Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this ...aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.
Abstract Background Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ...ancestry with the adjacent glandular adenocarcinoma. Objective We investigated for the co-occurrence of “aggression” factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors. Design, setting, and participants A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Québec-Université Laval, Memorial Sloan Kettering Cancer Center MSKCC, and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed. Outcome measurements and statistical analysis IDC/CA was separately assessed for biochemical relapse risk in the Canadian and MSKCC cohorts. Both cohorts were pooled for analyses on metastasis. Results and limitation Presence of IDC/CA independently predicted for increased risks of biochemical relapse (HRCanadian 2.17, p < 0.001; HRMSKCC 2.32, p = 0.0035) and metastasis (HRpooled 3.31, p < 0.001). IDC/CA+ cancers were associated with an increased percentage of genome alteration (PGA median 7.2 vs 3.0, p < 0.001), and hypoxia (64.0% vs 45.5%, p = 0.17). Combinatorial genomic–pathological indices offered the strongest discrimination for metastasis (C-index 0.805 clinical + IDC/CA + PGA vs 0.786 clinical + IDC/CA vs 0.761 clinical). Profiling of mRNA abundance revealed that long noncoding RNA, SChLAP1 , was the only gene expressed at >3-fold higher ( p < 0.0001) in IDC/CA+ than in IDC/CA– tumors, independently corroborated by increased SChLAP1 RNA in situ hybridization signal. Optimal treatment intensification for IDC/CA+ prostate cancer requires prospective testing. Conclusions The poor outcome associated with IDC and CA subpathologies is associated with a constellation of genomic instability, SChLAP1 expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer, “ nimbosus ” (gathering of stormy clouds, Latin), which manifests as increased metastatic capacity and lethality. Patient summary A constellation of unfavorable molecular characteristics co-occur with intraductal and cribriform subpathologies in prostate cancer. Modern imaging for surveillance and treatment intensification trials should be considered in this adverse subgroup.
We have designed a deep-learning model, an "Artificial Intelligent Endoscopist (a.k.a. AI-doscopist)", to localise colonic neoplasia during colonoscopy. This study aims to evaluate the agreement ...between endoscopists and AI-doscopist for colorectal neoplasm localisation. AI-doscopist was pre-trained by 1.2 million non-medical images and fine-tuned by 291,090 colonoscopy and non-medical images. The colonoscopy images were obtained from six databases, where the colonoscopy images were classified into 13 categories and the polyps' locations were marked image-by-image by the smallest bounding boxes. Seven categories of non-medical images, which were believed to share some common features with colorectal polyps, were downloaded from an online search engine. Written informed consent were obtained from 144 patients who underwent colonoscopy and their full colonoscopy videos were prospectively recorded for evaluation. A total of 128 suspicious lesions were resected or biopsied for histological confirmation. When evaluated image-by-image on the 144 full colonoscopies, the specificity of AI-doscopist was 93.3%. AI-doscopist were able to localise 124 out of 128 polyps (polyp-based sensitivity = 96.9%). Furthermore, after reviewing the suspected regions highlighted by AI-doscopist in a 102-patient cohort, an endoscopist has high confidence in recognizing four missed polyps in three patients who were not diagnosed with any lesion during their original colonoscopies. In summary, AI-doscopist can localise 96.9% of the polyps resected by the endoscopists. If AI-doscopist were to be used in real-time, it can potentially assist endoscopists in detecting one more patient with polyp in every 20-33 colonoscopies.
Congenital spinal hamartomas are rare benign tumors. They are mostly seen in infants and are typically asymptomatic at presentation. Spinal hamartomas have not been associated with any known cancer ...predisposition syndrome. DICER1 syndrome is a well-characterized cancer predisposition syndrome caused by a germline mutation in the
DICER1
gene, which shows variable expressivity. To our knowledge, spinal hamartoma has never been described in individuals with DICER1 syndrome. Here, we describe a rare association of congenital spinal hamartoma and DICER1 syndrome in a 5-week-old infant, with molecular findings suggestive of the implication of
DICER1
in the pathogenesis of this tumor.
Hemimegalencephaly is a hamartomatous malformation of one hemisphere. Functional hemispherectomy, the definitive treatment, is associated with significant morbidity and mortality in early infancy. ...Dysregulation of the mTOR pathway can result in malformations of cortical development, and mTOR inhibitors can effectively reduce seizures in tuberous sclerosis complex. We report a 6-day-old female with hemimegalencephaly and frequent seizures despite 9 antiseizure medications. At 3 months of age, while awaiting hemispherectomy, an mTOR inhibitor, rapamycin, was initiated by the neurologist. After 1 week of treatment, there was >50% reduction in seizures and total seizure burden, and after 2 weeks, development improved, resulting in deferral of surgery by 2.5 months with an increased body weight. Pathology demonstrated cortical dysplasia with upregulation of the mTOR pathway. Deep-sequencing of brain tissue demonstrated 16% mosaicism for a pathogenic de novo MTOR gene mutation. This case exemplifies how mTOR inhibitors could be considered for seizure reduction in patients with hemimegalencephaly while awaiting surgery.
Objective
Malnourished COVID‐19 patients were prone to higher mortality and longer length of stay (LOS). This study aims to investigate the malnutrition risk prevalence in the COVID‐19 patients and ...how other nutritional indicators are related to the clinical outcomes in a rehabilitation hospital.
Methods
A retrospective cross‐sectional study involved 174 COVID‐19 patients during the rehabilitation phase. Malnutrition risk, nutritional indicators, mortality, and LOS were compared among different risk groups. Albumin, nutrition intake, and body mass index (BMI) were investigated for their effects on the clinical outcomes.
Results
The prevalence of malnutrition risk was 94.9%; those older were higher in malnutrition risk. BMI, energy and protein intakes decreased as the malnutrition risk increased. Albumin, energy and protein intakes were lower in the death group. The high malnutrition risk group and severely underweight patients had 2.7 times and 2.2 times higher in‐hospital death, respectively. For subjects ≥75 years old, the odds ratio to death was 6.2 compared to those <75 years old.
Conclusion
We observed a high malnutrition risk of 94.9% in COVID‐19 patients. Patients with malnutrition risk had a lower BMI, lower nutritional intake, and a higher chance of in‐hospital death. These results reinforced the importance of nutrition management in COVID‐19 patients.
One hundred seventy‐four COVID‐19 patients were retrieved for analysis. The prevalence of malnutrition risk was 94.9%; those older were higher in malnutrition risk. BMI, energy and protein intake decreased as the malnutrition risk increased. Albumin, energy and protein intakes were lower in the death group. The high malnutrition risk group and severely underweight patients had 2.7 times and 2.2 times higher to in‐hospital death, respectively. In subjects ≥75 years old, the odds ratio to death is 6.2 compared to those <75 years old.
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and ...adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants (54% of patients) were of unanticipated timing and type, with over 20% derived from the germline. Corroborating mutational signatures (SBS3/BRCAness) in patients with germline homologous recombination defects demonstrates the potential utility of PARP inhibitors. Mutational burden was significantly elevated in 9% of patients. Sequential sampling identified changes in therapeutically targetable drivers in over one-third of patients, suggesting benefit from rebiopsy for genomic analysis at the time of relapse. Comprehensive cancer genomic profiling is useful at multiple points in the care trajectory for children and adolescents/young adults with cancer, supporting its integration into early clinical management.
•We estimate the aggregated demand and supply functions of airfreight in Hong Kong.•Air cargo transport demand in Hong Kong is inelastic in price.•Air cargo traffic is pro-cyclical with respect to ...the overall economy.•Airfreight demand elasticities increased after the 2008 global financial crisis.
This paper estimates the price and income elasticities of air cargo demand and examines how they may change after the 2008 financial crisis. Using a set of time series data, we simultaneously estimate the aggregated demand and supply functions of air cargo at Hong Kong International Airport (HKIA). We find that during the entire sampling period of 2001–2013, the price elasticity for air cargo transport demand at HKIA ranges from −0.74 to −0.29, suggesting that air cargo demand in Hong Kong reacts negatively to price (as expected) but does not appear to be very sensitive to price. The income elasticity ranges from 0.29 to 1.47 and appears sensitive to seasonality adjustment approaches. However, in terms of the speed of changes, air cargo demand changes much faster than overall economy, indicating the presence of a pro-cyclical pattern of air cargo traffic with respect to the overall economy. Our analysis shows that air cargo demand becomes more sensitive to changes in both price and income after 2008.
DIGITAL IMAGE PROCESSING LO, WINNIE Y.; PUCHALSKI, SARAH M.
Veterinary radiology & ultrasound,
01/2008, Letnik:
49, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
Image processing or digital image manipulation is one of the greatest advantages of digital radiography (DR). Preprocessing depends on the modality and corrects for system irregularities such as ...differential light detection efficiency, dead pixels, or dark noise. Processing is manipulation of the raw data just after acquisition. It is generally proprietary and specific to the DR vendor but encompasses manipulations such as unsharp mask filtering within two or more spatial frequency bands, histogram sliding and stretching, and gray scale rendition or lookup table application. These processing steps have a profound effect on the final appearance of the radiograph, but they can also lead to artifacts unique to digital systems. Postprocessing refers to manipulation of the final appearance of the radiograph by the end‐user and does not involve alteration of the raw data.
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