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What is Immunotherapy? Immunotherapies are biological treatments that harness the immune system to prevent, control and fight diseases and other conditions. The most familiar are vaccines, which train the immune system to recognise targets such as invading pathogens. Other immunotherapies boost immune responses when they are too weak, or dampen them down when they are out of control. Still others draw on engineered immune cells or lab-made antibodies to disrupt disease processes. The Evolution of Immunotherapy Efforts to prevent disease by boosting the immune system date back thousands of years, but advanced therapies for a wide range of illnesses have come to the fore in the past two decades. A global registry of clinical trials listed 1,257 trials of immunotherapies between 2006 and 2016. The figure leapt to 4,591 in the past decade. How Do Cancer Immunotherapies Work? Cancer patients have seen great benefits from immunotherapies and dozens are now approved for more than 30 types of cancer. Some tumours evade the body’s defences by switching off immune cells, but antibody-based drugs – called checkpoint inhibitors – reactivate them so they can recognise and attack the malignancies. The Future of Immunotherapy: Beyond Cancer Researchers are now testing whether existing immunotherapies can help a broader range of patients. This includes treating allergies, infections, brain diseases, and autoimmune disorders. Some of the most exciting new immunotherapies draw on recent Nobel prizewinning work on regulatory T-cells, or Tregs, which can be used to dampen down immune responses. The Potential of Tregs in Immunotherapy Tregs are unusual immune cells that stand the immune system down once the threat has been dealt with. Therapies are in the pipeline for dementia and autoimmune diseases from type 1 diabetes and rheumatoid arthritis to lupus and chronic inflammation. The potential for Tregs is vast, and researchers believe that half of all deaths have a component that is immunological.

The Legacy of Mohamed Salah at Liverpool Mohamed Salah's departure from Liverpool marks the end of an era for the Egyptian forward, who has been a key player for the club since his arrival in 2017. With 257 goals and 441 appearances, Salah has cemented his place in Liverpool's history books. A Career of Achievements Third-highest goalscorer in Liverpool's history Won the Premier League title, Champions League, and numerous other honors Four-time Premier League Golden Boot winner Hat-trick of clean sweeps of the Professional Footballers' Association and Football Writers' Association footballer of the year awards The Impact of Salah's Departure Salah's departure has been marked by controversy, with the player publicly criticizing manager Arne Slot and the team's style of play. However, it is seen as a necessary move for both parties, with Salah seeking a new challenge and Liverpool looking to refresh their squad. The Future for Salah and Liverpool As Salah moves on to a new chapter in his career, Liverpool will look to build on the foundations he has helped establish. With a legacy that will be remembered for generations to come, Salah's impact on the club will not be forgotten.

The Lead: Demands for Transparency on £5m Gift The defence secretary, John Healey, has urged Nigel Farage to provide transparency about the £5m gift he received from a billionaire businessman, in particular over whether any of the sum could have been linked to Russia-connected profits. In a letter to the Reform UK leader, Healey also asked him to address the possibility that the war against Iran might boost the revenues of AML Global, an aviation fuel company owned by Christopher Harborne, who gave Farage the £5m in 2024. Farage initially supported the US-Israeli attacks on Iran. The Financial Inquiry: Scrutinizing the Gift's Origins The letter, seen by the Guardian, asked Farage to confirm that none of the sum was "derived from transactions with Russian state-linked energy companies", and to give assurances that AML Global had complied fully with all sanctions on Russian energy since the full-scale invasion of Ukraine in 2022. In a statement to the Guardian, AML Global said it had complied fully with all UK and international sanctions, and screened any business partners to ensure the same. The Political Fallout: Investigation and Disclosure The Guardian revealed last month that shortly before the 2024 general election, Farage was given £5m by Harborne, a British-Thai dual citizen based in Thailand. Farage did not disclose the money at the time, and it only emerged when the Guardian reported it. He has argued that because it was an unconditional gift, and received before he announced he would run for parliament, there was no need to declare it once he did become an MP. However, after a complaint from the Conservatives, Farage faces a formal investigation by the parliamentary standards watchdog, Daniel Greenberg, into whether he should have done. The Geopolitical Concerns: Russia and Iran Connections In the letter, Healey noted that AML Global supplies jet fuel through a network of "main and regional oil companies" covering more than 1,200 locations worldwide, including central Asia, the Gulf and eastern Europe. Healey asked Farage to confirm that none of the profits which helped finance the £5m gift came from transactions with Russian state-linked energy companies, that AML Global had fully complied with all Russia sanctions, and that "no fuel sourced from Russian-controlled refineries has passed through its supply chain". The Public Interest: Demands for Open Books Citing previous comments by Farage about Russia – for example, that Nato "provoked" Russia's invasion of Ukraine by expanding eastwards – Healey said this wider situation "places Reform UK under a Russian cloud that only transparency can lift". On Iran, the letter asked Farage to say whether he was aware of a potential benefit to Harborne's company from rising aviation fuel prices when he made supportive comments about the attack on Iran, which led to Iran blockading the strait of Hormuz. Healey added: "The public is entitled to ask whether your financial interests were impacting on your political positioning and your initial support for throwing the UK armed forces headlong into a war in the Middle East without a plan."

The Churchill Exhibition: War Leader's Artistic EscapeBritain's eloquent war leader kept himself sane by puffing on cigars, swilling brandy – and painting the world around him. The Wallace Collection in London is hosting "Winston Churchill: The Painter" from 23 May to 29 November, offering a rare glimpse into the artistic side of the historical figure.New Voices in Contemporary ArtThe London art scene is buzzing with new exhibitions featuring contemporary artists:Kira Freije presents hollow metal people at Modern Art Oxford, showing shadows of Berlin Dada in her work. The exhibition runs from 23 May to 16 August.Miriam Elia, known for her witty take on Ladybird books, turns her eye towards Moses in this exhibition for Jewish Cultural Month at JW3, until 30 June.Liam Young offers futuristic but lo-fi worlds you can walk through at the Barbican, until 6 September, with installations finding hope for our planet.Zsuzsi Ujj presents her first UK solo show at Arcadia Missa, from 22 May until 18 July, establishing her presence from Hungary's dissident art and underground music scenes.Remembering Valie ExportThe art world mourns the passing of Austrian feminist artist and film-maker Valie Export, who died this week. Her 1968 performance piece "Tapp und Tastkinema" (Tap and Touch Cinema) is highlighted as typically provocative but playful, giving people the opportunity to interact with and appraise a real female body: her own. Export's fearless approach to challenging beauty standards continues to influence contemporary artists.Notable Art News and DevelopmentsThe week brought several significant stories from the art world:Taiba Akhuetie makes wild creations out of hair – Rihanna and Cate Blanchett are fansWhistler should have used better paint to capture his motherNina Simone's chewing gum is going on show in a new exhibition celebrating the superfanChristo made the invisible visibleGrayson Perry's life story is to be made into a musicalFlorentina Holzinger rocked this year's Venice Biennale with naked jetskiers, human bells and urine diversGen Z can't get enough of the king of colour, Mark RothkoSanya Kantarovsky's paintings of Christian iconography and children will haunt youMasterpiece of the Week: The Judgement of ParisJoachim Wtewael's "The Judgement of Paris" (1615) stands as this week's masterpiece. The painting depicts the moment when Trojan prince Paris foolishly rates the beauty of Minerva, Venus, and Juno, giving the prize to Venus in return for her helping him seduce Helen. This decision sparked the Trojan War, with the Greeks supported by the furious Juno. Wtewael's mannerist style, with its bony, angular forms and deliberate distortions, creates an overabundance that presages doom, reflecting the war-torn Europe of the 1600s. The painting is on display at the National Gallery in London.

The End of an EraPep Guardiola will leave Manchester City at the end of the season after a decade in charge, the club has confirmed, bringing an end to one of the most successful eras in English football and one of the most influential managerial reigns of all time.The departure of the 55-year-old Catalan coach will close the book on a remarkable chapter that has seen City transform into a footballing juggernaut. Guardiola had arrived in Manchester with a resume already stuffed with silverware from Barcelona and Bayern Munich, taking over from Manuel Pellegrini in July 2016.The Trophy-Laden ReignGuardiola, who took charge of City in 2016, has won six Premier League titles – including four in a row – three FA Cups, five League Cups and the Champions League, but his side have not won the league in two years.Although City sealed the domestic cup double this season, Guardiola saw his dreams of a seventh Premier League crown dashed when they drew 1-1 at Bournemouth on Tuesday to hand Arsenal the title, with City set to finish second. His final game in charge is Sunday's home fixture against Aston Villa.The Tactical RevolutionAfter inheriting a successful club financed by the Abu Dhabi United Group, Guardiola will walk away having built a footballing empire after overseeing a paradigm shift in Premier League tactics. As Guardiola faced the challenge of adapting to England's famously fast-paced and physical league, possession became an art form and a defensive tool at City as his teams craved complete control.The result was not just utter dominance – evidenced by record-breaking campaigns like the 100-point 2017-18 season with 106 goals scored – but also relentless consistency year after year, including a record four league titles in a row. Guardiola's squads set new standards, forcing other teams to evolve, while City's financial muscle, combined with shrewd signings such as the much-sought-after striker Erling Haaland helped deliver the treble in 2022-23.The Changing LandscapeHowever, the spectre of the 115 charges of alleged breaches of the Premier League's financial rules looms large over his tenure at the club. His rivalry with former Liverpool manager Jurgen Klopp raised the bar in the Premier League so high that even 97 points proved insufficient for the Anfield side to claim the title in 2018-19.More recently, Guardiola has faced a challenge from his protege and former coaching assistant Mikel Arteta, who took charge at Arsenal and finished second behind City twice before ultimately winning the trophy this season.The Guardiola LegacyGuardiola looked back fondly at his time in Manchester, remembering how the city came together after the Manchester Arena attack while also describing how the club helped him through a tough period when he lost his mother to COVID."The fans, the staff, the people of Manchester, you gave me strength when I needed it most," he added. "Players don't forget – every single instant, moment, me, my staff, this club, everything. What we have done, we have done it for all of you. And you have been just exceptional. You don't know it yet, but you are leaving a legacy.""Don't ask me the reasons I'm leaving. There is no reason, but deep inside, I know it's my time," Guardiola said in a statement on Friday. "Nothing is eternal, if it was, I would be here. Eternal will be the feeling, the people, the memories, the love I have for my Manchester City."

The Sequel Announcement The studio behind hit Michael Jackson biopic 'Michael' has revealed plans for a sequel despite the controversy that surrounded the original. Production Details Speaking in a quarterly earnings call, Lionsgate motion picture chair Adam Fogelson said that preparations for a projected sequel “continue to go exceptionally well”. Fogelson added that there is a lot of entertaining Michael Jackson story that was not touched upon in the first film. The Financial Impact The original film delivered record-breaking box office figures in both the US and UK, with its current revenue standing at $715.8m worldwide. Fogelson suggested that some of the previously shot footage could be utilised for the sequel, which would help lower the sequel’s production costs. Addressing Controversy The production of 'Michael' was dogged by issues surrounding allegations of child sex abuse against Jackson. It is not clear how or even if a sequel will deal with these allegations. However, Fogelson suggested that the sequel may not follow chronologically. The Future Outlook Lionsgate believes that they have 25 to 30% of a second movie already shot from the prior production activity. The studio is confident that the sequel will appeal once again to a global audience.

The Unseen Toll of War The conflict in Mali has had a profound impact on the mental health of its citizens. Beyond the physical destruction and loss of life, the war has left a lasting legacy of psychological trauma. Living with Trauma Survivors of the war often struggle with anxiety, depression, and post-traumatic stress disorder (PTSD). These conditions can make everyday tasks challenging and affect relationships with family and friends. The Need for Support Addressing the mental health needs of Malians affected by the war is essential for the country's recovery. This includes providing access to mental health services and supporting community-based initiatives. A Path Forward By acknowledging the mental trauma caused by the war, Mali can begin to heal and rebuild. It is crucial for the international community to provide support and resources to help the country address this critical issue.

The Childcare Crisis in BritainThe number of childminders in England has roughly halved over the past decade, with many citing rising costs, low pay and increasing paperwork as reasons for leaving the profession. Campaigners warn the decline is making it harder for families to find flexible and affordable childcare.Seeking Parent ExperiencesWe want to hear from parents and carers whose childminder has recently closed their business, stopped accepting certain age groups such those over three-year-olds or reduced the number of children they look after.Impact on FamiliesHow did it affect your family? Did you struggle to find alternative childcare? Have you been forced to move your child into a nursery setting despite feeling they were better suited to a smaller, home-from-home environment?Share Your StoryThe Guardian is collecting experiences from parents affected by the decline in childminding services. If you're 18 or over, you can share your story anonymously if you wish. Your responses are secure as the form is encrypted and only The Guardian has access to your contributions.Call for ActionAs the childcare landscape continues to change, it's crucial to understand how these changes are affecting families across the UK. By sharing your experiences, you can help highlight the challenges and potential solutions in the childcare sector.

Retatrutide Delivers Up to 28% Body‑Weight Reduction in Phase 3 StudyA new weight‑loss drug has helped participants in a sizable trial lose much more weight than other obesity drugs already on the market – up to an average of 28% of their body weight, Eli Lilly announced on Thursday. Phase 3 Trial Design and Dosing RegimenThe Indiana‑based company randomized 2,339 adults with obesity or overweight and at least one weight‑related comorbidity (no diabetes) to receive Retatrutide at 4 mg, 9 mg, 12 mg, or placebo for 80 weeks. The drug is a once‑weekly triple hormone receptor agonist targeting GLP‑1, GIP, and glucagon. Quantitative Outcomes and Safety ProfileAverage weight loss: 70.3 lb (28.3%) at the 12 mg dose.Average loss at 9 mg: 64.4 lb (25.9%).Average loss at 4 mg: 47.2 lb (19.0%).45.3% of 12 mg participants lost ≥30% of body weight.65.3% reduced BMI below 30; 37.5% of those starting with BMI ≥ 40 achieved this.Side‑effects increased with dose: nausea (28.6%‑42.4%), diarrhea (25.2%‑34.1%), vomiting (up to 25%).For comparison, Zepbound yields 15‑20% loss over 72 weeks and Wegovy 14‑19% over 64‑72 weeks. Implications for the Obesity‑Drug LandscapeThe magnitude of loss positions Retatrutide as the most effective pharmacologic option to date, potentially shifting prescriber preference away from existing GLP‑1 monotherapies. Its triple‑agonist mechanism adds glucagon, a hormone absent from current products, which may enhance metabolic control and appetite suppression. Future Outlook: Approval Path and Market PotentialAnalysts expect regulatory submissions within the next year, with a likely U.S. FDA review in 2027. If approved, Retatrutide could capture a sizable share of the rapidly expanding obesity‑treatment market, prompting competitors to explore multi‑agonist formulations.