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MedRxiv : the Preprint Server For... Feb 2023Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine...
MOTIVATION
Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-level diagnosis without identifying individual pathologic cells or are less effective for identifying heterogeneous cancer cell phenotypes.
RESULTS
We developed a generalized end-to-end differentiable model, the Cell Scoring Neural Network (CSNN), which takes the available sample-level training data and predicts both the diagnosis of the testing samples and the identity of the diagnostic cells in the sample, simultaneously. The cell-level density differences between samples are linked to the sample diagnosis, which allows the probabilities of individual cells being diagnostic to be calculated using backpropagation. We applied CSNN to two independent clinical flow cytometry datasets for leukemia diagnosis. In both qualitative and quantitative assessments, CSNN outperformed preexisting neural network modeling approaches for both cancer diagnosis and cell-level classification. Post hoc decision trees and 2D dot plots were generated for interpretation of the identified cancer cells, showing that the identified cell phenotypes match the cancer endotypes observed clinically in patient cohorts. Independent data clustering analysis confirmed the identified cancer cell populations.
AVAILABILITY
The source code of CSNN and datasets used in the experiments are publicly available on GitHub and FlowRepository.
CONTACT
Edgar E. Robles: [email protected] and Yu Qian: [email protected].
SUPPLEMENTARY INFORMATION
Supplementary data are available on GitHub and at online.
PubMed: 36798344
DOI: 10.1101/2023.02.07.23285606 -
World Journal of Clinical Cases Jan 2023Diffuse idiopathic skeletal hyperostosis (DISH) is a disorder characterised by the calcification and ossification of ligaments and entheses. It is a frequent occurrence...
BACKGROUND
Diffuse idiopathic skeletal hyperostosis (DISH) is a disorder characterised by the calcification and ossification of ligaments and entheses. It is a frequent occurrence in elderly males, but rarely encountered in younger individuals.
CASE SUMMARY
A 24-year-old male was admitted to the hospital due to low back pain accompanied with numbness in both lower limbs for 10 d. Upon clinical examination and imaging tests, the patient was diagnosed with DISH with Scheuermann disease and thoracic spinal stenosis. Before the operation and medical treatment, the patient had hypoesthesia of the skin below the xiphoid process. Afterward, a standard laminectomy was conducted using ultrasonic bone curette and internal fixation was applied. Subsequently, the patient was given corticosteroids, neurotrophic drugs, hyperbaric oxygen and electric stimulation. As a result of the treatment, the patient's sensory level decreased to the navel level and there was no major change in the muscle strength of the lower limbs. During follow-up, the patient's skin sensation has returned to normal.
CONCLUSION
This case is a rare instance of DISH co-existing with Scheuermann's disease in a young adult. This provides a valuable reference point for spine surgeons, as DISH is more commonly observed in middle-aged and elder adults.
PubMed: 36793636
DOI: 10.12998/wjcc.v11.i3.655 -
BioRxiv : the Preprint Server For... Jan 2023The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with...
The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4 T cell responses widely cross-recognizing different CoVs, we utilized samples collected pre-pandemic to systematically analyze T cell reactivity against representative alpha (NL63) and beta (OC43) common cold CoVs (CCC). Similar to previous findings on SARS-CoV-2, the S, N, M, and nsp3 antigens were immunodominant for both viruses while nsp2 and nsp12 were immunodominant for NL63 and OC43, respectively. We next performed a comprehensive T cell epitope screen, identifying 78 OC43 and 87 NL63-specific epitopes. For a selected subset of 18 epitopes, we experimentally assessed the T cell capability to cross-recognize sequences from representative viruses belonging to alphaCoV, sarbecoCoV, and beta-non-sarbecoCoV groups. We found general conservation within the alpha and beta groups, with cross-reactivity experimentally detected in 89% of the instances associated with sequence conservation of >67%. However, despite sequence conservation, limited cross-reactivity was observed in the case of sarbecoCoV (50% of instances), indicating that previous CoV exposure to viruses phylogenetically closer to this subgenera is a contributing factor in determining cross-reactivity. Overall, these results provided critical insights in the development of future pan-CoV vaccines.
PubMed: 36656777
DOI: 10.1101/2023.01.04.522794 -
Cureus Nov 2022Scheuermann kyphosis, also known as Scheuermann disease, juvenile kyphosis, or juvenile discogenic disease, is a condition involving an abnormal, excessive curvature of...
Scheuermann kyphosis, also known as Scheuermann disease, juvenile kyphosis, or juvenile discogenic disease, is a condition involving an abnormal, excessive curvature of the spine. It involves both the vertebral bodies and discs of the spine and is characterized by anterior wedging of greater than or equal to 5 degrees in three or more adjacent vertebral bodies. Type 1 Scheuermann's disease involves the thoracic spine, whereas type 2 involves both the thoracic and lumbar spine. Although no definitive cause for Scheuermann's disease has been found, we have reported a case that may explain further about this disease. This article elucidates a case of a 19-year-old boy experiencing pain in the lower back and showing various signs and symptoms of Scheuermann's disease and the diagnosis and steps taken by doctors toward its treatment.
PubMed: 36579214
DOI: 10.7759/cureus.31803 -
BMC Musculoskeletal Disorders Dec 2022Spondyloepiphyseal dysplasia tarda (SEDT) is a rare, hereditary, X-linked skeletal disorder. To our knowledge, there are few reports about orthopedic surgery in these... (Review)
Review
BACKGROUND
Spondyloepiphyseal dysplasia tarda (SEDT) is a rare, hereditary, X-linked skeletal disorder. To our knowledge, there are few reports about orthopedic surgery in these patients. This is the first report on patients with SEDT undergoing spinal and fracture reduction surgery.
CASE PRESENTATION
A 31-year-old male patient who had been misdiagnosed with juvenile idiopathic arthritis (JIA) for 20 years and who had been treated with femoral shaft internal fixation for lower extremity fracture caused by minor trauma presented at hospital with stiffness and weakness in the lower extremities for the past two years. Radiographs showed bony dysplastic features of flattened vertebral bodies, Scheuermann-like changes in the spine, and osteoarthritis-like changes in the joints. Laboratory examination, including routine blood tests and rheumatism-related indicators showed negative results. Considering the history, radiology, and genetic findings, a diagnosis of spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) was considered. Further neurological examination indicated that severe spinal cord compression was an important reason for the patient's inability to walk. Laminectomy, spinal canal decompression, internal fixation and fusion were performed. Clinical outcome was satisfactory at one-year follow-up. The lower-limb fatigue was relieved, the patient could walk independently, and his examination showed osseous fusion. The English database was searched and the literature was reviewed for the relevant keywords of "SEDT-PA".
CONCLUSIONS
Progress has been made in genetic research on SEDT; early diagnosis is particularly important, but the clinical diagnosis and treatment plans are still evaluated on a case-by-case basis. The best treatment for SEDT is to identify patients with progressive neurological and joint-mobility impairments and perform appropriate surgical intervention. Surgical intervention can improve neurological function and quality of life. However, surgery, as palliative care, does not alter the progression of the disease.
Topics: Male; Humans; Adult; Osteochondrodysplasias; Intervertebral Disc Displacement; Quality of Life; Osteoarthritis; Radiography
PubMed: 36514046
DOI: 10.1186/s12891-022-06064-4 -
EFORT Open Reviews Dec 2022Scheuermann's Kyphosis (SK) is a rigid spinal kyphosis. Several theories have been proposed concerning its pathogenesis, but it is, to this day, still unknown. It has a...
Scheuermann's Kyphosis (SK) is a rigid spinal kyphosis. Several theories have been proposed concerning its pathogenesis, but it is, to this day, still unknown. It has a prevalence of 0.4-8.3% in the population with a higher incidence in females. Clinical examination with x-rays is needed to differentiate and confirm this diagnosis. Non-surgical management is reserved for smaller deformities and in skeletally immature patients, whereas surgery is recommended for higher deformities. Combined anterior and posterior approach was considered the gold standard for the surgical treatment of this disease, but there is an increasing trend toward posterior-only approaches especially with use of segmental fixation. This study reviews the pathophysiology of SK while proposing a treatment algorithm for its management.
PubMed: 36475554
DOI: 10.1530/EOR-22-0063 -
Cell Host & Microbe Dec 2022The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is...
The monkeypox virus (MPXV) outbreak confirmed in May 2022 in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here, we leveraged the epitope information available in the Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4 and CD8 T cell responses. We found a high degree of conservation between VACV epitopes and MPXV and defined T cell immunodominant targets. These analyses enabled the design of peptide pools able to experimentally detect VACV-specific T cell responses and MPXV cross-reactive T cells in a cohort of vaccinated individuals. Our findings will facilitate the monitoring of cellular immunity following MPXV infection and vaccination.
Topics: Humans; Vaccinia virus; Monkeypox virus; Vaccinia; Mpox (monkeypox); Epitopes
PubMed: 36463861
DOI: 10.1016/j.chom.2022.11.003 -
Animals : An Open Access Journal From... Nov 2022Nicarbazin (NCZ) is a worldwide used anticoccidial in poultry farming to avoid coccidiosis disease when chickens are reared on conventional poultry litter. If proper...
Nicarbazin (NCZ) is a worldwide used anticoccidial in poultry farming to avoid coccidiosis disease when chickens are reared on conventional poultry litter. If proper dosage and withdrawal time are not followed, the component dinitrocarbanilide (DNC) of NCZ may be present in chicken tissues, therefore posing a risk to consumers if the residues are above 200 µg/kg. Litter reuse is a common and important practice in commercial chicken production. Literature is lacking about the influence of litter reuse on DNC deposition in chicken tissues and its impact on food safety. We aimed to evaluate DNC residues in breast and liver by LC-MS/MS from broilers from an experiment with 10 consecutive flocks during 2 years. The experiment included three treatments containing NCZ in the diet (T1 = 125 mg/kg, 1−21 d; T2 = 125 mg/kg, 1−32 d; T3 = 40 mg/kg, 1−32 d). DNC residues in chicken breast at 21 d in T1 ranged from 648.8−926 µg/kg, at 32 d in T2 and T3 varied, respectively, from 232−667 µg/kg and 52−189 µg/kg. Regarding liver, DNC residues at 21 days in T1 ranged from 11,754−15,281 µg/kg, at 32 days in T2 and T3 varied, respectively, from 10,168−15,021 µg/kg and 2899−4573 µg/kg. When NCZ was withdrawn from feed, DNC residues dropped to
PubMed: 36428335
DOI: 10.3390/ani12223107 -
Children (Basel, Switzerland) Nov 2022Persistent pain after posterior spinal fusion affects 12 to 42% of patients with adolescent idiopathic scoliosis. The incidence of persistent pain among surgically...
The Extension of Surgery Predicts Acute Postoperative Pain, While Persistent Postoperative Pain Is Related to the Spinal Pathology in Adolescents Undergoing Posterior Spinal Fusion.
Persistent pain after posterior spinal fusion affects 12 to 42% of patients with adolescent idiopathic scoliosis. The incidence of persistent pain among surgically treated children with Scheuermann kyphosis and spondylolisthesis is not known. The aim of our study was to determine the predictors and incidence of acute and chronic postoperative pain in adolescents undergoing posterior spinal fusion surgery. The study was a retrospective analysis of a prospectively collected pediatric spine register data. The study included 213 consecutive patients (158 AIS, 19 Scheuermann kyphosis, and 36 spondylolisthesis), aged 10-21 years undergoing posterior spinal fusion at a university hospital between March 2010 and March 2020. The mean (SD) daily postoperative opioid consumption per kilogram was significantly lower in the spondylolisthesis patients 0.36 mg/kg/day (0.17) compared to adolescent idiopathic scoliosis 0.51 mg/kg/day (0.25), and Scheuermann kyphosis 0.52 mg/kg/day (0.25) patients after surgery ( = 0.0004). Number of levels fused correlated with the daily opioid consumption (r = 0.20, = 0.0082). The SRS-24 pain domain scores showed a statistically significant improvement from preoperative levels to two-year follow-up in all three groups ( ≤ 0.03 for all comparisons). The spondylolisthesis patients had the lowest SRS pain domain scores (mean 4.04, SD 0.94), reporting more pain two years after surgery, in comparison to AIS (mean 4.31, SD 0.60) ( = 0.043) and SK (mean 4.43, SD 0.48) patients ( = 0.049). Persistent postoperative pain in adolescents undergoing posterior spinal fusion is related to disease pathology while higher acute postoperative pain is associated with a more extensive surgery. Spondylolisthesis patients report more chronic pain after surgery compared to AIS and SK patients.
PubMed: 36360457
DOI: 10.3390/children9111729 -
Journal of Children's Orthopaedics Aug 2022To assess the health-related quality of life and radiographic outcomes of surgically treated adolescent Scheuermann's kyphosis patients after minimum of 2-year follow-up...
Health-related quality of life outcomes in adolescent Scheuermann's kyphosis patients treated with posterior spinal fusion: A comparison with age- and sex-matched controls.
PURPOSE
To assess the health-related quality of life and radiographic outcomes of surgically treated adolescent Scheuermann's kyphosis patients after minimum of 2-year follow-up and to compare the health-related quality of life with age- and sex-matched healthy controls.
METHODS
Twenty-two consecutive adolescents (mean age = 16.7 years) undergoing posterior spinal fusion for Scheuermann's kyphosis were included and matched by age and sex with two healthy controls. The health-related quality of life was evaluated using the Scoliosis Research Society-24 questionnaire. Radiographic parameters were measured for comparison preoperatively and at 6 months and 2-year follow-ups. The health-related quality of life parameters were compared with healthy controls at 2 years of follow-up.
RESULTS
The mean maximal thoracic kyphosis improved from 79° (range = 75°-90°) to 55° (range = 45°-75°) ( < 0.001), and the mean lumbar lordosis was reduced from 71° (range = 51°-107°) to 52° (range = 34°-68°) ( < 0.001) after 2 years postoperatively. Incidence of proximal junctional kyphosis (PJK) was 18%. The scores of the Scoliosis Research Society-24 improved, with statistical significance observed in pain and self-image domains from preoperative to 2-year follow-up ( = 0.002 in both domains). The self-image and function were significantly lower in the operated patients at their 2-year follow-up visit compared to controls ( = 0.023 for self-image and < 0.001 for function).
CONCLUSION
Instrumented posterior spinal fusion improves the health-related quality of life of Scheuermann's kyphosis patients during the 2-year follow-up. The greatest improvement is observed in pain and self-image domains. The health-related quality of life in pain and activity domains reaches the level of healthy individuals, while function and self-image remain at a statistically lower level.
PubMed: 35992515
DOI: 10.1177/18632521221106384