Logistics for Rapid Isolation of Viruses From Humans.

An important aspect of microbiological surveillance is the ability to access live viruses for microneutralization assays, which enables the study of viral characteristics and mechanisms in vitro and production of positive controls for diagnostic methods. During the COVID-19 pandemic, the Public Health Agency of Sweden established a protocol for the rapid collection of clinical samples and subsequent isolation of novel virus variants.

A Gradual Transition Toward Anaplasia in Wilms Tumor Through Tolerance to Genetic Damage.

Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due to frequent resistance to chemotherapy. We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. Tissue sections from chemotherapy-treated DA WTs (n = 12) were compared with chemotherapy-treated nonanaplastic WTs (n = 15) in a tissue microarray system, enabling analysis of 769 tumor regions.

Wargaming cancer: a strategy for future precision oncology?

Development of drug resistance is a mounting problem in precision oncology, demanding a rethink of treatment strategy. Here, we apply concepts from military theory and espionage to the battle-like dynamics between cancer and its host, thereby identifying system vulnerabilities in cancer and ways of tricking cancer evolution into dead ends.

SIX1 as a Novel Immunohistochemical Marker in the Differential Diagnosis of Rhabdomyosarcoma.

Differential diagnosis of rhabdomyosarcoma (RMS) is challenging. Sineoculis homeobox homolog 1 (SIX1) is an oncogene involved in skeletal muscle differentiation. We compared protein expression patterns of SIX1 in RMS and its most common differential diagnoses.

Systematic orientation of fresh rectal suction biopsies improves histopathological diagnostics in hirschsprung's disease - a method description and preliminary report.

Background: Optimizing rectal suction biopsy (RSB) diagnostics in Hirschsprung's disease (HD) may shorten diagnostic time and prevent need for repeated biopsies.

Aim: To explore whether systematic orientation of fresh RSB specimens increased biopsy quality, diagnostic times, diagnostic efficacy, and histopathologic workload, and to explore these outcome measures for aganglionic specimens.

Materials/methods: This was an observational case-control study conducted at a national referral center for HD on data collected from the local HD-diagnostic register.

Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution.

Purpose: While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.

Experimental Design: We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction.

Macrophage infiltration promotes regrowth in MYCN-amplified neuroblastoma after chemotherapy.

Despite aggressive treatment, the 5-year event-free survival rate for children with high-risk neuroblastoma is <50%. While most high-risk neuroblastoma patients initially respond to treatment, often with complete clinical remission, many eventually relapse with therapy-resistant tumors. Novel therapeutic alternatives that prevent the recurrence of therapy-resistant tumors are urgently needed.

Building a precision medicine infrastructure at a national level: The Swedish experience.

Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens.

Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors.

The expansion of knowledge regarding driver mutations for Wilms tumor (WT) and malignant rhabdoid tumor of the kidney (MRT) and various translocations for other pediatric renal tumors opens up new possibilities for diagnosis and treatment. In addition, there are growing data surrounding prognostic factors that can be used to stratify WT treatment to improve outcomes. Here, we review the molecular landscape of WT and other pediatric renal tumors as well as WT prognostic factors.

Histopathological dimensions differ between aganglionic and ganglionic bowel wall in children with Hirschsprung's disease.

Background: In the validation of new imaging technology for children with Hirschsprung's disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group.

Aim: To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight.

Methods: This was an observational study of bowel specimens from children weighing 0-10 kg, operated on consecutively during 2018-2020.

Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance.

Chemotherapy resistance and relapses are common in high-risk neuroblastoma (NB). Here, we developed a clinically relevant in vivo treatment protocol mimicking the first-line five-chemotherapy treatment regimen of high-risk NB and applied this protocol to mice with -amplified NB patient-derived xenografts (PDXs). Genomic and transcriptomic analyses were used to reveal NB chemoresistance mechanisms.

Inactivation of RB1, CDKN2A, and TP53 have distinct effects on genomic stability at side-by-side comparison in karyotypically normal cells.

Chromosomal instability is a common feature in malignant tumors. Previous studies have indicated that inactivation of the classical tumor suppressor genes RB1, CDKN2A, and TP53 may contribute to chromosomal aberrations in cancer by disrupting different aspects of the cell cycle and DNA damage checkpoint machinery. We performed a side-by-side comparison of how inactivation of each of these genes affected chromosomal stability in vitro.

The immune cell atlas of human neuroblastoma.

Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for the development of immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 human NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison with normal fetal adrenal gland data. We provide a comprehensive immune cell landscape and characterize cell-state changes from normal tissue to NB.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

Objective: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress.

Design: Retrospective, observational.

Setting: Nationwide.

Diagnostic Efficacy of Rectal Suction Biopsy with Regard to Weight in Children Investigated for Hirschsprung's Disease.

Background/aim: Diagnostic efficacy, defined as the percentage of rectal suction biopsy (RSB) specimens sufficient enough to determine the absence of ganglia cells in Hirschsprung's disease (HD) diagnosis, has been reported to be low, requiring repeated biopsies. The aim was to explore whether RSB diagnostic efficacy was influenced by the child's weight and to ascertain whether RSB efficacy differed between aganglionic and ganglionic tissue.

Materials And Methods: Efficacy analyses were conducted in a national HD-center's register on children 0-15 kg, examined between 2011-2019.

Delineating the intra-patient heterogeneity of molecular alterations in treatment-naïve colorectal cancer with peritoneal carcinomatosis.

In a non-negligible number of patients with metastatic colorectal cancer (mCRC), the peritoneum is the predominant site of dissemination. Cure can be achieved by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but this procedure is associated with long-term morbidity and high relapse rates. Thus, there is a pressing need for improved therapeutic strategies and complementary biomarkers.

Branching Copy-Number Evolution and Parallel Immune Profiles across the Regional Tumor Space of Resected Pancreatic Cancer.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. The only option for curative treatment is resection of the tumor followed by standard adjuvant chemotherapy. Yet, early relapse due to chemoresistance is almost inevitable.