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RATIONALE: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing for timely and effective intervention before cancer development. OBJECTIVES: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. METHODS: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the transformation of premalignant lung lesions to advanced lung cancer. RESULTS: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages. CONCLUSIONS: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, along with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes.
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OBJECTIVES: Diabetes is highly prevalent worldwide, with an estimated 536 million living with diabetes in 2021, and that number projected to increase to 783 million by 2045. Diabetic bladder dysfunction is thought to affect up to 60%-90% of individuals with diabetes and can significantly impact quality of life. Despite the prevalence of diabetic bladder dysfunction, the exact pathophysiological mechanism, and resulting clinical presentation, remains debated. Our objective was to compare urodynamic parameters between diabetic and nondiabetic women, assessing the impact of various markers of diabetes severity on bladder function. METHODS: A retrospective chart review was conducted on female patients aged 18 and above who underwent urodynamic studies at a single tertiary care university hospital system from 2014 to 2020. Patients were categorized based on diabetes status, and diabetes severity including duration of disease, hemoglobin A1c levels, insulin dependence, and markers of end-organ dysfunction. Urodynamic variables, including compliance, bladder voided efficiency, bladder contractility index, postvoid residual, maximum flow rate, capacity, voided volume, and detrusor overactivity, were assessed by two independent reviewers. Statistical analyses were performed to assess the impact of diabetes and diabetic severity on urodynamic parameters. RESULTS: A total of 652 female patients were included in the study, of which, 152 (23.3%) had diabetes, with an average duration of diagnosis of 82.3 months. Diabetic women were older and had higher body mass index compared to nondiabetic women. Diabetic retinopathy and neuropathy were present in 18% and 54.6% of diabetic patients, respectively. Significant differences in urodynamic parameters were observed between diabetic and nondiabetic women, with diabetic women showing higher rates of detrusor overactivity (p = 0.01), particularly associated with increasing BMI (p = 0.03). However, classic markers of diabetes severity including duration, as well as markers of end-organ damage, showed mixed associations with urodynamic changes. CONCLUSIONS: Despite the prevalence of diabetic bladder dysfunction and its impact on patient quality of life, the exact mechanisms and clinical presentation remain elusive. Our study highlights the significant differences in urodynamic parameters between diabetic and nondiabetic women, emphasizing the need for further research into the relationship between diabetes and diabetic bladder dysfunction.
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OBJECTIVES: Fluoroscopy has significantly improved lead placement and decreased surgical time for implantable sacral neuromodulation (SNM). There is a paucity of data regarding radiation and safety of fluoroscopy during SNM procedures. Our study aims to characterize fluoroscopy time and dose used during SNM surgery across multiple institutions and assess for predictors of increased fluoroscopy time and radiation dose. METHODS: Electronic medical records were queried for SNM procedures (Stage 1 and full implant) from 2016 to 2021 at four academic institutions. Demographic, clinical, and intraoperative data were collected, including fluoroscopy time and radiation dose in milligray (mGy). The data were entered into a centralized REDCap database. Univariate and multivariate analysis were performed to assess for predictive factors using STATA/BE 17.0. RESULTS: A total of 664 procedures were performed across four institutions. Of these, 363 (54.6%) procedures had complete fluoroscopy details recorded. Mean surgical time was 58.8 min. Of all procedures, 79.6% were performed by Female Pelvic Medicine and Reconstructive Surgery specialists. There was significant variability in fluoroscopy time and dose based on surgical specialty and institution. Most surgeons (76.4%) were considered "low volume" implanters. In a multivariate analysis, bilateral finder needle testing, surgical indication, surgeon volume, and institution significantly predicted increased fluoroscopy time and radiation dose (p < 0.05). CONCLUSIONS: There is significant variability in fluoroscopy time and radiation dose utilized during SNM procedures, with differences across institutions, surgeons, and subspecialties. Increased radiation exposure can have harmful impacts on the surgical team and patient. These findings demonstrate the need for standardized fluoroscopy use during SNM procedures.
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Terapia por Estimulação Elétrica , Exposição à Radiação , Cirurgiões , Bexiga Urinária Hiperativa , Humanos , Feminino , Bexiga Urinária Hiperativa/terapia , Terapia por Estimulação Elétrica/métodos , Sacro , Exposição à Radiação/efeitos adversosRESUMO
Rationale: The current molecular classification of small-cell lung cancer (SCLC) on the basis of the expression of four lineage transcription factors still leaves its major subtype SCLC-A as a heterogeneous group, necessitating more precise characterization of lineage subclasses. Objectives: To refine the current SCLC classification with epigenomic profiles and to identify features of the redefined SCLC subtypes. Methods: We performed unsupervised clustering of epigenomic profiles on 25 SCLC cell lines. Functional significance of NKX2-1 (NK2 homeobox 1) was evaluated by cell growth, apoptosis, and xenograft using clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9)-mediated deletion. NKX2-1-specific cistromic profiles were determined using chromatin immunoprecipitation followed by sequencing, and its functional transcriptional partners were determined using coimmunoprecipitation followed by mass spectrometry. Rb1flox/flox; Trp53flox/flox and Rb1flox/flox; Trp53flox/flox; Nkx2-1flox/flox mouse models were engineered to explore the function of Nkx2-1 in SCLC tumorigenesis. Epigenomic landscapes of six human SCLC specimens and 20 tumors from two mouse models were characterized. Measurements and Main Results: We identified two epigenomic subclusters of the major SCLC-A subtype: SCLC-Aα and SCLC-Aσ. SCLC-Aα was characterized by the presence of a super-enhancer at the NKX2-1 locus, which was observed in human SCLC specimens and a murine SCLC model. We found that NKX2-1, a dual lung and neural lineage factor, is uniquely relevant in SCLC-Aα. In addition, we found that maintenance of this neural identity in SCLC-Aα is mediated by collaborative transcriptional activity with another neuronal transcriptional factor, SOX1 (SRY-box transcription factor 1). Conclusions: We comprehensively describe additional epigenomic heterogeneity of the major SCLC-A subtype and define the SCLC-Aα subtype by the core regulatory circuitry of NKX2-1 and SOX1 super-enhancers and their functional collaborations to maintain neuronal linage state.
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Neoplasias Pulmonares , Fatores de Transcrição SOXB1 , Carcinoma de Pequenas Células do Pulmão , Fator Nuclear 1 de Tireoide , Animais , Humanos , Camundongos , Transformação Celular Neoplásica , Pulmão , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator Nuclear 1 de Tireoide/genéticaRESUMO
Pokkah boeng disease (PBD), a sugarcane foliar disease, is caused by various Fusarium spp. within the Fusarium fujikuroi species complex (FFSC). In the current study, we investigated the diversity of Fusarium spp. associated with PBD in China. In total, 320 leaf samples displaying PBD symptoms were collected over 10 consecutive years (2012 to 2021), during winter and summer, from six various sugarcane-growing regions (Guangxi, Yunnan, Guangdong, Zhejiang, Hainan, and Fujian) in China. Phylogenetic analysis of Fusarium spp. was reconstructed using translation elongation factor 1-α, and DNA-directed RNA polymerase II largest subunit and second-largest subunit multigene sequences. Evolutionary studies of these regions categorized the isolates into four FFSC species (F. sacchari, F. proliferatum, F. verticillioides, and F. andiyazi). The identified isolates, which developed irregular necrotic patches and rotting symptoms on the sugarcane plant after approximately 30 days were tested for their pathogenicity. Symptoms that appeared during pathogenicity testing were consistent with those observed under field conditions. Each strain of the pathogenic Fusarium spp. belonged to different vegetative compatibility groups (VCGs), and there was no affinity between VCGs. Our results contribute to understanding FFSC and accurately identifying Fusarium spp. associated with the sugarcane crop.
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Fusarium , Saccharum , Filogenia , Virulência/genética , China , Grão Comestível , Variação GenéticaRESUMO
Nitrogen availability might play an essential role in plant diseases by enhancing fungal cell growth and influencing the expression of genes required for successful pathogenesis. Nitrogen availability could modulate secondary metabolic pathways as evidenced by the significant differential expression of several core genes involved in mycotoxin biosynthesis and genes encoding polyketide synthase/nonribosomal peptide synthetases, cytochrome P450 and carbohydrate-active enzymes in Fusarium sacchari, grown on different nitrogen sources. A combined analysis was carried out on the transcript and metabolite profiles of regulatory metabolic processes and the virulence of Fusarium sacchari grown on various nitrogen sources. The nitrogen regulation of the gibberellin gene cluster included the metabolic flux and multiple steps of gibberellin synthesis. UHPLC-MS/MS-based metabolome analysis revealed the coordination of these related transcripts and the accumulation of gibberellin metabolites. This integrated analysis allowed us to uncover additional information for a more comprehensive understanding of biological events relevant to fungal secondary metabolic regulation in response to nitrogen availability.
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Fusarium , Transcriptoma , Metabolismo Secundário/genética , Nitrogênio/metabolismo , Espectrometria de Massas em Tandem , Giberelinas/metabolismo , Regulação Fúngica da Expressão GênicaRESUMO
During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events..
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COVID-19/prevenção & controle , COVID-19/transmissão , Controle de Doenças Transmissíveis/métodos , Eventos de Massa , Cooperação do Paciente , SARS-CoV-2 , Humanos , Cidade de Nova Iorque/epidemiologia , Vigilância em Saúde Pública , Estados Unidos/epidemiologiaRESUMO
Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in Radiology and CHEST. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
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Sugarcane mosaic virus (SCMV), belonging to genus Potyvirus, family Potyviridae, is a severe pathogen of several agricultural important crops, mainly sugarcane. Due to complex nature of sugarcane, the effect of SCMV pathogenicity on sugarcane photosynthetic systems remains to be explored. In this study, we investigated the alterations occurring in the photosynthetic system in the sugarcane genotypes at the cytopathological, physiological and biological, transcriptome and proteome level. We generated the transcriptome assembly of two genotypes (susceptible Badila and resistant B-48) using Saccharum spontaneum L. as a reference genome. RNA-sequencing data revealed the significant upregulation of NAD(P)H, RubisCO, oxygen-evolving complex, chlorophyll a and b binding protein, Psb protein family, PSI reaction center subunit II, and IVgenes in B-48, as compared to its counterparts. Upregulated genes in B-48 are associated with various processes such as stability and assembly of photosystem, protection against photoinhibition and antiviral defense. The expression pattern of differentially abundant genes were further verified at the proteomics level. Overall, differentially expressed genes/proteins (DEGs/DEPs) showed the consistency of expression at both transcriptome and proteome level in B-48 genotype. Comprehensively, these data supported the efficiency of B-48 genotype under virus infection conditions and provided a better understanding of the expression pattern of photosynthesis-related genes in sugarcane.
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Potyvirus , Saccharum , Clorofila A , Fotossíntese/genética , Doenças das Plantas/genética , Saccharum/genéticaRESUMO
INTRODUCTION: There is a paucity of patient reported outcome measure (PROM) data for women with urethral strictures. To address this gap, we aim to evaluate change in PROM among women who underwent surgery for a stricture. METHODS: American Urological Association Symptom Index (AUA-SI) and Urogenital Distress Inventory (UDI-6) data from a multi-institutional retrospective cohort study of women treated for urethral stricture was assessed. RESULTS: Fifty-seven women had either AUA-SS or UDI-6 and 26 had baseline and postoperative data for either. Most women underwent urethroplasty (77%) and the majority (73%) remained stricture free at median follow-up of 21 months (interquartile range [IQR] 7-37). The median baseline AUA-SI was 21 (IQR 12-28) and follow-up was 10 (IQR 5-24). After treatment, there was a median decrease of 12 (IQR -18 to -2) in AUA-SI (p = 0.003). The median AUA Quality of life (QOL) score at baseline and follow-up were 6 (IQR 4-6) and 3 (IQR 2-5), respectively. There was a median AUA-QOL improvement of 2 points (-5,0; p = 0.007) from a baseline 5 (unhappy) to 3 (mixed). Median UDI-6 scores were 50 (IQR 33-75) at baseline and 17 (IQR 0-39), at follow-up. After treatment, there was a median decrease of 19 (-31 to -11; p = 0.01). CONCLUSION: Women with urethral strictures have severe lower urinary tract symptoms which improved after surgery. This study substantiates the claims that recognizing and treating women with urethral stricture disease greatly improves lower urinary tract symptoms and QOL.
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Estreitamento Uretral , Feminino , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Uretra , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos UrológicosRESUMO
BACKGROUND: Examinations based on lung tissue specimen can play a significant role in the diagnosis for critically ill and intubated patients with lung infiltration. However, severe complications including tension pneumothorax and intrabronchial hemorrhage limit the application of needle biopsy. METHODS: A refined needle biopsy technique, named bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB), was performed on four intubated patients between August 2020 and April 2021. BUS-PTNB was done at bedside, following an EPUBNOW (evaluation, preparation, ultrasound location, bronchus blocking, needle biopsy, observation, and withdrawal of blocker) workflow. Parameters including procedure feasibility, sample acquisition, perioperative conditions, and complications were observed. Tissue specimens were sent to pathological examinations and microbial tests. RESULTS: Adequate specimens were successfully obtained from four patients. Diagnosis and treatment were correspondingly refined based on pathological and microbial tests. Intrabronchial hemorrhage occurred in patient 1 but was stopped by endobronchial blocker. Mild pneumothorax happened in patient 4 due to little air leakage, and closed thoracic drainage was placed. During the procedure, peripheral capillary hemoglobin oxygen saturation (SPO2), blood pressure, and heart rate of patient 4 fluctuated but recovered quickly. Vital signs were stable for patient 1-3. CONCLUSIONS: BUS-PTNB provides a promising, practical and feasible method in acquiring tissue specimen for critically ill patients under intratracheal intubation. It may facilitate the pathological diagnosis or other tissue-based tests for intubated patients and improve clinical outcomes.
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Biópsia por Agulha , Brônquios , Biópsia Guiada por Imagem , Pneumopatias , Ultrassonografia de Intervenção , Biópsia por Agulha/métodos , Brônquios/diagnóstico por imagem , Brônquios/patologia , Estado Terminal , Humanos , Intubação Intratraqueal , Pneumopatias/patologia , Pneumopatias/terapiaRESUMO
Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants.Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs.Methods: DNA was extracted from 21 ADCs in situ (AISs), 27 minimally invasive ADCs (MIAs), and 54 fully invasive ADCs. This DNA was subjected to deep next-generation sequencing and tested against a custom panel of 347 cancer genes.Measurements and Main Results: Sequencing data was analyzed for associations among tumor mutation burden, frequency of mutations or copy number alterations, mutation signatures, intratumor heterogeneity, pathway alterations, histology, and overall survival. We found that deleterious mutation burden was significantly greater in invasive ADC, whereas more copy number loss was observed in AIS and MIA. Intratumor heterogeneity establishes early, as in AIS. Twenty-one significantly mutated genes were shared among the groups. Mutation signature profiling did not vary significantly, although the APOBEC signature was associated with ADC and poor survival. Subclonal KRAS mutations and a gene signature consisting of PIK3CG, ATM, EPPK1, EP300, or KMT2C mutations were also associated with poor survival. Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers.Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.
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Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/fisiopatologia , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Feminino , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Sugarcane mosaic virus (SCMV) is one of the major pathogens of sugarcane. SCMV infection causes dynamic changes in plant cells, including decreased photosynthetic rate, respiration, and sugar metabolism. To understand the basics of pathogenicity mechanism, we performed transcriptome and proteomics analysis in two sugarcane genotypes (Badila: susceptible to SCMV and B-48: SCMV resistant). Using Saccharum spontaneum L. genome as a reference, we identified the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) that participate in sugar metabolism, transport of their metabolites, and Carbohydrate Activating enZYmes (CAZymes). Sequencing data revealed 287 DEGs directly or indirectly involved in sugar metabolism, transport, and storage, while 323 DEGs are associated with CAZymes. Significant upregulation of glucose, sucrose, fructose, starch, and SWEET-related transcripts was observed in the Badila after infection of SCMV. B-48 showed resistance against SCMV with a limited number of sugar transcripts up-regulation at the post-infection stage. For CAZymes, only glycosyltransferase (GT)1 and glycosyl hydrolase (GH)17 were upregulated in B-48. Regulation of DEGs was analyzed at the proteomics level as well. Starch, fructose, glucose, GT1, and GH17 transcripts were expressed at the post-translational level. We verified our transcriptomic results with proteomics and qPCR data. Comprehensively, this study proved that Badila upregulated sugar metabolizing and transporting transcripts and proteins, which enhance virus multiplication and infectionl.
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Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Potyvirus/fisiologia , Saccharum/metabolismo , Saccharum/virologia , Açúcares/metabolismo , Transporte Biológico , Regulação da Expressão Gênica de Plantas , Metaboloma , Doenças das Plantas/genética , Proteínas de Plantas/genética , Potyvirus/patogenicidade , Proteômica , Saccharum/genética , TranscriptomaRESUMO
Phoma sorghina var. saccharum is a fungal pathogen that causes sugarcane twisted leaf disease in China. Here, we report complete genome assemblies of the Phoma sorghina var. saccharum isolate BS2-1, generated using single-molecule real-time sequencing. We present a high-quality genome sequence of a Phoma isolate that was assembled into 22 contigs with an N50 length of 1.92 Mb, a total length of 33.12 Mb, and a GC content of 52.12%. A total of 7,870 genes were annotated, using a combination of gene prediction tools, including 281 noncoding RNAs, 515 genes encoding carbohydrate-active enzymes, 2,440 genes associated with pathogen-host interactions, and 583 genes encoding secreted proteins. The complete genome sequence will be useful for understanding host-pathogen interaction and for improving disease management strategies.
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Ascomicetos , Genoma Fúngico , Doenças das Plantas/microbiologia , Saccharum/microbiologia , Ascomicetos/genética , China , Folhas de PlantaRESUMO
BACKGROUND: Viruses are infectious pathogens, and plant virus epidemics can have devastating consequences to crop yield and quality. Sugarcane mosaic virus (SCMV, belonging to family Potyviridae) is one of the leading pathogens that affect the sugarcane crop every year. To combat the pathogens' attack, plants generate reactive oxygen species (ROS) as the first line of defense whose sophisticated balance is achieved through well-organized antioxidant scavenging pathways. RESULTS: In this study, we investigated the changes occurring at the transcriptomic level of ROS associated and ROS detoxification pathways of SCMV resistant (B-48) and susceptible (Badila) sugarcane genotypes, using Saccharum spontaneum L. genome assembly as a reference genome. Transcriptomic data highlighted the significant upregulation of ROS producing genes such as NADH oxidase, malate dehydrogenase and flavin-binding monooxygenase, in Badila genotype after SCMV pathogenicity. To scavenge the ROS, the Badila genotype illustrated a substantial enhancement of antioxidants i.e. glutathione s-transferase (GST), as compared to its resistant counterpart. GST is supposed to be a key indicator of pathogen attacks on the plant. A remarkably lower GST expression in B-48, as compared to Badila, indicated the development of resistance in this genotype. Additionally, we characterized the critical transcription factors (TFs) involved in endowing resistance to B-48. Among these, WRKY, AP2, NAC, bZIP, and bHLH showed enhanced expression in the B-48 genotype. Our results also confirmed the linkage of transcriptomic data with the enzymatic and qPCR data. The estimation of enzymatic activities for superoxide dismutase, catalase, ascorbate peroxidase, and phenylalanine ammonia-lyase supported the transcriptomic data and evinced higher resistance in B-48 genotype. CONCLUSION: The current study supported the efficiency of the B-48 genotype under SCMV infection. Moreover, comparative transcriptomic data has been presented to highlight the role of significant transcription factors conferring resistance to this genotype. This study provides an in-depth knowledge of the expression profiling of defense mechanisms in sugarcane.
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Antioxidantes/metabolismo , Doenças das Plantas/imunologia , Potyvirus/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Saccharum/genética , Ascorbato Peroxidases/genética , Catalase/genética , Perfilação da Expressão Gênica , Genótipo , Fenilalanina Amônia-Liase/genética , Doenças das Plantas/virologia , Proteínas de Plantas/genética , Saccharum/imunologia , Saccharum/fisiologia , Saccharum/virologia , Superóxido Dismutase/genética , Fatores de Transcrição/genéticaRESUMO
PURPOSE: Anti-human epidermal growth factor receptor 2 (HER2) therapies are associated with interstitial lung disease (ILD), also referred to as pneumonitis. In this literature review, we describe the incidence of ILD among patients with HER2-positive metastatic breast cancer (MBC) receiving anti-HER2 therapies, and we describe existing recommendations for monitoring and managing drug-induced ILD among these patients. METHODS: We searched PubMed and Embase to identify clinical trials and postmarket observational studies that investigated anti-HER2 therapies for HER2-positive MBC, reported on ILD, and were published during January 1, 2009 to July 15, 2019. Articles were screened by two researchers; data were extracted from the full-text articles. RESULTS: The 18 articles selected for this review assessed 9,886 patients who received trastuzumab (8 articles), lapatinib (4 articles), trastuzumab emtansine (3 articles), trastuzumab deruxtecan (2 articles), or trastuzumab duocarmazine (1 article). The overall incidence of all-grade ILD was 2.4% (n = 234), with 66.7% (n = 156) occurring as grade 1-2 events, 0.5% grade 3-4 (n = 54; incidence), and 0.2% grade 5 (n = 16; incidence). The highest ILD incidence (21.4%) was among patients receiving trastuzumab combined with everolimus and paclitaxel. Ten studies indicated that ILD events were managed via dose interruption, dose reduction, or treatment discontinuation; two studies included detailed guidelines on managing drug-induced ILD. CONCLUSIONS: ILD is a well-described adverse drug reaction associated with several anti-HER2 drugs. Published ILD management guidelines are available for few anti-HER2 treatment regimens; however, guidance for monitoring for anti-HER2 drug-induced ILD is lacking.
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Ado-Trastuzumab Emtansina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados , Imunoconjugados/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Pneumonia/induzido quimicamente , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/efeitos adversos , Ado-Trastuzumab Emtansina/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Gerenciamento Clínico , Monitoramento de Medicamentos , Everolimo/administração & dosagem , Feminino , Humanos , Imunoconjugados/administração & dosagem , Incidência , Lapatinib/efeitos adversos , Doenças Pulmonares Intersticiais/epidemiologia , Metástase Neoplásica , Paclitaxel/administração & dosagem , Pneumonia/epidemiologia , Receptor ErbB-2/análise , Trastuzumab/administração & dosagemRESUMO
AIM: Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. METHODS: This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. RESULTS: Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. CONCLUSION: This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.
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Procedimentos de Cirurgia Plástica , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Vagina/cirurgia , Adulto , Idoso , Dilatação , Endoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Intensive care unit (ICU) resources are a costly but effective commodity used in the management of critically ill patients with chronic obstructive pulmonary disease (COPD). ICU admission decisions are determined by patient diagnosis and severity of illness, but also may be affected by hospital differences in quality and performance. We investigate the variability in ICU utilization for patients with COPD and its association with hospital characteristics. METHODS: Using a 3M administrative dataset spanning 2008-2013, we conducted a retrospective cohort study of adult patients discharged with COPD at hospitals in three state to determine variability in ICU utilization. Quality metrics were calculated for each hospital using observed-to-expected (O/E) ratios for overall mortality and length of stay. Logistic and multilevel multivariate regression models were constructed, estimating the association between hospital quality metrics on ICU utilization, after adjustment for available clinical factors and hospital characteristics. RESULTS: In 434 hospitals with 570,517 COPD patient visits, overall ICU admission rate was 33.1% [range 0-89%; median (IQR) 24% (8, 54)]. The addition of patient, hospital, and quality characteristics decreased the overall variability attributable to individual hospital differences seen within our cohort from 40.9 to 33%. Odds of ICU utilization were increased for larger hospitals and those seeing lower pulmonary case volume. Hospitals with better overall O/E ratios for length of stay or mortality had lower ICU utilization. CONCLUSIONS: Hospital characteristics, including quality metrics, are associated with variability in ICU utilization for COPD patients, with higher ICU utilization seen for lower performing hospitals.
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Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Mortalidade , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade da Assistência à Saúde , Idoso , Estudos Transversais , Feminino , Hospitais/normas , Hospitais/estatística & dados numéricos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise MultinívelRESUMO
BACKGROUND: The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS: The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS: The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS: Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.