Cancers are characterized by extensive heterogeneity that occurs intratumorally, between lesions, and across patients. To study cancer as a complex biological system, multidimensional analyses of the ...tumor microenvironment are paramount. Single-cell technologies such as flow cytometry, mass cytometry, or single-cell RNA-sequencing have revolutionized our ability to characterize individual cells in great detail and, with that, shed light on the complexity of cancer microenvironments. However, a key limitation of these single-cell technologies is the lack of information on spatial context and multicellular interactions. Investigating spatial contexts of cells requires the incorporation of tissue-based techniques such as multiparameter immunofluorescence, imaging mass cytometry, or
detection of transcripts. In this Review, we describe the rise of multidimensional single-cell technologies and provide an overview of their strengths and weaknesses. In addition, we discuss the integration of transcriptomic, genomic, epigenomic, proteomic, and spatially-resolved data in the context of human cancers. Lastly, we will deliberate on how the integration of multi-omics data will help to shed light on the complex role of cell types present within the human tumor microenvironment, and how such system-wide approaches may pave the way toward more effective therapies for the treatment of cancer.
Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by varying degrees of intellectual disability, severely delayed language development and specific facial features, and is ...caused by a deletion within chromosome 22q13.3. SHANK3, which is located at the terminal end of this region, has been repeatedly implicated in other neurodevelopmental disorders and deletion of this gene specifically is thought to cause much of the neurologic symptoms characteristic of PMS. However, it is still unclear to what extent SHANK3 deletions contribute to the PMS phenotype, and what other genes nearby are causal to the neurologic disease. In an effort to better understand the functional landscape of the PMS region during normal neurodevelopment, we assessed RNA-sequencing (RNA-seq) expression data collected from post-mortem brain tissue from developmentally normal subjects over the course of prenatal to adolescent age and analyzed expression changes of 65 genes on 22q13. We found that the majority of genes within this region were expressed in the brain, with ATNX10, MLC1, MAPK8IP2, and SULT4A1 having the highest overall expression. Analysis of the temporal profiles of the highest expressed genes revealed a trend towards peak expression during the early post-natal period, followed by a drop in expression later in development. Spatial analysis revealed significant region specific differences in the expression of SHANK3, MAPK8IP2, and SULT4A1. Region specific expression over time revealed a consistently unique gene expression profile within the cerebellum, providing evidence for a distinct developmental program within this region. Exon-specific expression of SHANK3 showed higher expression within exons contributing to known brain specific functional isoforms. Overall, we provide an updated roadmap of the PMS region, implicating several genes and time periods as important during neurodevelopment, with the hope that this information can help us better understand the phenotypic heterogeneity of PMS.
Objectives: To determine the incidence, risk factors, and maternal outcomes of "major degree" placenta previa (PP)/placenta accreta spectrum (PAS) in Abha Maternity and Children's Hospital, Abha, ...Saudi Arabia. Secondly, to compare our findings to those of previous studies on PP/PAS in Saudi Arabia. Methods: This is a retrospective study that included 299 patients diagnosed with major degree PP/PAS and admitted to Abha Maternity and Children's Hospital, Abha, Saudi Arabia, within 10 years (January 2012-December 2021). Also, we compared our results to the outcomes of PP/PAS patients in 6 previous Saudi studies. Results: The total number of deliveries was 54,341; PP minor and major degrees were diagnosed in 376 (0.69%) patients. Of them, 299 patients had PP major degree (79.5%). The pattern of main risk factors for major PP/PAS included: elder age, high parity, and previous cesarean deliveries. Nearly 30.5% had evidence of PAS on antenatal MRI (n=91). Approximately 68.5% (n=205) of patients were delivered <37 weeks. Of 299 patients, 29 (9.7%)patients had emergency cesarean hysterectomy. The maternal mortality rate was 0.3% (n=1). Generally, in many aspects, our results are comparable to similar Saudi studies on PP/PAS. Conclusion: Major degree of PP/PAS is associated with high maternal morbidity but rare mortality. Over 30 years, our patients' obstetric characteristics did not change, including both elder age and high parity. A substantial increase in the rate of cesarean deliveries is a leading cause of major PP/PAS. Keywords: placenta previa, risk factors, outcomes phrase omitted
The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further ...propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between these batches. Typically, these batch effects are resolved by matching similar cells across the different batches. Current approaches, however, do not take into account that we can constrain this matching further as cells can also be matched on their cell type identity. We use an auto-encoder to embed two batches in the same space such that cells are matched. To accomplish this, we use a loss function that preserves: (1) cell-cell distances within each of the two batches, as well as (2) cell-cell distances between two batches when the cells are of the same cell-type. The cell-type guidance is unsupervised, i.e., a cell-type is defined as a cluster in the original batch. We evaluated the performance of our cluster-guided batch alignment (CBA) using pancreas and mouse cell atlas datasets, against six state-of-the-art single cell alignment methods: Seurat v3, BBKNN, Scanorama, Harmony, LIGER, and BERMUDA. Compared to other approaches, CBA preserves the cluster separation in the original datasets while still being able to align the two datasets. We confirm that this separation is biologically meaningful by identifying relevant differential expression of genes for these preserved clusters.
Prominent or bat ear is not uncommon deformity as it affecting 5% of population. Plenty of procedures were reported for its correction. Being plenty means it is still a subject of research. The ...current procedures could be summarized as cartilage sparing and cartilage splitting ones.
During a period of 35 months a total of 31 patients were presented with bilateral prominent ears so the included a total of 62 ears. Their average age was 8 years (ranging from five to 18 years). All deformities were corrected using helix free otoplasty technique which included skin paddle excision, separation of helical cartilage (hence the name helix free), anterior scoring, backward folding, mattress and simple suturing of the folded cartilage, proper definition of antitragus and earlobe and concha-mastoid sutures. Outcomes including patient's and/or guardians' satisfaction were determined.
The postoperative period was uneventful except two cases that developed early postoperative hematomas, one case shows late postoperative antihelical fold irregularity in one ear and other case developed ill defined superior helix in one ear. The average follow up period of two years shows no recurrences. Almost all patients (96.85%) and their guardians were satisfied with the aesthetic results while only one (3.2%) was dissatisfied.
Helical free otoplasty technique addresses the deformity through a posterior approach with under vision correction. It has very low incidence of complications, high patient's satisfactions, no visible scars and no recurrences. It is a simple, short duration procedure, reliable and good option for correction of prominent ear.
Background Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. Objective To ...determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. Data sources Electronic medical record i.e. Cerner.sup.® system. Target population Adults patients with iron deficiency anaemia. Time horizon A 12-month period (01/01/2018-31/12/2018). Perspective Hamad Medical Corporation (HMC, a public hospital). Intervention IV Ferric Carboxymaltose versus IV Iron Sucrose. Outcome measures With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. Results of base-case analysis There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. Results of sensitivity analysis Not applicable. Limitations The study did not consider the clinical or humanistic outcome. Conclusions The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.
Adiposity is associated with high serum levels of adipokines and chemokines which are possibly implicated in a co-existence of obesity and asthma.
Elucidate the possible roles of leptin, interleukin ...(IL)-4, IL-5 and IL-21 in linking obesity with childhood asthma.
Cross-sectional, analytical.
Population of schoolchildren in a small Saudi city.
The study included a representative sample of Saudi schoolchildren grouped as obese asthmatics, non-obese asthmatics, or obese nonasthmatics, with nonobese nonasthmatics as a control group. An asthma control test was done for the asthmatic groups.
Serum levels of leptin, IL-4, IL-5, and IL-21.
345 male schoolchildren with a mean (SD) age of 13.0 (2.3) years.
Median serum leptin concentrations in obese asthmatics were significantly higher than in nonobese asthmatics ( P<.001). Uncontrolled asthmatics also had significantly higher leptin levels than controlled asthmatic children ( P<.002). Leptin levels were weakly but significantly correlated with the cytokines IL-4, IL-5, and IL-21.
Leptin may contribute to a link between obesity and childhood asthma. Differences in IL-21 levels between nonobese and obese asthmatics suggest that the co-existence of asthma and obesity increased IL-21 levels. Leptin plus some proinflammatory cytokines especially IL-21 may be potential predictors for asthma control in children.
Blood sampling at different stages of asthma might influence cytokine expression.
None.
Most regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, ...discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some computational models tackle this problem by predicting gene expression directly from the genomic sequence. These models are currently limited to predicting bulk measurements and mainly make tissue-specific predictions. Here, we present a model that leverages single-cell RNA-sequencing data to predict gene expression. We show that cell population-specific models outperform tissue-specific models, especially when the expression profile of a cell population and the corresponding tissue are dissimilar. Further, we show that our model can prioritize GWAS variants and learn motifs of transcription factor binding sites. We envision that our model can be useful for delineating cell population-specific regulatory elements.
Continuing medical education (CME) is an everlasting process throughout the physician's working life. It helps to deliver better services for the patients.
To explore CME among resident physicians in ...Abha City; their current practices, their opinions, and barriers faced.
A cross-sectional study was conducted among resident physicians at the Ministry of Health hospitals in Abha City using a validated self-administered questionnaire. It included personal characteristics, current CME practices, satisfaction with CME, and barriers to attendance.
The present study included 300 residents from 15 training specialties. Their reported CME activities during the previous year were lectures and seminars (79.7%) followed by conferences (43.7%), case presentations (39.7%), workshops (34.0%), group discussion (29/7%), and journal clubs (27.3%). Astonishingly enough, very few (8%) attended online electronic CME activities. There were significant differences in CME satisfaction scores by different training specialties. Regarding residents' perceptions of the effectiveness of different CME activities (conferences/symposia, workshops/courses, and interdepartmental activities) the results showed that workshops and courses were significantly the most effective method compared to the other two methods in retention of knowledge, improving attitudes, improving clinical skills, improving managerial skills, and in improving practice behaviors. Barriers reported were being busy, lack of interest, high cost, and lack of suitable providers.
Based on the findings of this study, it is recommended that online learning be promoted as a CME format for trainees. There should be support of residents and clinicians through the provision of protected time for their CME activities outside their daily clinical commitments.
Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the family Coronaviridae, and is named for the crown-like spikes on its surface. The clinical presentation of MERS-CoV infection ...ranges from asymptomatic to very severe disease, and the classical presentation includes fever, cough chills, sore throat, myalgia, and arthralgia.
A cross-sectional study of 339 healthcare personnel was conducted over an 8-month period in the Aseer region of Saudi Arabia using a structured survey that included demographic information and questions testing participant’s knowledge.
Approximately two-thirds of the respondents properly identified the causative agent of MERS-CoV as an RNA virus (66.4%, n=225) that is enveloped (68.1%, n=231). On the other hand, few respondents identified the proper number of strains or the genus (16.5% and 17.4%, respectively). More than half of the study sample identified the disease as zoonotic (57.2%, n=194). Similarly, 89.1% (n=302) identified that camels and bats are prone to infection with coronaviruses. Only 23.9% (n=81) properly identified March through May as the season with the highest transmission rate. There was a massive lack of adequate knowledge regarding prevalence of antibodies. Only 18.3% (n=62) of respondents identified PCR as the proper diagnostic confirmatory test for MERS-CoV infection. Regarding MERS-CoV clinical features, 76.4% (n=259) recognized the presence of sub-clinical infection, 64.7% (n=218) indicated that cases should be immediately isolated, and 46.9% (n=159) identified the main cause of mortality as respiratory failure.
There is limited microbiological and virological knowledge of MERS-CoV infection among healthcare personnel in the southern region of Saudi Arabia, although the clinical aspects are known.
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