bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Stress Tolerance Gene FpHsp104 Affects Conidiation and Pathogenicity of Fusarium pseudograminearum
Authors: Xia Huiqing , Chen Linlin , Fan Zhuo , Peng Mengya , Zhao Jingya , Chen Wenbo , Li Haiyang , Shi Yan , Ding Shengli , Li Honglian
Published: July 2021

Heat shock protein Hsp104, a homolog of the bacterial chaperone ClpB and plant Hsp100, plays an essential part in the response to heat and various chemical agents in Saccharomyces cerevisiae. However, their functions remain largely unknown in plant fungal pathogens. Here, we report the identification and functional characterization of a plausible ortholog of yeast Hsp104 in Fusarium pseudograminearum, which we termed FpHsp104. Deletion mutant of FpHsp104 displayed severe defects in the resistance of heat shock during F. pseudograminearum mycelia and conidia when exposed to extreme heat. We also found that the protein showed dynamic localization to small particles under high temperature. However, no significant differences were detected in osmotic, oxidative, or cell wall stress responses between the wild-type and Δfphsp104 strains. Quantitative real-time PCR analysis showed that FpHsp104 was upregulated in the conidia, and disruption of FpHsp104 gene resulted in defects in conidia production, morphology, and germination. The transcript levels of conidiation-related genes of FpFluG, FpVosA, FpWetA, and FpAbaA were reduced in the Δfphsp104 mutant vs. the wild-type strain, but heat-shocked mRNA splicing repair was not affected in Δfphsp104. Moreover, Δfphsp104 mutant also showed attenuated virulence, but its DON synthesis was normal. These data from the first study of Hsp104 in F. pseudograminearum strongly suggest that FpHsp104 gene is an important element in the heat tolerance, development, and pathogenicity processes of F. pseudograminearum.
Herbal Extract Mixture Modulates Intestinal Antioxidative Capacity and Microbiota in Weaning Piglets
Authors: Wang Meiwei , Huang Huijun , Wang Lei , Yang Huansheng , He Shengwen , Liu Feng , Tu Qiang , He Shanping
Published: July 2021

Recently, herbal extracts have been applied in multiple aspects, such as medicine and animal feed. Different compositions of herbal extract mixture (HEM) have various components and diverse functions. This study aimed to evaluate the effects of HEM (Lonicera japonica, Astragalus membranaceus, Eucommia folium, and Codonopsis pilosula) on intestinal antioxidant capacity and colonic microbiota in weaned pigs. A total of 18 piglets [Duroc × (Landrace × Yorkshire)] with the initial body weight of 5.99 ± 0.13 kg (weaned at 21 days) were randomly divided into two groups (n = 9): the control group (CON, basal diet) and the HEM treatment group (HEM, 1,000 mg/kg HEM + basal diet). The experiment period lasted for 14 days. Our results showed that dietary supplementation with HEM modulated the antioxidant capacity through decreasing the activity of superoxide dismutase (SOD) in the ileum and glutathione peroxidase (GSH-PX) in the serum, and decreasing the mRNA expression of Kelch like-ECH-associated protein 1 (Keap1) in the jejunum and the protein level of Keap1 in the ileum. Moreover, the HEM group modified the composition of colonic microbiota with affecting relative abundances of the Firmicutes and Bacteroidetes at the phylum level. Taken together, supplementation of HEM can regulate the antioxidant capacity and modify the composition of colonic bacteria in weaning piglets. This study provides new insights into the combination effects of herbal extracts on weaning piglets.
The EcoCyc Database in 2021
Authors: Keseler Ingrid M. , Gama-Castro Socorro , Mackie Amanda , Billington Richard , Bonavides-Martínez César , Caspi Ron , Kothari Anamika , Krummenacker Markus , Midford Peter E. , Muñiz-Rascado Luis , Ong Wai Kit , Paley Suzanne , Santos-Zavaleta Alberto , Subhraveti Pallavi , Tierrafría Víctor H. , Wolfe Alan J. , Collado-Vides Julio , Paulsen Ian T. , Karp Peter D.
Published: July 2021

The EcoCyc model-organism database collects and summarizes experimental data for Escherichia coli K-12. EcoCyc is regularly updated by the manual curation of individual database entries, such as genes, proteins, and metabolic pathways, and by the programmatic addition of results from select high-throughput analyses. Updates to the Pathway Tools software that supports EcoCyc and to the web interface that enables user access have continuously improved its usability and expanded its functionality. This article highlights recent improvements to the curated data in the areas of metabolism, transport, DNA repair, and regulation of gene expression. New and revised data analysis and visualization tools include an interactive metabolic network explorer, a circular genome viewer, and various improvements to the speed and usability of existing tools.
Trypanosoma brucei Lipophosphoglycan Induces the Formation of Neutrophil Extracellular Traps and Reactive Oxygen Species Burst via Toll-Like Receptor 2, Toll-Like Receptor 4, and c-Jun N-Terminal Kinase Activation
Authors: Zhang Kai , Jiang Ning , Sang Xiaoyu , Feng Ying , Chen Ran , Chen Qijun
Published: July 2021

Trypanosoma brucei brucei is the causative agent of African animal trypanosomosis, which mainly parasitizes the blood of the host. Lipophosphoglycan (LPG), a polymer anchored to the surface of the parasites, activates the host immune response. In this study, we revealed that T. brucei LPG stimulated neutrophils to form neutrophil extracellular traps (NETs) and release the reactive oxygen species (ROS). We further analyzed the involvement of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and explored the activation of signaling pathway enzymes in response to LPG stimulation. During the stimulation of neutrophils by LPG, the blockade using anti-TLR2 and anti-TLR4 antibodies reduced the phosphorylation of c-Jun N-terminal kinase (JNK), the release of DNA from the NETs, and the burst of ROS. Moreover, the addition of JNK inhibitor and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor exhibited similar effects. Our data suggest that T. brucei LPG activates the phosphorylation of JNK through TLR2 and TLR4 recognition, which causes the formation of NETs and the burst of ROS.
Current Nosology of Neural Autoantibody-Associated Dementia
Authors: Hansen Niels
Published: July 2021

Background

The detection of neural autoantibodies in patients with cognitive decline is an increasingly frequent phenomenon in memory clinics, and demanding as it does a specific diagnostic approach and therapeutic management, it deserves greater attention. It is this review’s aim to present the latest nosology of neural autoantibody-associated dementia.

Methods

A specific literature research via PubMed was conducted to describe the nosology of neural autoantibody-associated dementia.

Results

An autoimmune dementia comprises with an early onset, atypical clinical presentation and rapid progression in conjunction with neural antibodies, signs of inflammation in the cerebrospinal fluid, and a non-neurodegenerative pattern in neuroimaging. An autoimmune dementia is probably present if the patient responds to immunotherapy. Atypical dementia involving neural autoantibodies with mostly N-methyl-D-aspartate receptor antibodies might not fulfill all the autoimmune-dementia criteria, thus it may constitute an independent disease entity. Finally, a neurodegenerative dementia such as the frontotemporal type also coincides with neural autoantibodies such as the subunit ionotropic glutamate receptors 3 of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies, dementia with Lewy bodies with myelin oligodendrocytic protein, myelin basic protein antibodies, or Creutzfeldt-Jakob disease with Zic4 or voltage gated potassium channel antibodies. These dementia entities may well overlap in their clinical features and biomarkers, i.e., their neural autoantibodies or neuroimaging patterns.

Conclusion

There are three main forms of neural autoantibody-associated dementia we can distinguish that might also share certain features in their clinical and laboratory presentation. More research is urgently necessary to improve the diagnosis and therapy of these patients, as the progression of their dementia might thus be improved or even reversed.
Synaptic Scaffolds, Ion Channels and Polyamines in Mouse Photoreceptor Synapses: Anatomy of a Signaling Complex
Authors: Vila Alejandro , Shihabeddin Eyad , Zhang Zhijing , Santhanam Abirami , Ribelayga Christophe P. , O’Brien John
Published: July 2021

Synaptic signaling complexes are held together by scaffold proteins, each of which is selectively capable of interacting with a number of other proteins. In previous studies of rabbit retina, we found Synapse-Associated Protein-102 (SAP102) and Channel Associated Protein of Synapse-110 (Chapsyn110) selectively localized in the tips of horizontal cell processes at contacts with rod and cone photoreceptors, along with several interacting ion channels. We have examined the equivalent suites of proteins in mouse retina and found similarities and differences. In the mouse retina we identified Chapsyn110 as the scaffold selectively localized in the tips of horizontal cells contacting photoreceptors, with Sap102 more diffusely present. As in rabbit, the inward rectifier potassium channel Kir2.1 was present with Chapsyn110 on the tips of horizontal cell dendrites within photoreceptor invaginations, where it could provide a hyperpolarization-activated current that could contribute to ephaptic signaling in the photoreceptor synapses. Pannexin 1 and Pannexin 2, thought to play a role in ephaptic and/or pH mediated signaling, were present in the outer plexiform layer, but likely not in the horizontal cells. Polyamines regulate many ion channels and control the degree of rectification of Kir2.1 by imposing a voltage-dependent block. During the day polyamine immunolabeling was unexpectedly high in photoreceptor terminals compared to other areas of the retina. This content was significantly lower at night, when polyamine content was predominantly in Müller glia, indicating daily rhythms of polyamine content. Both rod and cone terminals displayed the same rhythm. While polyamine content was not prominent in horizontal cells, if polyamines are released, they may regulate the activity of Kir2.1 channels located in the tips of HCs. The rhythmic change in polyamine content of photoreceptor terminals suggests that a daily rhythm tunes the behavior of suites of ion channels within the photoreceptor synapses.
Deep Gated Hebbian Predictive Coding Accounts for Emergence of Complex Neural Response Properties Along the Visual Cortical Hierarchy
Authors: Dora Shirin , Bohte Sander M. , Pennartz Cyriel M. A.
Published: July 2021

Predictive coding provides a computational paradigm for modeling perceptual processing as the construction of representations accounting for causes of sensory inputs. Here, we developed a scalable, deep network architecture for predictive coding that is trained using a gated Hebbian learning rule and mimics the feedforward and feedback connectivity of the cortex. After training on image datasets, the models formed latent representations in higher areas that allowed reconstruction of the original images. We analyzed low- and high-level properties such as orientation selectivity, object selectivity and sparseness of neuronal populations in the model. As reported experimentally, image selectivity increased systematically across ascending areas in the model hierarchy. Depending on the strength of regularization factors, sparseness also increased from lower to higher areas. The results suggest a rationale as to why experimental results on sparseness across the cortical hierarchy have been inconsistent. Finally, representations for different object classes became more distinguishable from lower to higher areas. Thus, deep neural networks trained using a gated Hebbian formulation of predictive coding can reproduce several properties associated with neuronal responses along the visual cortical hierarchy.
Detecting Residual Awareness in Patients With Prolonged Disorders of Consciousness: An fNIRS Study
Authors: Li Meng , Yang Yi , Zhang Yujin , Gao Yuhang , Jing Rixing , Dang Yuanyuan , Chen Xueling , He Jianghong , Si Juanning
Published: July 2021

Recent advances in neuroimaging technologies have provided insights into detecting residual consciousness and assessing cognitive abilities in patients with disorders of consciousness (DOC). Functional near-infrared spectroscopy (fNIRS) is non-invasive and portable and can be used for longitudinal bedside monitoring, making it uniquely suited for evaluating brain function in patients with DOC at appropriate spatiotemporal resolutions. In this pilot study, an active command-driven motor imagery (MI) paradigm based on fNIRS was used to detect residual consciousness in patients with prolonged DOC. A support vector machine (SVM) classifier was used to classify yes-or-no responses. The results showed that relatively reliable responses were detected from three out of five patients in a minimally consciousness state (MCS). One of the patients answered all the questions accurately when assessed according to this method. This study confirmed the feasibility of using portable fNIRS technology to detect residual cognitive ability in patients with prolonged DOC by active command-driven motor imagery. We hope to detect the exact level of consciousness in DOC patients who may have a higher level of consciousness.
Advanced Care Planning in Parkinson's Disease: In-depth Interviews With Patients on Experiences and Needs
Authors: Kurpershoek Elisabeth , Hillen Marij A. , Medendorp Niki M. , de Bie Rob M. A. , de Visser Marianne , Dijk Joke M.
Published: July 2021

Introduction:Advance care planning (ACP) is an iterative process of discussing the needs, wishes, and preferences of patients regarding disease-specific and end-of-life issues. There is ample evidence that ACP improves the quality of life and promotes the autonomy of patients with cancer and motor neuron disease who have a high disease burden and shortened life expectancy. In Parkinson's disease (PD) though, knowledge about the experiences and preferences of patients regarding ACP is scarce, despite the major disease burden associated with PD.

Aim:This study aims to explore the experiences, needs, and preferences of PD patients regarding the content and timing of ACP.

Methods:In-depth interviews were conducted with a purposively selected sample of patients diagnosed with PD. Using a semi-structured topic list, the participants were asked about their prospects for a future living with PD and with whom they wanted to discuss this. Qualitative analysis was performed in parallel with data collection using a data-driven constant comparative approach. The transcribed interviews were coded and analyzed by two researchers using MAXQDA software.

Results:Of all 20 patients (13 males; age 47–82; disease duration 1–27 years), most expressed a wish to talk about ACP with a healthcare provider, enabling them to anticipate the uncertain future. The majority of patients preferred their healthcare provider to initiate the discussion on ACP, preferably at an early stage of the disease. Nearly all patients expressed the wish to receive more information regarding the long-term impact of PD, although, the preferred timing varied between patients. They also perceived that their neurologist was primarily focused on medication and had little time to address their need for a more holistic approach toward living with PD.

Conclusion:Our results suggest that PD patients are in need of discussing ACP with their healthcare provider (HCP), even in the early stages of the disease. In addition, PD patients perceive a lack of information on their disease course and miss guidance on available supportive care. We recommend HCPs to inquire the information requirements and preferences of patients regarding ACP regularly, starting soon after diagnosis.
Clinical Outcome of Pulsed-Radiofrequency Combined With Transforaminal Epidural Steroid Injection for Lumbosacral Radicular Pain Caused by Distinct Etiology
Authors: Yang Liuqing , Huang Yuzhao , Ma Jiahui , Li Zhenxing , Han Rui , Guo Gangwen , Ni Yuncheng , Hu Rong , Yan Xuebin , Zhou Haocheng , Huang Dong
Published: July 2021

Background

Lumbosacral radicular pain (LSRP) can be caused by disc herniation, spinal stenosis, and failed back surgery syndrome. The clinical effect of pulsed-radiofrequency (PRF) combined with transforaminal epidural steroid injection (TESI) for radiating pain in different population remains unclear.

Methods

We retrospectively reviewed the medical recordings of patients with LSRP caused by different etiologies, who underwent PRF and TESI treatment. The primary clinical outcome was assessed by a 10-point Visual Analog Scale (VAS) pre- and post-treatment.

Results

A total of 34 LSRP patients were identified and classified into 3 subgroups (disc herniation, spinal stenosis, and failed back surgery syndrome). The overall immediate pain reduction was 4.4 ± 1.1 after procedure. After a median follow-up of 9.5 months, the VAS decreased from 6.5 ± 1.0 to 2.4 ± 1.9 at the last follow-up.

Conclusion

PRF combined with TESI is an effective approach to treat persistent LSRP in distinct population.
Trigeminal Contributions to the Dorsal Cochlear Nucleus in Mouse
Authors: Balmer Timothy S. , Trussell Laurence O.
Published: July 2021

The dorsal cochlear nucleus (DCN) is the first site of multisensory integration in the auditory pathway of mammals. The DCN circuit integrates non-auditory information, such as head and ear position, with auditory signals, and this convergence may contribute to the ability to localize sound sources or to suppress perceptions of self-generated sounds. Several extrinsic sources of these non-auditory signals have been described in various species, and among these are first- and second-order trigeminal axonal projections. Trigeminal sensory signals from the face and ears could provide the non-auditory information that the DCN requires for its role in sound source localization and cancelation of self-generated sounds, for example, head and ear position or mouth movements that could predict the production of chewing or licking sounds. There is evidence for these axonal projections in guinea pigs and rats, although the size of the pathway is smaller than might be expected for a function essential for a prey animals’ survival. However, evidence for these projections in mice, an increasingly important species in auditory neuroscience, is lacking, raising questions about the universality of such proposed functions. We therefore investigated the presence of trigeminal projections to the DCN in mice, using viral and transgenic approaches. We found that the spinal trigeminal nucleus indeed projects to DCN, targeting granule cells and unipolar brush cells. However, direct axonal projections from the trigeminal ganglion itself were undetectable. Thus, secondary brainstem sources carry non-auditory signals to the DCN in mice that could provide a processed trigeminal signal to the DCN, but primary trigeminal afferents are not integrated directly by DCN.
Inhibition and Facilitation of the Spinal Locomotor Central Pattern Generator and Reflex Circuits by Somatosensory Feedback From the Lumbar and Perineal Regions After Spinal Cord Injury
Authors: Merlet Angèle N. , Harnie Jonathan , Frigon Alain
Published: July 2021

Somatosensory feedback from peripheral receptors dynamically interacts with networks located in the spinal cord and brain to control mammalian locomotion. Although somatosensory feedback from the limbs plays a major role in regulating locomotor output, those from other regions, such as lumbar and perineal areas also shape locomotor activity. In mammals with a complete spinal cord injury, inputs from the lumbar region powerfully inhibit hindlimb locomotion, while those from the perineal region facilitate it. Our recent work in cats with a complete spinal cord injury shows that they also have opposite effects on cutaneous reflexes from the foot. Lumbar inputs increase the gain of reflexes while those from the perineal region decrease it. The purpose of this review is to discuss how somatosensory feedback from the lumbar and perineal regions modulate the spinal locomotor central pattern generator and reflex circuits after spinal cord injury and the possible mechanisms involved. We also discuss how spinal cord injury can lead to a loss of functional specificity through the abnormal activation of functions by somatosensory feedback, such as the concurrent activation of locomotion and micturition. Lastly, we discuss the potential functions of somatosensory feedback from the lumbar and perineal regions and their potential for promoting motor recovery after spinal cord injury.
Circular RNA Protein Tyrosine Kinase 2 Promotes Cell Proliferation, Migration and Suppresses Apoptosis via Activating MicroRNA-638 Mediated MEK/ERK, WNT/β-Catenin Signaling Pathways in Multiple Myeloma
Authors: Zhou Fan , Wang Dongjiao , Zhou Nian , Chen Haimin , Shi Haotian , Peng Rong , Wei Wei , Wu Lixia
Published: July 2021

Our previous study observed that circular RNA protein tyrosine kinase 2 (circ-PTK2) was upregulated and correlated with worse clinical features and unfavorable prognosis in multiple myeloma (MM) patients. Thus, this study aimed to further characterize the regulatory function of circ-PTK2 on cell malignant activities and its target microRNA-638 (miR-638) as well as downstream MEK/ERK, WNT/β-catenin signaling pathways in MM. The effect of circ-PTK2 on MM cell proliferation, apoptosis, migration, invasion and its potential target miRNAs was assessed by transfecting circ-PTK2 overexpression plasmids into U226 cells and circ-PTK2 knock-down plasmids into LP-1 cells. Furthermore, the interaction between circ-PTK2 and miR-638 mediated MEK/ERK and WNT/β-catenin signaling pathways was validated by rescue experiments. Circ-PTK2 was overexpressed in most MM cell lines compared to normal plasma cells. Overexpressing circ-PTK2 promoted proliferation and migration, inhibited apoptosis in U266 cells, but did not affect cell invasion; knocking down circ-PTK2 achieved opposite effect in LP-1 cells. Besides, circ-PTK2 reversely regulated miR-638 expression but not miR-4690, miR-6724, miR-6749 or miR-6775. The following luciferase reporter assay illustrated the direct bind of circ-PTK2 towards miR-638. In rescue experiments, overexpressing miR-638 suppressed proliferation, migration, while promoted apoptosis in both wild U266 cells and circ-PTK2-overexpressed U266 cells; meanwhile, overexpressing miR-638 also suppressed MEK/ERK and WNT/β-catenin pathways in both wild U266 cells and circ-PTK2-overexpressed U266 cells. Knocking down miR-638 achieved opposite effect in both wild LP-1 cells and circ-PTK2-knocked-down LP-1 cells. In conclusion, circ-PTK2 promotes cell proliferation, migration, suppresses cell apoptosis via miR-638 mediated MEK&ERK and WNT&β-catenin signaling pathways in MM.
Prognostic Factors of Survival of Advanced Liver Cancer Patients Treated With Palliative Radiotherapy: A Retrospective Study
Authors: Hua Qingling , Zhang Dejun , Li Yunqiao , Hu Yue , Liu Pian , Xiao Guangqin , Zhang Tao , Xue Jun
Published: July 2021

Aims

Survival benefit of liver cancer patients who undergo palliative radiotherapy varies from person to person. The present study aims to identify indicators of survival of advanced liver cancer patients receiving palliative radiotherapy.

Patients and Methods

One hundred and fifty-nine patients treated with palliative radiotherapy for advanced liver cancer were retrospectively assessed. Of the 159 patients, 103 patients were included for prediction model construction in training phase, while other 56 patients were analyzed for external validation in validation phase. In model training phase, clinical characteristics of included patients were evaluated by Kaplan-Meier curves and log-rank test. Thereafter, multivariable Cox analysis was taken to further identify characteristics with potential for prediction. In validation phase, a separate dataset including 56 patients was used for external validation. Harrell’s C-index and calibration curve were used for model evaluation. Nomograms were plotted based on the model of multivariable Cox analysis.

Results

Thirty-one characteristics of patients were investigated in model training phase. Based on the results of Kaplan-Meier plots and log-rank tests, 6 factors were considered statistically significant. On multivariable Cox regression analysis, bone metastasis (HR = 1.781, P = 0.026), portal vein tumor thrombus (HR = 2.078, P = 0.015), alpha-fetoprotein (HR = 2.098, P = 0.007), and radiation dose (HR = 0.535, P = 0.023) show significant potential to predict the survival of advanced liver cancer patients treated with palliative radiotherapy. Moreover, nomograms predicting median overall survival, 1- and 2-year survival probability were plotted. The Harrell’s C-index of the predictive model is 0.709(95%CI, 0.649-0.769) and 0.735 (95%CI, 0.666-0.804) for training model and validation model respectively. Calibration curves of the 1- and 2-year overall survival of the predictive model indicate that the predicted probabilities of OS are very close to the actual observed outcomes both in training and validation phase.

Conclusion

Bone metastasis, portal vein tumor thrombus, alpha-fetoprotein and radiation dose are independent prognostic factors for the survival of advanced liver cancer patients treated with palliative radiotherapy.
Clinicopathological Analysis of the ISUP Grade Group And Other Parameters in Prostate Cancer: Elucidation of Mutual Impact of the Various Parameters
Authors: Okubo Yoichiro , Sato Shinya , Osaka Kimito , Yamamoto Yayoi , Suzuki Takahisa , Ida Arika , Yoshioka Emi , Suzuki Masaki , Washimi Kota , Yokose Tomoyuki , Kishida Takeshi , Miyagi Yohei
Published: July 2021

Background

Prostate cancer has become increasingly common worldwide. Although Grade group (GG) is widely accepted as an indicator of prostate cancer grade, there are malignancies that cannot be defined by GG alone. Moreover, the relationship between GG and other parameters remains unclear. Herein, we aimed to explore the biological characteristics of prostate cancer.

Methods

This study included 299 radical prostatectomy cases. The Chi-square test and analysis of variance were used to analyze the association of GG with binary and continuous variables. We then conducted morphological analyses. Multivariate analyses were performed to extract the data on risk factors for biochemical recurrence (BCR) and lymph node metastasis.

Results

The lymphatic, venous, perineural, and seminal vesicle invasion rates were 37/299 (12.4%), 25/299 (8.4%), 280/299 (93.6%), and 23/299 (7.7%), respectively. The extraprostatic extension (EPE), positive surgical margin, tertiary Gleason pattern 5, intraductal carcinoma of the prostate gland, and lymph node metastasis rates were 89/299 (29.8%), 106/299 (35.5%), 33/260 (12.7%), 56/299 (18.7%), and 23/299 (7.7%), respectively. As GG increased, various parameters became easier to visualize; however, there were differences between the parameters. Postoperative BCR was observed in 31/242 (12.8%) cases without preoperative hormone therapy; GG2, GG3, GG4, and GG5 accounted for 4, 7, 7, and 13 cases, respectively. Multivariate analyses revealed that GG and tumor diameter were significant risk factors for early BCR, whereas lymphatic invasion, EPE, and seminal vesicle invasion were significant risk factors for lymph node metastasis. For BCR, the odds ratios (ORs) for GG and tumor diameter were 2.253 (95% confidence interval (CI]): 1.297–3.912; P=0.004) and 1.074 (95% CI: 1.011–1.142; P=0.022), respectively. For lymph node metastasis, ORs for the presence of lymphatic invasion, EPE, and seminal vesicle invasion were 7.425 (95% CI: 1.688–22.583; P=0.004), 4.391 (95% CI: 1.037–18.589; P=0.044), and 5.755 (95% CI: 1.308–25.316; P=0.021), respectively.

Conclusions

We summarized various parameters correlating with each GG. Through multivariate analyses, we established the independent risk factors for early BCR and lymph node metastasis. In addition to GG, other important indices of malignancy were determined and weighted to provide a basis for future investigations.
Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas
Authors: Harbers Luuk , Agostini Federico , Nicos Marcin , Poddighe Dimitri , Bienko Magda , Crosetto Nicola
Published: July 2021

Somatic copy number alterations (SCNAs) are a pervasive trait of human cancers that contributes to tumorigenesis by affecting the dosage of multiple genes at the same time. In the past decade, The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) initiatives have generated and made publicly available SCNA genomic profiles from thousands of tumor samples across multiple cancer types. Here, we present a comprehensive analysis of 853,218 SCNAs across 10,729 tumor samples belonging to 32 cancer types using TCGA data. We then discuss current models for how SCNAs likely arise during carcinogenesis and how genomic SCNA profiles can inform clinical practice. Lastly, we highlight open questions in the field of cancer-associated SCNAs.
Complications of Radiofrequency Ablation for Hepatic Hemangioma: A Multicenter Retrospective Analysis on 291 Cases
Authors: Wu Shilun , Gao Ruize , Yin Tao , Zhu Ruhang , Guo Shigang , Xin Zonghai , Li Aolei , Kong Xinliang , Gao Jun , Sun Wenbing
Published: July 2021

Purpose

To report the complications of radiofrequency ablation (RFA) for hepatic hemangioma.

Patients and Methods

Investigators from six centers performed RFA for hepatic hemangioma and used a standardized follow-up protocol. Data were collected from 291 patients, including 253 patients with hepatic hemangioma 5 to 9.9 cm in diameter (group A) and 38 with hepatic hemangioma ≥ 10 cm (group B). Technical success, complete ablation, and complications attributed to the RFA procedure were reported. Analysis of variance was used to determine whether the major complication rate was related to tumor size or clinical experience.

Results

A total of 304 lesions were treated in 291 patients. Technical success was achieved without adverse events in all cases. A total of 301 lesions were completely ablated, including 265 of 265 (100%) lesions in group A, and 36 of 39 (92.31%) in group B. The rate of technology-related complications was similar in groups A and B (5.14% (13/253) and 13.16% (5/38), respectively; P = 0.121). Moreover, all technology-related complications occurred during the early learning curve period. The rate of hemolysis-related complications in two groups were 83.40% (211/253) and 100% (38/38) (P =0.007) and the systemic inflammatory response syndrome-related complications in two groups were 33.99% (86/253) and 86.84% (33/38) (P<0.001). There were no delayed complications in either group.

Conclusion

RFA is minimally invasive, safe, and effective for hepatic hemangiomas 5 to 9.9 cm in diameter. More clinical data are needed to confirm the safety of RFA for hepatic hemangiomas ≥ 10 cm.
Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma
Authors: Liao Wei-Hao , Hsiao Ming-Yen , Kung Yi , Huang Abel Po-Hao , Chen Wen-Shiang
Published: July 2021

Background

Glioblastoma multiforme (GBM) is currently the most devastating brain tumor globally and produces a high mortality rate. GBM is also challenging to eradicate using surgery due to its invasive characteristics. Moreover, the blood-brain barrier (BBB) increases the difficulty of transporting most therapeutic drugs to tumor sites. The use of transcranial focused ultrasound (FUS) has recently been investigated for opening the BBB to facilitate drug delivery. A special form of FUS, the shockwave (SW), has also been shown to open BBB efficiently. SW has several advantages including no heating effect, less reactive oxygen species production, good transcranial ability, and no need to supply microbubbles.

Methods

We employed a commercial SW device, which is a common tool used for musculoskeletal disorders, to improve doxorubicin delivery across the BBB and evaluated its therapeutic efficacy on GBM rat models. SW emits relatively short but stronger mechanical pulses comparing with FUS.

Results

The results demonstrated that doxorubicin combined with SW treatment substantially inhibited tumor growth and prolonged overall survival.

Conclusions

The present study shows the non-invasive transcranial SW may have potential for the treatment of GBM in future clinical setting.
AI-Based Drug Discovery of TKIs Targeting L858R/T790M/C797S-Mutant EGFR in Non-small Cell Lung Cancer
Authors: Choi Geunho , Kim Daegeun , Oh Junehwan
Published: July 2021

Lung cancer has a high mortality rate, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Patients have been observed to acquire resistance against various anticancer agents used for NSCLC due to L858R (or Exon del19)/T790M/C797S-EGFR mutations. Therefore, next-generation drugs are being developed to overcome this problem of acquired resistance. The goal of this study was to use artificial intelligence (AI) to discover drug candidates that can overcome acquired resistance and reduce the limitations of the current drug discovery process, such as high costs and long durations of drug design and production. To generate ligands using AI, we collected data related to tyrosine kinase inhibitors (TKIs) from accessible libraries and used LSTM (Long short term memory) based transfer learning (TL) model. Through the simplified molecular-input line-entry system (SMILES) datasets of the generated ligands, we obtained drug-like ligands via parameter-filtering, cyclic skeleton (CSK) analysis, and virtual screening utilizing deep-learning method. Based on the results of this study, we are developing prospective EGFR TKIs for NSCLC that have overcome the limitations of existing third-generation drugs.
Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial
Authors: Deng Junzhu , Hu Haiyang , Huang Feihong , Huang Chunlan , Huang Qianqian , Wang Long , Wu Anguo , Yang Jing , Qin Dalian , Zou Wenjun , Wu Jianming
Published: July 2021

Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs via indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the Medline, PubMed, Embase, the Cochrane Library, and Web of Science databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 109/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.
8-Gingerol Ameliorates Myocardial Fibrosis by Attenuating Reactive Oxygen Species, Apoptosis, and Autophagy via the PI3K/Akt/mTOR Signaling Pathway
Authors: Xue Yucong , Zhang Muqing , Liu Miaomiao , Liu Yu , Li Li , Han Xue , Sun Zhenqing , Chu Li
Published: July 2021

8-gingerol (8-Gin) is the series of phenolic substance that is extracted from ginger. Although many studies have revealed that 8-Gin has multiple pharmacological properties, the possible underlying mechanisms of 8-Gin against myocardial fibrosis (MF) remains unclear. The study examined the exact role and potential mechanisms of 8-Gin against isoproterenol (ISO)-induced MF. Male mice were intraperitoneally injected with 8-Gin (10 and 20 mg/kg/d) and concurrently subcutaneously injected with ISO (10 mg/kg/d) for 2 weeks. Electrocardiography, pathological heart morphology, myocardial enzymes, reactive oxygen species (ROS) generation, degree of apoptosis, and autophagy pathway-related proteins were measured. Our study observed 8-Gin significantly reduced J-point elevation and heart rate. Besides, 8-Gin caused a marked decrease in cardiac weight index and left ventricle weight index, serum levels of creatine kinase and lactate dehydrogenase (CK and LDH, respectively), ROS generation, and attenuated ISO-induced pathological heart damage. Moreover, treatment with 8-Gin resulted in a marked decrease in the levels of collagen types I and III and TGF-β in the heart tissue. Our results showed 8-Gin exposure significantly suppressed ISO-induced autophagosome formation. 8-Gin also could lead to down-regulation of the activities of matrix metalloproteinases-9 (MMP-9), Caspase-9, and Bax protein, up-regulation of the activity of Bcl-2 protein, and alleviation of cardiomyocyte apoptosis. Furthermore, 8-Gin produced an obvious increase in the expressions of the PI3K/Akt/mTOR signaling pathway-related proteins. Our data showed that 8-Gin exerted cardioprotective effects on ISO-induced MF, which possibly occurred in connection with inhibition of ROS generation, apoptosis, and autophagy via modulation of the PI3K/Akt/mTOR signaling pathway.
B0-Shimming Methodology for Affordable and Compact Low-Field Magnetic Resonance Imaging Magnets
Authors: Wenzel Konstantin , Alhamwey Hazem , O’Reilly Tom , Riemann Layla Tabea , Silemek Berk , Winter Lukas
Published: July 2021

Low-field (B0< 0.2 T) magnetic resonance imaging (MRI) is emerging as a low cost, point-of-care alternative to provide access to diagnostic imaging technology even in resource scarce environments. MRI magnets can be constructed based on permanent neodymium-iron-boron (NdFeB) magnets in discretized arrangements, leading to substantially lower mass and costs. A challenge with these designs is, however, a goodB0field homogeneity, which is needed to produce high quality images free of distortions. In this work, we describe an iterative approach to build a low-field MR magnet based on aB0-shimming methodology using genetic algorithms. The methodology is tested by constructing a small bore (inner bore diameter = 130 mm) desktop MR magnet (<15 kg) at a field strength ofB0= 0.1 T and a target volume of 4 cm in diameter. The configuration consists of a base magnet and shim inserts, which can be placed iteratively without modifying the base magnet assembly and without changing the inner dimensions of the bore or the outer dimensions of the MR magnet. Applying the shims,B0field inhomogeneity could be reduced by a factor 8 from 5,448 to 682 ppm in the target central slice of the magnet. Further improvements of these results can be achieved in a second or third iteration, using more sensitive magnetic field probes (e.g., nuclear magnetic resonance based magnetic field measurements). The presented methodology is scalable to bigger magnet designs. The MR magnet can be reproduced with off-the-shelf components and a 3D printer and no special tools are needed for construction. All design files and code to reproduce the results will be made available as open source hardware.
Insulin Resistance and Type 2 Diabetes in Asymptomatic Obstructive Sleep Apnea: Results of the PROOF Cohort Study After 7 Years of Follow-Up
Authors: Vacelet Laurine , Hupin David , Pichot Vincent , Celle Sébastien , Court-Fortune Isabelle , Thomas Thierry , Garcin Arnauld , Barthélémy Jean-Claude , Gozal David , Roche Frédéric
Published: July 2021

The aim of the study was to assess potential associations between obstructive sleep apnea (OSA) and the occurrence of diabetes mellitus and insulin resistance in the elderly. Nondiabetic volunteers (n = 549) with undiagnosed or untreated asymptomatic OSA (66.2+/−1 years at the inclusion) were evaluated as an ancillary study of the PROOF cohort study (n = 1,011). After 7 years follow-up, 494 subjects underwent assessment of fasting insulin and glucose levels. OSA was defined by an apnea-hypopnea index (AHI) of ≥15/h using polygraphy. Diabetes mellitus was defined by a fasting glucose ≥ 1.26 g/L and/or when requiring pharmacological treatment, while insulin resistance corresponded to HOMA-IR ≥ 2. Asymptomatic OSA subjects (men or women) did not display increased risk of incident diabetes (2.8 vs. 3.9%, p = 0.51). However, there was a greater frequency of insulin resistance in subjects with severe OSA (AHI > 30) [OR 2.21; 95% CI (1.22–4.02); p = 0.009]. Furthermore, multiple logistic regression showed that triglycerides levels [OR 1.61; 95% CI (1.10–2.36); p = 0.01] and fasting glycaemia [OR 4.69; 95% CI (1.12–192.78); p = 0.04], but not AHI or oxyhemoglobin desaturation index were independently associated with higher rate of insulin resistance. The deleterious metabolic effect of asymptomatic OSA in the population may be indirectly mediated via perturbations in lipids, and is particularly likely to become manifest in severe apneic subjects with higher glycemic levels.
A Detailed Spatial Expression Analysis of Wing Phenotypes Reveals Novel Patterns of Odorant Binding Proteins in the Soybean Aphid, Aphis glycines
Authors: Wang Ling , Yin Hang , Zhu Zhiguo , Yang Shuai , Fan Jia
Published: July 2021

The wide range of insect niches has led to a rapid expansion of chemosensory gene families as well as their relatively independent evolution and a high variation. Previous studies have revealed some functions for odorant-binding proteins (OBPs) in processes beyond olfaction, such as gustation and reproduction. In this study, a comparative transcriptomic analysis strategy was applied for the soybean aphid, Aphis glycines, focusing on various functional tissues and organs of winged aphids, including the antenna, head, leg, wing, thorax, cauda, and cornicle. Detailed spatial OBP expression patterns in winged and wingless parthenogenetic aphids were detected by RT-qPCR. Twelve OBPs were identified, and three new OBPs in A. glycines are first reported. All OBPs showed comparatively higher expression in sensory organs and tissues, such as the antenna, head, or leg. Additionally, we found some novel expression patterns for aphid OBPs (Beckendorf et al., 2008). Five OBPs exhibited high-expression levels in the cauda and four in the cornicle (Biasio et al., 2015). Three genes (OBP2/3/15) were highly expressed in the wing (Calvello et al., 2003). Two (OBP3/15) were significantly more highly expressed in the wingless thorax than in the winged thorax with the wings removed, and these transcripts were significantly enriched in the removed wings. More details regarding OBP spatial expression were revealed under our strategy. These findings supported the existence of carrier transport functions other than for foreign chemicals and therefore broader ligand ranges of aphid OBPs. It is important for understanding how insect OBPs function in chemical perception as well as their other potential physiological functions.
Genome-Wide Association Study of Root and Shoot Related Traits in Spring Soybean (Glycine max L.) at Seedling Stages Using SLAF-Seq
Authors: Mandozai Ajmal , Moussa Abdourazak Alio , Zhang Qi , Qu Jing , Du Yeyao , Anwari Gulaqa , Al Amin Noor , Wang Piwu
Published: July 2021

Root systems can display variable genetic architectures leading to nutrient foraging or improving abiotic stress tolerance. Breeding for new soybean varieties with efficient root systems has tremendous potential in enhancing resource use efficiency and plant adaptation for challenging climates. In this study, root related traits were analyzed in a panel of 260 spring soybean with genome-wide association study (GWAS). Genotyping was done with specific locus amplified fragment sequencing (SLAF-seq), and five GWAS models (GLM, MLM, CMLM, FaST-LMM, and EMMAX) were used for analysis. A total of 179,960 highly consistent SNP markers distributed over the entire genome with an inter-marker distance of 2.36 kb was used for GWAS analysis. Overall, 27 significant SNPs with a phenotypic contribution ranging from 20 to 72% and distributed on chromosomes 2, 6, 8, 9, 13, 16 and 18 were identified and two of them were found to be associated with multiple root-related traits. Based on the linkage disequilibrium (LD) distance of 9.5 kb for the different chromosomes, 11 root and shoot regulating genes were detected based on LD region of a maximum 55-bp and phenotypic contribution greater than 22%. Expression analysis revealed an association between expression levels of those genes and the degree of root branching number. The current study provides new insights into the genetic architecture of soybean roots, and the underlying SNPs/genes could be critical for future breeding of high-efficient root system in soybean.