Combating chemoresistance: Current approaches & nanocarrier mediated targeted delivery.

Chemoresistance, a significant challenge in effective cancer treatment needs clear elucidation of the underlying molecular mechanism for the development of novel therapeutic strategies. Alterations in transporter pumps, oncogenes, tumour suppressor genes, mitochondrial function, DNA repair processes, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, epigenetic modifications, and exosome secretion lead to chemoresistance. Despite notable advancements in targeted cancer therapies employing both small molecules and macromolecules success rates remain suboptimal due to adverse effects like drug efflux, target mutation, increased mortality of normal cells, defective apoptosis, etc.

Engineering nanoliposomal tiotropium bromide embedded in a lactose-arginine carrier forming Trojan-particle dry powders for efficient pulmonary drug delivery: A combined approach of in vitro-3D printing and in silico-CFD modeling.

Nanocarrier-based dry powders for lung disease treatment are crucial, with in vitro and in silico research being pivotal to their success. This study introduces a method for creating Tiotropium-bromide liposomal inhalation dry powder, termed "Trojan-particles," utilizing thin-film hydration and spray-drying with lactose-arginine carriers. Encapsulating tiotropium-bromide in nanoliposomes enhances lung treatment via liposomes' unique features.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Imageless imagery in aphantasia revealed by early visual cortex decoding.

Activity in the early visual cortex is thought to tightly couple with conscious experience, including feedback-driven mental imagery. However, in aphantasia (a complete lack of visual imagery), the state of mental imagery, what takes its place, or how any activity relates to qualia remains unknown. This study analyzed univariate (amplitude) and multivariate (decoding) blood-oxygen-level-dependent (BOLD) signals in primary visual cortex during imagery attempts.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

Six months of hybrid closed-loop therapy improves diabetes-specific positive well-being, and reduces diabetes distress and fear of hypoglycemia: secondary analysis of a randomized controlled trial.

Introduction: This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research Design And Methods: In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial.

Proposal and exploration of a novel score to quantify patient-perceived burden of inflammatory bowel disease under routine care.

Background: The burden of inflammatory bowel disease (IBD) is often reported on from a system or cost viewpoint. We created and explored a novel patient-perceived burden of disease (PPBoD) score in a large Australasian cohort.

Aim: To create and explore a novel patient-perceived burden of disease (PPBoD) score in a large Australasian cohort, and correlate PPBoD scores with demographics, disease and treatment factors.

Risk factors associated with 30-day mortality following COVID-19 infection in patients receiving kidney replacement therapy in Australian and New Zealand.

Background And Aims: The COVID-19 pandemic impacted greatest among patients with pre-existing chronic health conditions, including chronic kidney disease. This retrospective cohort study aimed to investigate the 30-day mortality of patients receiving kidney replacement therapy (KRT) after infection with COVID-19, living in Australia and New Zealand between 2020 and 2022, including patients on haemodialysis (HD), peritoneal dialysis (PD) and renal transplant (KT) recipients.

Methods: This is a retrospective cohort study using data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA).

From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.

Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions.

Advancing Quality and Safety Culture in Healthcare: Insights From the Evaluation of an Improvement Science Program for Nurses and Midwives.

Aims: This paper presents the outcomes and insights gained from the implementation of an Improvement Science program tailored for nursing and midwifery staff within a large local health district in New South Wales. The programme aimed to enhance frontline clinicians' confidence and capability in quality improvement, ultimately improving patient outcomes and safety culture.

Design: Through an explanatory sequential mixed-methods evaluation study, we assessed the programme's effectiveness in building capacity, sustaining practice changes and fostering a culture of continuous improvement.

Retrieving and Identifying Remnants of Artefacts on Local Devices Using Sync.com Cloud.

Most current research in cloud forensics is focused on tackling the challenges encountered by forensic investigators in identifying and recovering artifacts from cloud devices. These challenges arise from the diverse array of cloud service providers as each has its distinct rules, guidelines, and requirements. This research proposes an investigation technique for identifying and locating data remnants in two main stages: artefact collection and evidence identification.

The Role of Nutrient Supplements in Female Infertility: An Umbrella Review and Hierarchical Evidence Synthesis.

Background And Objectives: Nutrient supplements are commonly used to improve fertility outcomes by women with infertility trying to conceive spontaneously or utilising medically assisted reproduction (MAR). However, despite their widespread use and perceived safety, there is a lack of clear guidance on the efficacy and safety of these supplements for female infertility. The aim of this umbrella review was to identify the best available and most recent evidence on the efficacy and safety of nutrient supplements for female infertility to provide evidence-based guidance for clinicians and reproductive couples.

Portrait of a Cerebral Killer.

: Primary amebic meningoencephalitis (PAM) caused by is a rare and devastating infection of the central nervous system, often diagnosed late, due to its rapid progression and nonspecific symptoms. We report one of the youngest documented pediatric Vietnamese cases of PAM in a 10-month-old girl from the Mekong Delta, Vietnam. The diagnosis was confirmed through multiplex real-time PCR (MPL-rPCR), microscopy, and sequencing.

Seizures Following Carotid Endarterectomy: A Comprehensive Meta-Analysis of 69,479 Patients and Evidence-Based Recommendations for Perioperative Care.

Seizures are a rare but potentially serious complication following carotid endarterectomy (CEA). Understanding their prevalence and associated factors is crucial for optimizing perioperative care and improving patient outcomes. This meta-analysis aimed to estimate the pooled prevalence of seizures following CEA and explore clinical and procedural factors contributing to their occurrence.

Impact of Year and Genotype on Benzoxazinoids and Their Microbial Metabolites in the Rhizosphere of Early-Vigour Wheat Genotypes in Southern Australia.

Wheat () is grown on more arable acreage than any other food crop and has been well documented to produce allelochemicals. Wheat allelochemicals include numerous benzoxazinoids and their microbially transformed metabolites that actively suppress growth of weed seedlings. Production and subsequent release of these metabolites by commercial wheat cultivars, however, has not yet been targeted by focussed breeding programmes seeking to develop more competitive crops.

Comparative Analysis of Mechanistic and Correlative Models for Global and Bhutan-Specific Suitability of Parthenium Weed and Vulnerability of Agriculture in Bhutan.

Parthenium weed ( L.) is one of the most noxious and fast-spreading invasive alien species, posing a major threat to ecosystems, agriculture, and public health worldwide. Mechanistic and correlative species distribution models are commonly employed to determine the potential habitat suitability of parthenium weed.

Scaffolding informed consent.

The principle of respecting patient autonomy underpins the concept and practice of informed consent. Yet current approaches to consent often ignore the ways in which the exercise of autonomy is deeply epistemically dependent.In this paper, we draw on philosophical descriptions of autonomy 'scaffolding' and apply them to informed consent in medicine.

Big-Hearted Invaders: The Impacts of Range Expansion and Parasite Infection on Heart Mass in Cane Toads.

The invasion of cane toads (Rhinella marina) across tropical Australia has resulted in the rapid evolution of traits that enable higher rates of dispersal, and that adapt toads to hot dry climates. In anurans, a larger heart facilitates both locomotor activity and desiccation tolerance. Heart size is also often affected, either directly or indirectly, by parasite infections.

Health Care Utilisation and Unmet Needs in Survivors of Head and Neck Cancer in Regional Australia: A Cross-Sectional Survey.

Background: The post-treatment survivorship period marks the transition away from acute care and poses distinct challenges for individuals with head and neck cancer (HNC). This can be especially challenging for people in regional areas who travel long distances to access care and experience unique challenges in accessing health services.

Aim: To investigate unmet needs and healthcare utilisation of survivors of HNC in regional areas.

Regulatory responses to ultra-processed foods are skewed towards behaviour change and not food system transformation.

Growing evidence suggests that diets high in ultra-processed foods (UPFs) are harming human and planetary health. UPFs therefore pose a complex regulatory challenge, yet, to date, little research has systematically assessed how governments have responded to UPFs in national food policies. Here we analyse data from the NOURISHING database to assess the scope and strength of UPF-related regulatory interventions worldwide, using three frameworks-namely, NOURISHING, the Nuffield Ladder and the Modalities of Control framework.

The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.

Male rats choose higher doses of nicotine in anticipation of a signalled period of drug non-availability.

Humans and animals use information about future access to rewards to influence their behaviour in the present, however the evidence for this is largely anecdotal. Here we use the nicotine intravenous self-administration paradigm to ask whether rats can use an auditory stimulus signalling a long (450 s) signalled time-out on the next trial to influence their nicotine intake in the present. Rats were trained to choose between low (15 µg/kg/infusion), medium (30 µg/kg/infusion) or high (60 µg/kg/infusion) doses of nicotine on any given trial.

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.

Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.

Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.

Protocol for extracting flow hydrograph shape metrics for use in time-series flood hydrology analysis.

The shape characteristics of flow hydrographs hold essential information for understanding, monitoring and assessing changes in flow and flood hydrology at reach and catchment scales. However, the analysis of individual hydrographs is time consuming, making the analysis of hundreds or thousands of them unachievable. A method or protocol is needed to ensure that the datasets being generated, and the metrics produced, have been consistently derived and validated.