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Background: In previous studies, teriflunomide significantly reduced the annualised relapse rate (ARR) and disability progression. Objective: This phase 3, rater-blinded study (NCT00883337) compared teriflunomide with interferon-beta-1a (IFNβ-1a). Methods: Patients with relapsing multiple sclerosis were randomised (1:1:1) to oral teriflunomide 7-or 14mg, or subcutaneous IFNβ-1a 44µg. The primary composite endpoint was time to failure, defined as first occurrence of confirmed relapse or permanent treatment discontinuation for any cause. Secondary endpoints included ARR, Fatigue Impact Scale (FIS) and Treatment Satisfaction Questionnaire for Medication (TSQM). The study was completed 48 weeks after the last patient was randomised. Results: Some 324 patients were randomised (IFNβ-1a: 104; teriflunomide 7 mg: 109; teriflunomide 14 mg: 111). No difference in time to failure was observed. There was no difference in ARR between teriflunomide 14 mg and IFNβ-1a, but ARR was significantly higher with teriflunomide 7 mg. FIS scores indicated more frequent fatigue with IFNβ-1a, though differences were only significant with teriflunomide 7 mg. TSQM scores were significantly higher with teriflunomide. There were no unexpected safety findings. Conclusion: Effects on time to failure were comparable between teriflunomide and IFNβ-1a. There was no difference between teriflunomide 14 mg and IFNβ-1a on ARR, though ARR was higher with teriflunomide 7 mg. The teriflunomide safety profile was consistent with previous studies.

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n = 89, 68%), followed by null (n = 12, 9%) and cytoplasmic (n = 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLE mutations and/or MMRd (n = 22/27; p < 0.001). Agreement between p53 IHC and TP53 NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC).

The church, located at the corner of Rex and Regina, will be showing an exhibit of 30 photographs by Ontario photographer Carl Herbert. It features powerful images of the HIV/AIDS epidemic in Malawi. Through the camera's lens we see its impact on those in the developing world who are infected, their families and their communities.

The event is sponsored by the Lutheran Women's Missionary League to spotlight an international mission project sponsored by the Lutheran Church-Missouri Synod. The Tanzania mission is sponsored by the Lutheran Church- Missouri Synod, through its congregations in the Mid-South in partnership with the East of Lake Victoria Diocese (ELVD) of the Evangelical Lutheran Church of Tanzania.

At Wednesday's virtual summit hosted by German Chancellor Friedrich Merz, European leaders, and Ukrainian President Zelenskyy pressed Donald Trump to include Ukraine in any peace talks with Putin, warning that past meetings have seen Trump drift toward Moscow's narrative and expressing concern over his openness to territorial land swaps. European officials expressed alarm over U.S. Special Envoy Steve Witkoff's handling of Kremlin talks, criticizing his approach as amateurish amid rising tensions over Trump's proposed Alaska summit with Putin, where territorial recognition and secondary sanctions, particularly targeting India's Russian oil imports, remain contentious issues. Just over a year after returning from Russian imprisonment, Paul Whelan told CNN that Trump's upcoming summit with Putin is a fool's errand, warning that Putin seeks concessions without offering peace or territory in return. Geoffrey Hinton, the godfather of A.I., warns that efforts to keep superintelligent A.I. submissive will fail and instead urges developers to embed maternal instincts into A.I. systems so they genuinely care for and protect humans, even when they surpass us in intelligence. Rural health clinics may be forced to close due to a provision in the Trump Administration's Big, Beautiful Bill focused on abortion; Bride-to-be digs out raw diamond for her wedding ring, Fox searched for almost three weeks at Crater of Diamonds State Park; Taylor Swift took over the \"New Heights\" podcast on Wednesday to give new details on her upcoming 12th studio album, \"The Life of a Showgirl\" which will release on October 3rd. GUESTS: Steven Piper

The call between U.S. President Donald Trump and RussianPresident Vladimir Putin end with no breakthrough from both partiesand instead, the United States will back off from the peace talks.Trump has signed a bill that will take down deep fakes and explicitly-generative pornographic images from Artificial Intelligence. FormerU.S. President Joe Biden thanked his well wishers in his social mediapost and he shared his diagnosis of prostate cancer days after theannouncement that worried many, including those in the politicalspectrum. North Korea abruptly announced the closure of its borders toforeign nationals months after it was reopened, without anyexplanations or warnings. GUESTS: William Taylor, Marta Wosinska

Democrat Standard Bearer Kamala Harris answered tough questionsfrom undecided voters in a CNN Town Hall where she slammed possibledangers of another Trump presidency and shared some of her personalstories. U.S. Secretary of State Antony Blinken is expected to arrivein Qatar after he visited Saudi Arabia to meet with the Crown Princeas part of his Middle East Tour to revive Ceasefire-Hostage talks toend the war in Gaza. CNN's Clarissa Ward and her team were heldcaptives by a Sudanese militia group, but they were eventuallyreleased after 48 hours when the group initially thought that her teamwere spies. The U.S. Centers for Disease Control and Prevention iscurrently working on the details of the E. coli outbreak that linkedto McDonald's Quarter Pounders that led the company to pull out someingredients in the affected stores' menu. GUESTS: Faith Pinho, Benjamin Radd

The ongoing general election in India, the world's largestdemocracy, is highly competitive and could result in a third term forPrime Minister Narendra Modi. Prime Minister Netanyahu disputes U.S.President Biden's plan, insisting on Hamas' elimination. Concerns wereraised over the deaths of 4 Israeli hostages held by Hamas in Gazaduring Israeli military operations, as their families are urging theIsraeli government to accept the peace proposal.. Claudia Sheinbaumwins presidency in a landslide, 61-year-old will be Mexico's firstfemale, first Jewish president; Biden to limit asylum-seekers enteringU.S. illegally, border would essentially be shut down when daily limitexceeded; Nigel Farage seeking seat with far-right Reform U.K. Party,Brexiteer to contest seat in Clacton, despite failing to become an MPseven times; Kafka's letter complaining of writer's block up forauction at Sotheby's in London from June 26 to July 10. GUESTS: Guadalupe Correa-Cabrera, Alon Pinkas

Stock Markets around the world are starting to rebound afterdays of being in the red following sweeping tariffs and loomingrecession. The tariffs set by U.S. President Donald Trump to its tradepartners may lead to the scarcity of cooking products from theEuropean Union where Americans rely. U.S. Secretary of State MarcoRubio has revoked all visas to South Sudanese passport holders forrefusing the repatriation of its nationals. The Florida Gatorsdefeated Houston Cougars to capture their third national title in theNCAA Men's Basketball Finals. GUESTS: Larry Sabato