Enhanced tumor response to adoptive T cell therapy with PHD2/3-deficient CD8 T cells.

While adoptive cell therapy has shown success in hematological malignancies, its potential against solid tumors is hindered by an immunosuppressive tumor microenvironment (TME). In recent years, members of the hypoxia-inducible factor (HIF) family have gained recognition as important regulators of T-cell metabolism and function. The role of HIF signalling in activated CD8 T cell function in the context of adoptive cell transfer, however, has not been explored in full depth.

Cardiophrenic lymph node metastasis as the sole presentation of high grade serous ovarian carcinoma.

Key Clinical Message: Cardiophrenic metastasis is typically a late stage manifestation of ovarian high grade serous carcinoma. Here we present a case where this was the sole presentation of this disease. This case challenges our current understanding of the natural course of ovarian high grade serous carcinoma.

Sodium compensation: a critical technology for transforming batteries from sodium-starved to sodium-rich systems.

Sodium-ion batteries (SIBs) have attracted wide attention from academia and industry due to the low cost and abundant sodium resources. Despite the rapid industrialization development of SIBs, it still faces problems such as a low initial coulombic efficiency (ICE) leading to a significant decrease in battery energy density (., 20%).

Sexual selection and life history interact to influence the evolution of paternal care.

Parental care is essential to offspring survival in many species. Understanding why males of some species provide care, whereas others do not, has received substantial attention. Previous research has found that sexual selection can favor paternal care, yet we still do not fully understand why sexual selection favors male care in some species but not others.

Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double-blind, placebo-controlled feasibility trial.

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 10/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure.

Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease.

Introduction: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology.

Methods: The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging).

Googling and health anxiety in older age-A case study of CBT incorporating a single case experimental design.

The use of online search engines to "google" health-related information is common in health anxiety, and requires careful consideration within psychological treatment. Its nature in older adult populations is less closely understood. This report demonstrates the reduction in googling frequency using cognitive-behavioral therapy in an 83-year-old female with health anxiety.

The Impacts of Climate Change on the Emergence and Reemergence of Mosquito-Borne Diseases in Temperate Zones: An Umbrella Review Protocol.

Introduction: Mosquito-borne diseases represent a global public health concern and are responsible for over 700 000 deaths globally every year. Additionally, many mosquito species have undergone a dramatic global expansion due to various factors, including climate change, and forecasts indicate that mosquito populations will persist in dispersing beyond their present geographic range, namely in temperate climates. The research literature on this topic has grown in recent years, including some systematic evidence synthesis.

Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation.

Glypican-3 (GPC3) is overexpressed in hepatocellular carcinomas and hepatoblastomas and represents an important therapeutic target but the biologic importance of GPC3 in liver cancer is unclear. To date, there are limited data characterizing the biological implications of GPC3 knockout (KO) in liver cancers that intrinsically express this target. Here, we report on the development and characterization of GPC3-KO liver cancer cell lines and compare to them to parental lines.

Modular and automated synthesis of oligonucleotide-small molecule conjugates for cathepsin B mediated traceless release of payloads.

The reversible attachment of small molecules to oligonucleotides provides versatile tools for the development of improved oligonucleotide therapeutics. However, cleavable linkers in the oligonucleotide field are scarce, particularly with respect to the requirement for traceless release of the payload . Herein, we describe a cathepsin B-cleavable dipeptide phosphoramidite, Val-Ala(NB) for the automated synthesis of oligonucleotide-small molecule conjugates.

Complex hidradenitis suppurativa on a background of long-standing Crohn's disease requiring radical pelvic and perineal reconstruction: A case report.

Key Clinical Message: A surgical MDT approach to high-complexity surgeries can allow maximal resection in order to achieve disease control and excellent functional outcomes, as demonstrated here for a case of hidradenitis suppurativa in a patient with Crohn's disease.

Abstract: Hidradenitis suppurativa is an autoimmune disease characterized by abscess and fistula formation with purulent discharge in intertriginous zones, and is associated with inflammatory bowel disease. We present the case of a patient with severe ongoing hidradenitis suppurativa causing osteomyelitis and affecting the perineum, on a background of Crohn's disease previously treated with panprotocolectomy and permanent ileostomy.

Rhodanine derived enethiols react to give 1,3-dithiolanes and mixed disulfides.

Rhodanines have been characterised as 'difficult to progress' compounds for medicinal use, though one rhodanine is used for diabetes mellitus treatment and others are in clinical development. Rhodanines can undergo hydrolysis to enethiols which are inhibitors of metallo-enzymes, such as metallo β-lactamases. We report that in DMSO, rhodanine derived enethiols undergo dimerisations to give 1,3-dithiolanes and mixed disulfides.

Process-Informed Subsampling Improves Subseasonal Rainfall Forecasts in Central America.

Subseasonal rainfall forecast skill is critical to support preparedness for hydrometeorological extremes. We assess how a process-informed evaluation, which subsamples forecasting model members based on their ability to represent potential predictors of rainfall, can improve monthly rainfall forecasts within Central America in the following month, using Costa Rica and Guatemala as test cases. We generate a constrained ensemble mean by subsampling 130 members from five dynamic forecasting models in the C3S multimodel ensemble based on their representation of both (a) zonal wind direction and (b) Pacific and Atlantic sea surface temperatures (SSTs), at the time of initialization.

Plasma exchange and intravenous immunoglobulin for the peri-operative management of type 2 heparin-induced thrombocytopaenia in a patient requiring urgent surgery for critical limb ischaemia.

We report the case of a 61-year-old female who developed heparin-induced thrombocytopaenia following treatment of a submassive pulmonary embolism, and who then required an above knee amputation for critical limb ischaemia. Heparin-induced thrombocytopaenia is a rare, immune-mediated complication associated with an in-hospital mortality rate of 10%. It is more common in surgical patients, with patients undergoing orthopaedic surgery more likely to develop it than patients undergoing cardiac surgery, but heparin-dependent immunoglobulin G antibodies are more likely to be formed in the latter.

Radical total pelvic exenteration with concomitant right nephrectomy in the management of recurrent endometrioid ovarian adenocarcinoma: A case report and literature review.

Endometrioid ovarian adenocarcinoma is a common subtype of epithelial ovarian cancer that can arise on a background of endometriosis. Maximal cytoreductive effort with an aim to remove all macroscopic disease (achieve R0) is the single independent prognostic factor for survival. Complex multidisciplinary surgeries may be required in order to achieve this.

Temporal patterns in multiple stressors shape the vulnerability of overwintering Arctic zooplankton.

The Arctic polar nights bring extreme environmental conditions characterised by cold and darkness, which challenge the survival of organisms in the Arctic. Additionally, multiple anthropogenic stressors can amplify the pressure on the fragile Arctic ecosystems during this period. Determining how multiple anthropogenic stressors may affect the survival of Arctic life is crucial for ecological risk assessments and management, but this topic is understudied.

Filamentation and inhibition of prokaryotic CTP synthase with ligands.

Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels.

Scalable purification of extracellular vesicles with high yield and purity using multimodal flowthrough chromatography.

Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell-cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co-isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins.

Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI.

Oxidative stress-induced changes in the transcriptomic profile of extracellular vesicles.

Extracellular vesicles (EVs) have been proposed to play dual roles in cellular homeostasis, functioning both to remove unwanted intracellular molecules, and to enable communication between cells as a means of modulating cellular responses in different physiological and pathological scenarios. EVs contain a broad range of cargoes, including multiple biotypes of RNA, which can vary depending on the cell status, and may function as signalling molecules. In this study, we carried out comparative transcriptomic analysis of EVs and cells, demonstrating that the RNA profile of EVs is distinct from cells and shows dose-dependent changes in response to oxidative stress.