Correction: HIV retesting for pregnant and breastfeeding women across maternal child health services in Nampula, Mozambique.

[This corrects the article DOI: 10.1371/journal.pone.

An Improved Focus-Forming Assay for Determination of the Dengue Virus Titer.

Dengue virus (DENV), a common and prevalent mosquito-borne endemic disease, is caused by four serotypes (DENV-1-4) and has spread rapidly on a global scale over the past decade. A crucial step in the development of antiviral therapeutics requires the utilization of in vitro cell-based techniques, such as plaque assays and focus-forming assays (FFA) for virus quantification. Vero cells have been widely used for FFA and plaque assay; however, there are instances when their efficacy and efficiency in the detection of certain clinical DENV isolates are low.

A protein phosphatase 1 specific phatase rgeting eptide (PhosTAP) to identify the PP1 phosphatome.

Phosphoprotein phosphatases (PPPs) are the key serine/threonine phosphatases that regulate all essential signaling cascades. In particular, Protein Phosphatase 1 (PP1) dephosphorylates ~80% of all ser/thr phosphorylation sites. Here, we developed a phosphatase targeting peptide (PhosTAP) that binds all PP1 isoforms and does so with a stronger affinity than any other known PP1 regulator.

Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial.

Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC.

Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1).

A prM mutation that attenuates dengue virus replication in human cells enhances midgut infection in mosquitoes.

Dengue viruses (DENVs), like all viruses, evolve to perpetuate transmission of their species in their hosts. However, how DENV genetics influences dengue disease outbreaks remains poorly understood. Here, we examined isolates of the South Pacific dengue virus type 2 (DENV-2) that emerged in the 1970s and caused major dengue outbreaks in islands in this region until it reached Tonga, where only a few mild cases were reported.

Diffusion tensor MRI is sensitive to fibrotic injury in a mouse model of oxalate-induced chronic kidney disease.

Chronic kidney disease (CKD) is characterized by inflammation and fibrosis in the kidney. Renal biopsies and estimated glomerular filtration rate (eGFR) remain the standard of care, but these endpoints have limitations in detecting the stage, progression, and spatial distribution of fibrotic pathology in the kidney. MRI diffusion tensor imaging (DTI) has emerged as a promising noninvasive technology to evaluate renal fibrosis in vivo both in clinical and preclinical studies.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia.

Serotype-Specific Regulation of Dengue Virus NS5 Protein Subcellular Localization.

Dengue virus (DENV) nonstructural protein 5 (NS5), consisting of methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, is critical for viral RNA synthesis within endoplasmic reticulum-derived replication complexes in the cytoplasm. However, a significant proportion of NS5 is localized to the nucleus of infected cells for DENV2, 3, and 4, whereas DENV1 NS5 is localized diffusely in the cytoplasm. We still have an incomplete understanding of how the DENV NS5 subcellular localization is regulated.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab.

What to do when traditional rescue therapies fail in acute severe ulcerative colitis.

Acute severe ulcerative colitis (ASUC) is a medical emergency that affects approximately 25% of patients with ulcerative colitis at some point in time in their lives. Outcomes of ASUC are highly variable. Approximately 30% of patients do not respond to corticosteroids and up to 50% of patients do not respond to rescue therapy (infliximab or cyclosporin) and require emergency colectomy.

Physiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation.

Lactation insufficiency affects many women worldwide. During lactation, a large portion of mammary gland alveolar cells become polyploid, but how these cells balance the hyperproliferation occurring during normal alveologenesis with terminal differentiation required for lactation is unknown. Here, we show that DNA damage accumulates due to replication stress during pregnancy, activating the DNA damage response.

Evaluating the Digital Health Experience for Patients in Primary Care: Mixed Methods Study.

Background: The digital health divide for socioeconomic disadvantage describes a pattern in which patients considered socioeconomically disadvantaged, who are already marginalized through reduced access to face-to-face health care, are additionally hindered through less access to patient-initiated digital health. A comprehensive understanding of how patients with socioeconomic disadvantage access and experience digital health is essential for improving the digital health divide. Primary care patients, especially those with chronic disease, have experience of the stages of initial help seeking and self-management of their health, which renders them a key demographic for research on patient-initiated digital health access.

Digital health access, uptake, literacy and trust in people with experience of homelessness.

Background And Objectives: Although digital health promises improved healthcare efficiency and equity, access and uptake might be low in disadvantaged populations. We measured access to digital health technology, the uptake of digital health, digital health literacy and COVID-19 vaccination intentions in an inner-city Australian population experiencing homelessness.

Method: An existing Australian survey, including a validated digital health literacy measure (eHealth Literacy Scale [eHEALS]), was modified and distributed in three general practices specifically targeting the homeless population.

Safety and Effectiveness of Janus Kinase Inhibitors in the Management of Inflammatory Bowel Disease Following Liver Transplantation.

Background: The management of inflammatory bowel disease [IBD] patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase [JAK] inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia.

Methods: All liver transplant recipients from the Australian states of Victoria, New South Wales, and Tasmania, who required tofacitinib or upadacitinib for the treatment of IBD, were identified using prospectively maintained liver transplant databases.

Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

Aim: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care.

Comparison of differences in sensory, volatile odour-activity and volatile profile of commercial plant-based meats.

Descriptive sensory analysis was paired with temporal check-all-that-apply gas-chromatography olfactometry (TCATA GC-O) to compare differences in perceived flavour and volatile odour activity across a series of commercial plant-based meat analogues (PBMAs) versus conventional beef products. Multiple factor analysis separated PBMAs in two clusters along the first principal axis. The first cluster, rated higher in meaty flavour and odour, also showed higher citation proportions of sulfurous odourants.

Upadacitinib in end stage renal disease: A case of acute severe ulcerative colitis.

Recent data, indicating that inflammatory bowel disease (IBD) may be a risk factor for future chronic kidney disease, highlight the need to study the safety and clinical effectiveness of advanced IBD therapies in patients with end stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m. Upadacitinib, a selective oral Janus kinase (JAK) 1 inhibitor, has demonstrated efficacy in the management of moderate to severe ulcerative colitis.

Spectral Grouping of Electrically Encoded Sound Predicts Speech-in-Noise Performance in Cochlear Implantees.

Objectives: Cochlear implant (CI) users exhibit large variability in understanding speech in noise. Past work in CI users found that spectral and temporal resolution correlates with speech-in-noise ability, but a large portion of variance remains unexplained. Recent work on normal-hearing listeners showed that the ability to group temporally and spectrally coherent tones in a complex auditory scene predicts speech-in-noise ability independently of the audiogram, highlighting a central mechanism for auditory scene analysis that contributes to speech-in-noise.

The SDS22:PP1:I3 complex: SDS22 binding to PP1 loosens the active site metal to prime metal exchange.

SDS22 and Inhibitor-3 (I3) are two ancient regulators of protein phosphatase 1 (PP1) that regulate multiple essential biological processes. Both SDS22 and I3 form stable dimeric complexes with PP1; however, and atypically for PP1 regulators, they also form a triple complex, where both proteins bind to PP1 simultaneously (SPI complex). Here we report the crystal structure of the SPI complex.

Prognostic impact of abnormal sodium burden in heart failure patients with preserved ejection fraction.

Background: Sodium abnormality is common in patients with heart failure (HF) and is associated with adverse clinical outcomes. The aim of this study is to determine the impact of abnormal sodium burden on long-term mortality and hospitalization in HF with preserved ejection fraction (HFpEF).

Methods: We analysed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial with available baseline and follow-up data (n = 1717).

Associations between long-term averages of metabolic parameters in adulthood and cardiac structure and function in later life.

The effects of long-term levels of body mass index (BMI), blood pressure (BP), plasma lipids and fasting blood glucose (FBG) on the cardiac structure and function in later life in general population are to evaluate. We included adult participants without heart failure from Framingham Heart Study. The respective averages over a span of 30-36 years of seven parameters were pooled into linear regression models simultaneously to evaluate their associations with subsequent left atrial internal dimension (LAID), left ventricular mass index (LVMi), internal dimension (LVID), ejection fraction (LVEF), global longitudinal strain (GLS) and mitral inflow velocity to early diastolic mitral annular velocity (E/é).

Factors Associated With Response to Rescue Therapy in Acute Severe Ulcerative Colitis.

Background: Acute severe ulcerative colitis (ASUC) is a medical emergency for which colectomy is required in patients who do not respond to rescue therapy. While previous studies have predominantly focused on predicting outcome to first-line corticosteroid therapy, there is a need to understand the factors associated with response to rescue therapies in order to improve clinical outcomes. We reviewed the evidence regarding factors associated with response to rescue therapy in adults with ASUC and identified future directions for research.

Outcomes out to 12 months after sequential use of high-dose tofacitinib following infliximab in acute severe ulcerative colitis.

Acute severe colitis (ASUC) remains a significant cause of morbidity in up to 25% of patients with ulcerative colitis during their disease course. We present the outcomes out to 12 months following the use of high-dose tofacitinib, 10 mg three times daily (TDS), in patients with steroid and infliximab refractory ASUC. A total of 11 patients with ASUC who were treated with high-dose tofacitinib after failing sequential infliximab therapy between 2019 and 2021 were identified at an Australian tertiary centre.