bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database
Authors: Pestana Roberto Carmagnani , Serrano César 
Published: January 2023

BackgroundThe development of novel therapies for patients with sarcoma is challenging due to the rarity and diversity of these mesenchymal neoplasms. Hence, histology-agnostic approvals can be of particular interest for the treatment of patients with soft tissue and bone sarcoma.MethodsWe queried the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database Cohort v12.0-Public to investigate the prevalence of currently Food and Drug Administration (FDA)-approved and other potentially actionable histology-agnostic alterations in patients with soft tissue and bone sarcoma. Targets were identified by a literature review by the authors. Results are presented for each cohort identified in the GENIE database, namely: (1) soft tissue sarcoma (STS), (2) gastrointestinal stromal tumor (GIST), (3) bone sarcoma, (4) uterine sarcoma, and (5) breast sarcoma.ResultsWe identified 7,512 samples of 6,955 patients with sarcoma in the AAACR GENIE database v12.0-Public. Molecular alterations that could lead to the clinical use of a currently approved histology-agnostic therapy were identified in 2.1% of sarcomas (2.6% STS, 1.3% GIST, 1.4% bone, 2.7% uterine, and 0% breast). In addition, 2.9% of patients could be eligible for future histology-agnostic approvals. These specific mutations, fusions, and amplifications occurred in multiple histotypes in all cohorts.DiscussionExploring a public large-scale genomic database, we identified that 5% of patients with sarcoma could be eligible for current histology-agnostic FDA-approved drugs or future potential histology-agnostic indications. These actionable alterations were present in a wide variety of histologies in soft tissue and bone sarcomas, highlighting that next-generation sequencing can be considered for patients with advanced sarcoma to guide treatment strategies.
Whole-lesion histogram analysis of multiple diffusion metrics for differentiating lung cancer from inflammatory lesions
Authors: Li Jiaxin , Wu Baolin , Huang Zhun , Zhao Yixiang , Zhao Sen , Guo Shuaikang , Xu Shufei , Wang Xiaolei , Tian Tiantian , Wang Zhixue , Zhou Jun 
Published: January 2023

BackgroundWhole-lesion histogram analysis can provide comprehensive assessment of tissues by calculating additional quantitative metrics such as skewness and kurtosis; however, few studies have evaluated its value in the differential diagnosis of lung lesions.PurposeTo compare the diagnostic performance of conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) in differentiating lung cancer from focal inflammatory lesions, based on whole-lesion volume histogram analysis.MethodsFifty-nine patients with solitary pulmonary lesions underwent multiple b-values DWIs, which were then postprocessed using mono-exponential, bi-exponential and DKI models. Histogram parameters of the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f), apparent diffusional kurtosis (Kapp) and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the lung cancer and inflammatory lesion groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance.ResultsThe ADCmean, ADCmedian, Dmean and Dmedian values of lung cancer were significantly lower than those of inflammatory lesions, while the ADCskewness, Kappmean, Kappmedian, KappSD, Kappkurtosis and Dappskewness values of lung cancer were significantly higher than those of inflammatory lesions (all p &lt; 0.05). ADCskewness (p = 0.019) and Dmedian (p = 0.031) were identified as independent predictors of lung cancer. Dmedian showed the best performance for differentiating lung cancer from inflammatory lesions, with an area under the ROC curve of 0.777. Using a Dmedian of 1.091 × 10-3 mm2/s as the optimal cut-off value, the sensitivity, specificity, positive predictive value and negative predictive value were 69.23%, 85.00%, 90.00% and 58.62%, respectively.ConclusionsWhole-lesion histogram analysis of DWI, IVIM and DKI parameters is a promising approach for differentiating lung cancer from inflammatory lesions, and Dmedian shows the best performance in the differential diagnosis of solitary pulmonary lesions.
Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients
Authors: Jia Bin , Xia Peiyi , Dong Junqiang , Feng Wenhao , Wang Wenjia , Liu Enjie , Jiang Guozhong , Qin Yanru 
Published: January 2023

BackgroundSarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC.MethodsIn this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX’s model was used for survival analysis (OS) of patients’ clinical characteristics.ResultThe median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs.ConclusionsThis study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC.
Prognostic risk analysis related to radioresistance genes in colorectal cancer
Authors: Qin Haoren , Zhang Heng , Li Haipeng , Xu Qiong , Sun Wanjun , Zhang Shiwu , Zhang Xipeng , Zhu Siwei , Wang Hui 
Published: January 2023

BackgroundRadiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients.MethodsThe radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated.ResultsA total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups.ConclusionsThe risk score model built with five radioresistance genes in this study, including TNFRSF13C, CD36, ANGPTL4, LAMB3, and SERPINA1, showed favorable performance in prognosis prediction after radiotherapy for CRC.
Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy
Authors: Wu Hao , Zhang Tianyi , Liu Qi , Wei Min , Li Yuping , Ma Qiang , Wang Lianhui , Zhu Yufu , Zhang Hengzhu 
Published: January 2023

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p &lt; 0.05).Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.
Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR
Authors: Huangfu Yaru , Yu Xiuxian , Wan Chengyu , Zhu Yuda , Wei Zeliang , Li Fan , Wang Yilan , Zhang Kun , Li Shiyi , Dong Yuman , Li Yangying , Niu Hai , Xin Guang , Huang Wen 
Published: January 2023

Severe acute pancreatitis (SAP) is a lethal gastrointestinal disorder, yet no specific and effective treatment is available. Its pathogenesis involves inflammatory cascade, oxidative stress, and autophagy dysfunction. Xanthohumol (Xn) displays various medicinal properties,including anti-inflammation, antioxidative, and enhancing autophagic flux. However, it is unclear whether Xn inhibits SAP. This study investigated the efficacy of Xn on sodium taurocholate (NaT)-induced SAP (NaT-SAP) in vitro and in vivo. First, Xn attenuated biochemical and histopathological responses in NaT-SAP mice. And Xn reduced NaT-induced necrosis, inflammation, oxidative stress, and autophagy impairment. The mTOR activator MHY1485 and the AKT activator SC79 partly reversed the treatment effect of Xn. Overall, this is an innovative study to identify that Xn improved pancreatic injury by enhancing autophagic flux via inhibition of AKT/mTOR. Xn is expected to become a novel SAP therapeutic agent.
Rehabilitation assisted by Space technology—A SAHC approach in immobilized patients—A case of stroke
Authors: Kourtidou-Papadeli Chrysoula , Frantzidis Christos , Machairas Ilias , Giantsios Christos , Dermitzakis Emmanouil , Kantouris Nikolaos , Konstantinids Evdokimos , Bamidis Panagiotis , Vernikos Joan 
Published: January 2023

Introduction: The idea behind the presentation of this case relates to utilizing space technology in earth applications with mutual benefit for both patients confined to bed and astronauts. Deconditioning and the progressiveness of skeletal muscle loss in the absence of adequate gravity stimulus have been of physiological concern. A robust countermeasure to muscle disuse is still a challenge for both immobilized patients and astronauts in long duration space missions. Researchers in the space medicine field concluded that artificial gravity (AG) produced by short-radius centrifugation on a passive movement therapy device, combined with exercise, has been a robust multi-system countermeasure as it re-introduces an acceleration field and gravity load.Methods: A short-arm human centrifuge (SAHC) alone or combined with exercise was evaluated as a novel, artificial gravity device for an effective rehabilitation strategy in the case of a stroke patient with disability. The results reveal valuable information on an individualized rehabilitation strategy against physiological deconditioning. A 73-year-old woman was suddenly unable to speak, follow directions or move her left arm and leg. She could not walk, and self-care tasks required maximal assistance. Her condition was getting worse over the years, also she was receiving conventional rehabilitation treatment. Intermittent short-arm human centrifuge individualized protocols were applied for 5 months, three times a week, 60 treatments in total.Results: It resulted in significant improvement in her gait, decreased atrophy with less spasticity on the left body side, and ability to walk at least 100 m with a cane. Balance and muscle strength were improved significantly. Cardiovascular parameters improved responding to adaptations to aerobic exercise. Electroencephalography (EEG) showed brain reorganization/plasticity evidenced through functional connectivity alterations and activation in the cortical regions, especially of the precentral and postcentral gyrus. Stroke immobility-related disability was also improved.Discussion: These alterations were attributed to the short-arm human centrifuge intervention. This case study provides novel evidence supporting the use of the short-arm human centrifuge as a promising therapeutic strategy in patients with restricted mobility, with application to astronauts with long-term muscle disuse in space.
Relationship of strength, joint kinesthesia, and plantar tactile sensation to dynamic and static postural stability among patients with anterior cruciate ligament reconstruction
Authors: Hu Shanshan , Ma Xiaoli , Ma Xiaoyuan , Sun Wei , Zhou Zhipeng , Chen Yan , Song Qipeng 
Published: January 2023

Objective: Postural stability is essential for high-level physical activities after anterior cruciate ligament reconstruction (ACLR). This study was conducted to investigate the relationship of muscle strength, joint kinesthesia, and plantar tactile sensation to dynamic and static postural stability among patients with anterior cruciate ligament reconstruction.Methods: Forty-four patients over 6 months post anterior cruciate ligament reconstruction (age: 27.9 ± 6.8 years, height: 181.7 ± 8.7 cm, weight: 80.6 ± 9.4 kg, postoperative duration: 10.3 ± 3.6 months) participated in this study. Their static and dynamic postural stability, muscle strength, hamstring/quadriceps ratio, joint kinesthesia, and plantar tactile sensation were measured. Partial correlations were used to determine the correlation of the above-mentioned variables with time to stabilization (TTS) and root mean square of the center of pressure (COP-RMS) in anterior-posterior (AP) and mediolateral (ML) directions.Results: Both TTSAP and TTSML were related to muscle strength and joint kinesthesia of knee flexion and extension; COP-RMSAP was correlated with plantar tactile sensations at great toe and arch, while COP-RMSML was correlated with joint kinesthesia of knee flexion, and plantar tactile sensation at great toe and heel. Dynamic stability was sequentially correlated with strength and joint kinesthesia, while static stability was sequentially correlated with plantar tactile sensation and joint kinesthesia.Conclusion: Among patients with anterior cruciate ligament reconstruction, strength is related to dynamic postural stability, joint kinesthesia is related to dynamic and static postural stability, and plantar tactile sensation is related to static postural stability. Strength has a higher level of relationship to dynamic stability than joint kinesthesia, and plantar tactile sensation has a higher level of relationship to static stability than joint kinesthesia.
Rice immediately adapts the dynamics of photosynthates translocation to roots in response to changes in soil water environment
Authors: Miyoshi Yuta , Soma Fumiyuki , Yin Yong-Gen , Suzui Nobuo , Noda Yusaku , Enomoto Kazuyuki , Nagao Yuto , Yamaguchi Mitsutaka , Kawachi Naoki , Yoshida Eiji , Tashima Hideaki , Yamaya Taiga , Kuya Noriyuki , Teramoto Shota , Uga Yusaku 
Published: January 2023

Rice is susceptible to abiotic stresses such as drought stress. To enhance drought resistance, elucidating the mechanisms by which rice plants adapt to intermittent drought stress that may occur in the field is an important requirement. Roots are directly exposed to changes in the soil water condition, and their responses to these environmental changes are driven by photosynthates. To visualize the distribution of photosynthates in the root system of rice plants under drought stress and recovery from drought stress, we combined X-ray computed tomography (CT) with open type positron emission tomography (OpenPET) and positron-emitting tracer imaging system (PETIS) with 11C tracer. The short half-life of 11C (20.39 min) allowed us to perform multiple experiments using the same plant, and thus photosynthate translocation was visualized as the same plant was subjected to drought stress and then re-irrigation for recovery. The results revealed that when soil is drier, 11C-photosynthates mainly translocated to the seminal roots, likely to promote elongation of the root with the aim of accessing water stored in the lower soil layers. The photosynthates translocation to seminal roots immediately stopped after rewatering then increased significantly in crown roots. We suggest that when rice plant experiencing drought is re-irrigated from the bottom of pot, the destination of 11C-photosynthates translocation immediately switches from seminal root to crown roots. We reveal that rice roots are responsive to changes in soil water conditions and that rice plants differentially adapts the dynamics of photosynthates translocation to crown roots and seminal roots depending on soil conditions.
Metabolic relay gene of aphid and primary symbiont as RNAi target loci for aphid control
Authors: Li Qian , Cheng Yu , Fan Jia , Chen Julian 
Published: January 2023

IntroductionAphids form a stable and mutually beneficial relationship with their primary symbiont Buchnera aphidicola, which play an important role in providing the missing nutrients to the host aphid. Based on the genome sequence of wheat aphid Siotobion miscanthi and its primary symbiont Buchnera that we obtained in our previously study, we identified a metabolic relay gene, ilvA, involved in the isoleucine synthesis pathway between aphids and Buchnera.MethodIn this study, we identified the location and sequence structure of ilvA gene in aphid genome, the expression level in different instars and tissues of aphids, and the effect of reducing ilvA expression on the growth and development of aphids by bioinformatics analysis, quantitative PCR, RNAi and bioassay experiments.ResultOur study showed that ilvA was expressed at the highest level in the 2nd instar of the aphid, while the expression of this gene was significantly higher in the aphid bacteriocytes than in other tissues. Notably, this gene is localized on the aphid sex chromosome and remains highly conserved and collinearity across different aphid genomes. Knocking down the expression of ilvA reduced the aphid body weight and production. However, the indices of mortality decreased slightly, but were not significantly different, compared to the control.DiscussionThe results show that the relay genes between aphids and their symbionts in the metabolism of essential nutrients have potential roles in the growth and development of aphids, meanwhile, providing target loci and new ideas for RNAi-based aphid green control strategies.
A high-throughput yeast approach to characterize aquaporin permeabilities: Profiling the Arabidopsis PIP aquaporin sub-family
Authors: Groszmann Michael , De Rosa Annamaria , Chen Weihua , Qiu Jiaen , McGaughey Samantha A. , Byrt Caitlin S. , Evans John R. 
Published: January 2023

IntroductionEngineering membrane transporters to achieve desired functionality is reliant on availability of experimental data informing structure-function relationships and intelligent design. Plant aquaporin (AQP) isoforms are capable of transporting diverse substrates such as signaling molecules, nutrients, metalloids, and gases, as well as water. AQPs can act as multifunctional channels and their transport function is reliant on many factors, with few studies having assessed transport function of specific isoforms for multiple substrates.MethodsHigh-throughput yeast assays were developed to screen for transport function of plant AQPs, providing a platform for fast data generation and cataloguing of substrate transport profiles. We applied our high-throughput growth-based yeast assays to screen all 13 Arabidopsis PIPs (AtPIPs) for transport of water and several neutral solutes: hydrogen peroxide (H2O2), boric acid (BA), and urea. Sodium (Na+) transport was assessed using elemental analysis techniques.ResultsAll AtPIPs facilitated water and H2O2 transport, although their growth phenotypes varied, and none were candidates for urea transport. For BA and Na+ transport, AtPIP2;2 and AtPIP2;7 were the top candidates, with yeast expressing these isoforms having the most pronounced toxicity response to BA exposure and accumulating the highest amounts of Na+. Linking putative AtPIP isoform substrate transport profiles with phylogenetics and gene expression data, enabled us to align possible substrate preferences with known and hypothesized biological roles of AtPIPs.DiscussionThis testing framework enables efficient cataloguing of putative transport functionality of diverse AQPs at a scale that can help accelerate our understanding of AQP biology through big data approaches (e.g. association studies). The principles of the individual assays could be further adapted to test additional substrates. Data generated from this framework could inform future testing of AQP physiological roles, and address knowledge gaps in structure-function relationships to improve engineering efforts.