RESUMO
The overwhelming majority of proliferating somatic human cells are diploid, and this genomic state is typically maintained across successive cell divisions. However, failures in cell division can induce a whole-genome doubling (WGD) event, in which diploid cells transition to a tetraploid state. While some WGDs are developmentally programmed to produce nonproliferative tetraploid cells with specific cellular functions, unscheduled WGDs can be catastrophic: erroneously arising tetraploid cells are ill-equipped to cope with their doubled cellular and chromosomal content and quickly become genomically unstable and tumorigenic. Deciphering the genetics that underlie the genesis, physiology, and evolution of whole-genome doubled (WGD+) cells may therefore reveal therapeutic avenues to selectively eliminate pathological WGD+ cells.
Assuntos
Neoplasias , Tetraploidia , Humanos , Neoplasias/genética , Divisão Celular , Genoma/genética , Fenômenos Fisiológicos CelularesRESUMO
BACKGROUND: Characterization of microbial growth is of both fundamental and applied interest. Modern platforms can automate collection of high-throughput microbial growth curves, necessitating the development of computational tools to handle and analyze these data to produce insights. RESULTS: To address this need, here I present a newly-developed R package: gcplyr. gcplyr can flexibly import growth curve data in common tabular formats, and reshapes it under a tidy framework that is flexible and extendable, enabling users to design custom analyses or plot data with popular visualization packages. gcplyr can also incorporate metadata and generate or import experimental designs to merge with data. Finally, gcplyr carries out model-free (non-parametric) analyses. These analyses do not require mathematical assumptions about microbial growth dynamics, and gcplyr is able to extract a broad range of important traits, including growth rate, doubling time, lag time, maximum density and carrying capacity, diauxie, area under the curve, extinction time, and more. CONCLUSIONS: gcplyr makes scripted analyses of growth curve data in R straightforward, streamlines common data wrangling and analysis steps, and easily integrates with common visualization and statistical analyses.
Assuntos
Software , Biologia Computacional/métodos , Análise de DadosRESUMO
To determine the kinetics of hepatitis E virus (HEV) in asymptomatic persons and to evaluate viral load doubling time and half-life, we retrospectively tested samples retained from 32 HEV RNA-positive asymptomatic blood donors in Germany. Close-meshed monitoring of viral load and seroconversion in intervals of ≈4 days provided more information about the kinetics of asymptomatic HEV infections. We determined that a typical median infection began with PCR-detectable viremia at 36 days and a maximum viral load of 2.0 × 104 IU/mL. Viremia doubled in 2.4 days and had a half-life of 1.6 days. HEV IgM started to rise on about day 33 and peaked on day 36; IgG started to rise on about day 32 and peaked on day 53. Although HEV IgG titers remained stable, IgM titers became undetectable in 40% of donors. Knowledge of the dynamics of HEV viremia is useful for assessing the risk for transfusion-transmitted hepatitis E.
Assuntos
Doadores de Sangue , Vírus da Hepatite E , Hepatite E , RNA Viral , Carga Viral , Viremia , Humanos , Hepatite E/epidemiologia , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Masculino , Adulto , Imunoglobulina M/sangue , Feminino , Imunoglobulina G/sangue , Cinética , Pessoa de Meia-Idade , Infecções Assintomáticas/epidemiologia , Estudos Retrospectivos , Anticorpos Anti-Hepatite/sangue , Alemanha/epidemiologia , Adulto JovemRESUMO
PURPOSE: Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. METHODS: This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. RESULTS: Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p < 0.01). Adenocarcinoma was the most common cell type in both groups but more frequent in cancers occurring in non-fibrotic tissue. In the non-fibrotic lung, 1 of 126 (0.8%) of nodules measuring 1 to 6 mm were cancer. In contrast, 5 of 49 (10.2%) of nodules in fibrosis measuring 1 to 6 mm represented biopsy-proven cancer (p < 0.01). The doubling time for squamous cell cancer was shorter in the fibrotic lung compared to non-fibrotic lung, however, the difference was not statistically significant (p = 0.24). 15 incident lung nodules on second CT obtained ≤ 18 months after first CT scan was found in fibrotic lung and eight (53%) were diagnosed as cancer. CONCLUSIONS: Nodules occurring in fibrotic lung tissue are more likely to be cancer than nodules in the nonfibrotic lung. Incident pulmonary nodules in pulmonary fibrosis have a high likelihood of being cancer.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Fibrose Pulmonar , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Nódulos Pulmonares Múltiplos/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Formic acid (HCOOH) has attracted much attention as a promising power source for portable electronic devices because of its ease of storage and transportation. Here we report that a simple HCOOH photo-fuel cell (PFC) consisting of mesoporous anatase TiO2 photoanode and Pt cathode stably delivers a short-circuit photocurrent (Jsc) of 5.94 mA cm-2 and an open-circuit voltage of 0.94 V under UV-light irradiation (light intensity, I = 200 mW cm-2). The incident photon-to-current conversion efficiency and Faradaic efficiency reach ~90% and ~100%, respectively. The excellent performances of this HCOOH PFC, designed based on the discovery that HCOOH provides a large photocurrent by current doubling even in the presence of O2, not only solves the problem of conventional HCOOH FCs, but also achieves the performances far exceeding those of PFCs using biomass-derived organics reported so far.
RESUMO
OBJECTIVES: The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6â¯% in CA15-3 to 22â¯% in CA125. When decisions are made on the basis of DT or t1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables. METHODS: We related equations for calculating DT and t1/2 to the reference change values in tumor markers. RESULTS: The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios. CONCLUSIONS: Intraindividual variation affects the calculation of DT and t1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.
Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Neoplasias/patologia , Biomarcadores Tumorais/sangue , Variação Biológica Individual , Meia-VidaRESUMO
Access to safe and stable housing is important for child and adult well-being. Yet many low-income households face severe challenges in maintaining stable housing. In this article, we examine the impact of the 2021 temporary expansion to the Child Tax Credit (CTC) on housing affordability and the living arrangements of families with low incomes. We employ a parameterized difference-in-differences method and leverage national data from a sample of parents who are receiving or recently received Supplemental Nutrition Assistance Program benefits (N = â¼20,500), many of whom became newly eligible for the CTC. We find that the monthly CTC reduced parents' past-due rent/mortgages (both amounts and incidence) and their reports of potential moves due to difficulties affording rent/mortgages. The CTC increased the likelihood that parents reported a change in their living arrangements and reduced their household size, both effects driven by fewer mothers living with a partner (and not a reduction in doubling up). We find some differences in effects by race and ethnicity and earnings. Our findings illustrate that the monthly credit improved low-income parents' ability to afford housing, gain residential independence from partners, and reduce the number of people residing in their household.
Assuntos
Habitação , Pobreza , Características de Residência , Humanos , Habitação/estatística & dados numéricos , Habitação/economia , Pobreza/estatística & dados numéricos , Feminino , Masculino , Características de Residência/estatística & dados numéricos , Criança , Adulto , Características da Família , Estados Unidos , Impostos/estatística & dados numéricos , Assistência Alimentar/estatística & dados numéricos , Fatores Socioeconômicos , Pré-Escolar , AdolescenteRESUMO
BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.
Assuntos
Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Terapia de Salvação , Humanos , Masculino , Terapia de Salvação/métodos , Prostatectomia/métodos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Antígeno Prostático Específico/sangue , Gradação de Tumores , Intervalo Livre de Doença , Margens de ExcisãoRESUMO
We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest. The theory is independent of which of the classically associated oncogenic mutations have already occurred. PACCs have been generally disregarded as senescent or dying cells. Our theory states that therapeutic resistance is driven by PACC formation that is enabled by accessing a polyploid program that allows an aneuploid cancer cell to double its genomic content, followed by entry into a nondividing cell state to protect DNA integrity and ensure cell survival. Upon removal of stress, e.g., chemotherapy, PACCs undergo depolyploidization and generate resistant progeny that make up the bulk of cancer cells within a tumor.
Assuntos
Aneuploidia , Pontos de Checagem do Ciclo Celular , Neoplasias/genética , Poliploidia , Animais , Sobrevivência Celular , Evolução Molecular , Humanos , Neoplasias/patologiaRESUMO
Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and relatively slow growth compared to other soft tissue sarcomas. Some patients with SS experience long-standing pain at the tumor site before the development of a palpable mass. Herein, we report the case of a 39-year-old woman with SS in the upper arm who presented with pain for > 20 years. The tumor detected on magnetic resonance imaging at 17 years was an SS. To the best of our knowledge, no English-language reports on imaging study-based identification of SS, which was undiagnosed for > 20 years, are known in the literature. This report discusses the imaging features of this latent lesion and the volume-doubling time of this unusual tumor.
RESUMO
PURPOSE: Latent lymph node metastasis is a clinical concern in the surgical treatment of non-small cell lung cancer (NSCLC). The present study identified a simple tool, including the volume-doubling time (VDT), for evaluating the risk of nodal metastasis. METHODS: We reviewed, retrospectively, 560 patients who underwent radical resection for cN0M0 NSCLC. The whole tumor VDT and solid component VDT (SVDT) for differentiating the histological type and adenocarcinoma subtype were analyzed and a nomogram was constructed using variables selected through a stepwise selection method. The model was assessed through a calibration curve and decision curve analysis (DCA). RESULTS: Lymph node metastases were detected in 89 patients (15.9%). The SVDT tended to be longer in patients with adenocarcinoma (294.5 days, p < 0.0001) than in those with other histological types of NSCLC, but was shorter when the solid/micropapillary component was predominant (127.0 days, p < 0.0001). The selected variables (tumor location, solid component diameter, consolidation tumor ratio, SVDT, and carcinoembryonic antigen) demonstrated significant differences and were used for the nomogram. The calibration curve indicated consistency, and the DCA showed validity across most threshold ranges from 0 to 68%. CONCLUSIONS: The established nomogram is a useful tool for the preoperative prediction of lymph node metastasis, and the SVDT was the most influential factor in the nomogram.
Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Nomogramas , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Adenocarcinoma/patologia , Tomografia Computadorizada por Raios X , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
Identifying brain-tissue types holds significant research value in the biomedical field of non-contact brain-tissue measurement applications. In this paper, a layered metastructure is proposed, and the second harmonic generation (SHG) in a multilayer metastructure is derived using the transfer matrix method. With the SHG conversion efficiency (CE) as the measurement signal, the refractive index ranges that can be distinguished are 1.23~1.31 refractive index unit (RIU) and 1.38~1.44 RIU, with sensitivities of 0.8597 RIU-1 and 1.2967 RIU-1, respectively. It can distinguish various brain tissues, including gray matter, white matter, and low-grade glioma, achieving the function of a second harmonic mode sensor (SHMS). Furthermore, temperature has a significant impact on the SHG CE, which can be used to define the switch signal indicating whether the SHMS is functioning properly. When the temperature range is 291.4~307.9 Kelvin (K), the temperature switch is in the "open" state, and the optimal SHG CE is higher than 0.298%, indicating that the SHMS is in the working state. For other temperature ranges, the SHG CE will decrease significantly, indicating that the temperature switch is in the "off" state, and the SHMS is not working. By stimulating temperature and using the response of SHG CE, the temperature-switch function is achieved, providing a new approach for temperature-controlled second harmonic detection.
RESUMO
Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.
Assuntos
Neoplasias , Poliploidia , Núcleo Celular , Cromatina/genética , Genoma , Humanos , Neoplasias/genética , Neoplasias/terapiaRESUMO
BACKGROUND: Along with global warming, resulting in crop production, exacerbating the global food crisis. Therefore, it is urgent to study the mechanism of plant heat resistance. However, crop resistance genes were lost due to long-term artificial domestication. By analyzing the potential heat tolerance genes and molecular mechanisms in other wild materials, more genetic resources can be provided for improving the heat tolerance of crops. Elephant grass (Pennisetum purpureum Schum.) has strong adaptability to heat stress and contains abundant heat-resistant gene resources. RESULTS: Through sequence structure analysis, a total of 36 RWP-RK members were identified in elephant grass. Functional analysis revealed their close association with heat stress. Four randomly selected RKDs (RKD1.1, RKD4.3, RKD6.6, and RKD8.1) were analyzed for expression, and the results showed upregulation under high temperature conditions, suggesting their active role in response to heat stress. The members of RWP-RK gene family (36 genes) in elephant grass were 2.4 times higher than that of related tropical crops, rice (15 genes) and sorghum (15 genes). The 36 RWPs of elephant grass contain 15 NLPs and 21 RKDs, and 73% of RWPs are related to WGD. Among them, combined with the DAP-seq results, it was found that RWP-RK gene family expansion could improve the heat adaptability of elephant grass by enhancing nitrogen use efficiency and peroxidase gene expression. CONCLUSIONS: RWP-RK gene family expansion in elephant grass is closely related to thermal adaptation evolution and speciation. The RKD subgroup showed a higher responsiveness than the NLP subgroup when exposed to high temperature stress. The promoter region of the RKD subgroup contains a significant number of MeJA and ABA responsive elements, which may contribute to their positive response to heat stress. These results provided a scientific basis for analyzing the heat adaptation mechanism of elephant grass and improving the heat tolerance of other crops.
Assuntos
Pennisetum , Termotolerância , Pennisetum/genética , Termotolerância/genética , Aclimatação , Produtos Agrícolas , DomesticaçãoRESUMO
BACKGROUND: Whole-genome doubling (WGD) has been observed in 30% of cancers, followed by a highly complex rearranged karyotype unfavourable to breast cancer's outcome. However, the macro-alterations that characterise liver metastasis in breast cancer(BC) are poorly understood. Here, we conducted a whole-genome sequencing analysis of liver metastases to explore the status and the time frame model of these macro-alterations in pre-treatment patients with metastatic breast cancer. RESULTS: Whole-genome sequencing was conducted in 11 paired primary tumours, lymph node metastasis, and liver metastasis fresh samples from four patients with late-stage breast cancer. We also chose five postoperative frozen specimens from patients with early-stage breast cancer before any treatment as control. Surprisingly, all four liver metastasis samples were classified as WGD + . However, the previous study reported that WGD happened in 30% of cancers and 2/5 in our early-stage samples. WGD was not observed in the two separate primary tumours and one lymph node metastasis of one patient with metastatic BC, but her liver metastasis showed an early burst of bi-allelic copy number gain. The phylogenetic tree proves her 4 tumour samples were the polyclonal origin and only one WGD + clone metastasis to the liver. Another 3 metastatic BC patients' primary tumour and lymph node metastasis experienced WGD as well as liver metastasis, and they all showed similar molecular time-frame of copy number(CN) gain across locations within the same patient. These patients' tumours were of monoclonal origin, and WGD happened in a founding clone before metastasis, explaining that all samples share the CN-gain time frame. After WGD, the genomes usually face instability to evolve other macro-alterations. For example, a greater quantity and variety of complex structural variations (SVs) were detected in WGD + samples. The breakpoints were enriched in the chr17: 39 Mb-40 Mb tile, which contained the HER2 gene, resulting in the formation of tyfonas, breakage-fusion-bridge cycles, and double minutes. These complex SVs may be involved in the evolutionary mechanisms of the dramatic increase of HER2 copy number. CONCLUSION: Our work revealed that the WGD + clone might be a critical evolution step for liver metastasis and favoured following complex SV of breast cancer.
Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Humanos , Feminino , Neoplasias da Mama/genética , Metástase Linfática , Filogenia , Neoplasias Hepáticas/genética , DNARESUMO
Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.
Assuntos
Neoplasias da Mama , Progesterona , Feminino , Humanos , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Ciclo Menstrual/fisiologia , Estrogênios , Estradiol , Preparações FarmacêuticasRESUMO
Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and not into myoepithelium. In this study, we performed a detailed histopathological and genomic analysis of 6 cases of HCCC, including 2 atypical subtypes-a case of "high-grade transformation" and 1 "possessing a novel partner gene for EWSR1." We performed a sequential analysis of the primary and recurrent tumor by whole-exome sequencing, RNA sequencing, Sanger sequencing, and fluorescence in situ hybridization to investigate the effect of genomic changes on histopathology and clinical prognosis. A fusion gene involving the EWSR1 gene was detected in all cases. Five cases, including the "high-grade transformation," harbored a known EWSR1::ATF1 fusion gene; however, 1 case harbored a novel EWSR1::LARP4 fusion gene. This novel EWSR1::LARP4-fused HCCC has a SOX10-positive staining, which is different from the EWSR1::ATF1-fused HCCC. According to whole-exome sequencing and fluorescence in situ hybridization analysis, the "whole-genome doubling" and focal deletion involving CDKN2A, CDKN2B, and PTEN were detected in HCCC with "high-grade transformation." Conclusively, we identified a novel partner gene for EWSR1, LARP4, in indolent HCCC. Importantly, "high-grade transformation" and poor prognosis were caused by whole-genome doubling and subsequent genomic aberrations.
Assuntos
Adenocarcinoma de Células Claras , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Hibridização in Situ Fluorescente , Proteína EWS de Ligação a RNA/genética , Glândulas Salivares/patologia , Sequência de Bases , Genes cdc , Proteínas de Fusão Oncogênica/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Fatores de Transcrição SOXE/genéticaRESUMO
BACKGROUND: Doubled haploid technology offers the fastest route of inbred line development by rapidly fixing the desirable combinations in a single year. However, the differential response of haploid induction to genetic background of maternal lines accompanied with low induction rate and high mortality rate due to artificial chromosomal doubling of haploid seedlings creates hindrance in doubled haploid production on a commercial scale under tropical conditions. To speed up the hybrid breeding programme in sub-tropical maize, efforts are reported here to optimize the protocol for efficient production of fixed lines using haploid inducers. The second-generation haploid inducers i.e. CIM2GTAILs obtained from CIMMYT, Mexico were used for haploid induction in 13 F1s of diverse backgrounds. For standardization of chromosomal doubling protocol, various concentrations of colchicine and two seedling growth stages were used to determine the extent of chromosomal doubling and survival rate of doubled haploid plants. RESULTS: A high mean haploid induction rate is obtained from CIM2GTAIL P2 (10%) as compared to CIM2GTAIL P1 (7.46%). Out of four treatments, CIMMYT reported protocol of chromosome doubling in tropical maize comprising combination of 0.07% colchicine and 0.1% DMSO at V2 stage is highly effective for acquiring doubled haploid plants in sub-tropical adapted maize with high survival rate of 52.7%. However, increasing the colchicine concentration from 0.07 to 0.1% led to high mortality rate. CONCLUSION: According to the findings, the haploid induction rate, survival rate and overall success rate varied depending upon the genotype of the inducer and the source population along with the concentrations of chemical used. The optimized protocol developed using CIMMYT haploid inducer CIM2GTAIL P2 for efficient doubled haploid production will not only fasten the breeding programme but will also reduce the production cost of doubled haploid with great efficiency in sub-tropical maize.
Assuntos
Melhoramento Vegetal , Zea mays , Zea mays/genética , Haploidia , Melhoramento Vegetal/métodos , Genótipo , Cromossomos de Plantas/genéticaRESUMO
Monkeypox, a zoonotic disease, is emerging as a potential sexually transmitted infection/disease, with underlying transmission mechanisms still unclear. We devised a risk-structured, compartmental model, incorporating sexual behavior dynamics. We compared different strategies targeting the high-risk population: a scenario of control policies geared toward the use of condoms and/or sexual abstinence (robust control strategy) with risk compensation behavior change, and a scenario of control strategies with behavior change in response to the doubling rate (adaptive control strategy). Monkeypox's basic reproduction number is 1.464, 0.0066, and 1.461 in the high-risk, low-risk, and total populations, respectively, with the high-risk group being the major driver of monkeypox spread. Policies imposing condom use or sexual abstinence need to achieve a 35% minimum compliance rate to stop further transmission, while a combination of both can curb the spread with 10% compliance to abstinence and 25% to condom use. With risk compensation, the only option is to impose sexual abstinence by at least 35%. Adaptive control is more effective than robust control where the daily sexual contact number is reduced proportionally and remains constant thereafter, shortening the time to epidemic peak, lowering its size, facilitating disease attenuation, and playing a key role in controlling the current outbreak.
Assuntos
Mpox , Infecções Sexualmente Transmissíveis , Humanos , Mpox/epidemiologia , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Canadá/epidemiologia , Surtos de Doenças/prevenção & controleRESUMO
BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. STUDY TYPE: Retrospective. SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days). FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.