Performance of a Paired-End Sequencing-Based Noninvasive Prenatal Screening Test in the Detection of Genome-Wide Fetal Chromosomal Anomalies.

Background: Noninvasive prenatal tests (NIPTs) detect fetal chromosomal anomalies with high clinical sensitivity and specificity. We examined the performance of a paired-end sequencing-based NIPT in the detection of genome-wide fetal chromosomal anomalies including common trisomies, sex chromosomal aneuploidies (SCA), rare autosomal aneuploidies (RAAs), and partial deletions/duplications ≥7 Mb.

Methods: Frozen plasma samples from pregnant women were tested using the VeriSeq NIPT Solution v2 assay.

Facilitators and barriers to employment for persons with chronic spinal cord injury or disorder: A qualitative study framed by the person-environment-occupation model.

Context/objective: Prolonged unemployment is common for people living with a spinal cord injury or disorder (SCI/D) and can impact negatively on quality of life. The present study examines stakeholder perspectives and experiences with the job search process in order to identify service gaps and return-to-work solutions.

Design: In-depth semi-structured interviews were thematically analysed, with questions focused on factors that can help or hinder efforts to gain employment.

Truncated Actin-Targeting Macrolide Derivative Blocks Cancer Cell Motility and Invasion of Extracellular Matrix.

Cancer metastasis is a complex process involving highly motile tumor cells that breach tissue barriers, enter the bloodstream and lymphatic system, and disseminate throughout the body as circulating tumor cells. The primary cellular mechanism contributing to these critical events is the reorganization of the actin cytoskeleton. Mycalolide B (MycB) is an actin-targeting marine macrolide that can suppress proliferation, migration, and invasion of breast and ovarian cancer cells at low nanomolar doses.

Case-Control Study of Nodding Syndrome in Acholiland: Urinary Multi-Mycotoxin Screening.

This case-control study adds to the growing body of knowledge on the medical, nutritional, and environmental factors associated with Nodding Syndrome (NS), a seizure disorder of children and adolescents in northern Uganda. Past research described a significant association between NS and prior history of measles infection, dependence on emergency food and, at head nodding onset, subsistence on moldy maize, which has the potential to harbor mycotoxins. We used LC-MS/MS to screen for current mycotoxin loads by evaluating nine analytes in urine samples from age-and-gender matched NS cases (n = 50) and Community Controls (CC, n = 50).

Short Diagnosis-to-Treatment Interval Is Associated With Higher Circulating Tumor DNA Levels in Diffuse Large B-Cell Lymphoma.

Purpose: Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.

Accuracy of estimated fetal weight assessment in fetuses with abdominal wall defects.

Background: Gastroschisis and omphalocele are congenital abdominal wall defects in which the bowel and other abdominal contents extrude from the fetal abdominal cavity. Standard formulas for estimated fetal weight using ultrasound include fetal abdominal circumference measurement and have a range of error of approximately 10%. It is unknown whether the accuracy of estimated fetal weight assessment is compromised in fetuses with abdominal wall defects because of the extrusion of abdominal contents.

Impacts of injury severity on long-term outcomes following motor vehicle crashes.

Background: There is growing evidence that a range of pre-injury, injury related and post-injury factors influence social and health outcomes across the injury severity spectrum. This paper documents health related outcomes for people with mild, moderate and severe injury after motor vehicle crash (MVC) injuries in New South Wales, Australia.

Methods: This inception cohort study followed 2019 people injured in MVCs, for 6 and 12 months post-injury.

Citizen science as a tool for arboviral vector surveillance in a resourced-constrained setting: results of a pilot study in Honiara, Solomon Islands, 2019.

Background: Recent arboviral disease outbreaks highlight the value a better understanding of the spread of disease-carrying mosquitoes across spatial-temporal scales can provide. Traditional surveillance tools are limited by jurisdictional boundaries, workforce constraints, logistics, and cost; factors that in low- and middle-income countries often conspire to undermine public health protection efforts. To overcome these, we undertake a pilot study designed to explore if citizen science provides a feasible strategy for arboviral vector surveillance in small developing Pacific island contexts.

The role of stress reactivity and pre-injury psychosocial vulnerability to psychological and physical health immediately after traumatic injury.

Background: Traumatic injuries can have long-term negative impacts on health, especially psychological health. A biopsychosocial approach is recommended to identify those likely to experience psychosocial stress, however large individual differences exist in stress reactivity and post-injury health that remain unexplored. Therefore, we investigated autonomic nervous system (ANS) stress responses and pre-existing psychosocial vulnerability as contributors to health in individuals who sustained a traffic-related injury.

GluD to the edge: synaptic organizer competition shapes dendrite arbors.

The relationship between synaptogenesis and dendritogenesis is poorly understood, particularly in mammals. In this issue of Neuron, Takeo et al. (2021) manipulate synaptic organizers GluD2 and cerebellin-1 to show that Purkinje cells regulate how their dendrites branch by competing with neighboring cells for synaptic real estate.

Coronavirus disease 2019 vaccines in pregnancy.

As of December 1, 2020, nearly 64 million people have been infected with the severe acute respiratory syndrome coronavirus 2 worldwide with nearly 1.5 million global deaths. The impact of this virus has continued to overwhelm hospital infrastructure and demanded remodeling of healthcare systems.

Pilot study assessing the effect of osteopathic manipulative treatment (OMT) on length of stay in neonates after therapeutic hypothermia.

Context: Term neonates treated with therapeutic hypothermia (TH) may experience delays in acquiring skills for oral feeding, thus prolonging hospital admission.

Objective: To determine whether osteopathic manipulative treatment (OMT) can decrease the overall length of stay (LOS) for term neonates by accelerating the transition to full oral feeds.

Methods: A pilot study was conducted to compare LOS in term neonates treated with OMT to matched historical controls.

Perspectives of people with late age-related macular degeneration on mental health and mental wellbeing programmes: a qualitative study.

Purpose: People with age-related macular degeneration (AMD) experience high rates of depression, but rarely engage in or have access to tailored mental wellbeing programmes. This qualitative study investigated the perspectives of those primarily with late AMD on mental health and mental wellbeing programmes.

Methods: Twenty-eight people with late AMD in at least one eye, and one person with early AMD in both eyes, aged 56-87 years (mean age 78 years) attending a private eye clinic between December 2019 and January 2020 in Sydney, New South Wales, Australia, participated.

Heated column experiments: A proxy for investigating the effects of in situ thermal recovery operations on groundwater geochemistry.

In situ thermal recovery is utilized extensively for unconventional bitumen extraction in the Cold Lake-Beaver River (CLBR) basin in Alberta, Canada. Public health concerns have been raised over potable groundwater contamination and arsenic release adjacent to these operations within the CLBR basin, which have been linked to subsurface heating of aquifer sediments. Under localized heated conditions, As-bearing aquifer sediments have been shown to undergo water-rock interactions and release constituents at near neutral pH conditions; however, release mechanisms have yet to be conclusively reported.

Synthesis, crystal structure, and electronic structure of LiPbSiS: a quaternary thiosilicate with a compressed chalcopyrite-like structure.

The new quaternary thiosilicate, LiPbSiS (dilithium lead silicon tetrasulfide), was prepared in an evacuated fused-silica tube via high-temperature, solid-state synthesis at 800 °C, followed by slow cooling. The crystal structure was solved and refined using single-crystal X-ray diffraction data. By strict definition, the title compound crystallizes in the stannite structure type; however, this type of structure can also be described as a compressed chalcopyrite-like structure.

Human Lung-Resident Macrophages Colocalize with and Provide Costimulation to PD1 Tissue-Resident Memory T Cells.

Tissue-resident memory T cells (T) play a critical role in the defense against inhaled pathogens. The isolation and study of human lung tissue-resident memory T cells and lung-resident macrophages (M) are limited by experimental constraints. To characterize the spatial and functional relationship between M and human lung tissue-resident memory T cells using lung perfusion (EVLP).

Central systolic blood pressure relates inversely to nitric oxide synthesis in young black adults: the African-PREDICT study.

Lower nitric oxide (NO) bioavailabilty associates with hypertension in patients and elderly populations. With hypertension known to develop earlier in black populations, we compared both plasma and urinary NO-related markers and their associations with central systolic blood pressure (cSBP) and arterial stiffness in healthy young black and white adults. We included healthy black and white men and women (n = 1110; 20-30 years) and measured cSBP and pulse wave velocity (PWV), along with both plasma and urinary arginine, homoarginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), as well as urinary ornithine/citrulline, nitrite and nitrate.

Understanding tumour cell heterogeneity and its implication for immunotherapy in liver cancer using single-cell analysis.

Over the last decade, precision medicine and immunotherapeutic approaches have become increasingly popular in oncology. Early clinical trials reported promising results, but response rates in phase III clinical trials have been suboptimal. Knowledge gained from subsequent translational studies indicates the importance of targeting the tumour microenvironment to overcome resistance to immunotherapy.

DNA Methylation Profiling of Human Hepatocarcinogenesis.

Background And Aims: Mutations in TERT (telomerase reverse transcriptase) promoter are established gatekeepers in early hepatocarcinogenesis, but little is known about other molecular alterations driving this process. Epigenetic deregulation is a critical event in early malignancies. Thus, we aimed to (1) analyze DNA methylation changes during the transition from preneoplastic lesions to early HCC (eHCC) and identify candidate epigenetic gatekeepers, and to (2) assess the prognostic potential of methylation changes in cirrhotic tissue.

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis.

PAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events.