Title: Health Highlights: April 27, 2012
Category: Health News
Created: 4/27/2012 2:05:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM

Title: Health Highlights: April 30, 2012
Category: Health News
Created: 4/30/2012 2:05:00 PM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: Magnetic Brain Stimulation May Temporarily Dull Nicotine Craving
Category: Health News
Created: 4/26/2013 12:36:00 PM
Last Editorial Review: 4/29/2013 12:00:00 AM

Title: Temporarily Turning Blue Sometimes Normal for Babies, Doctors Say
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 12:00:00 AM

Title: Got Unwanted Pills? Drug Take-Back Day Is April 30
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Kevzara (sarilumab)
Category: Medications
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

The question of the relative evolutionary roles of adaptive and nonadaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation, genetic drift (as modulated by the demographic history of the population) and purifying selection, is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at "neutral" sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we reanalyze genome-wide population-level data from a Zambian population of Drosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.

Human adenoviruses have many attractive features for gene therapy applications. However, the high prevalence of preexisting immunity against these viruses in general populations worldwide has greatly limited their clinical utility. In addition, the most commonly used human adenovirus, human adenovirus subgroup C serotype 5 (HAd5), when systemically administered, triggers systemic inflammation and toxicity, with the liver being the most severely affected organ. Here, we evaluated the utility and safety of a new low-seroprevalence gorilla adenovirus (GAd; GC46) as a gene transfer vector in mice. Biodistribution studies revealed that systemically administered GAd had a selective and robust lung endothelial cell (EC) tropism with minimal vector expression throughout many other organs and tissues. Administration of a high dose of GAd accomplished extensive transgene expression in the lung yet elicited no detectable inflammatory histopathology in this organ. Furthermore, GAd, unlike HAd5, did not exhibit hepatotropism or induce liver inflammatory toxicity in mice, demonstrating the exceptional safety profile of the vector vis-à-vis systemic utility. We further demonstrated that the GAd capsid fiber shared the flexibility of the HAd5 equivalent for permitting genetic modification; GAd with the pan-EC-targeting ligand myeloid cell-binding peptide (MBP) incorporated in the capsid displayed a reduced lung tropism and efficiently retargeted gene expression to vascular beds in other organs.

IMPORTANCE In the aggregate, our mouse studies suggest that GAd is a promising gene therapy vector that utilizes lung ECs as a source of therapeutic payload production and a highly desirable toxicity profile. Further genetic engineering of the GAd capsid holds the promise of in vivo vector tropism modification and targeting.

G-quadruplex, assembled from a square array of guanine (G) molecules, is an important structure with crucial biological roles in vivo but also a versatile template for ordered functional materials. Although the understanding of G-quadruplex structures is the focus of numerous studies, little is known regarding the control of G-quartet stacking...

The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.

⁶⁸Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as ⁶⁸Ga-PSMA-11, are promising small molecules for targeting prostate cancer (PCa). Although this radiopharmaceutical was produced mostly by means of manual synthesis and automated synthesis modules, a sterile cold kit was recently introduced. The aim of our study was to evaluate the image quality of ⁶⁸Ga-PSMA-11 PET/CT (PSMA-PET) in a population of PCa patients after the injection of comparable activities of ⁶⁸Ga-PSMA-11 obtained with the 2 different synthetic procedures. A secondary aim was to identify secondary factors that may have an impact on image quality and, thus, final interpretation. Methods: Two different groups of 100 consecutive PCa patients who underwent PSMA-PET were included in the study. The first group of patients was imaged with ⁶⁸Ga-PSMA-11 obtained using synthesis modules, whereas the second group’s tracer activity was synthesized using a sterile cold kit. All PET images were independently reviewed by 2 nuclear medicine diagnosticians with at least 2 y of experience in PSMA-based imaging and unaware of the patients’ clinical history. The 2 reviewers independently rated the quality of each PSMA-PET scan using a 3-point Likert-type scale. In cases of discordance, the operators together reviewed the images and reached a consensus. Performance was evaluated on the basis of the expected biodistribution, lesion detection rate, and physiologic background uptake. Results: Overall, 104 of 200 (52%) PSMA-PET scans were positive for PCa-related findings. No significant differences in image quality between cold kits and synthesis modules were found (P = 0.13), although a higher proportion of images was rated as excellent by the observers for kits than for modules (45% vs. 34%). Furthermore, after image quality had been dichotomized as excellent or not excellent, multivariate regression analysis found several factors to be significantly associated with a not-excellent quality: an increase in patient age (+5 y: odds ratio [OR], 1.40; 95% confidence interval [CI], 1.12–1.75), an increase in patient weight (+5 kg: OR, 1.89; 95% CI, 1.53–2.32), an increase in ⁶⁸Ga-PSMA-11 uptake time (+10 min: OR, 1.45; 95% CI, 1.08–1.96), and a decrease in injected activity (–10 MBq: OR, 1.28; 95% CI, 1.07–1.52). Conclusion: No significant differences were identified between the 2 groups of patients undergoing PSMA-PET; therefore, we were not able to ascertain any significant influences of tracer production methodology on final scan quality. However, increased patient age, increased patient weight, decreased injected activity, and increased ⁶⁸Ga-PSMA-11 uptake time were significantly associated with an overall poorer image quality.

There is a pressing need for new exploration tools to target and vector towards mineralization in covered terrains. Groundwater provides a valuable and under-utilized geochemical sampling medium, and represents an important and cost-effective tool to expose covered terrains to systematic exploration. For Au exploration, researchers agree the best hydrogeochemistry pathfinder is dissolved Au itself, with additional potential from other pathfinders (albeit non-unique) such as As, Ag, W and Mo. Despite Au's relatively low solubility, with rigorous field protocols and appropriate analytical methods, explorers can respond to dissolved Au directly with robust parts per trillion (ppt)-level analyses.

Even with ppt-level analyses, a practical implication of Au's low solubility is that a deposit's dissolved Au signature is generally weaker than seen in other more mobile pathfinders, producing a smaller detectable footprint, which must be considered when designing exploration programmes. Using purpose-drilled groundwater sampling bores, explorers can collect groundwater samples at the density required to respond to dissolved Au where existing borehole coverage is otherwise insufficient. In addition to its use at the regional scale, with even tighter sample density, hydrogeochemistry also shows promise at the project scale, allowing the 3D modelling of pathfinder dispersion.

For hydrogeochemistry to be widely adopted for Au exploration, explorers need confidence in ppt-level dissolved Au analyses, and the context to understand their significance. This paper aims to address these topics and provide a straightforward starting point for Au explorers interested in applying hydrogeochemistry by: (i) summarizing examples of regional sampling programmes and more focused case studies to illustrate how covered Au deposits create measurable dissolved Au footprints distinguishable from background; and (ii) sharing examples of dissolved Au analyses that are being integrated into exploration at the regional and project scales.

As seen in the results, the distributions of dissolved Au in the regional- and project-scale programmes show remarkably similar and easy to interpret high-contrast, low-frequency anomalies against relatively low backgrounds. These are desirable attributes of any geochemical pathfinder. When combined with the benefits of hydrogeochemistry v. other geochemical exploration tools (e.g. groundwater can create larger footprints requiring fewer samples to detect, and groundwater can recharge from depth to reflect deeper mineralization), dissolved Au is a powerful pathfinder ideally suited for Au exploration in covered terrains.

While this paper focuses on the use of dissolved Au, additional pathfinders can provide valuable information, including indications of lithological changes, hydrothermal alteration and different styles of mineralization, as well as opportunities to use secondary pathfinders when sample density or local conditions may not result in detectable dissolved Au signatures.

Thematic collection: This article is part of the Exploration 17 collection available at: https://www.lyellcollection.org/cc/exploration-17

Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality—iatrogenic hyperinsulinemia—principally drives insulin resistance and its consequences in this population and has not been addressed. We review this evidence to show that injecting insulin into the peripheral circulation bypasses first-pass hepatic insulin clearance, which leads to the unintended metabolic consequence of whole-body insulin resistance. We propose restructuring insulin therapy to restore the physiological insulin balance between the hepatic portal and peripheral circulations and thereby avoid the complications of life-long insulin resistance. As technology rapidly advances and our ability to ensure euglycemia improves, iatrogenic insulin resistance will become the final barrier to overcome to restore normal physiology, health, and life in type 1 diabetes.

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of B. mandrillaris in vitro. Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.

BACKGROUND AND PURPOSE:

Endolymphatic hydrops in patients with Menière disease relies on delayed postcontrast 3D-FLAIR sequences. The purpose of this study was to compare the degree of perilymphatic enhancement and the detection rate of endolymphatic hydrops using constant and variable flip angles sequences.

Augmented, Virtual, and other mixed reality technologies are rapidly emerging and advancing, creating new and exciting opportunities for training and education. XR for Learning Weekly […]

The post XR for Learning Weekly – April 29, 2020 appeared first on e-Learning Feeds.

Augmented, Virtual, and other mixed reality technologies are rapidly emerging and advancing, creating new and exciting opportunities for training and education. XR for Learning Weekly […]

The post XR for Learning Weekly – April 22, 2020 appeared first on e-Learning Feeds.

Electronic Arts in their fiscal year Q4 2020 results said they plan to release 14 titles in the 2021 fiscal year, which ends on March 31, 2021. Electronic Arts labeled one of the game as "an HD remake of an EA game."

VentureBeat is reporting this HD remake is an HD remaster of the Mass Effect Trilogy.

"We are planning to launch 14 new titles to players this fiscal year," said EA CEO Andrew Wilson. "hat includes four new EA Sports titles — FIFA, Madden, NHL, and one more unannounced sports game — all of which deliver on the mix of creativity, authenticity, and quality that sets EA Sports apart.

"Our FY21 plans also include four more games drawing on the breadth of our IP, from Command & Conquer Remastered to unannounced games for our console and PC players. We’ll have more games from indie developers launching this year through EA Partners, and two new mobile titles leveraging top IP that we’ll bring to players worldwide."

Read EA's full lineup for the 2021 fiscal year below:

1. Burnout Paradise Remastered (Nintendo Switch)
2. Command & Conquer Remastered (PC)
3. Medal of Honor VR
4. FIFA 21
5. Madden NFL 21
6. NHL 21
7. Unannounced sports game
8. An HD remake of an EA game
9. EA Partner game
10. EA Partner game
11. EA Partner game
12. EA Partner game
13. EA Mobile game
14. EA Mobile game

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443409/rumor-mass-effect-trilogy-hd-remaster-to-launch-by-march-31-2021/

Sony has released the US PlayStation Store downloads charts for March 2020. Final Fantasy VII Remake topped the PS4 charts, Beat Saber topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Here is the complete list of charts:

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443430/final-fantasy-vii-remake-tops-the-us-playstation-store-downloads-in-april-2020/

Sony has released the Europe PlayStation Store downloads charts for April 2020. Grand Theft Auto V topped the PS4 charts, Blood and Truth topped the PlayStation VR charts, and Call of Duty: Warzone topped the Free-to-Play Games chart. Fortnite – The Iris Pack topped the DLC and Expansions chart.

Final Fantasy VII Remake debuted in fourth on the PS4 charts. Resident Evil 3 debuted in 10th place.

Here is the complete list of charts:

PlayStation 4

1. Grand Theft Auto V (3)
2. EA SPORTS FIFA 20 (2)
3. Call of Duty: Modern Warfare (1)
4. FINAL FANTASY VII REMAKE (New)
5. NBA 2K20 (RE)
6. Call of Duty: Modern Warfare 2 Campaign Remastered (20)
7. EA SPORTS UFC 3 (RE)
8. Minecraft (5)
9. Marvel’s Spider-Man (RE)
10. RESIDENT EVIL 3 (New)
11. MONOPOLY PLUS (RE)
12. Rocket League (11)
13. Assassin’s Creed Odyssey (10)
14. Days Gone (RE)
15. TOM CLANCY’S RAINBOW SIX | SIEGE (RE)
16. Red Dead Redemption 2 (19)
17. The Crew 2 (13)
18. Tom Clancy’s The Division 2 (RE)
19. eFootball PES 2020 (RE)
20. Need for Speed Heat (RE)

PlayStation VR

1. Blood and Truth (5)
2. Beat Saber (1)
3. Creed: Rise to Glory (9)
4. Job Simulator (2)
5. RICK AND MORTY: VIRTUAL RICK-ALITY (RE)
6. ASTRO BOT Rescue Mission (RE)
7. Until Dawn: Rush of Blood (RE)
8. BOXVR (RE)
9. Farpoint (RE)
10. SUPERHOT VR (4)

DLC

1. Fortnite – The Iris Pack (1)
2. Fortnite – Bassassin Challenge Pack (3)
3. GTA Online: Criminal Enterprise Starter Pack (5)
4. Marvel’s Spider-Man: The City That Never Sleeps – Season Pass (RE)
5. Assassin’s Creed Odyssey – Season pass (RE)
6. Fortnite: Save the World – Standard Founder’s Pack (10)
7. The Division 2 – Warlords of New York – Expansion (2)
8. Need for Speed Heat – McLaren F1 Black Market Delivery (6)
9. Modern Warfare – Atlanta FaZe Pack (New)
10. Assassin’s Creed Origins – The Hidden Ones (RE)

Free-to-Play

1. Call of Duty: Warzone (1)
2. Fortnite (2)
3. Apex Legends (3)
4. Brawlhalla (5)
5. DON’T EVEN THINK (New)
6. eFootball PES 2020 LITE (4)
7. Destiny 2 (New)
8. WORLD OF WARSHIPS: LEGENDS (7)
9. DRAGON BALL XENOVERSE 2 Lite Version (6)
10. Paladins (9)

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443431/gtav-tops-the-eu-playstation-store-downloads-in-april-2020-final-fantasy-vii-remake-debuts-in-4th/

Fancy a 1v1 match on Shipment? Of course not. Duels to the death are played out and boring. Subscribing to the view that bigger is indeed always better, Call Of Duty: Modern Warfare has brought back its 10v10 Shipment playlist. After briefly appearing as an April Fool’s jab, Infinity Ward have decided to make 20-player […]

Adrian Tchaikovsky's latest novel The Doors of Eden rewrites Earth's evolutionary history, with highlights including fish that upload their minds to supercomputers and cats that rule over primates

This post contains spoilers for Dead to Me Season 2.

Maybe it’s the surreality of, well, everything lately—or maybe it’s just aged like the fine wines all of its characters toss back by the bottle. Whatever the reason, Dead to Me Season 2 hits even better than Season 1—fighting off a sophomore slump with a fresh batch of twists, dramatic ironies, and, most importantly, some more Christina Applegate angsting out to metal. Perhaps this season’s smartest move, however, is a trope pulled straight out of Soapy Dramas 101: Bringing James Marsden back to play his own twin.

Series creator Liz Feldman was sending the usual thank-you notes back and forth with cast and crew after Season 1 wrapped when she received a particularly amusing message from Marsden.

Read more at The Daily Beast.

Brown dwarfs, which are halfway between huge planets and small stars, have extremely powerful winds whipping around them at speeds of about 650 metres per second

Chris Hemsworth plays a super-tough mercenary on an all-guns-blazing mission to rescue a crime lord’s kidnapped son

Sadly, this has nothing to do with dentistry. Extraction is a made-for-Netflix action thriller from veterans of the Marvel Comic Universe – screenwriter Joe Russo, stunt-specialist-turned-director Sam Hargrave and star Chris Hemsworth. It’s based on the graphic novel Ciudad (which Russo co-authored), transferring the action from the Paraguayan city of Ciudad Del Este to Dhaka in Bangladesh.

Extraction is a little bit hokey and absurd, and the very end has an exasperating cop-out – but it has to be admitted that, in terms of pure action octane, Russo and Hargrave bring the noise, and there are quite a few long-distance “sniper” scenes in which people get taken out from miles away as the bullet travels through their skulls with a resonant thoonk.

A ridiculously titled film about a couple who stumble upon a stash of money is absurd and cliched but mostly entertaining

One of the most surprising reveals of last October’s unprecedented Netflix data dump was the astounding popularity of cheap psycho-thriller Secret Obsession. While the streamer proudly touted new films from Alfonso Cuarón, Paul Greengrass and the Coens in the same period, it was a no-star, dim-plotted slab of schlock that netted more viewers, with an estimated 40m households eager to find out just how secret that obsession really was. Modelled after a Lifetime TV movie (with a Lifetime TV director at the helm), it was an important victory for Netflix because it revealed a substantial audience for tiny-budgeted thrillers with generic titles, a bracket they could easily fill at little expense.

Related: The Half of It review – charming Netflix teen comedy takes on Cyrano

We've picked some of the best projects recently completed in our project log forum.

Data leaks of this magnitude are virtually unheard of in Canada

Roughly three million jobs have been lost over the past two months, the steepest consecutive monthly declines in employment ever recorded

Lawsuits are pending from groups who have challenged the constitutionality of shrinking Bears Ears and Grand Staircase-Escalante

Plans finalized on Thursday for two national monuments in Utah downsized by Donald Trump would ensure that lands previously off-limits to energy development will be open to mining and drilling.

The move comes despite pending lawsuits from conservation, tribal and paleontology groups, who have challenged the constitutionality of the president’s action. The Trump administration slashed the size of Bears Ears national monument by 85% and Grand Staircase-Escalante national monument by nearly half in December 2017, in what represented the largest elimination of public lands protections in US history.

Conservation groups criticized the Trump administration on Thursday for spending time on management plans they believe will become moot when the court sides with their assertion that Trump misused the Antiquities Act to reverse decisions by previous presidents.

Energy companies have leased 9.9m acres from the administration – and the fossil fuels extracted could equal half a year of emissions from China

The Trump administration has offered oil companies a chunk of the American west and the Gulf of Mexico that’s four times the size of California – an expansive drilling plan that threatens to entrench the industry at the expense of other outdoor jobs, while locking in enough emissions to undermine global climate policy.

Energy companies have leased 9.9m acres from the unprecedented 461m acres put up for rent by the Trump administration, according to a new analysis from the Wilderness Society.

Long victimized by poaching and deforestation, the primate species is in the midst of a surprising rebound that is sparking new hopes of recovery

The plunge in jobs was 73,800 relative to February, but Saskatchewan saw a shallower decline than any other province as COVID-19 devastates labour markets across Canada.

The U.S. economy likely lost a staggering 22 million jobs in April, in what would be the steepest plunge in payrolls since the Great Depression and the starkest sign yet of how the novel coronavirus pandemic is battering the world's biggest economy.

The fed funds futures market is pricing in negative U.S. interest rates next year, a scenario the Federal Reserve has said it wants to avoid as many doubt that it would be an effective tool to stimulate growth.

Temperatures in parts of Britain are likely to soar to 24C over the Easter Bank Holiday weekend, but the sunshine could be interrupted by some April showers.

The Foreign Secretary showed some cautious optimism as he revealed the latest data suggested the UK was "starting to win this struggle," three weeks after restrictions were imposed.

The Advertising Standards Agency (ASA) found the fast food giant had also failed to make it immediately clear its new product was dressed with an egg-based mayonnaise.

Donald Trump has instructed his administration to temporarily halt funding to the World Health Organisation over its handling of the coronavirus pandemic.

The Government is today set to extend the coronavirus lockdown until at least May 7 amid fresh warnings it is too soon to start easing the restrictions.

Follow our live coronavirus updates here

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Temperatures in the UK could reach are set to reach up to 24C over the next couple days as a "remarkably" warm and dry April continues, the Met Office has said.

The UK is set for more warm weather over the weekend while temperatures soared to more than 24C on Thursday.

Countdown presenter Rachel Riley has won the first round of a High Court libel case against a former aide to Jeremy Corbyn.

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