GradeDiff-IM: An Ensembles Model-based Grade Classification of Breast Cancer.

Cancer grade classification is a challenging task identified from the cell structure of healthy and abnormal tissues. The partitioner learns about the malignant cell through the grading and plans the treatment strategy accordingly. A major portion of researchers used DL models for grade classification.

The 1831 CE mystery eruption identified as Zavaritskii caldera, Simushir Island (Kurils).

Polar ice cores and historical records evidence a large-magnitude volcanic eruption in 1831 CE. This event was estimated to have injected ~13 Tg of sulfur (S) into the stratosphere which produced various atmospheric optical phenomena and led to Northern Hemisphere climate cooling of ~1 °C. The source of this volcanic event remains enigmatic, though one hypothesis has linked it to a modest phreatomagmatic eruption of Ferdinandea in the Strait of Sicily, which may have emitted additional S through magma-crust interactions with evaporite rocks.

Methodology for the Positive Voices 2022 Survey of People With HIV Accessing Care in England, Wales, and Scotland: Cross-Sectional Questionnaire Study.

Background: Due to advances in treatment, HIV is now a chronic condition with near-normal life expectancy. However, people with HIV continue to have a higher burden of mental and physical health conditions and are impacted by wider socioeconomic issues. Positive Voices is a nationally representative series of surveys of people with HIV in the United Kingdom.

Age and biologic survival in patients with moderate-to-severe psoriasis: A cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

Background: The current management of psoriasis does not differentiate between young and old patients in selecting the safest and/or most effective biologic.

Objectives: To explore the effect of age at treatment initiation in response to biologics in patients with moderate-to-severe psoriasis in the UK and Eire.

Methods: Data from patients registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2024 on first course of Tumour Necrosis Factor (TNF), interleukin (IL) 12/13, IL-17 and IL-23 inhibitors (i) with at least 6 months' follow-up were included.

Are we ready for self-sampling for cervical cancer screening? Insights from service providers and policy makers in Nepal.

Cervical cancer is the leading cancer among women in Nepal, but the country has very low screening rate, with only 8.2% of women being screened. In recent years, a self-sampling kit for testing for the human papillomavirus (HPV) has been developed to allow self-sampling and enable early detection of cervical abnormalities.

Artificial Intelligence for Predicting HER2 Status of Gastric Cancer Based on Whole-Slide Histopathology Images: A Retrospective Multicenter Study.

Human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC) shows a robust response to the combined therapy based HER2-targeted therapy. The application of these therapies is highly dependent on the evaluation of tumor HER2 status. However, there are many risks and challenges in HER2 assessment in GC.

Preservation and early evolution of scalidophoran ventral nerve cord.

Ecdysozoan worms (Nematoida + Scalidophora) are typified by disparate grades of neural organization reflecting a complex evolutionary history. The fossil record offers a unique opportunity to reconstruct the early character evolution of the nervous system via the exceptional preservation of extinct representatives. We focus on their nervous system as it appears in early and mid-Cambrian fossils.

Redesigning protonic ceramic electrochemical cells to lower the operating temperature.

Protonic ceramic electrochemical cells (PCECs) can operate at intermediate temperatures (450° to 600°C) for power generation and hydrogen production. However, the operating temperature is still too high to revolutionize ceramic electrochemical cell technology. Lowering the operating temperature to <450°C will enable a wider material choice and reduce system costs.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.

Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney.

The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models.

Recent research has shown that mtDNA-deficient cancer cells (ρ cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1) mice markedly delayed tumor formation after grafting ρ cancer cells.

The role of mobile DNA elements in the dynamic of plants genome plasticity.

Plants host a range of DNA elements capable of self-replication. These molecules, usually associated to the activity of transposable elements or viruses, are found integrated in the genome or in the form of extrachromosomal DNA. The activity of these elements can impact genome plasticity by a variety of mechanisms, including the generation of structural variants, the shuffling of regulatory or coding DNA sequences across the genome, and DNA endoduplication.

Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Ganaxolone: A Review in Epileptic Seizures Associated with Cyclin-Dependent Kinase-Like 5 Deficiency Disorder.

Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Critical Structures of Bisphenol Analogues on Embryonic Toxicity Identified by a Computational Approach.

Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives.

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies.

Purpose: This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies.

Methods: Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024.

A Consistent Lack of Consistency: Definitions, Evidentiary Expectations and Potential Use of Meaningful Change Data in Clinical Outcome Assessments Across Stakeholders. Results from a DIA Working Group Literature Review and Survey.

Background: Clinical outcome assessments (COAs) measure how patients feel or function and can be used to understand which patients experience benefits of treatment and which do not. Interpretation of COA data is influenced by how meaningful change is defined. We aimed to compare how different stakeholders define, assess, and use meaningful change for decisions that impact patients.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

The Impact of Artificial Intelligence and Machine Learning in Organ Retrieval and Transplantation: A Comprehensive Review.

This narrative review examines the transformative role of Artificial Intelligence (AI) and Machine Learning (ML) in organ retrieval and transplantation. AI and ML technologies enhance donor-recipient matching by integrating and analyzing complex datasets encompassing clinical, genetic, and demographic information, leading to more precise organ allocation and improved transplant success rates. In surgical planning, AI-driven image analysis automates organ segmentation, identifies critical anatomical features, and predicts surgical outcomes, aiding pre-operative planning and reducing intraoperative risks.

Cardiovascular magnetic resonance-estimated pulmonary capillary wedge pressure, congestion markers, and effect of empagliflozin in patients with heart failure with reduced ejection fraction and dysglycaemia (SUGAR-DM-HF).

Aims: A cardiovascular magnetic resonance (CMR) approach to non-invasively estimate left ventricular (LV) filling pressure was recently developed and shown to correlate with invasively measured pulmonary capillary wedge pressure (PCWP). We examined the association between CMR-estimated PCWP (CMR-PCWP) and other imaging and biomarker measures of congestion, and the effect of empagliflozin on these, in the SUGAR-DM-HF trial (NCT03485092).

Methods And Results: SUGAR-DM-HF enrolled 105 patients with heart failure with reduced ejection fraction (HFrEF) and pre-diabetes or type 2 diabetes who were randomly assigned to empagliflozin 10 mg or placebo once daily for 36 weeks.

Novel digital leakage notification system can promote better stoma management routines: a multicentre clinical trial.

Background: Most people with a stoma are anxious about stoma-related leakage.

Aims: To investigate the impact of a novel digital leakage notification system on worry related to stoma leakage, and to evaluate the effect on overall stoma care management.

Method: A 12-week interventional, single-arm, multicentre study was conducted in the UK to evaluate the novel digital leakage notification system, including a telemedicine-based support service (=test product), as part of routine stoma care in patients with a recent stoma formation (ClinicalTrials.

Developing structured clinical review templates in an integrated respiratory team during COVID-19: a qualitative review.

Introduction: In response to the SARS-CoV-2 pandemic in March 2020 and required adherence to infection control measures and patient and staff safety, an integrated respiratory team (IRT) developed guideline-based templates to support the team in teleconsultation reviews of their patients. Patients had been diagnosed with sleep disordered breathing, chronic obstructive pulmonary disease, asthma, interstitial lung disease or had oxygen assessment needs.

Methods: Nine IRT members collaboratively developed content for the templates to assist in clinical reviews.