Epidemiological observations and management challenges in extrapedal mycetoma: A three-decade review of 420 cases.

Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts.

Temporal trends in colorectal cancer mortality rates (1999-2022) in the United States.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the United States (U.S.). Our study aims to analyze CRC mortality patterns in the U.S., focusing on gender and age groups from 1999 to 2022. We analyzed Age-Adjusted Mortality Rates (AAMRs) for CRC-related deaths using the CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database and assessed differences between age and sex. CRC-related mortality decreased significantly from 1999 to 2011 (-2.81% APC) and from 2011 to 2020 (-1.95% APC) but a not significant uptrend from 2020 to 2022 (2% APC). Males experienced a more significant decrease. Among age groups, crude mortality decreased until 2020, except in age group 45-54, which showed an annual increase in mortality of 0.9% from 2004 to 2022. Furthermore, individuals aged 75-84 and 85+ saw a nonsignificant annual increase of 1.8% and 4.5% from 2020 to 2022, respectively. Our study highlights a significant decline in age and gender-specific CRC-related mortality from 1999 to 2020. However, the worrisome uptrend observed in the younger age group of 45-54 emphasizes the importance of implementing targeted public health measures and evidence-based interventions.

Location matters: spatial dynamics of tumor-infiltrating T cell subsets is prognostic in colon cancer.

Background: Colon cancer is a heterogeneous disease and consists of various molecular subtypes. Despite advances in high-throughput expression profiling, limitations remain in predicting clinical outcome and assigning specific treatment to individual cases. Tumor-immune interactions play a critical role, with tumors that activate the immune system having better outcome for the patient. The localization of T cells within tumor epithelium, to enable direct contact, is essential for antitumor function, but bulk DNA/RNA sequencing data lacks spatial distribution information. In this study, we provide spatial T cell tumor distribution and connect these data with previously determined genomic data in the AC-ICAM colon cancer patient cohort. Methods: Colon cancer patients (n=90) with transcriptome data available were selected. We used a custom multiplex immunofluorescence assay on colon tumor tissue sections for quantifying T cell subsets spatial distribution in the tumor microenvironment, in terms of cell number, location, mutual distance, and distance to tumor cells. Statistical analyses included the previously determined Immunologic Constant of Rejection (ICR) transcriptome correlation and patient survival, revealing potential prognostic value in T cell spatial distribution. Results: T cell phenotypes were characterized and CD3+CD8-FoxP3- T cells were found to be the predominant tumor-infiltrating subtype while CD3+FoxP3+ T cells and CD3+CD8+ T cells showed similar densities. Spatial distribution analysis elucidated that proliferative T cells, characterized by Ki67 expression, and Granzyme B-expressing T cells were predominantly located within the tumor epithelium. We demonstrated an increase in immune cell density and a decrease in the distance of CD3+CD8+ T cells to the nearest tumor cell, in the immune active, ICR High, immune subtypes. Higher densities of stromal CD3+FoxP3+ T cells showed enhanced survival outcomes, and patients exhibited superior clinical benefits when greater spatial distances were observed between CD3+CD8-FoxP3- or CD3+CD8+ T cells and CD3+FoxP3+ T cells. Conclusion: Our study's in-depth analysis of the spatial distribution and densities of major T cell subtypes within the tumor microenvironment has provided valuable information that paves the way for further research into the intricate relationships between immune cells and colon cancer development.

A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer.

BACKGROUND: Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC. METHODS: Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials. RESULTS: A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression-based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1. CONCLUSIONS: This DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy. TRIAL REGISTRATION: CheckMate 026; NCT02041533, registered January 22, 2014. CheckMate 227; NCT02477826, registered June 23, 2015.

The nutritional status of mycetoma affected patients seen at the Mycetoma Research Center, Sudan.

Nutrition plays a critical and crucial role in addressing neglected tropical diseases (NTDs) and their complications, as they often contribute to malnutrition, which can worsen the impact of these conditions. Therefore, it is necessary to investigate the nutritional status of mycetoma patients, which has not been explored previously. This descriptive cross-sectional hospital-based study was conducted at the Mycetoma Research Center (MRC), University of Khartoum, Sudan. The study included 179 confirmed mycetoma patients and an equal number of age- and sex-matched normal controls. The nutritional status of the mycetoma patients was assessed and compared with that of the control group. The majority of the patients were young adults with varying educational levels, predominantly from Central Sudan. The foot was the most commonly affected part; most patients had lesions more than 10 cm in diameter. The Body Mass Index (BMI) was calculated for both study groups, revealing that 43.5% of the patients and 53.6% of controls had a normal BMI. Furthermore, 36% of patients were underweight, contrasting with only 11% in the control group. Correlation analyses indicated no significant associations between BMI and age groups, educational levels, daily meals, food quantity, and appetite in the study population (p > 0.05). Similarly, no significant differences were observed in BMI concerning disease duration and affected sites (p = 0.0577). The Kruskal-Wallis test did not reveal significant differences in BMI means among the groups. The study revealed that most participants consumed three meals daily, and the control group showed a more robust appetite and consumed more food than the patient group (p = 0.005). Nevertheless, there were no significant differences in the consumption of different food types between the patient and control groups and among different BMI categories (p = 0.025 and 0.040, respectively).

Modulation of SLFN11 induces changes in DNA Damage response in breast cancer.

BACKGROUND: Lack of Schlafen family member 11 (SLFN11) expression has been recently identified as a dominant genomic determinant of response to DNA damaging agents in numerous cancer types. Thus, several strategies aimed at increasing SLFN11 are explored to restore chemosensitivity of refractory cancers. In this study, we examined various approaches to elevate SLFN11 expression in breast cancer cellular models and confirmed a corresponding increase in chemosensitivity with using the most successful efficient one. As oncogenic transcriptomic downregulation is often driven by methylation of the promotor region, we explore the demethylation effect of 5-aza-2'-deoxycytidine (decitabine), on the SLFN11 gene. Since SLFN11 has been reported as an interferon inducible gene, and interferon is secreted during an active anti-tumor immune response, we investigated the in vitro effect of IFN-γ on SLFN11 expression in breast cancer cell lines. As a secondary approach to pick up cross talk between immune cells and SLFN11 expression we used indirect co-culture of breast cancer cells with activated PBMCs and evaluated if this can drive SLFN11 upregulation. Finally, as a definitive and specific way to modulate SLFN11 expression we implemented SLFN11 dCas9 (dead CRISPR associated protein 9) systems to specifically increase or decrease SLFN11 expression. RESULTS: After confirming the previously reported correlation between methylation of SLFN11 promoter and its expression across multiple cell lines, we showed in-vitro that decitabine and IFN-γ could increase moderately the expression of SLFN11 in both BT-549 and T47D cell lines. The use of a CRISPR-dCas9 UNISAM and KRAB system could increase or decrease SLFN11 expression significantly (up to fivefold), stably and specifically in BT-549 and T47D cancer cell lines. We then used the modified cell lines to quantify the alteration in chemo sensitivity of those cells to treatment with DNA Damaging Agents (DDAs) such as Cisplatin and Epirubicin or DNA Damage Response (DDRs) drugs like Olaparib. RNAseq was used to elucidate the mechanisms of action affected by the alteration in SLFN11 expression. In cell lines with robust SLFN11 promoter methylation such as MDA-MB-231, no SLFN11 expression could be induced by any approach. CONCLUSION: To our knowledge this is the first report of the stable non-lethal increase of SLFN11 expression in a cancer cell line. Our results show that induction of SLFN11 expression can enhance DDA and DDR sensitivity in breast cancer cells and dCas9 systems may represent a novel approach to increase SLFN11 and achieve higher sensitivity to chemotherapeutic agents, improving outcome or decreasing required drug concentrations. SLFN11-targeting therapies might be explored pre-clinically to develop personalized approaches.

Quality of Life of Mothers and Fathers of Children with Autism Spectrum Disorder in Jordan.

Background: Parenting children with autism spectrum disorder (ASD) is widely identified to be associated with life-long impairment in parents' quality of life (QoL). However, there has been little information on the QoL of parents of children with ASD in the Jordanian context. Objective: This study aimed to assess the QoL among mothers and fathers who have children with ASD in Jordan and to identify factors associated with it. Methods: In this cross-sectional study, respondents were mothers and fathers of children with ASD attending autism rehabilitation centers in Amman. Data were collected from 206 participants using a validated questionnaire. Descriptive statistics, T-test, ANOVA and logistic regression, were applied. Results: Overall quality of life was low (mean= 2.32). The physical dimension scored the highest (mean =2.79), and the environmental dimension scored the lowest (mean= 2.06). Results indicated that fathers and parents with low education reported significantly lower QoL scores (p = .024 and 0.001, respectively). Conclusion: Among parents of children with ASD, parents at risk for low QoL were recognized. Our results can be utilized to design interventions to support mothers and fathers at risk in Jordan to enhance their QoL.

V4 C3 MXene Immune Profiling and Modulation of T Cell-Dendritic Cell Function and Interaction.

Although vanadium-based metallodrugs are recently explored for their effective anti-inflammatory activity, they frequently cause undesired side effects. Among 2D nanomaterials, transition metal carbides (MXenes) have received substantial attention for their promise as biomedical platforms. It is hypothesized that vanadium immune properties can be extended to MXene compounds. Therefore, vanadium carbide MXene (V4 C3 ) is synthetized, evaluating its biocompatibility and intrinsic immunomodulatory effects. By combining multiple experimental approaches in vitro and ex vivo on human primary immune cells, MXene effects on hemolysis, apoptosis, necrosis, activation, and cytokine production are investigated. Furthermore, V4 C3 ability is demonstrated to inhibit T cell-dendritic cell interactions, evaluating the modulation of CD40-CD40 ligand interaction, two key costimulatory molecules for immune activation. The material biocompatibility at the single-cell level on 17 human immune cell subpopulations by single-cell mass cytometry is confirmed. Finally, the molecular mechanism underlying V4 C3 immune modulation is explored, demonstrating a MXene-mediated downregulation of antigen presentation-associated genes in primary human immune cells. The findings set the basis for further V4 C3 investigation and application as a negative modulator of the immune response in inflammatory and autoimmune diseases.

An integrated tumor, immune and microbiome atlas of colon cancer.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Knowledge and attitudes towards cervical cancer prevention among women in Khartoum state, Sudan.

BACKGROUND: Cervical cancer is considered the third leading cause of death among women worldwide, and human papillomavirus was identified as a major causative agent for developing cervical cancer. OBJECTIVES: This study aimed to assess the knowledge and attitudes towards cervical cancer prevention among women in Khartoum state, Sudan. DESIGN: A community-based cross-sectional study implemented in Khartoum state, Sudan, from 1 August 2020 to 1 September 2020. METHODS: We conducted a descriptive cross-sectional community-based study using an electronic questionnaire for data collection. Descriptive statistics, frequency, mean, and percentage were computed. RESULTS: The study included 716 female participants with a mean age of 27.6 + 8.7 years. 580 (81.0%) and 229 (32.0%) had heard about cervical cancer and Pap test, respectively. cervical cancer was assumed related to alcohol consumption 109 (15.2%), giving birth to many children 51 (7.1%), ageing 118 (16.5%), and having many sexual partners 335 (46.8%). In addition, 300 (41.9%) attributed cervical cancer to having human papillomavirus infection, 256 (35.6%) to the prolonged use of contraceptives, and 162 (22.6%) to smoking. Knowledge about the best time to be vaccinated against human papillomavirus, 110 (15.4%) stated it is better after marriage. Regression models to predict the effectors on participants' knowledge and attitudes showed a low standard deviation of the estimates with higher values of the adjusted R2 [R: 0.041, 0.017, and 0.006; std: 1.527, 0.417, and 0.426]. This indicates the combined influence of occupation, educational level, family income, and marital status on the participant's knowledge and attitude levels. CONCLUSION: This study revealed that the participant's knowledge and attitudes levels are mainly driven by their occupation, educational level, family income, and marital status altogether. This underscores the need for a countrywide community engagement campaign through health education and raising awareness sessions, and massive social media to sensitize the community and healthcare providers about the risk of cervical cancer and the available prevention and control measures.

Guillain-Barre syndrome associated with COVID-19 infection: A case series.

In this communication, we reported a series of six patients presented with Guillain-Barré syndrome that associated with COVID-19 infection, which was confirmed with RT-PCR. Here we discuss the laboratory investigation and case management, as well as clinical presentation and outcome of each case. The current report demonstrated the first case series of COVID-19-associated GBS-cases in Sudan.

Comparing the performance of the common used eumycetoma diagnostic tests.

OBJECTIVES: Mycetoma is a neglected tropical implantation disease caused by 70 different infectious agents. Identifying the causative organism to the species level is essential for appropriate patient management. Ultrasound, histopathology, culture and two species-specific PCRs are most the commonly used methods for species identification in endemic regions. The aim of this study was to compare the diagnostic performance of these commonly used assays using sequencing of barcoding genes as the gold standard. METHODS: This descriptive cross-sectional study was conducted at the Mycetoma Research Centre, University of Khartoum, Sudan. It included 222 patients suspected of fungal mycetoma caused by Madurella mycetomatis. RESULTS: 154 (69.3%) were correctly identified by ultrasound, histology, culture and both species-specific PCRs. In 60 patients, at least one of the diagnostic tests failed to identify M. mycetomatis. Five patients had no evidence of eumycetoma, and for three, only the ultrasound was indicative of mycetoma. The two species-specific PCRs were the most sensitive and specific methods, followed by culture and histology. Ultrasound was the least specific as it only allowed differentiation between actinomycetoma and eumycetoma. The time to result was 9.38 minutes for ultrasound, 3.76 hours for PCR, 8.5 days for histopathology and 21 days for grain culturing. CONCLUSION: Currently, PCR directly on DNA isolated from grains is the most rapid and reliable diagnostic tool to identify M. mycetomatis eumycetoma.

Privacy Attitudes and COVID Symptom Tracking Apps: Understanding Active Boundary Management by Users.

Multiple symptom tracking applications (apps) were created during the early phase of the COVID-19 pandemic. While they provided crowdsourced information about the state of the pandemic in a scalable manner, they also posed significant privacy risks for individuals. The present study investigates the interplay between individual privacy attitudes and the adoption of symptom tracking apps. Using the communication privacy theory as a framework, it studies how users' privacy attitudes changed during the public health emergency compared to the pre-COVID times. Based on focus-group interviews (N=21), this paper reports significant changes in users' privacy attitudes toward such apps. Research participants shared various reasons for both increased acceptability (e.g., disease uncertainty, public good) and decreased acceptability (e.g., reduced utility due to changed lifestyle) during COVID. The results of this study can assist health informatics researchers and policy designers in creating more socially acceptable health apps in the future.

Staphylococcus aureus causing primary foot botryomycosis mimicking actinomycetoma: a case report from Sudan.

OBJECTIVES: Botryomycosis is a rare chronic granulomatous inflammatory disease of bacterial origin. Two forms of the disease exist; the cutaneous and the visceral form. The subcutaneous form mimics actinomycetoma clinically and histologically; however, the treatment is different. In this communication, we report on a Sudanese male patient who presented with foot botryomycosis. DESIGN: Case report. RESULTS: The patient was initially diagnosed with actinomycetoma by the presence of Streptomyces somaliensis like-grains in the histological slides. The patient was treated with a combination of co-trimoxazole and amikacin sulfate and shifted after 1 year to co-trimoxazole, amoxicillin, and clavulanic acid. Despite treatment, the infection progressed, and the bone was invaded. The infected limb was amputated. The histopathological report of the surgical biopsy showed gram-positive cocci inside the grain. The 16S sequence identified these cocci as Staphylococcus aureus. CONCLUSION: This is the first reported botryomycosis case from Sudan, and it highlights why molecular identification is vital in diagnosis.

Immune Profiling and Multiplexed Label-Free Detection of 2D MXenes by Mass Cytometry and High-Dimensional Imaging.

There is a critical unmet need to detect and image 2D materials within single cells and tissues while surveying a high degree of information from single cells. Here, a versatile multiplexed label-free single-cell detection strategy is proposed based on single-cell mass cytometry by time-of-flight (CyTOF) and ion-beam imaging by time-of-flight (MIBI-TOF). This strategy, "Label-free sINgle-cell tracKing of 2D matErials by mass cytometry and MIBI-TOF Design" (LINKED), enables nanomaterial detection and simultaneous measurement of multiple cell and tissue features. As a proof of concept, a set of 2D materials, transition metal carbides, nitrides, and carbonitrides (MXenes), is selected to ensure mass detection within the cytometry range while avoiding overlap with more than 70 currently available tags, each able to survey multiple biological parameters. First, their detection and quantification in 15 primary human immune cell subpopulations are demonstrated. Together with the detection, mass cytometry is used to capture several biological aspects of MXenes, such as their biocompatibility and cytokine production after their uptake. Through enzymatic labeling, MXenes' mediation of cell-cell interactions is simultaneously evaluated. In vivo biodistribution experiments using a mixture of MXenes in mice confirm the versatility of the detection strategy and reveal MXene accumulation in the liver, blood, spleen, lungs, and relative immune cell subtypes. Finally, MIBI-TOF is applied to detect MXenes in different organs revealing their spatial distribution. The label-free detection of 2D materials by mass cytometry at the single-cell level, on multiple cell subpopulations and in multiple organs simultaneously, will enable exciting new opportunities in biomedicine.

Pelvi-abdominal ACTINOMYCOSIS as a complication of long-term use of intrauterine device (IUD). The important role of imaging in diagnosis and follow-up.

ACTINOMYCOSIS is a rare chronic granulomatous disease caused by anaerobic filamentous gram-positive bacteria, the most common of which is Actinomyces israelii. Actinomycetes are commensal inhabitants of the oral cavity and gastrointestinal tract, but they may become pathogenic through invasion of breached or necrotic tissue. Pelviabdominal ACTINOMYCOSIS is uncommon and can mimic a variety of disease processes, including abdominal mass mimicking malignancy, acute abdomen, asthenia, and weight loss. We describe a 38-year-old woman who presented with acute abdominal pain and tenderness, as well as constitutional manifestations and elevated inflammatory markers. On initial computerized tomography (CT) and MRI, a large fluid collection underlining the anterior abdominal wall at the false pelvic cavity, as well as parietal peritoneal enhancement and smudging of the mesenteric fat and a bulky fibroid uterus with an implanted IUD, were identified. The ultrasound guided aspiration and anaerobic culture revealed positive growth for Actinomyces bacteria. An exploratory laparoscopy revealed extensive adhesions between the abdominal wall and the small intestine, as well as hyperemic and thickened peritoneum, and peritoneal biopsy confirmed ACTINOMYCOSIS. After the diagnosis was established, the IUD was removed and the patient was given Ceftriaxone 2 gm once daily for 6 weeks before switching to oral doxycycline 100 mg twice daily for another 3 months. A significant regression of the suprapubic fluid collection, and peritoneal-mesenteric changes were confirmed on follow-up. The case is discussed, and the relevant literature reviewed and analyzed.

The immune landscape of solid pediatric tumors.

BACKGROUND: Large immunogenomic analyses have demonstrated the prognostic role of the functional orientation of the tumor microenvironment in adult solid tumors, this variable has been poorly explored in the pediatric counterpart. METHODS: We performed a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types (408 patients): Wilms tumor (WLM), neuroblastoma (NBL), osteosarcoma (OS), clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RT). We assessed the performance of the Immunologic Constant of Rejection (ICR), which captures an active Th1/cytotoxic response. We also performed gene set enrichment analysis (ssGSEA) and clustered more than 100 well characterized immune traits to define immune subtypes and compared their outcome. RESULTS: A higher ICR score was associated with better survival in OS and high risk NBL without MYCN amplification but with poorer survival in WLM. Clustering of immune traits revealed the same five principal modules previously described in adult tumors (TCGA). These modules divided pediatric patients into six immune subtypes (S1-S6) with distinct survival outcomes. The S2 cluster showed the best overall survival, characterized by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration, while the reverse was observed in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS. CONCLUSIONS: We demonstrated that extracranial pediatric tumors could be classified according to their immune disposition, unveiling similarities with adults' tumors. Immunological parameters might be explored to refine diagnostic and prognostic biomarkers and to identify potential immune-responsive tumors.

Obstacles faced by healthcare providers during COVID-19 pandemic in Sudan.

The impacts of COVID -19 pandemic have been quite significant on healthcare providers. I was particularly challenging for those in Low and Middle-Income Countries including Sudan . Unfortunately, the pandemic has hit Sudan on extremely difficult time for the country and its people. The country was coming out of long-brutal and devastating dictatorship and transitioning to new democracy with civilian leadership. In addition to the pandemic related issues, trying to rebuild the health system during socioeconomic crisis, healthcare providers  in the country were challenged personally and professionally. These challenges include the stress of working in under-resourced settings with limited access to personal-protection equipment and testing kits raised the fear of contracting the virus and spreading it to their families. The professional, social, and personal life of healthcare providers have been dramatically changed by the ongoing pandemic, however, they are heroically accepting this change in a hope that, this will save the life of many more people. Nevertheless, their fights and sacrifices should at least be rewarded by governments and communities altogether strictly enforce the implementation of other preventive measures including vaccination, face masking, and social distancing and get all protected. We should all understand that, unless we are all protected no one is protected, so all must adapt to the new norm of life and collaborate not only on ending this pandemic but to prevent similar ones in the future.