Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells.

Metastasis frequently targets bones, where cancer cells from the primary tumour migrate to the bone marrow, initiating new tumour growth. Not only is bone the most common site for metastasis, but it also often marks the first site of metastatic recurrence. Despite causing over 90% of cancer-related deaths, effective treatments for bone metastasis are lacking, with current approaches mainly focusing on palliative care.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC.

Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Small cell lung cancers (SCLC) are comprised of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLC, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes, including non-canonical BAF (ncBAF) complexes, as top dependencies specific to POU2F3-positive SCLC.

Corrigendum: Systematic review and meta-analysis of screening tools for language disorder.

[This corrects the article DOI: 10.3389/fped.2022.

Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis.

The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK.

Association of Molnupiravir and Nirmatrelvir-Ritonavir with reduced mortality and sepsis in hospitalized omicron patients: a territory-wide study.

This study evaluates the association between antivirals (Molnupiravir and Nirmatrelvir-Ritonavir) and all-cause and respiratory mortality and organ dysfunction among high-risk COVID-19 patients during an Omicron outbreak. Two cohorts, Nirmatrelvir-Ritonavir versus control and Molnupiravir versus control, were constructed with inverse probability treatment weighting to balance baseline characteristics. Cox proportional hazards models evaluated the association of their use with all-cause mortality, respiratory mortality, and all-cause sepsis (a composite of circulatory shock, respiratory failure, acute liver injury, coagulopathy, and acute liver impairment).

Systematic Review and Meta-Analysis of Screening Tools for Language Disorder.

Unlabelled: Language disorder is one of the most prevalent developmental disorders and is associated with long-term sequelae. However, routine screening is still controversial and is not universally part of early childhood health surveillance. Evidence concerning the detection accuracy, benefits, and harms of screening for language disorders remains inadequate, as shown in a previous review.

Brahma safeguards canalization of cardiac mesoderm differentiation.

Differentiation proceeds along a continuum of increasingly fate-restricted intermediates, referred to as canalization. Canalization is essential for stabilizing cell fate, but the mechanisms that underlie robust canalization are unclear. Here we show that the BRG1/BRM-associated factor (BAF) chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells.

Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial.

Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by Ga-labelled prostate-specific membrane antigen positron emission tomography (Ga-PSMA-PET).

Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1-2.

Molecular basis of CTCF binding polarity in genome folding.

Current models propose that boundaries of mammalian topologically associating domains (TADs) arise from the ability of the CTCF protein to stop extrusion of chromatin loops by cohesin. While the orientation of CTCF motifs determines which pairs of CTCF sites preferentially stabilize loops, the molecular basis of this polarity remains unclear. By combining ChIP-seq and single molecule live imaging we report that CTCF positions cohesin, but does not control its overall binding dynamics on chromatin.

Elimination of long 3'-UTR mRNA isoform by CRISPR-Cas9 gene editing impairs dorsal root ganglion development and hippocampal neuron activation in mice.

The majority of mouse and human genes are subject to alternative cleavage and polyadenylation (APA), which most often leads to the expression of two or more alternative length 3' untranslated region (3'-UTR) mRNA isoforms. In neural tissues, there is enhanced expression of APA isoforms with longer 3'-UTRs on a global scale, but the physiological relevance of these alternative 3'-UTR isoforms is poorly understood. ( is a key integrator of calcium signaling that generates short () and long () 3'-UTR mRNA isoforms via APA.

Elav-Mediated Exon Skipping and Alternative Polyadenylation of the Dscam1 Gene Are Required for Axon Outgrowth.

Many metazoan genes express alternative long 3' UTR isoforms in the nervous system, but their functions remain largely unclear. In Drosophila melanogaster, the Dscam1 gene generates short and long (Dscam1-L) 3' UTR isoforms because of alternative polyadenylation (APA). Here, we found that the RNA-binding protein Embryonic Lethal Abnormal Visual System (Elav) impacts Dscam1 biogenesis at two levels, including regulation of long 3' UTR biogenesis and skipping of an upstream exon (exon 19).

Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: Interim outcomes of a prospective clinical trial.

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa.

Small-molecule anticancer agents kill cancer cells by harnessing reactive oxygen species in an iron-dependent manner.

In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner. Results of the preliminary studies are consistent with the recently described cell death mechanism ferroptosis. Studies are in progress to confirm ferroptosis as the cell death mechanism and to identify the specific molecular targets of these small molecule anticancer agents.

Evaluation of the preimplantation worksheet in determining Calypso eligibility for men prescribed postprostatectomy radiotherapy with electromagnetic transponder guidance.

This study aimed to assess the design and performance of the preimplant suitability worksheet in determining Calypso eligibility for prostate cancer patients prescribed postprostatectomy radiotherapy with electromagnetic transponder guidance. The medical records and radiotherapy planning datasets of 75 patients prospectively recruited between June 2015 and September 2016 to a Phase 2 trial evaluating electromagnetic transponder-guided postprostatectomy radiotherapy were retrospectively examined. Correlation and differences between computed tomography (CT)-defined greater trochanter and prostatic fossa landmarks were evaluated.

Radiotherapy in anaplastic thyroid carcinoma: An Australian experience.

Introduction: Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period.

Methods: A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013.

Radiotherapy in well-differentiated thyroid cancer: is it underutilized?

Background: The usual management of thyroid cancer is surgery and radioactive iodine. The role of external beam radiotherapy (EBRT) in well-differentiated thyroid carcinoma remains controversial. Indications for the use of EBRT, contained within both the American and British Thyroid Association published guidelines, include unresectable or non-iodine avid disease, extra-thyroidal extension or distant metastatic disease.

MBD4-mediated glycosylase activity on a chromatin template is enhanced by acetylation.

The ability of the MBD4 glycosylase to excise a mismatched base from DNA has been assessed in vitro using DNA substrates with different extents of cytosine methylation, in the presence or absence of reconstituted nucleosomes. Despite the enhanced ability of MBD4 to bind to methylated cytosines, the efficiency of its glycosylase activity on T/G mismatches was slightly dependent on the extent of methylation of the DNA substrate. The reduction in activity caused by competitor DNA was likewise unaffected by the methylation status of the substrate or the competitor.

Relationship between sleep/wake patterns, temperament and overall development in term infants over the first year of life.

Background: This study sought to assess the relationship between the development of infant sleep/wake patterns, temperament and overall mental, motor and behavioural development over the first year of life. We hypothesised that infants with more regular sleep/wake patterns and longer sleep durations would have an easier temperament and higher developmental scores.

Study Design: Sleep/wake characteristics were recorded with the use of both parental sleep diary and actigraphy (Actiwatch AW64, Mini Mitter Company Inc, Sunriver, OR, USA) in 20 healthy term infants at monthly intervals over the first year of life.

The use of actigraphy for assessment of the development of sleep/wake patterns in infants during the first 12 months of life.

Maturation of sleep/wake patterns is one of the most important physiological developments during the first year of life. In this study, we aimed to compare the use of actigraphy and parental sleep diaries (SD) for recording the development of sleep/wake patterns longitudinally in term infants in their own home environments over the first 12 months of life. Twenty healthy term infants (7F/13M) were studied for 3 days each month in their own homes over the first 12 months of life.

Actigraphy correctly predicts sleep behavior in infants who are younger than six months, when compared with polysomnography.

Actigraphy has been widely used in adults and children. In infants, validation of actigraphy has typically used a comparison with behaviorally determined sleep state classification rather than polysomnography (PSG). This study validated actigraphy against PSG for determining sleep and waking states in infants who were younger than 6 mo.