Orthopedic disease classification based on breadth-first search algorithm.

Orthopedic diseases are widespread worldwide, impacting the body's musculoskeletal system, particularly those involving bones or hips. They have the potential to cause discomfort and impair functionality. This paper aims to address the lack of supplementary diagnostics in orthopedics and improve the method of diagnosing orthopedic diseases. The study uses binary breadth-first search (BBFS), binary particle swarm optimization (BPSO), binary grey wolf optimizer (BGWO), and binary whale optimization algorithm (BWAO) for feature selections, and the BBFS makes an average error of 47.29% less than others. Then we apply six machine learning models, i.e., RF, SGD, NBC, DC, QDA, and ET. The dataset used contains 310 instances and six distinct features. Through experimentation, the RF model led to optimal outcomes during comparison to the remaining models, with an accuracy of 91.4%. The parameters of the RF model were optimized using four optimization algorithms: BFS, PSO, WAO, and GWO. To check how well the optimized RF works on the dataset, this paper uses prediction evaluation metrics such as accuracy, sensitivity, specificity, F-score, and the AUC curve. The results showed that the BFS-RF can improve the performance of the original classifier compared with others with 99.41% accuracy.

Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges.

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro . In vivo , while deletion of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby metastatic cancer cells awake locally-generated developmental cues for metabolically reprograming, suggesting novel therapeutic approaches.

Microglia depletion and repopulation do not alter the effects of cranial irradiation on hippocampal neurogenesis.

Cranial radiotherapy can cause lifelong cognitive complications in childhood brain tumor survivors, and reduced hippocampal neurogenesis is hypothesized to contribute to this. Following irradiation (IR), microglia clear dead neural progenitors and give rise to a neuroinflammatory microenvironment, which promotes a switch in surviving progenitors from neuronal to glial differentiation. Recently, depletion and repopulation of microglia were shown to promote neurogenesis and ameliorate cognitive deficits in various brain injury models. In this study, we utilized the Cx3cr1CreERt2-YFP/+Rosa26DTA/+ transgenic mouse model to deplete microglia in the juvenile mouse brain before subjecting them to whole-brain IR and investigated the short- and long-term effects on hippocampal neurogenesis. Within the initial 24 h after IR, the absence of microglia led to an accumulation of dead cells in the subgranular zone, and 50-fold higher levels of the chemokine C-C motif ligand 2 (CCL2) in sham brains and 7-fold higher levels after IR. The absence of microglia, and the subsequent repopulation within 10 days, did neither affect the loss of proliferating or doublecortin-positive cells, nor the reduced growth of the granule cell layer. Our results argue against a role for a pro-inflammatory microenvironment in the dysregulation of hippocampal neurogenesis and suggest that the observed reduction of neurogenesis was solely due to IR.

Rapid and robust isolation of microglia and vascular cells from brain subregions for integrative single-cell analyses.

Cell isolation protocols from brain tissue include prolonged ex vivo processing durations, rendering them suboptimal for transcriptomic studies. Particularly for microglia and vascular cells, current isolation methods produce lower yields, necessitating addition of an enrichment step, and use of large tissue volumes - in most cases whole brain tissue - to obtain sufficient yields. Here, we developed a simple, rapid, and reproducible cell isolation method for generating single-cell suspensions from micro-dissected brain regions, enriched for microglia and vascular cells, without an enrichment step. Cells isolated using this method are suitable for molecular profiling studies using 10 × Genomics Chromium single-cell RNA sequencing with high reproducibility. Our method is valuable for longitudinal unbiased molecular profiling of microglia and vascular cells within different brain regions, spanning multiple time points across physiological development or disease progression.

EDA2R reflects the acute brain response to cranial irradiation in liquid biopsies.

BACKGROUND: Cranial radiotherapy is standard of care for high-grade brain tumors and metastases; however, it induces debilitating neurocognitive impairments in cancer survivors, especially children. As the numbers of pediatric brain cancer survivors continue improving, the numbers of individuals developing life-long neurocognitive sequalae are consequently expected to rise. Yet, there are no established biomarkers estimating the degree of the irradiation-induced brain injury at completion of radiotherapy to predict the severity of the expected neurocognitive complications. We aimed to identify sensitive biomarkers associated with brain response to irradiation that can be measured in easily accessible clinical materials, such as liquid biopsies. METHODS: Juvenile mice were subjected to cranial irradiation with 0.5, 1, 2, 4, and 8 Gy. Cerebrospinal fluid (CSF), plasma, and brains were collected at acute, subacute, and subchronic phases after irradiation, and processed for proteomic screens, and molecular and histological analyses. RESULTS: We found that the levels of ectodysplasin A2 receptor (EDA2R), member of tumor necrosis factor receptor superfamily, increased significantly in the CSF after cranial irradiation, even at lower irradiation doses. The levels of EDA2R were increased globally in the brain acutely after irradiation and decreased over time. EDA2R was predominantly expressed by neurons, and the temporal dynamics of EDA2R in the brain was reflected in the plasma samples. CONCLUSIONS: We propose EDA2R as a promising potential biomarker reflecting irradiation-induced brain injury in liquid biopsies. The levels of EDA2R upon completion of radiotherapy may aid in predicting the severity of IR-induced neurocognitive sequalae at a very early stage after treatment.

Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E.

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation.

Introduction: Cranial irradiation (IR) negatively regulates hippocampal neurogenesis and causes cognitive dysfunctions in cancer survivors, especially in pediatric patients. IR decreases proliferation of neural stem/progenitor cells (NSPC) and consequently diminishes production of new hippocampal neurons. Memantine, an NMDA receptor antagonist, used clinically to improve cognition in patients suffering from Alzheimer's disease and dementia. In animal models, memantine acts as a potent enhancer of hippocampal neurogenesis. Memantine was recently proposed as an intervention to improve cognitive impairments occurring after radiotherapy and is currently under investigation in a number of clinical trials, including pediatric patients. To date, preclinical studies investigating the mechanisms underpinning how memantine improves cognition after IR remain limited, especially in the young, developing brain. Here, we investigated whether memantine could restore proliferation in the subgranular zone (SGZ) or rescue the reduction in the number of hippocampal young neurons after IR in the juvenile mouse brain. Methods: Mice were whole-brain irradiated with 6 Gy on postnatal day 20 (P20) and subjected to acute or long-term treatment with memantine. Proliferation in the SGZ and the number of young neurons were further evaluated after the treatment. We also measured the levels of neurotrophins associated with memantine improved neural plasticity, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Results: We show that acute intraperitoneal treatment with a high, non-clinically used, dose of memantine (50 mg/kg) increased the number of proliferating cells in the intact brain by 72% and prevented 23% of IR-induced decrease in proliferation. Long-term treatment with 10 mg/kg/day of memantine, equivalent to the clinically used dose, did not impact proliferation, neither in the intact brain, nor after IR, but significantly increased the number of young neurons (doublecortin expressing cells) with radial dendrites (29% in sham controls and 156% after IR) and enhanced their dendritic arborization. Finally, we found that long-term treatment with 10 mg/kg/day memantine did not affect the levels of BDNF, but significantly reduced the levels of NGF by 40%. Conclusion: These data suggest that the enhanced dendritic complexity of the hippocampal young neurons after treatment with memantine may contribute to the observed improved cognition in patients treated with cranial radiotherapy.

Vaccination with bacterial ghosts of Streptococcus iniae and Lactococcus garvieae originated from outbreak of marine fish streptococcosis, induce potential protection against the disease in Nile tilapia, Oreochromis niloticus (Linnaeus, 1758).

Streptococcosis is an important bacterial disease affects fresh, brackish and marine fish. The disease caused annual severe economic losses in Egyptian Mari-culture. S. iniae and L. garvieae usually the main causative agents isolated. The presented study conducted to prepare bacterial ghost vaccine (BGV) candidates from isolated strains of marine streptococcosis outbreaks using NaOH chemical approach. Selected strains confirmed as pathogenic for Nile tilapia, therefore the fish selected as an experimental model. In such respect, the re-isolated S. iniae and L. garvieae were used for ghost preparations, BGVs evaluation and fish challenges. Apart of four, three fish groups namely, A, B, C designated for BGVs evaluations, while the fourth one (D) designated as control. Vaccination experiments performed via intra-peritoneal injection with 0.1 mL (1.5 × 108 CFU/mL/fish) of their corresponding BGVs twice with 2 weeks' interval; however, control fish received 0.1 mL of fish saline instead. Blood, serum, and tissue samples collected from all groups at 2 and 4 weeks post immunization (PI) for estimation of hematological, innate, and specific immune parameters. At the end, all remained fish challenged with appropriated pathogen (s) and the relative percentage of survival (RPS) calculated. Three BGVs generated namely, SiG, in addition to, novel contributions of LgG and SiLgG. Ghosts were corresponding to S. iniae, L. garvieae and their both ghost mixtures, respectively. Fish groups immunized with prepared BGVs revealed variable significant increases in PCV, GLB, PP, SOD, CAT, C5, IL-ß1, LZM, specific antibody titers and CD4 expression 2 and 4 weeks PI. MDA decreased in all vaccinated groups that was significantly with group C. Expression of MHC-II showed elevations 2 weeks PI, however, it significantly decreased at 4 weeks. The RPS recorded 90, 88.89 and 95.46% in immunized groups A, B and C, respectively. At all levels tested, obtained results proposed SiG, LgG and SiLgG as innovative vaccine candidates, which can protect cultured fish from being attacked by S. iniae, and/or L. garvieae.

ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain.

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.

Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases.

PURPOSE: Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response. EXPERIMENTAL DESIGN: We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan-Meier analysis was used to associate genomic changes with survival. RESULTS: The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5-21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05). CONCLUSIONS: In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.

Diagnostic accuracy of point-of-care knee ultrasound for evaluation of meniscus and collateral ligaments pathology in comparison with MRI.

BACKGROUND: Although magnetic resonance imaging (MRI) is often the "gold standard" for diagnosing knee problems, it has many limitations. Therefore, ultrasonography has been suggested as an effective rapid alternative in many knee abnormalities, especially after injuries of the meniscus and collateral ligaments. PURPOSE: To determine the diagnostic accuracy of point-of-care ultrasound (POCUS) in detecting injuries of the meniscus and collateral ligament compared to MRI. MATERIAL AND METHODS: An observational cross-sectional blinded study was conducted of 60 patients with clinically suspicious meniscus and collateral ligament injuries who were planned for an arthroscopy and or operative procedure. These patients underwent both blinded POCUS and MRI of the knees before the intervention procedure and results of both imaging modalities were compared according to the operative and arthroscopic findings. RESULTS: The preoperative reliability of POCUS compared to MRI for the assessment of meniscus injuries was sensitivity (92.9% vs. 90.5%), specificity (88.9% vs. 83.3%), positive predictive value (PPV; 95.1% vs. 92.7%), negative predictive value (NPV; 84.2% vs. 79%), and overall accuracy (91.7% vs. 88.3%). However, for diagnosing collateral ligament injures, POCUS versus MRI assessed sensitivity (92.3% vs. 88.5%), specificity (100% vs. 97.1%), PPV (100% vs. 95.8%), NPV (94.4% vs. 91.7%), and overall accuracy (96.7% vs. 93.3%). CONCLUSION: Ultrasonography is a useful screening tool for the initial diagnosis of meniscal and collateral ligament pathology compared to or even with potential advantages over MRI, especially when MRI is unavailable or contraindicated. As newly advanced portable ultrasonography becomes available, it could be considered as a point-of-injury diagnostic modality.

In-house protocol: spin-based viral RNA purification.

A worldwide shortage of molecular biology consumables is in surge. This includes filter tips, nucleic acid purification kits, polymerases, reverse-transcriptase, and different types of reagents which are included in viral diagnostic kits. In developing countries, the problem is even worse, since there is few capital enterprise to adopt this kind of industry. So, our aim is to develop a suitable, functional, comparable to commercial ones, and affordable in-house protocol to purify viral RNA. We sought some published and commercial RNA purification solutions to set-up an in-house protocol for viral RNA extraction. Solution was prepared accordingly. Also, LPA (linearized polyacrylamide) carrier was evaluated. The whole setting of in-house solutions with addition of LPA carrier was compared to QIAamp viral RNA minikit solutions. Our results showed that linearized polyacrylamide (LPA) carrier in homemade solutions is comparable to poly A carrier which is used in the most commercial kit. In addition, the whole setting of RNA purification solutions did achieve the purpose of viral RNA purification. Also, the result was confirmed using sputum of a Sars-Cov2 infected patient. Our experiments did end up with an affordable homemade solutions for viral RNA purification.

An overlooked subset of Cx3cr1wt/wt microglia in the Cx3cr1CreER-Eyfp/wt mouse has a repopulation advantage over Cx3cr1CreER-Eyfp/wt microglia following microglial depletion.

BACKGROUND: Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have facilitated cellular investigations of physiological and pathological processes, including the widespread use of the Cx3cr1CreER-Eyfp/wt mouse strain for studies of microglia. METHODS: Immunohistochemistry, Flow Cytometry, RNA sequencing and whole-genome sequencing were used to identify the subpopulation of microglia in Cx3cr1CreER-Eyfp/wt mouse brains. Genetically mediated microglia depletion using Cx3cr1CreER-Eyfp/wtRosa26DTA/wt mice and CSF1 receptor inhibitor PLX3397 were used to deplete microglia. Primary microglia proliferation and migration assay were used for in vitro studies. RESULTS: We unexpectedly identified a subpopulation of microglia devoid of genetic modification, exhibiting higher Cx3cr1 and CX3CR1 expression than Cx3cr1CreER-Eyfp/wtCre+Eyfp+ microglia in Cx3cr1CreER-Eyfp/wt mouse brains, thus termed Cx3cr1highCre-Eyfp- microglia. This subpopulation constituted less than 1% of all microglia under homeostatic conditions, but after Cre-driven DTA-mediated microglial depletion, Cx3cr1highCre-Eyfp- microglia escaped depletion and proliferated extensively, eventually occupying one-third of the total microglial pool. We further demonstrated that the Cx3cr1highCre-Eyfp- microglia had lost their genetic heterozygosity and become homozygous for wild-type Cx3cr1. Therefore, Cx3cr1highCre-Eyfp- microglia are Cx3cr1wt/wtCre-Eyfp-. Finally, we demonstrated that CX3CL1-CX3CR1 signaling regulates microglial repopulation both in vivo and in vitro. CONCLUSIONS: Our results raise a cautionary note regarding the use of Cx3cr1CreER-Eyfp/wt mouse strains, particularly when interpreting the results of fate mapping, and microglial depletion and repopulation studies.

Translation and adaptation of the EORTC QLQ-LC 29 for use in Chinese patients with lung cancer.

BACKGROUND: The latest European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 29 (QLQ-LC29) has been translated and validated in several languages but not yet in simplified Chinese. This study aimed to translate this questionnaire into simplified Chinese and adapt it for use in Chinese patients with lung cancer. METHODS: The translation and adaptation process followed the EORTC translation procedure, and consisted of eight steps, namely, translation preparation, forward translations, reconciled translation, back translations, a back translation report, proofreading, pilot testing, and finalisation. The pilot testing included 10 patients with lung cancer. RESULTS: We obtained the permission to perform the EORTC QLQ-LC29 translation work on November 17, 2020. Thereafter, it took 3 weeks to complete the forward translations, reconciled translation, and back translations. After several rounds of discussion with the EORTC Translation Unit, 19 items used the existing translations from the EORTC Item Library (a database of EORTC questionnaire items and their translations), and 10 items were translated from scratch. The 10 patients included in the pilot testing phase had a median age of 64 years (range 31-69 years); five were male, five had an educational level of high school or above, and six had undergone surgery. Eight items received comments from patients (six items by one patient alone and the other two items by three patients). No patients commented on the instructions or the format used for responses. After discussion with the EORTC Translation Unit, we modified the Chinese wording in item 50 to ensure that the meaning of "lifeless" was clear. No changes were made to the remaining items. CONCLUSIONS: The simplified Chinese version of the EORTC QLQ-LC29 is now available on the EORTC website. This translation may contribute to the application of the EORTC QLQ-LC29 scale in both research and clinical practice in the Chinese population with lung cancer. Further evaluation of the psychometric properties of the translated EORTC QLQ-LC29 is warranted.

Presence of HPV, EBV and HMTV Viruses Among Egyptian Breast Cancer Women: Molecular Detection and Clinical Relevance.

BACKGROUND: Oncogenic viruses, their possible association with breast cancer (BC) and effect on its clinical course are interesting issue. The present study evaluates the presence of human papillomavirus (HPV), EpsteinBarr virus (EBV), and human mammary tumor virus (HMTV) in BC and their relation with clinico-pathological characteristics. PATIENTS AND METHODS: This study was conducted on 80 Egyptian women with BC and 30 control women without known oncological disease. Forty formalin-fixed paraffin-embedded (FFPE) tissues, forty fresh tissue samples, and white blood cells (WBCs) of BC patients and WBCs of controls were subjected to a qualitative polymerase chain reaction (PCR). Quantitative real-time PCR was used to measure viral loads in fresh tissues of BC. The result was correlated with clinico-pathological characteristics of BC. RESULTS: HPV was detected in 33 (41.25%), EBV in 30 (37.5%) and HMTV in 33 (41.25%) BC patients. None of the control women was positive for HPV or EBV while HMTV was detected in 7 (23.3%). Among 40 BC WBCs specimens, HPV/HMTV were found together in 25%, followed by EBV/HMTV in 2.5% and EBV/HPV in 2.5%. However, the three viruses (HPV/EBV/HMTV) were found together in only 5%. In the 40 fresh BC tissues, the three viruses were found together in 12 (30%), EBV/HMTV in 7 (17.5%), HPV/HMTV in 4 (10%), and HPV/EBV in 4 (10%). EBV, HMTV, or multiple viral infections were associated with younger age of BC women. HPV, EBV, and HMTV median loads in fresh tissues were 4.8×103 copies/µL, 6.3×103 copies/µL, and 97 copies/µL, respectively. CONCLUSION: WBCs could be a more suitable specimen instead of fresh tissue for HMTV detection in BC patients to avoid invasive procedures. The presence of HPV, EBV, and HMTV together in Egyptian women with BC was significantly associated with younger age.

Spectrum of childhood interstitial and diffuse lung diseases at a tertiary hospital in Egypt.

BACKGROUND: Childhood interstitial and diffuse lung diseases (chILD) encompass a broad spectrum of rare pulmonary disorders. In most developing Middle Eastern countries, chILD is still underdiagnosed. Our objective was to describe and investigate patients diagnosed with chILD in a tertiary university hospital in Egypt. METHODS: We analysed data of consecutive subjects (aged <18 years) referred for further evaluation at the Children's Hospital, Ain Shams University (Cairo, Egypt). Diagnosis of chILD was made in accordance with the ChILD-EU criteria. The following information was obtained: demographic data, clinical characteristics, chest computed tomography findings, laboratory studies, spirometry, bronchoalveolar lavage and histopathology findings. RESULTS: 22 subjects were enrolled over 24 months. Median age at diagnosis was 7 years (range 3.5-14 years). The most common manifestations were dyspnoea (100%), cough (90.9%), clubbing (95.5%) and tachypnoea (90.9%). Systematic evaluation led to the following diagnoses: hypersensitivity pneumonitis (n=3), idiopathic interstitial pneumonias (n=4), chILD related to chronic granulomatous disease (n=3), chILD related to small airways disease (n=3), post-infectious chILD (n=2), Langerhans cell histiocytosis (n=2), idiopathic pulmonary haemosiderosis (n=2), granulomatous lymphocytic interstitial lung disease (n=1), systemic sclerosis (n=1) and familial interstitial lung disease (n=1). Among the subjects who completed the diagnostic evaluation (n=19), treatment was changed in 13 (68.4%) subjects. CONCLUSION: Systematic evaluation and multidisciplinary peer review of chILD patients at our tertiary hospital led to changes in management in 68% of the patients. This study highlights the need for an Egyptian chILD network with genetic testing, as well as the value of collaborating with international groups in improving healthcare for children with chILD.

Eliciting SF-6Dv2 health state utilities using an anchored best-worst scaling technique.

There is an increasing interest in using ordinal data collection methods, such as the best-worst scaling (BWS), to develop preference-based tariffs (value sets) for health-related quality of life instruments, yet the evidence on their performance is limited. This paper proposed to use an anchored BWS technique (in which the state of "death" served as an anchoring state) to directly develop a utility weight that lies on a scale anchored at 0 = death and 1 = full health for the Simplified Chinese version of the Short Form 6 Dimension version 2 (SF-6Dv2). An online panel from the general population of Mainland China completed an online survey between 20th July and 19th August, 2019 and 463 respondents were included in the main analysis. The Conditional Logit (CL) model, which assumes a homogeneous preference, as well as a Hierarchical Bayes (HB) model, which accounts for preference heterogeneity, were used to analyze the BWS data. The model performances were evaluated based on monotonicity and model-fit statistics. The majority of respondents indicated that the BWS questions were easy to understand and complete. Initial analyses suggested that the best and worst choices should not be pooled together. Based on model fit statistics of separated estimations and previous literature on health state valuation studies using BWS, the best choices were used for developing the final algorithm. The HB estimates were found to have better model performance than the CL estimates. This study provides an essential insight into using an anchored BWS approach in health state valuation. Furthermore, it demonstrates the advantage of using HB compared to the traditional CL model in producing preference values.

Strain analysis using feature tracking cardiac magnetic resonance (FT-CMR) in the assessment of myocardial viability in chronic ischemic patients.

The purpose of this study is to test the capability of a commercially available feature tracking-cardiac magnetic resonance (FT-CMR) strain analysis software module in differentiating between viable and non-viable myocardium in chronic ischemic patients. Thirty chronic ischemic patients and 10 healthy volunteers were enrolled. Cine images were used for peak circumferential and radial strains quantification using dedicated FT-CMR software. Global strain was compared between patients and controls. In patients, segmental strain was compared in viable and non-viable myocardium determined by late gadolinium enhancement (LGE); and in segments with wall abnormalities. Among 480 myocardial segments analyzed in patients, 76 segments were non-viable on LGE. The mean left ventricular ejection fraction (LVEF) of the patients (87% males, mean age 55 ± 12 years) was 40 ± 12% vs. 61 ± 5% for the controls (80% males, mean age 39 ± 11 years). Peak global circumferential strain (GCS) and global radial strain (GRS) were significantly impaired in patients compared to controls (-13.89 ± 4.12% vs. -19.84 ± 1.47%), p < 0.001 and (23.11 ± 6.59% vs. 31.72 ± 5.52%), p = 0.001. Segmental circumferential strain (SCS) and segmental radial strain (SRS) were significantly impaired in non-viable compared to viable segments (-9.47 ± 7.26% vs. -14.72 ± 7.5%), p < 0.001 and (15.67 ± 12.11% vs. 24.51 ± 16.22%), p < 0.001. Cut-off points of -9.36% for the SCS (AUC = 0.7, 95% CI = 0.63-0.77) and 19.5% for the SRS (AUC = 0.67, 95%CI = 0.61-0.73) were attained above which the segment is considered viable.SCS was able to discriminate between normokinetic, hypokinetic and akinetic segments (mean = 27.6 ± 17.13%, 18.66 ± 12.88% and 15.24 ± 10.70% respectively, p < 0.001). Circumferential and radial segmental strain analysis by FT-CMR was able to discriminate between viable and non-viable segments of the myocardium defined by LGE and between normokinetic, hypokinetic and akinetic segments, using routinely acquired cine images, and thus can provide a more objective metric for risk stratification in chronic ischemic patients.

Female pelvic congestion syndrome: how can CT and MRI help in the management decision?

OBJECTIVE: Diagnosis of female pelvic congestion syndrome (PCS) is challenging. Although invasive venography is the gold-standard for diagnosis, however, CT and MRI are important in the assessment. In this study, we tried to highlight the role of CT and MRI as non-invasive tools in the diagnosis and management of PCS. METHODS AND MATERIAL: This was a retrospective study of 50 patients confirmed clinically to have PCS. These patients had already done CT and MRI before venography or surgery. RESULTS: The mean age of the patients was 48 years ± 12 years SD. Vaginal discharge and pelvic heaviness were the commonest symptoms (46 and 42% respectively). The commonest risk factor was multiparity (56%) followed by the RVF uterus (26%). No significant difference was found between CT, MRI, and venography as regarding the diameter of the ovarian vein, diameter, and the number of the varicose veins. The sensitivity of CT and MRI was 94.8 and 96%. CT and MRI discovered five cases with local pelvic obstructing cause,14 cases with evidence of vascular compression syndrome, and the rest 31 cases diagnosed to have primary non-obstructing PCS which was effective in decision-making with the surgery indicated in the first group while stenting of the vascular obstruction followed by bilateral ovarian veins coiling was the better option for the second group and only bilateral coiling was needed for the last group. CONCLUSION: CT and MRI play important roles in the diagnosis and even management decision in cases of PCS. ADVANCES IN KNOWLEDGE:: Identification of the importance of diagnostic radiology before management decisions of cases with PCS.