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1.
Virol J ; 19(1): 80, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35570277

RESUMO

BACKGROUND: Bats were identified as a natural reservoir of emerging and re-emerging infectious pathogens threatening human health and life. METHODS: This study collected 21 fecal samples of Hipposideros armiger in Mengla County of Xishuangbanna Prefecture Yunnan Province to combine one pool for viral metagenomic sequencing. RESULTS: Two nearly complete genomes of parechoviruses, BPeV11 and BPeV20, were sequenced. Genome analysis revealed that BPeV11 and BPeV20 follow a 3-3-4 genome layout: 5' UTR-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The prevalence of BPev11 and BPev20 by Nested-PCR showed that 1 of 21 fecal samples was positive. Based on amino acid identity comparison and phylogenetic analysis of P1, 2C, and 3D, BPeV11 and BPeV20 were closely related to but distinct from FPeVs. CONCLUSION: It was probably proposed to be a novel species in the genus Parechovirus of the family Picornaviridae. The isolation of BPev11 and BPev20 from H. armiger in China is the first complete genome of parechovirus isolations from bat feces of the genus Hipposideros.

2.
Front Oncol ; 12: 871871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547874

RESUMO

As a useful tool, artificial intelligence has surpassed human beings in many fields. Artificial intelligence-based automated radiotherapy planning strategies have been proposed in lots of cancer sites and are the future of treatment planning. Postmastectomy radiotherapy (PMRT) decreases local recurrence probability and improves overall survival, and volumetric modulated arc therapy (VMAT) has gradually become the mainstream technique of radiotherapy. However, there are few customized effective automated treatment planning schemes for postmastectomy VMAT so far. This study investigated an artificial intelligence based automated planning using the MD Anderson Cancer Center AutoPlan (MDAP) system and Pinnacle treatment planning system (TPS), to effectively generate high-quality postmastectomy VMAT plans. In this study, 20 patients treated with PMRT were retrospectively investigated, including 10 left- and 10 right-sided postmastectomy patients. Chest wall and the supraclavicular, subclavicular, and internal mammary regions were delineated as target volume by radiation oncologists, and 50 Gy in 25 fractions was prescribed. Organs at risk including heart, spinal cord, left lung, right lung, and lungs were also contoured. All patients were planned with VMAT using 2 arcs. An optimization objective template was summarized based on the dose of clinical plans and requirements from oncologists. Several treatment planning parameters were investigated using an artificial intelligence algorithm, including collimation angle, jaw collimator mode, gantry spacing resolution (GSR), and number of start optimization times. The treatment planning parameters with the best performance or that were most preferred were applied to the automated treatment planning method. Dosimetric indexes of automated treatment plans (autoplans) and manual clinical plans were compared by the paired t-test. The jaw tracking mode, 2-degree GSR, and 3 rounds of optimization were selected in all the PMRT autoplans. Additionally, the 350- and 10-degree collimation angles were selected in the left- and right-sided PMRT autoplans, respectively. The uniformity index and conformity index of the planning target volume, mean heart dose, spinal cord D0.03cc, mean lung dose, and V5Gy and V20Gy of the lung of autoplans were significantly better compared with the manual clinical plans. An artificial intelligence-based automated treatment planning method for postmastectomy VMAT has been developed to ensure plan quality and improve clinical efficiency.

3.
Appetite ; 175: 106063, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35513206

RESUMO

Ovarian hormonal changes along the female menstrual cycle are believed to adapt women to the external environment through various adaptive strategies, including modulating appetite and eating behavior. We aimed to compare food-associated behavioral responses between two distinct menstrual phases (late follicular vs. mid-luteal) and investigate the underlying neural mechanism. Attentional bias towards visual food cues was repeatedly measured in 29 healthy young women during these two menstrual phases in a counterbalanced manner. Combining an emotional dot-probe task with frequency-tagged electroencephalography (EEG), we confirmed that the menstrual cycle modulated healthy women's attentional bias towards appealing and disgusting food cues. Women in the mid-luteal phase showed more avoidance of disgusting food cues, as reflected by a significantly longer response time. Steady-state visual evoked potential (SSVEP) results indicated that they exhibited a trend of transiently enhanced attentional bias towards appealing food cues and another trend of speeded attentional withdrawal from disgusting food cues during the mid-luteal phase relative to the late follicular phase, albeit non-significant after correction for multiple testing. Moreover, a significantly larger P3 amplitude was evoked by probes following the presentation of disgusting food cues in the mid-luteal phase than the late follicular phase. These findings indicate divergent attentional deployments on emotional food cues across menstrual phases and suggest the mid-luteal phase as a relatively sensitive stage in the menstrual cycle for women to regulate their appetite and eating behavior.

4.
Contrast Media Mol Imaging ; 2022: 8952357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386727

RESUMO

Objective: To identify the incremental value of magnetic resonance imaging (MRI) features beyond key molecular biomarkers for the risk stratification of high-grade gliomas (HGGs). Methods: A total of 241 patients with preoperative magnetic resonance (MR) images and clinical and genetic data were retrospectively collected from our institution and The Cancer Genome Atlas/The Cancer Imaging Archive (TCGA/TCIA) dataset. Radiomic features (n = 1702) were extracted from both postcontrast T1-weighted (CE-T1) and T2-weighted fluid attenuation inversion recovery (T2FLAIR) MR images. The least absolute shrinkage and selection operator (LASSO) method was used to select effective features. A multivariate Cox proportional risk regression model was established to explore the prognostic value of clinical features, molecular biomarkers, and radiomic features. Kaplan-Meier survival analysis and the log-rank test were used to evaluate the prognostic model, and a stratified analysis was conducted to demonstrate the incremental value of the radiomics signature. A nomogram was developed to predict the 1-year, 2-year, and 3-year overall survival (OS) probabilities of the patients with HGGs. Results: The radiomics signature provided significant prognostic value for the risk stratification of patients with HGGs. The combined model integrating the radiomics signature with clinical data (age) and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status had the best prognostic value, with C-index values of 0.752 and 0.792 in the training set and external validation set, respectively. Stratified Kaplan-Meier survival analysis showed that the radiomics signature could identify the risk subgroups in different clinical and molecular subgroups. Conclusion: This radiomics signature can be used for the risk stratification of patients with HGGs and has incremental value beyond key molecular biomarkers, providing a preoperative basis for individualized diagnosis and treatment decision-making.


Assuntos
Glioma , Biomarcadores , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Medição de Risco
5.
Microbiome ; 10(1): 60, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413940

RESUMO

BACKGROUND: Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. RESULTS: Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). CONCLUSIONS: The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract.


Assuntos
Vírus de RNA , Vírus , Animais , Animais Selvagens , Aves , Cloaca , Filogenia , Vírus de RNA/genética , Viroma/genética , Vírus/genética
6.
Ann Transl Med ; 10(6): 293, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35434005

RESUMO

Background: Anisotropy which encodes rich structure and function information is one of the key and unique characteristics of tissues. Polarized photoacoustic imaging shows tremendous potential for the detection and quantification of the anisotropy of tissues. The existing polarized photoacoustic imaging methods cannot quantify anisotropy and detect the orientation of the optical axis in 3D imaging. Methods: We proposed a versatile polarized photoacoustic imaging method based on the detection of high-order harmonics of the photoacoustic signal, which can be used for both 2D and 3D polarized photoacoustic imaging, This method can detect and quantify the anisotropy and the orientation of the optical axis of the anisotropic objects by the amplitude and initial phase of the high-order harmonics. A double-focusing polarized photoacoustic microscopy was developed to validate the proposed method. Experiments were conducted on 2D and 3D anisotropic phantoms. Results: The results showed that the anisotropy and the orientation of the optical axis of the anisotropic object can be detected and quantified accurately by the amplitude and initial phase of the high-order harmonics, even at a depth of triple transport mean free path. The imaging depth of the polarized photoacoustic microscopy is mainly limited by laser energy attenuation rather than depolarization. Conclusions: Polarized photoacoustic microscopy based on high-order harmonics has tremendous potential for imaging the anisotropy of deep biological tissues in vivo. It also extends the capability of photoacoustic microscopy to image the anisotropy of tissues.

7.
Virol Sin ; 37(1): 82-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35234620

RESUMO

Diarrhea is the third leading cause of death in developing countries in children under the age of five. About half a million children die of diarrhea every year, most of which in developing countries. Viruses are the main pathogen of diarrhea. In China, the fecal virome of children with diarrhea has been rarely studied. Using an unbiased viral metagenomics approach, we analyzed the fecal virome in children with diarrhea. Many DNA or RNA viruses associated with diarrhea identified in those fecal samples were mainly from six families of Adenoviridae, Astroviridae, Caliciviridae, Parvoviridae, Picornaviridae, and Reoviridae. Among them, the family of Caliciviridae accounts for the largest proportion of 78.42%, following with Adenoviridae (8.94%) and Picornaviridae (8.36%). In addition to those diarrhea-related viruses that have already been confirmed to cause human diarrhea, the viruses not associated with diarrhea were also identified including anellovirus and picobirnavirus. This study increased our understanding of diarrheic children fecal virome and provided valuable information for the prevention and treatment of viral diarrhea in this area.


Assuntos
Picornaviridae , Vírus , Criança , Diarreia , Fezes , Humanos , Metagenômica , Filogenia , Vírus/genética
8.
Virol Sin ; 37(1): 60-69, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35234628

RESUMO

Viruses in aquatic ecosystems are characterized by extraordinary abundance and diversity. Thus far, there have been limited studies focused on viral communities in river water systems. Here, we investigated the virome of the Yangtze River Delta using viral metagenomic analysis. The compositions of viral communities from six sampling sites were analyzed and compared. By using library construction and next generation sequencing, contigs and singlet reads similar to viral sequences were classified into 17 viral families, including nine dsDNA viral families, four ssDNA viral families and four RNA viral families. Statistical analysis using Friedman test suggested that there was no significant difference among the six sampling sites (P â€‹> â€‹0.05). The viromes in this study were all dominated by the order Caudovirales, and a group of Freshwater phage uvFW species were particularly prevalent among all the samples. The virome from Nanjing presented a unique pattern of viral community composition with a relatively high abundance of family Parvoviridae. Phylogenetic analyses based on virus hallmark genes showed that the Caudovirales order and CRESS-DNA viruses presented high genetic diversity, while viruses in the Microviridae and Parvoviridae families and the Riboviria realm were relatively conservative. Our study provides the first insight into viral community composition in large river ecosystem, revealing the diversity and stability of river water virome, contributing to the proper utilization of freshwater resource.


Assuntos
Ecossistema , Vírus , Vírus de DNA/genética , Eucariotos/genética , Água Doce , Genoma Viral , Humanos , Metagenômica , Filogenia , Rios , Vírus/genética
9.
Front Med (Lausanne) ; 9: 835467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265642

RESUMO

The immune development and regulation of living individuals are affected by the gut microbiota. The imbalance of gut microbiota is considered to be a key factor that easily induces immune dysregulation and the development of atopic diseases. Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects nearly 20% of children. To date, metagenomics research on AD has mainly focused on the skin and gut microbiome. However, here we assessed the composition of the virome in the gut of AD patients and healthy controls for the first time. This study has obtained possible dominant viruses at different viral classification levels. In terms of diversity, the alpha diversity of the patients group was significantly lower than that of the healthy controls group, and the beta diversity of the two groups was significantly different from phylum to family level. These findings provide a new perspective for us to better understand the effect of the gut microecological environment on AD.

10.
Tuberculosis (Edinb) ; 134: 102186, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35245739

RESUMO

COVID-19 has affected the progress made in the prevention and treatment of tuberculosis (TB); hence, the mortality of tuberculosis has risen. Different strategies-based novel TB vaccine candidates have been developed. This study identifies strategies to overcome the limitations of Bacille Calmette-Guérin (BCG) in preventing latent infection and reactivation of TB. The latency antigen Rv0572c was selected based on the mechanism of interaction between Mycobacterium tuberculosis and its host. The rRv0572c protein was used to stimulate whole blood samples derived from patients with clinically diagnosed active TB (ATBs) or latent TB infections (LTBIs) and healthy control (HCs) donors, confirming that this protein can be recognized by T cells in patients with TB, especially LTBIs. C57BL/6 mice were used to investigate the immunogenicity of the rRv0572c protein emulsified in the liposome adjuvant dimethyldioctadecylammonium [DDA], monophosphoryl lipid A [MPLA], trehalose-6, 6'-dibehenate [TDB] (DMT). The results demonstrated that rRv0572c/DMT could boost BCG-primed mice to induce antigen-specific CD4+ T cell production and generate functional T cells dominated by antigen-specific CD8+ T cells. The rRv0572c/DMT vaccine could also trigger limited Th2 humoral immune responses. These findings suggest that rRv0572c/DMT is a potential subunit vaccine candidate that can be used as a booster vaccine for BCG.

11.
Nanoscale ; 14(10): 3777-3787, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35179162

RESUMO

The composition of protein corona affects the behavior and fate of nanoparticles in biological systems, which strongly relates to the intrinsic properties of nanoparticles and proteins. Here, three types of MXene Ti3C2Tx nanosheets are prepared by different etching methods, and certain physicochemical characteristics of the nanosheets before and after exposure to human plasma (HP) are characterized. The Ti3C2Tx nanosheets with protein coronas suffer more easily from aggregation than pristine Ti3C2Tx. The composition of protein coronas by LC-MS/MS-based label-free proteomic analysis reveals a high overlap of protein types and functions but a significant difference in relative protein abundance for the three Ti3C2Tx. Immunoglobulins and coagulation proteins are highly enriched while albumin is depleted in the coronas compared with their abundance in original HP. The random forest classification model predicts that the main driving forces for the adsorption of HP proteins on Ti3C2Tx are hydrogen bonding, steric hindrance, and hydrophobic interaction. This study provides insights into the colloidal stability of Ti3C2Tx nanosheets and their interaction with human plasma proteins.


Assuntos
Nanoestruturas/química , Plasma/química , Coroa de Proteína , Titânio , Cromatografia Líquida , Humanos , Coroa de Proteína/química , Proteômica , Espectrometria de Massas em Tandem , Titânio/química
12.
Microbiol Spectr ; 10(1): e0187221, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35196818

RESUMO

The gut virome is a reservoir of diverse symbiotic and pathogenic viruses coevolving with their hosts, and yet limited research has explored the gut viromes of highland-dwelling rare species. Using viral metagenomic analysis, the viral communities of the Phrynocephalus lizards living in the Qinghai-Tibet Plateau were investigated. Phage-encoded functional genes and antibiotic resistance genes (ARGs) were analyzed. The viral communities of different lizard species were all predominated by bacteriophages, especially the Caudovirales order. The virome of Phrynocephalus erythrurus living around the Namtso Lake possessed a unique structure, with the greatest abundance of the Parvoviridae family and the highest number of exclusive viral species. Several vertebrate-infecting viruses were discovered, including caliciviruses, astroviruses, and parvoviruses. Phylogenetic analyses demonstrated that the virus hallmark genes of bacteriophages possessed high genetic diversity. After functional annotation, the majority of phage-associated functional genes were classified in the energy metabolism category. In addition, plenty of ARGs belonging to the multidrug category were discovered, and five ARGs were exclusive to the virome from Phrynocephalus theobaldi. This study provided the first insight into the structure and function of the virome in highland lizards, contributing to the protection of threatened lizard species. Also, our research is of exemplary significance for the gut virome research of lizard species and other cold-blooded and highland-dwelling animals, prompting a better understanding of the interspecific differences and transmission of commensal viruses. IMPORTANCE The Phrynocephalus lizards inhabiting the Qinghai-Tibet Plateau (QTP) are considered to be the highest-altitude lizard species in the world, and they have been added to the IUCN list of threatened species. Living in the QTP with hypoxic, arid, natural conditions, the lizards presented a unique pattern of gut virome, which could provide both positive and negative effects, such as the enrichment of functional genes and the dissemination of antibiotic resistance genes (ARGs). This work provides the foundation for further research on the gut virome in these endangered lizard species and other cold-blooded and highland-dwelling animals, contributing to the maintenance of ecological balance on the plateau.


Assuntos
Microbioma Gastrointestinal , Lagartos/virologia , Simbiose/fisiologia , Viroma , Animais , Bacteriófagos/genética , Lagartos/metabolismo , Metagenoma , Metagenômica , Filogenia , Tibet , Viroma/fisiologia , Vírus/classificação , Vírus/genética
13.
Brain Sci ; 12(2)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35204041

RESUMO

It has been shown that learned temporal information can be exploited to help facilitate the target identification in the attentional blink task. Here, we tested whether similar exploitation also worked on short-term temporal information, even when it did not reliably predict the target onset. In two experiments, we randomly manipulated either the interval between targets (T1 and T2; Experiment 1) or the temporal regularity of stimulus presentation (Experiment 2) in each trial. The results revealed evidence of effects of immediate temporal experience mainly on T2 performances but also occasionally on T1 performances. In general, the accuracy of T2 was enhanced when a longer inter-target interval was explicitly processed in the preceding trial (Experiment 1) or the temporal regularity, regardless of being explicitly or implicitly processed, was present in the stimulus stream, especially after T1 (Experiment 2). These results suggest that, under high temporal uncertainty, both interval and rhythmic cues can still be exploited to regulate the allocation of processing resources, thus, modulating the target identification in the attentional blink task, consistent with the view of flexible attentional allocation, and further highlighting the importance of the interplay between temporal processing and attentional control in the conscious visual perception.

14.
Eye (Lond) ; 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35173270

RESUMO

PURPOSE: To evaluate the changes of corneal biomechanics in granular, lattice and macular corneal dystrophy (GCD, LCD and MCD), and to assess the agreement of intraocular pressure (IOP) between Corvis ST tonometer (CST) and Goldmann applanation tonometer (GAT) and the agreement of central corneal thickness (CCT) between CST and ultrasound pachymeter (USP) in patients with corneal dystrophy. METHODS: Fifty-nine eyes with corneal dystrophy (26 eyes with GCD, 18 eyes with LCD and 15 eyes with MCD) and 48 eyes from healthy subjects were included in this study. All subjects received ocular examination and anterior segment photography under slit-lamp microscope. Corneal biomechanical parameters were obtained using CST. IOP and CCT were obtained using GAT and USP, respectively. Mixed-effects models were fitted for group comparisons and Bland-Altman analyses were applied for assessing the agreement of IOP or CCT between devices. RESULTS: GCD, LCD and MCD showed higher First Applanation Deformation Amplitude (A1DA) and Corvis Biomechanical Index (CBI), and a lower Stiffness Parameter at First Applanation (SPA1), compared to controls. After CCT adjustment, MCD group showed a higher A1DA compared to GCD or LCD. The IOP measured by CST demonstrated an overestimated bias to the one obtained by GAT in all groups. The CCT measured by CST and USP showed good agreement in healthy eyes but not in those with corneal dystrophy. CONCLUSION: Corneal biomechanical alterations were observed in GCD, LCD and MCD. IOP and CCT measured by CST should be interpreted carefully in eyes with corneal dystrophy.

15.
Front Neurosci ; 16: 826547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173576

RESUMO

Ovarian hormones modulate women's physical and psychological states periodically. Although the olfactory function is increasingly recognized as a reflection of physical and mental health conditions in the clinic, the role of olfaction in emotional and cognitive functions for healthy individuals has yet to be elucidated, especially when taking the menstrual cycle into account. We carried out a comprehensive investigation to explore whether the menstrual cycle could modulate women's olfactory function and whether healthy women's emotional symptoms and behavioral impulsivity could be characterized by their olfactory abilities at a specific menstrual cycle stage. Twenty-nine healthy young women were evaluated repeatedly using a standard olfactory test battery during the late follicular and mid-luteal phases. Their emotional symptoms and behavioral impulsivity were separately quantified via psychometric scales and a stop-signal task. We observed enhanced olfactory discrimination performance during the mid-luteal phase than the late follicular phase. We also found that women's better olfactory discrimination and worse olfactory threshold in the mid-luteal phase predicted fewer individual emotional symptoms and lower behavioral impulsivity, respectively. These relationships were nonetheless absent in the late follicular phase. Our data extend previous clinical observations of the coexistence of olfactory deficits and neuropsychiatric disorders, providing new insights into the significance of olfaction and ovarian hormones for emotional and cognitive functions.

16.
Sci Total Environ ; 820: 153317, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35066043

RESUMO

Cross-species transmission events were commonplace, with numerous cases of host-switching during the viral evolutionary history, but relatively little evidence for onward transmission in different species living in the same ecosystem. For understanding the communications of viruses in giant pandas (Ailuropoda melanoleuca) and their associated organisms, based on a large size of samples (N = 2305) collected between 2015 and 2020 from giant panda (N = 776) and other four giant panda-associated organisms in the same ecosystem, red pandas (N = 700), stray cats (N = 32), wild rats (N = 42), and mosquitoes (N = 755), viromics was used for the virus identification and subsequent virus traceability. The results showed that a feline panleukopenia virus (FPV) was found in giant pandas with clinical signs of vomiting and mild diarrhea. Meanwhile, the same FPV strain was also prevalent in the healthy red panda (Ailurus fulgens) population. From the viromes of the five different organisms, 250 virus genomes were determined. Our data revealed that besides FPV, other putative pathogenic viruses, such as red panda amdoparvoviruses (RPAVs) and Getah viruses (GETVs) were responsible for previous disease or death of some red pandas. We also demonstrated that a number of viruses were involved in potential interspecies jumping events between giant pandas and their associated species. Collectively, our results shed light on the genetic diversity and relationship of diverse viral pathogens in 'Giant pandas-Associated animals-Arthropods' and report some cases of possible viral host-switching among these host species living in the same ecosystem.


Assuntos
Ursidae , Vírus , Animais , Gatos , Ecossistema , Metagenômica , Filogenia , Ratos
17.
Radiat Oncol ; 17(1): 4, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991637

RESUMO

BACKGROUND: Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). METHODS: The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/ß of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. RESULTS: Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2-3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. CONCLUSIONS: This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.


Assuntos
Algoritmos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Reirradiação/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos
18.
J Med Virol ; 94(6): 2500-2509, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34978087

RESUMO

The pangolin is the only scaly mammal in the world and also an important reservoir of pathogenic viruses. Habitat loss and poaching have been shrinking the survival range of pangolins. More information on pangolin virus populations is needed to better understand and assess potential disease risks. In this study, viral metagenomic data were used to reinvestigate the virome in pangolin lung tissue. Complete genome sequences of two novel anelloviruses were acquired and clustered with the referenced feline strains belonging to genus Tettorquevirus and genus Etatorquevirus, respectively. Two genomes belonging to the genus Gemykibivirus, and species Bat-associated cyclovirus 9 were detected, respectively. One genome with a large contig belonging to the genus Senecavirus were also characterized, according to phylogenetic analysis, which can be presumed to be a novel species. In addition, a full genome of endogenous retroviruse (ERV) was assembled from the lungs of pangolin, and this virus may have the possibility of cross-species transmission during the evolution. This virological investigation has increased our understanding of the virome carried by pangolins and provided a reference baseline for possible zoonotic infectious diseases in the future.


Assuntos
Anelloviridae , Pangolins , Anelloviridae/genética , Animais , Gatos , Genoma Viral , Humanos , Metagenômica , Filogenia
19.
Mol Ther Nucleic Acids ; 27: 241-255, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-34976441

RESUMO

MEX3A is an RNA-binding protein that mediates mRNA decay through binding to 3' untranslated regions. However, its role and mechanism in clear cell renal cell carcinoma remain unknown. In this study, we found that MEX3A expression was transcriptionally activated by ETS1 and upregulated in clear cell renal cell carcinoma. Silencing MEX3A markedly reduced clear cell renal cell carcinoma cell proliferation in vitro and in vivo. Inhibiting MEX3A induced G1/S cell-cycle arrest. Gene set enrichment analysis revealed that E2F targets are the central downstream pathways of MEX3A. To identify MEX3A targets, systematic screening using enhanced cross-linking and immunoprecipitation sequencing, and RNA-immunoprecipitation sequencing assays were performed. A network of 4,000 genes was identified as potential targets of MEX3A. Gene ontology analysis of upregulated genes bound by MEX3A indicated that negative regulation of the cell proliferation pathway was highly enriched. Further assays indicated that MEX3A bound to the CDKN2B 3' untranslated region, promoting its mRNA degradation. This leads to decreased levels of CDKN2B and an uncontrolled cell cycle in clear cell renal cell carcinoma, which was confirmed by rescue experiments. Our findings revealed that MEX3A acts as a post-transcriptional regulator of abnormal cell-cycle progression in clear cell renal cell carcinoma.

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