Brain-Specific Relative Biological Effectiveness of Protons Based on Long-term Outcome of Patients With Nasopharyngeal Carcinoma.

PURPOSE: Uncertainties in relative biological effectiveness (RBE) constitute a major pitfall of the use of protons in clinics. An RBE value of 1.1, which is based on cell culture and animal models, is currently used in clinical proton planning. The purpose of this study was to determine RBE for temporal lobe radiographic changes using long-term follow-up data from patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Five hundred sixty-six patients with newly diagnosed nasopharyngeal carcinoma received double-scattering proton therapy or intensity modulated radiation therapy at our institutions. The 2 treatment cohorts were well matched. Proton dose distributions were simulated using Monte Carlo and compared with those obtained from the proton clinical treatment planning system. Late treatment effect was defined as development of enhancement of temporal lobe on T1-weighted magnetic resonance imaging, with or without accompanying clinical symptoms. The tolerance dose was calculated with receiving operator characteristic analysis and the Youden index. Tolerance curves, expressed as a cumulative dose-volume histogram, were generated using the cutoff points. RESULTS: With a median follow-up period >5 years for both cohorts, 10% of proton patients and 4% of patients undergoing intensity modulated radiation therapy developed temporal lobe enhancement in unilateral temporal lobe. There was no significant difference in dose distributions between the Monte Carlo method and treatment planning system. The tolerance dose-volume levels were V10 (26.1%), V20 (21.9%), V30 (14.0%), V40 (7.7%), V50 (4.8%), and V60 (3.3%) for proton therapy (P < .03). Comparison of the two tolerance curves revealed that tolerance doses of proton treatments were lower than that of photon treatments at all dose levels. The dose tolerance at D1% was 58.56 Gy for protons and 69.07 Gy for photons. The RBE for temporal lobe enhancement from proton treatments were calculated to be 1.18. CONCLUSIONS: Using long-term clinical outcome of patients with nasopharyngeal carcinoma, our data suggest that the RBE for temporal lobe enhancement is 1.18 at D1%. A prospective study in a large cohort would be necessary to confirm these findings.

[Comparison of Three CNN Models Applied in Bone Age Assessment of Pelvic Radiographs of Adolescents].

ABSTRACT: Objective To compare the performance of three deep-learning models （VGG19, Inception-V3 and Inception-ResNet-V2） in automatic bone age assessment based on pelvic X-ray radiographs. Methods A total of 962 pelvic X ray radiographs taken from adolescents （481 males, 481 females） aged from 11.0 to 21.0 years in five provinces and cities of China were collected, preprocessed and used as objects of study. Eighty percent of these X ray radiographs were divided into training set and validation set with random sampling method and used for model fitting and hyper-parameters adjustment. Twenty percent were used as test sets, to evaluate the ability of model generalization. The performances of the three models were assessed by comparing the root mean square error （RMSE）, mean absolute error （MAE） and Bland-Altman plots between the model estimates and the chronological ages. Results The mean RMSE and MAE between bone age estimates of the VGG19 model and the chronological ages were 1.29 and 1.02 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-V3 model and the chronological ages were 1.17 and 0.82 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-ResNet-V2 model and the chronological ages were 1.11 and 0.84 years, respectively. The Bland-Altman plots showed that the mean value of differences between bone age estimates of Inception-ResNet-V2 model and the chronological ages was the lowest. Conclusion In the automatic bone age assessment of adolescent pelvis, the Inception-ResNet-V2 model performs the best while the Inception-V3 model achieves a similar accuracy as VGG19 model.

Assessment of long non-coding RNA expression reveals novel mediators of the lung tumour immune response.

The tumour immune microenvironment is a crucial mediator of lung tumourigenesis, and characterizing the immune landscape of patient tumours may guide immunotherapy treatment regimens and uncover novel intervention points. We sought to identify the landscape of tumour-infiltrating immune cells in the context of long non-coding RNA (lncRNAs), known regulators of gene expression. We examined the lncRNA profiles of lung adenocarcinoma (LUAD) tumours by interrogating RNA sequencing data from microdissected and non-microdissected samples (BCCRC and TCGA). Subsequently, analysis of single-cell RNA sequencing data from lung tumours and flow-sorted healthy peripheral blood mononuclear cells identified lncRNAs in immune cells, highlighting their biological and prognostic relevance. We discovered lncRNA expression patterns indicative of regulatory relationships with immune-related protein-coding genes, including the relationship between AC008750.1 and NKG7 in NK cells. Activation of NK cells in vitro was sufficient to induce AC008750.1 expression. Finally, siRNA-mediated knockdown of AC008750.1 significantly impaired both the expression of NKG7 and the anti-tumour capacity of NK cells. We present an atlas of cancer-cell extrinsic immune cell-expressed lncRNAs, in vitro evidence for a functional role of lncRNAs in anti-tumour immune activity, which upon further exploration may reveal novel clinical utility as markers of immune infiltration.

Research Progress and Prospect of Machine Learning in Bone Age Assessment.

ABSTRACT: Bone age assessment has always been one of the key issues and difficulties in forensic science. With the gradual development of machine learning in many industries, it has been widely introduced to imageology, genomics, oncology, pathology, surgery and other medical research fields in recent years. The reason why the above research fields can be closely combined with machine learning, is because the research subjects of the above branches of medicine belong to the computer vision category. Machine learning provides unique advantages for computer vision research and has made breakthroughs in medical image recognition. Based on the advantages of machine learning in image recognition, it was combined with bone age assessment research, in order to construct a recognition model suitable for forensic skeletal images. This paper reviews the research progress in bone age assessment made by scholars at home and abroad using machine learning technology in recent years.

Assessment of the Original Height of L1~2 after Vertebral Compression Fracture.

OBJECTIVES: To explore the assessment method of original height of L1-2 after vertebral compression fracture and its application value in forensic clinical practice. METHODS: A total of 154 normal thoracic and lumbar X-ray films were collected, and 140 cases were used as experimental group while 14 cases as validation group. The heights of anterior （Ha） and posterior （Hp） vertebral body of T12-L3 vertebrae in each X-ray image were measured. In the experimental group, the correlation analysis between HaL1 and HaT12, HpT12, HpL1, HaL2 and HpL2 was carried out, and regression equation was established via fitting. The correlation analysis between HaL2 and HaL1, HpL1, HpL2, HaL3, HpL3 was performed, and the regression equation was also established via fitting. The difference between the predicted and measured values of HaL1 and HaL2 in validation group was compared. RESULTS: In the 140 normal subjects, HaL1 （y1） was well correlated with HaT12 （x1） and HaL2（x2）, and the multiple linear regression equation was y1=2.545+0.423 x1+0.486 x2 （determining coefficient R²=0.712, P<0.05; F=169.206, P<0.05）. There was no significant difference between the predicted and actual measured values of HaL1 in the validation group （ P>0.05）. HaL2 （y2） was well correlated with HaL1 （x3） and HaL3 （x4）, and the multiple linear regression equation was y2=4.354+0.530 x3+0.349 x4 （determining coefficient R²=0.689, P<0.05; F=151.575, P<0.05）. There was no significant difference between the predicted and actual measured values of HaL2 in the validation group （ P>0.05）. CONCLUSIONS: It is more appropriate to evaluate the original height of L1 or L2 single vertebrae by comparing with the height of the anterior edge of the upper and lower adjacent vertebral bodies.

[Automated Assessment for Bone Age of Left Wrist Joint in Uyghur Teenagers by Deep Learning].

OBJECTIVES: To realize the automated bone age assessment by applying deep learning to digital radiography （DR） image recognition of left wrist joint in Uyghur teenagers, and explore its practical application value in forensic medicine bone age assessment. METHODS: The X-ray films of left wrist joint after pretreatment, which were taken from 245 male and 227 female Uyghur nationality teenagers in Uygur Autonomous Region aged from 13.0 to 19.0 years old, were chosen as subjects. And AlexNet was as a regression model of image recognition. From the total samples above, 60％ of male and female DR images of left wrist joint were selected as net train set, and 10％ of samples were selected as validation set. As test set, the rest 30％ were used to obtain the image recognition accuracy with an error range in ±1.0 and ±0.7 age respectively, compared to the real age. RESULTS: The modelling results of deep learning algorithm showed that when the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the net train set was 81.4% and 75.6% in male, and 80.5% and 74.8% in female, respectively. When the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the test set was 79.5% and 71.2% in male, and 79.4% and 66.2% in female, respectively. CONCLUSIONS: The combination of bone age research on teenagers' left wrist joint and deep learning, which has high accuracy and good feasibility, can be the research basis of bone age automatic assessment system for the rest joints of body.

[Advantages and Application Prospects of Deep Learning in Image Recognition and Bone Age Assessment].

Deep learning and neural network models have been new research directions and hot issues in the fields of machine learning and artificial intelligence in recent years. Deep learning has made a breakthrough in the applications of image and speech recognitions, and also has been extensively used in the fields of face recognition and information retrieval because of its special superiority. Bone X-ray images express different variations in black-white-gray gradations, which have image features of black and white contrasts and level differences. Based on these advantages of deep learning in image recognition, we combine it with the research of bone age assessment to provide basic datum for constructing a forensic automatic system of bone age assessment. This paper reviews the basic concept and network architectures of deep learning, and describes its recent research progress on image recognition in different research fields at home and abroad, and explores its advantages and application prospects in bone age assessment.

[Clinical effects assessment of nasal cellulose powder on allergic rhinitis].

Objective:To evaluate the role of nasal cellulose powder locally applied in allergic rhinitis patients.Method:Fifty patients with allergic rhinitis were divided randomly into two groups: the study group and the control group. The study group were treated with nasal cellulose powder while the control group were treated with physiological sea water.Objective and subjective examinations (nasal airway resistance, nasal syndrome score, rhinoconjunctivitis qualityof life questionnaire and olfactory function,nasal mucus cilia clearance ) were performed before and 3 months after treatment.Result:After treatment, partial parameters in nasal syndrome store ( nasal itching, nasal discharge,sneezing and total store) and rhinoconjunctivitis qualityof life questionnaire (sleep, nasal symptom, non-hay-fever symptom, emotional function and total score) in the study group were significantly improved than those in the control group (P< 0.05). However, no significant difference was found in olfactory function, Nasal airway resistance, nasal mucus cilia clearance and the eye symptom in rhinoconjunctivitis qualityof life questionnaire between the two groups after treatment (P> 0.05). No adverse reaction was found in both groups.Conclusion:Nasal cellulose powder can help alleviate clinical symptoms and improve the quality of life in allergic rhinitis patients with no significant side effect.

Assessment of the clinical relevance of 17q25.3 copy number and three-dimensional telomere organization in non-small lung cancer patients.

PURPOSE: To identify potential biomarkers that may provide new therapeutic targets or prognostic indicators for non-small cell lung cancer (NSCLC), we investigated the three-dimensional (3D) organization of telomeres and cytoband 17q25.3 copy number in NSCLC tissues. METHODS: NSCLC paraffin-embedded tissue specimens from 18 patients were assessed for 3D telomere organization by 3D nuclear telomere imaging followed by quantitative analysis. Patients were stratified by smoking, histology, and EGFR status. Cytoband 17q25.3 was examined by fluorescent in situ hybridization. Data from comparative genomic hybridization and/or single nucleotide polymorphism arrays for cytoband 17q25.3 were obtained and correlated with Q-FISH and 3D telomere results. RESULTS: 3D telomeric profiling demonstrated that the smokers, EGFR-negative, and squamous cell carcinoma subgroups tended to have higher numbers of lower-intensity telomeres, indicative of shorter telomeres, as well as higher numbers of telomeric aggregations compared to non-smokers, EGFR-positive, and adenocarcinomas, respectively. Gains of cytoband 17q25.3 in conjunction with an increase in the control region 17p11.2 were observed in 7 of 18 (38.9 %) patients, reflecting a gain of chromosome 17. Clonal gains of cytoband 17q25.3 were observed in 11 of 18 (61 %) patients, highlighting a potential biological significance for the genes in this region in NSCLC tumourigenesis. CONCLUSIONS: The 3D telomere profiles may differentiate NSCLC patients with different histologies, EGFR, and smoking statuses, rendering them a potential biomarker for distinguishing these clinically relevant histological and molecular subtypes of lung cancer. Highly frequent clonal gain of cytoband 17q25.3 was also demonstrated, suggesting an important biological role for the genes in this region.

Reliability and validity of the acquired brain injury challenge assessment (ABI-CA) in children.

PRIMARY OBJECTIVE: The Acquired Brain Injury Challenge Assessment (ABI-CA) was created to fill a measurement gap and evaluate deficits in advanced motor skills in children with acquired brain injury (ABI). Study objectives were to refine ABI-CA response options and evaluate (i) inter-/intra-rater reliability, (ii) concurrent validity and difficulty level in relation to the Community Balance & Mobility Scale (CB&M) and (iii) administration efficiency of the refined ABI-CA. RESEARCH DESIGN: Measurement study. METHODS: Phase I involved ABI-CA revisions. Phase 2 consisted of live-/video-scoring of the ABI-CA with 15 typically-developing (TD) children and 15 with ABI (7-17 years) to assess reliability/validity. RESULTS: The revised 20-item ABI-CA displayed excellent reliability for the entire sample (ICCs > 0.90; 95% CI = 0.92-1.00; SEM ≤ 3.60) and within ABI and TD sub-groups. The ABI-CA and CB&M correlated strongly (r = 0.75, p < 0.0001). The ABI-CA mean score (/100) was 11.3 points lower (p < 0.0001) than the CB&M's mean score (/100). CONCLUSION: The ABI-CA demonstrated excellent reliability and initial evidence of validity. ABI-CA scores were lower overall than the CB&M, indicating the ABI-CA may have greater capacity to evaluate improvements in advanced motor skills in children with ABI. Multi-centre research is needed to confirm the ABI-CA's test-retest reliability and, assuming acceptability, assess responsiveness to change.

Copy number alterations at polymorphic loci may be acquired somatically in patients with myelodysplastic syndromes.

Loss of genomic integrity is thought to be one of the underlying causes of myelodysplastic syndromes (MDS). However, it is unclear whether changes in copy number at loci that are common sites of copy number polymorphisms play a pathogenic role. Here we show that copy number changes in the MDS clone that occur at polymorphic loci are frequently somatic alterations rather than constitutional variants, and the extent of copy number changes at polymorphic loci is increased in CD34(+) cells of MDS patients compared to age-matched controls. This study suggests a potential pathophysiological role for copy number alterations at polymorphic loci in patients with MDS, and highlights the need for somatic control tissues for each patient studied in high-resolution genome-wide investigations.

Resolving the resolution of array CGH.

Many recent technologies have been designed to supplant conventional metaphase CGH technology with the goal of refining the description of segmental copy number status throughout the genome. However, the emergence of new technologies has led to confusion as to how to describe adequately the capabilities of each array platform. The design of a CGH array can incorporate a uniform or a highly variable element distribution. This can lead to bias in the reporting of average or median resolutions, making it difficult to provide a fair comparison of platforms. In this report, we propose a new definition of resolution for array CGH technology, termed "functional resolution," that incorporates the uniformity of element spacing on the array, as well as the sensitivity of each platform to single-copy alterations. Calculation of these metrics is automated through the development of a Java-based application, "ResCalc," which is applicable to any array CGH platform.

Integrating copy number polymorphisms into array CGH analysis using a robust HMM.

MOTIVATION: Array comparative genomic hybridization (aCGH) is a pervasive technique used to identify chromosomal aberrations in human diseases, including cancer. Aberrations are defined as regions of increased or decreased DNA copy number, relative to a normal sample. Accurately identifying the locations of these aberrations has many important medical applications. Unfortunately, the observed copy number changes are often corrupted by various sources of noise, making the boundaries hard to detect. One popular current technique uses hidden Markov models (HMMs) to divide the signal into regions of constant copy number called segments; a subsequent classification phase labels each segment as a gain, a loss or neutral. Unfortunately, standard HMMs are sensitive to outliers, causing over-segmentation, where segments erroneously span very short regions. RESULTS: We propose a simple modification that makes the HMM robust to such outliers. More importantly, this modification allows us to exploit prior knowledge about the likely location of "outliers", which are often due to copy number polymorphisms (CNPs). By "explaining away" these outliers with prior knowledge about the locations of CNPs, we can focus attention on the more clinically relevant aberrated regions. We show significant improvements over the current state of the art technique (DNAcopy with MergeLevels) on previously published data from mantle cell lymphoma cell lines, and on published benchmark synthetic data augmented with outliers. AVAILABILITY: Source code written in Matlab is available from http://www.cs.ubc.ca/~sshah/acgh.

[Long-term intermittent renal replacement therapy at an intensive care unit].

Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

An efficient method for the assessment of DNA quality of archival microdissected specimens.

There will be an increasing need of methods for assessing the suitability of specimens for genetic-based assays as DNA markers become an integral part of molecular diagnosis. The targeting of specimens for specific analyses will require the ability to rapidly screen for DNA quality. Conventional methods such as Southern analysis and gene specific-polymerase chain reaction (PCR) often require quantities of material that represent a significant portion of the specimen, especially in microdissected samples. Here we describe a novel application of a commonly used PCR-based DNA-fingerprinting technology that requires minimal quantities of DNA to simultaneously assess multiple regions throughout the genome for DNA quality. Randomly amplified polymorphic DNA (RAPD) PCR generates DNA fragments of a broad size range with the product size reflecting the degree of sample fragmentation. Fourteen DNA samples extracted from cells microdissected from seven formalin-fixed, paraffin-embedded oral cancer biopsies were assessed for DNA quality using gene-specific PCR and RAPD-PCR. Although the more conventional assay required 2-ng DNA (or 300-cell equivalents) to examine DNA quality at a single locus, RAPD-PCR provided a more informative profile of DNA quality from the same microdissected archival specimens.

Endometrial brush biopsy for the diagnosis of endometrial cancer.

OBJECTIVE: To evaluate a new technique for processing endometrial cytology for the diagnosis and exclusion of endometrial cancer. STUDY DESIGN: All women at risk for endometrial cancer with clinical indications for endometrial biopsy were evaluated by endometrial brush biopsy (Tao Brush, Cook OB-GYN, Bloomington, Indiana) and Pipelle (Cooper Surgical, Shelton, Connecticut) endometrial biopsies during one office visit. Patients were followed longitudinally for the development of endometrial cancer or until undergoing dilatation and curettage or hysterectomy. All comparisons were analyzed using the chi 2 or t test. RESULTS: One hundred one women (mean age, 58; range, 35-86) had endometrial biopsies performed. Median follow-up was > 21 months (range, 3-29). Twenty-two had cancer or atypia, while the remaining had benign diagnoses. When correlated with the final diagnosis, the Tao Brush had 95.5% sensitivity and the Pipelle, 86% sensitivity. Both devices had 100% specificity, positive predictive value of 100% and negative predictive value of 98%. When the results of the two biopsy devices are considered together, the positive and negative predictive value for detecting or excluding endometrial cancer was 100%. Based on 1998 Medicare reimbursements, a simultaneous second office biopsy using the Tao brush could save approximately $67 per case as compared to a sonohistogram and much more when compared to dilatation and curettage. CONCLUSION: Endometrial cancer can be reliably detected and excluded using these two distinct office biopsy devices simultaneously during one office visit. In patients with an indication for endometrial biopsy, no further diagnostic test may be necessary to exclude or diagnose endometrial cancer or atypia.

Low-cost image-capture system for a scanning electron microscope.

We describe a PC-based active-capture system for recording digital images from a scanning electron microscope. The system is based on a National Instruments data-acquisition board and a Pentium computer, controlled by software that we have written in Visual Basic.

[Implementation of mid-term national tuberculosis control programme].

OBJECTIVE: To evaluate the implementation of mid-term National Tuberculosis Control Programme (NTP). METHOD: The construction of tuberculosis control organizations, implementation of tuberculosis control work, etc, were investigated retrospectively. RESULTS: Almost all the tuberculosis control indices had reached the mid-term NTP target except the case-finding index. CONCLUSIONS: Much more efforts are required to reach the NTP target of year 2000 that the prevalence of smear positive pulmonary tuberculosis decrease to 70 per 100,000 populations.