkun , Wang Shaofang , Wang Danning , Xu Hui
Published: November 2022

Background

Given the mortality benefit of low-dose computed tomography (LDCT) screening on high-risk populations, the retrospective investigation intended to identify the benefits of LDCT on lung cancer screening among the general demographic cohorts.

Methods

We used an opportunistic screening with LDCT implemented during the pandemic in Wuhan to study the impact on subsequent thoracic surgeries, especially surgeries for lung cancer. Patients who received LDCT from October 1, 2019, to July 31, 2020, in three Triple-A accredited hospitals in Wuhan were included in the study. Relative week volumes of both surgeries before and after the chest LDCT screening were compared pairwise. The counts of surgeries for pulmonary nodules or masses, and corresponding pathological results among different gender and age groups were also compared.

Result

The relative weekly volumes of thoracic surgery were significantly greater than those of stomach surgery after the opportunistic screening with LDCT. They were 33% (95% CI, 0.20-0.46; p<0. 001) higher than those of stomach surgery. For every 1,000 chest LDCT scans conducted in a given week, on average, 3.52(95% CI,0.56-6.49, p =0.03) thoracic surgeries were performed in the following week. After the implementation of opportunistic screening with LDCT, there was a higher percentage of young females with pulmonary nodule or mass (64.4% vs. 45.8%, p = 0.032). The fraction of lung cancer surgery in the treatment period was significantly greater than that in the control period (74.09% vs. 68.79%, p=0.007). There was a higher percentage of stage I lung cancer surgery in young and mid-age females than in the senior age group (64% vs. 53%, p= 0.05).

Interpretation

Opportunistic screening with LDCT can advance the early diagnosis window of lung cancer in non-high-risk populations, especially young women who are easy to be ignored.
Effects of active musical engagement during physical exercise on anxiety, pain and motivation in patients with chronic pain
Authors: Schneider Lydia , Egle Ulrich Tiber , Klinger Doris , Schulz Wolfgang , Villringer Arno , Fritz Thomas Hans
Published: November 2022

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (N = 24, 20 female and 4 men; age range 34–64, M = 51.67, SD = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, Jymmin, where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a conventional workout condition where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during Jymmin more strongly perceived motivation through others. The observed diminishing effects of Jymmin on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.
Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia
Authors: Cebey-López M. , Currás-Tuala M. J. , Gómez-Rial J. , Rivero-Calle I. , Pardo-Seco J. , Mendez-Gallart R. , Pischedda S. , Gómez-Carballa A. , Barral-Arca R. , Justicia-Grande A. , Viz-Lasheras S. , Rodríguez-Tenreiro C. , Gómez R. , Salas A. , Martinón-Torres F.
Published: November 2022

Background

Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH.

Methods

Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity.

Results

The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, β-CTX (r2 = −0.576, P-value = 0.016) and PNIP (r2 = −0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels.

Conclusions

Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.
Smart triage: Development of a rapid pediatric triage algorithm for use in low-and-middle income countries
Authors: Mawji Alishah , Li Edmond , Dunsmuir Dustin , Komugisha Clare , Novakowski Stefanie K. , Wiens Matthew O. , Vesuvius Tagoola Abner , Kissoon Niranjan , Ansermino J. Mark
Published: November 2022

Introduction

Early and accurate recognition of children at risk of progressing to critical illness could contribute to improved patient outcomes and resource allocation. In resource limited settings digital triage tools can support decision making and improve healthcare delivery. We developed a model for rapid identification of critically ill children at triage.

Methods

This was a prospective cohort study of acutely ill children presenting at Jinja Regional Referral Hospital in Eastern Uganda. Variables collected in the emergency department informed the development of a logistic model based on hospital admission using bootstrap stepwise regression. Low and high-risk thresholds for 90% minimum sensitivity and specificity, respectively generated three risk level categories. Performance was assessed using receiver operating characteristic curve analysis on a held-out test set generated by an 80:20 split with 10-fold cross validation. A risk stratification table informed clinical interpretation.

Results

The model derivation cohort included 1,612 participants, with an admission rate of approximately 23%. The majority of admitted patients were under five years old and presenting with sepsis, malaria, or pneumonia. A 9-predictor triage model was derived: logit (p) = −32.888 + (0.252, square root of age) + (0.016, heart rate) + (0.819, temperature) + (−0.022, mid-upper arm circumference) + (0.048 transformed oxygen saturation) + (1.793, parent concern) + (1.012, difficulty breathing) + (1.814, oedema) + (1.506, pallor). The model afforded good discrimination, calibration, and risk stratification at the selected thresholds of 8% and 40%.

Conclusion

In a low income, pediatric population, we developed a nine variable triage model with high sensitivity and specificity to predict who should be admitted. The triage model can be integrated into any digital platform and used with minimal training to guide rapid identification of critically ill children at first contact. External validation and clinical implementation are in progress.
LC–TOF-MS/MS and GC-MS based phytochemical profiling and evaluation of wound healing activity of Oroxylum Indicum (L.) Kurz (Beka)
Authors: Abdulhafiz Ferid , Reduan Mohd Farhan Hanif , Hisam Anwar Hazim , Mohammad Ibtihal , Abdul Wahab Ikarastika Rahayu , Abdul Hamid Fathin Faahimaah , Mohammed Arifullah , Nordin Muhammad Luqman , Shaari Rumaizi , Bakar Luqman Abu , Kari Zulhisyam Abdul , Wei Lee Seong , Goh Khang Wen , Ahmad Mohd Zain Muhammad Rajaei
Published: November 2022

Background:Beka (Oroxylum indicum(L.) Kurz) has been used as a culinary herb and natural remedy by the local communities in Malaysia. The leaf ofO. indicumis traditionally used for the treatment of diarrhea, high blood pressure, and improving digestive health.

Objectives:The present study was conducted to evaluate the phytochemical constituents and wound healing properties (in vitroandin vivomodels) of aqueous and ethanol extracts ofO. indicumleaves.

Methods:The total phenolic (TPC) and total flavonoid (TFC) contents in the plant extracts were determined by the spectrophotometric methods. Further, the extract was characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF-MS/MS) and Gas Chromatography-Mass Spectrometry (GC-MS). The wound healing activity was assessed using thein vitroscratch wound-healing assay andin vivoexcisional wound model.

Results:The results show the ethanol leaves extract had the higher TPC (164 mg GAE/g) when compared with the aqueous leaves extract (30 mg gallic acid equivalents/g). The ethanol leaves extract was also found to have higher TFC (101 mg Catechin equivalents/g) than the aqueous leaves extract (76 mg Catechin equivalents/g). The ethanol leaves extract was then used for further chemical analysis. The LC–TOF-MS/MS analysis showed that the leaves extracts ofO. indicumcontains many important compounds such as Orientin, Chrysin, Pinoquercetin, Cupressuflavone, Puerarin xyloside, Forsythiaside and Paederoside. In GC-MS analysis, 19 compounds were identified in ethanolic leaves extract. The wound healing studies shows thatO. indicumhas promising wound healing activity by increasing the rate of wound contraction significantly (p< 0.05).

Conclusion:In conclusion, the present study showed thatO. indicumleaf contains important phytochemicals and the wound healing potential of theO. indicumextract may probably be as a result of the presence of various phytoconstituents.
Rheological comparison between control and Dupuytren fibroblasts when plated in circular micropatterns using atomic force microscopy
Authors: Pérez-Domínguez Sandra , Werkmeister Elisabeth , Marini Maria Luisa , Dupres Vincent , Janel Sébastien , Lafont Frank , Radmacher Manfred
Published: November 2022

In tissue, cells are obliged to confine and adapt to a specific geometric shape due to the surrounding environmental constraints. Under healthy conditions, fibroblasts present an elongated shape; however, changes in biochemical and physical properties of the extracellular matrix could distort the cell shape, inducing a pathological state. We have studied fibroblasts’ mechanical behavior under circular geometrical constraints. Circular micropatterns force fibroblasts to acquire a different shape from that of a healthy tissue, inducing a possible pathological condition. In total, three different fibroblast types from Dupuytren’s disorder, all obtained from the same patient, were confined in circular-shaped micropatterns of three different diameters (25, 35, and 45 µm), and mechanical properties were evaluated using an atomic force microscope (AFM). We found that control fibroblast mechanics (apparent Young’s modulus) increases with the increasing pattern diameter and comes together with a decrease in cell height and in loss tangent, translated into a more solid-like behavior. We hypothesize that these results resemble the transition toward the myofibroblast phenotype, ameliorating cytoskeleton formation and organization and enhancing cell contraction. Scar and Dupuytren fibroblasts did not display major changes in cell mechanics and cell height when changing the pattern diameter, suggesting that they are less affected by physical changes in the environment as they can adapt their shape to the geometrical dimensions. Therefore, our findings demonstrate that combining micropatterning and AFM measurements provides a powerful tool to study cell mechanics inducing constraints onto the cell, thus mimicking certain aspects of the tissue environment in both healthy and pathological states.
Research progress and development trend of smart metamaterials
Authors: Zheng Yongju , Dai Huajie , Wu Junyi , Zhou Chuanping , Wang Zhiwen , Zhou Rougang , Li Wenxin
Published: November 2022

The development of smart metamaterials has brought changes to human society, and various new products based on smart metamaterials are emerging endlessly. In recent years, smart electromagnetic metamaterials, smart acoustic metamaterials, smart mechanical metamaterials, smart thermal metamaterials and machine learning have attracted much attention in metamaterials. These fields share similar theories, such as multiphysics coupling fields, novel artificial cells and programmability. Through theoretical and technical research, smart metamaterials will show exquisite applications in many fields, such as antenna and optical communication systems, microwave imaging, acoustic stealth, thermal camouflage, etc. In particular, the characteristics of the personalized microstructure design of smart metamaterials perfectly match the characteristics of 3D printing. The combination of them leads the development of metamaterials, which are undoubtedly of great value. In this paper, focusing on the representative key technologies, we review the development history, main research directions and latest applications of smart metamaterials. Finally, the possible development direction of metamaterials is predicted.
Oat chromosome and genome evolution defined by widespread terminal intergenomic translocations in polyploids
Authors: Tomaszewska Paulina , Schwarzacher Trude , Heslop-Harrison J. S. (Pat)
Published: November 2022

Structural chromosome rearrangements involving translocations, fusions and fissions lead to evolutionary variation between species and potentially reproductive isolation and variation in gene expression. While the wheats (Triticeae, Poaceae) and oats (Aveneae) all maintain a basic chromosome number of x=7, genomes of oats show frequent intergenomic translocations, in contrast to wheats where these translocations are relatively rare. We aimed to show genome structural diversity and genome relationships in tetraploid, hexaploid and octoploid Avena species and amphiploids, establishing patterns of intergenomic translocations across different oat taxa using fluorescence in situ hybridization (FISH) with four well-characterized repetitive DNA sequences: pAs120, AF226603, Ast-R171 and Ast-T116. In A. agadiriana (2n=4x=28), the selected probes hybridized to all chromosomes indicating that this species originated from one (autotetraploid) or closely related ancestors with the same genomes. Hexaploid amphiploids were confirmed as having the genomic composition AACCDD, while octoploid amphiploids showed three different genome compositions: AACCCCDD, AAAACCDD or AABBCCDD. The A, B, C, and D genomes of oats differ significantly in their involvement in non-centromeric, intercalary translocations. There was a predominance of distal intergenomic translocations from the C- into the D-genome chromosomes. Translocations from A- to C-, or D- to C-genome chromosomes were less frequent, proving that at least some of the translocations in oat polyploids are non-reciprocal. Rare translocations from A- to D-, D- to A- and C- to B-genome chromosomes were also visualized. The fundamental research has implications for exploiting genomic biodiversity in oat breeding through introgression from wild species potentially with contrasting chromosomal structures and hence deleterious segmental duplications or large deletions in amphiploid parental lines.