Nanotechnology for CAR T cells and tumour-infiltrating lymphocyte therapies.

Adoptive T-cell therapies, and particularly CAR T cells and tumour-infiltrating lymphocytes, have transformed cancer treatment by selectively targeting malignant cells. Despite their clinical success, these therapies face substantial challenges, including costly manufacturing processes and tumour-imposed barriers that limit efficacy. Advances in understanding the nanoscale mechanisms governing T-cell activation and the role of the tumour microenvironment in restricting T-cell responses have driven the development of nanotechnology-based strategies that integrate key chemical and physical cues.

Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics.

Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion.

Causal inference unveils how forest coverage mitigates excess snakebite cases during rainfall seasons in Colombia.

Snakebite envenoming is a neglected tropical disease that affects mainly rural populations, where antivenom is scarce. Understanding environmental drivers of snakebite incidence is critical for public health preparedness. This study employs causal inference to assess the impact of rainfall on snakebite surges in Colombia, with broader implications for tropical regions.

Digging into the evolutionary history of the fungus-growing-ant symbiont, Escovopsis (Hypocreaceae).

Symbiotic relationships shape the evolution of organisms. Fungi in the genus Escovopsis share an evolutionary history with the fungus-growing "attine" ant system and are only found in association with these social insects. Despite this close relationship, there are key aspects of Escovopsis evolution that remain poorly understood.

Modulating the PPARγ pathway upregulates NECTIN4 and enhances chimeric antigen receptor (CAR) T cell therapy in bladder cancer.

With the approval of the antibody-drug conjugate enfortumab vedotin (EV), NECTIN4 has emerged as a bona fide therapeutic target in urothelial carcinoma (UC). Here, we report the development of a NECTIN4-directed chimeric antigen receptor (CAR) T cell, which exhibits reactivity across cells expressing a range of endogenous NECTIN4, with enhanced activity in high expressors. We demonstrate that the PPARγ pathway, critical for luminal differentiation, transcriptionally controls NECTIN4, and that the PPARγ agonist rosiglitazone primes and augments NECTIN4 expression, thereby increasing sensitivity to NECTIN4-CAR T cell-mediated killing.

Trans-synaptic interaction with mGluR6 contributes to ELFN1 presynaptic enrichment in rod photoreceptors.

At the glutamatergic synapses between rod photoreceptors and ON-type bipolar cells, neurotransmitter is detected by the postsynaptic metabotropic glutamate receptor mGluR6. This receptor forms trans-synaptic interactions with ELFN1, a presynaptic cell adhesion molecule expressed in rods, and ELFN1 is important for mGluR6 localization at bipolar cell dendritic tips. Here, we show that in mice of either sex lacking mGluR6, the presynaptic localization of ELFN1 is disrupted.

Association between community assault and adverse renal outcomes among patients with crush injury in South Africa: a retrospective cohort study.

Background: Civilians in South Africa experience a high incidence of crush injury, or traumatic rhabdomyolysis. Community assault (CA) is a common mechanism of crush injury in South Africa, where victims are assaulted by multiple persons using a variety of objects. A crush injury places patients at risk of renal dysfunction.

[Understanding biology to identify new therapeutic targets beyond chemotherapy in ovarian granulosa cell tumors].

Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis.

Oxytocin-mediated empathy internally facilitates cooperative behaviors in rats.

Reciprocity is considered one of the vital mechanisms that sustain the evolution of cooperative behavior. However, free-riding, where assistance is received but not reciprocated, poses a serious threat to reciprocity behavior, which relies on future payback. Previous theories proposed that third-party punishment plays a vital role in preventing free-riding behavior.

Quantification of breath metabolites in labouring versus non-labouring patients: a feasibility study.

clinicaltrials.gov NCT04564196.

Photoacoustic detection of propofol in breath gas for monitoring depth of anaesthesia: from bench to bedside.

Background: Ensuring adequate depth of i.v. anaesthesia by measuring propofol in breath gas could increase patient safety.

Association of intraoperative end-tidal CO levels with postoperative outcomes: a patient-level analysis of two randomised clinical trials.

Background: The relationship between intraoperative end-tidal CO (etCO) levels and postoperative outcomes remains unclear. We conducted a post hoc analysis of two randomised trials in adults undergoing major surgery under general anaesthesia.

Methods: We re-analysed individual participant data comparing high or low positive end-expiratory pressure with low tidal volume intraoperative ventilation using a merged database derived from two randomised trials in non-obese (PROVHILO: ISRCTN70332574) and obese (PROBESE: NCT02148692) patients.

Hybrid AI in synthetic biology: next era in agriculture.

Synthetic biology holds great potential to transform agriculture, yet its progress is constrained by the complexity of multigenomic, multitrait, and multi-environment data. Desirable traits often arise from complex gene networks acting across diverse conditions, making them difficult to predict and optimize manually. In the past decade, artificial intelligence (AI) has supported this process, but its large data needs and poor integration limit its role to pattern recognition rather than explanatory trait design.

Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.

Background: Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumor control than monospecific CAR-T cells on heterogeneous models. To overcome tumor heterogeneity, we targeted mesothelin (meso) and Mucin 16 (MUC16), two antigens commonly expressed in solid tumors, using a tandem CAR design.

Relevance of Georg Grosz's Weimar-era drawings to promoting social justice and health equity in contemporary society.

The arts and humanities can direct attention to the health-threatening effects of adverse living and working conditions and the political and economic systems that spawn them. Most of these efforts aim to improve healthcare by promoting empathy and sensitivity among health professionals towards patients and improving clinical skills. However, less effort is devoted towards improving living and working conditions-the structural and social determinants of health-that cause illness and make managing illness difficult.

From digital trace to evidence: Challenges and insights from a trial case study.

Technology's rapid evolution has made digital traces a common part of our lives, holding significant value for investigations and legal cases across various national jurisdictions. However, law enforcement and judicial systems often struggle to adapt to these changes, resulting in possible misinterpretations of digital evidence in criminal trials. Drawing on insights from a qualitative analysis of a terrorism-related court case, this research aims to gain a deeper understanding of the fundamental challenges of decision-making in digital forensics and how they can impact a criminal case.

Latent fingermark recovery in a simulated café setting: an exploratory study of cyanoacrylate fuming on disposable nonporous plastic and semiporous paper cups.

Latent fingermark recovery from beverage containers is an important aspect of forensic investigations, yet the influence of substrate properties and beverage temperatures on fingermark development remains understudied. This exploratory study assessed the development and quality of latent fingermarks on disposable beverage cups made of nonporous plastic and semiporous paper using cyanoacrylate (CA) fuming, under conditions approximating a typical café environment. A total of 255 cups (107 plastic, 148 paper) were collected after participants consumed hot and iced beverages in a controlled classroom setting.

When work stays in the family: Parent-child employment configurations, safety communication, and young workers' injury risk.

Introduction: This study examines how specific parent-child employment configurations shape family safety communication and injury risk among young workers in family-owned businesses.

Method: Drawing on cross-domain multiplex theory (Methot et al., 2024), we analyze survey data from 2,275 young workers (M age = 16.

The prevalence of benzodiazepines and other hypnotics and their impact on injury severity among older adults involved in motor vehicle collisions: a multicenter retrospective cohort study.

Introduction: Older adults are increasingly involved in motor vehicle collisions (MVCs). Hypnotics are known to impair driving ability. This study investigated the prevalence of hypnotics use among older adult drivers involved in MVCs and evaluated their impact on injury severity and co-prevalence with other central nervous system (CNS) depressants.

Is it safe for children to ride youth-sized all-terrain vehicles?

Introduction: All-terrain vehicles (ATVs) contribute significantly to fatalities and injuries among young individuals. This is despite the availability of youth-sized ATVs in the market, suggesting that these vehicles may not be as suitable for young riders as their name implies. This study aims to assess the suitability of youth-sized ATVs for their intended demographic.

How often did syphilis tests have corresponding HIV tests in Ontario, Canada? A retrospective analysis of comprehensive laboratory data.

Objectives: Canadian guidelines recommend HIV testing for individuals being evaluated for syphilis. Our objective was to examine three aspects of HIV testing (ie, if an HIV test occurred, the timing of the HIV test in relation to the syphilis test and the proportion with a positive HIV test result) among syphilis tests between 2017 and 2022 from individuals with no evidence of a previous HIV diagnosis.

Design And Setting: This study is a retrospective analysis of comprehensive laboratory testing data from Ontario's provincial public health laboratory.

Validation of a standardised approach to collect sociodemographic and social needs data in Canadian primary care: cross-sectional study of the SPARK tool.

Objective: This study validates the previously tested Screening for Poverty And Related social determinants to improve Knowledge of and access to resources ('SPARK Tool') against comparison questions from well-established national surveys (Post Survey Questionnaire (PSQ)) to inform the development of a standardised tool to collect patients' demographic and social needs data in healthcare.

Design: Cross-sectional study.

Setting: Pan-Canadian study of participants from four Canadian provinces (SK, MB, ON and NL).

Visualizing intracellular glycine with two-dye and single-dye ratiometric RNA-based sensors.

Glycine is an important metabolite and cell signal in diverse organisms, yet tools to visualize intracellular glycine dynamics have not been developed. In this study, diverse and bright RNA-based glycine biosensors were developed by fusing the architecturally complex glycine riboswitch with Broccoli class fluorogenic aptamers. The brightest sensor with the highest activation, glyS, and its two-dye ratiometric counterpart, Pepper-glyS, allowed for visualization of a drug-induced accumulation of endogenous glycine in live Escherichia colicells.