Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of ⁶⁸Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUV_max and SUV_mean showed a positive correlation with the immunohistochemical FAP expression score (SUV_max: r = 0.57, P = 0.001; SUV_mean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [¹¹C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60–90 or 70–90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD.

Over 4 decades of research support the link between Alzheimer disease (AD) and somatostatin [somatotropin-releasing inhibitory factor (SRIF)]. SRIF and SRIF-expressing neurons play an essential role in brain function, modulating hippocampal activity and memory formation. Loss of SRIF and SRIF-expressing neurons in the brain rests at the center of a series of interdependent pathological events driven by amyloid-β peptide (Aβ), culminating in cognitive decline and dementia. The connection between the SRIF and AD further extends to the neuropsychiatric symptoms, seizure activity, and inflammation, whereas preclinical AD investigations show SRIF or SRIF receptor agonist administration capable of enhancing cognition. SRIF receptor subtype-4 activation in particular presents unique attributes, with the potential to mitigate learning and memory decline, reduce comorbid symptoms, and enhance enzymatic degradation of Aβ in the brain. Here, we review the links between SRIF and AD along with the therapeutic implications.

α-Synuclein (α-Syn) aggregation in Lewy bodies and Lewy neurites has emerged as a key pathogenetic feature in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Various factors, including posttranslational modifications (PTMs), can influence the propensity of α-Syn to misfold and aggregate. PTMs are biochemical modifications of a protein that occur during or after translation and are typically mediated by enzymes. PTMs modulate several characteristics of proteins including their structure, activity, localization, and stability. α-Syn undergoes various posttranslational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, O-GlcNAcylation, nitration, oxidation, polyamination, arginylation, and truncation. Different PTMs of a protein can physically interact with one another or work together to influence a particular physiological or pathological feature in a process known as PTMs crosstalk. The development of detection techniques for the cooccurrence of PTMs in recent years has uncovered previously unappreciated mechanisms of their crosstalk. This has led to the emergence of evidence supporting an association between α-Syn PTMs crosstalk and synucleinopathies. In this review, we provide a comprehensive evaluation of α-Syn PTMs, their impact on misfolding and pathogenicity, the pharmacological means of targeting them, and their potential as biomarkers of disease. We also highlight the importance of the crosstalk between these PTMs in α-Syn function and aggregation. Insight into these PTMS and the complexities of their crosstalk can improve our understanding of the pathogenesis of synucleinopathies and identify novel targets of therapeutic potential.

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders.

BACKGROUND AND PURPOSE:

Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

BACKGROUND AND PURPOSE:

Previous studies have reported metal accumulation and microstructure changes in deep gray nuclei (DGN) in Wilson disease (WD). However, there are limited studies that investigate whether there is metal accumulation and microstructure changes in DGN of patients with WD with normal-appearing routine MRI. This study aimed to evaluate multiparametric changes in DGN of WD and whether the findings correlate with clinical severity in patients with WD.

BACKGROUND AND PURPOSE:

Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD.

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

α-Synuclein (AS) is a small presynaptic protein that is genetically, biochemically, and neuropathologically linked to Parkinson's disease (PD) and related synucleinopathies. We present here a review of the topic of this relationship, focusing on more recent knowledge. In particular, we review the genetic evidence linking AS to familial and sporadic PD, including a number of recently identified point mutations in the SNCA gene. We briefly go over the relevant neuropathological findings, stressing the evidence indicating a correlation between aberrant AS deposition and nervous system dysfunction. We analyze the structural characteristics of the protein, in relation to both its physiologic and pathological conformations, with particular emphasis on posttranslational modifications, aggregation properties, and secreted forms. We review the interrelationship of AS with various cellular compartments and functions, with particular focus on the synapse and protein degradation systems. We finally go over the recent exciting data indicating that AS can provide the basis for novel robust biomarkers in the field of synucleinopathies, while at the same time results from the first clinical trials specifically targeting AS are being reported.

Shetland Library and the National Library of Scotland have been praised for "providing optimist for the future."

Josh learns that despite Bethesda's best efforts, Starfield is not Fallout 76. Robert learns the taste of Amiibo blood. Chris is just here to ask, "kink-why?" And Kelley is obsessed with Red XIII on a chocobo.

The post RPG Cast – Episode 692: “Vending Machine Isekai” appeared first on RPGamer.

Kelley starts a Reddit fight. Robert learns about purrkour gaming. Pascal makes plans to be a booth babe. Chris eats the mic like it's meat flavored cereal. Mung beans.

The post RPG Cast – Episode 732: “Excited PoE Noises” appeared first on RPGamer.

Paul Cousins presents a multi-channel installation in which the listener becomes the performer.

The post Patch Notes: Atomised Listening appeared first on Fact Magazine.

ENERGY giant Rosneft is poised to take control of a new Arctic Circle LNG project planned for an area of northern Russia fronting the Barents Sea.

There’s plenty that you could justifiably expect from a Bioware RPG: chats with mates, opportunities to get those mates horribly killed, surviving mates turning to the side then walking offscreen. But I don’t think anyone expected Dragon Age: The Veilguard to be, at least on a purely technical level, one of the smoothest-performing, settings-rich AAA PC releases of the year so far.

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Like a plague doctor delicately administering another handful of leeches, Ice Pick Lodge have shared a bit more about the recently announced Pathologic 3, explaining how their plans for the cult epidemic-battling series have progressed since the release of Pathologic 2.

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As a yearly blockbuster, Call of Duty, through sheer expense and effort, would like you to think it is the Die Hard of video games. Or, depending on the setting, the Saving Private Ryan of video games. But it is barely Black Hawk Down. This latest campaign in Call Of Duty: Black Ops 6 reminds me more of the forgettable Netflix shootfests that thumbnail their way across your TV screen as you try to find some gritty nothing to aid you in zoning out of life. Still, there is an anecdotal contingent of casual sofa sitters for whom Call Of Duty is the game. A balls-to-the-wall shooter to return to every winter and rinse through in a weekend. Ed has already gestured at its multiplayer, announcing: "yup, it's COD", like a deeply tired Captain Birdseye inspecting the day's catch, wondering when his life will change. But never mind that. How does the single player story mode hold up? Some are calling it the best campaign in years. And I guess that's true, in the sense that it is the least worst.

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Call Of Duty: Black Ops 6 has been out for a little while already, what with me giving its multiplayer largely a thumbs up. Still, it's an ever-evolving thing and Activision have announced the game's first seasonal drop. It's a hefty one with a lot of additions, so I'll try my best to break down the good stuff. TLDR: there's some new maps for multiplayer and zombies, new modes, and a few extra bits. I'm mildly excited for more. More in this case is good.

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The Rise Of The Golden Idol will crack its new case wide open on November 12th, but the detective sequel is just the beginning. Color Gray Games are planning another tranche of DLC akin to that received by the first game, The Case Of The Golden Idol: four standalone mysteries that introduce more mysteries to solve.

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Here’s a Steam quote for you: ‘The Rise Of The Golden Idol is the best game I’ve ever played where I spent most of my time staring at the screen going “well what chuffing well is it, then?!” Fiendish but fair, this detective puzzler demands a heady mix of observation, deduction, and logic, but rewards you with a progressively engaging story, and steadily more infuriatingly brilliant puzzles. Despite teaching you everything you need to know in the tutorial, it still manages to introduce new wrinkles and twists on the formula with each fresh chapter. My verdict? Imagine me lying my floor, massaging my temple with one hand and giving a fat thumbs up with the other.

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Secretary of State was questioned on Good Morning Britain over the pledge - with host asking 'how much will it have gone up by then?'

October marked the "biggest" sales month for supermarkets in the UK so far despite food price hikes.

NASA is investigating a strange noise coming through the speaker on Boeing’s Starliner capsule, which has been beset with technical issues

Space missions are extremely hard. Things going wrong should be expected, so having a sensible plan B is crucial

Autonomous taxis are already operating on US streets, while Elon Musk has spent years promising a self-driving car and failing to deliver. The newly announced Tesla Cybercab is unlikely to change that

What happens if AI is trained to write choral music by feeding it a specially created vocal dataset? Moving new exhibition The Call tackles some thorny questions about AI and creativity – and stirs the soul with music

From Goats to airplanes, Xbox Game Pass has another bumper month in store for subscribers. Here's everything you need to know about what is heading to PC and console this November 2024

Death Stranding, originally launched in 2019, has finally come to Xbox consoles five years after its initial debut as a Director's Cut version from Hideo Kojima.

Certain strains of E. coli are capable of causing severe disease, by rapidly spreading through the human digestive system, wreaking havoc throughout the bloodstream, and eventually damaging the delicate kidneys. That's the situation right now during a large outbreak in Alberta, with hundreds of children now affected.

A biologist at Cape Breton University is hoping a piece of technology used to keep people safe in the pandemic can help protect Nova Scotia's oysters against the effects of warming waters.

Kurt “CyberGuy" Knutsson says there’s been a rise in cybercriminal services using hacked police and government emails to send subpoenas and data requests to U.S. companies.

NASA discovered the cause of a pulsating noise coming from a speaker on the Boeing Starliner spacecraft after astronaut Butch Wilmore reported the sound.

U.S.-based startup company Heliospect Genomics reportedly is offering wealthy couples embryo screening for IQ and other traits at $50,000 for 100 embryos.

Three people have been taken to hospital after a car mounted the pavement and smashed into a restaurant in Piccadilly Circus, the Metropolitan Police have said.

Dis-Ease by Mariam Ghani uses strong visuals and compelling interviews to argue that how we see and describe disease affects how we deal with it, says Simon Ings

Red and processed meat, and even poultry, seem to raise the risk of developing type 2 diabetes, according to a study of nearly 2 million adults, but not everyone is convinced

Flu and other respiratory viruses seem to barely exist outside of winter, but covid-19 cases have consistently risen every summer over the past few years

A new test spots Lyme disease faster than the existing go-to approach and, if approved, could reduce the risk of complications

Our immune cells change a lot as the decades progress, which could explain why we become more susceptible to certain conditions

Mosquito larvae die after consuming hemp leaves because they react strongly to the cannabidiol in the foliage. The discovery might lead to the development of a new pesticide to control mosquito numbers

A beam of radioactive carbon ions has been used to destroy cancer cells in mice, demonstrating a therapy that may cause less collateral damage than current techniques

The compound creatine, a popular exercise supplement that only occurs naturally in animal products, could one day be produced in edible plants

Popular weight-loss medications including Ozempic and Wegovy contain a drug that seems to decrease cravings for food and drugs – and now there’s evidence that it might make exercise less rewarding, too