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  • Multi-Parameter Optimization in Drug Discovery

    Multi-Parameter Optimization in Drug Discovery

    By optimizing potency, pharmacokinetics and safety simultaneously, it enables high quality compounds with balanced biological and physicochemical properties to be identified.

    Key highlights of the poster include:

    • The use of multi-parameter optimization scoring as a decision-making tool
    • How the multi-parameter optimization scoring is updated as the project advances through drug discovery
    • Incorporation of considerations such as target tissue, administration route and safety liabilities at an early stage to drive design

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  • Time for Team Penske To Step Up at Iowa Playground

    Time for Team Penske To Step Up at Iowa Playground

    It’s Team Penske time, or so it would seem.

    Iowa Speedway is the next venue on tap for the NTT INDYCAR SERIES, and this weekend’s short oval is where Roger Penske’s organization has won eight of the past nine races, sweeping the doubleheaders each of the past two years with three different drivers.

    Scott McLaughlin and Will Power won last year’s races; Josef Newgarden captured the two in 2023 as part of his five wins for Penske at Iowa since 2017.

    This track couldn’t arrive on the schedule soon enough for Team Penske, which is riding its longest winless drought since the one Ryan Briscoe ended at Milwaukee in 2008. The team and the aforementioned drivers have not been to victory lane this season and have gone 11 races since McLaughlin won the second race of last year’s September visit to The Milwaukee Mile. Team Penske failed to win in the last 10 races of the 2007 season and the first five of 2008 to produce a 15-race drought.

    This year’s troubles run deep, too. Power is the highest-ranked Team Penske driver in the standings in ninth place. McLaughlin is 11th, Newgarden is 19th. Their seasons can be summed up by Sunday’s The Honda Indy 200 at Mid-Ohio presented by the All-New 2026 Passport when they finished 23rd (McLaughlin), 26th (Power) and 27th (Newgarden) in the 27-car field.

    For the first time in Newgarden’s career dating to 2012, his car has been involved in an accident in three consecutive races. The most recent occurred Sunday just past the starting line when the rear brakes locked on his No. 2 PPG Team Penske Chevrolet, leading to a spin that collected Rahal Letterman Lanigan Racing’s Graham Rahal. Both cars ended up in the gravel pit at Turn 4. Minutes later, Power’s No. 12 Verizon Team Penske Chevrolet was on pit road with a mechanical issue that led to his exit after just 11 laps. McLaughlin also failed to complete all 90 laps.

    Newgarden was leading last month’s Bommarito Automotive Group 500 presented by Axalta and Valvoline at World Wide Technology Raceway and was about to lap NTT INDYCAR SERIES points leader Alex Palou of Chip Ganassi Racing when the car of RLL rookie Louis Foster spun in front of him, collecting Newgarden. The impact was one of the fiercest of Newgarden’s career. He also spun into a barrier last month in the XPEL Grand Prix at Road America.

    The NTT INDYCAR SERIES has staged 21 races at Iowa Speedway since 2007, but only four drivers in this field have gone to victory lane: Newgarden (six times, including once in 2016 with CFH Racing), Arrow McLaren’s Pato O’Ward (2022), McLaughlin and Power. If ever Team Penske was going to get back to its winning ways, it feels like now.

    In last year’s second race, Palou had the best short-oval performance of his career, finishing second to Power. He crashed out of the weekend’s first race with an uncharacteristic spin on the front straightaway. He enters this race, the 11th of the season, with a 113-point lead over Andretti Global’s Kyle Kirkwood, the winner of the only short-oval race held so far this season (at WWTR).

    The first practice of the Sukup INDYCAR Race Weekend is set for Friday at 3:30 p.m. ET (FS2, FOX Sports app, INDYCAR Radio Network). The lineups for both races will be set in qualifying Saturday at noon (FS1). The Synk 275 powered by Sukup is at 5 p.m. ET Saturday, the Farm to Finish 275 powered by Sukup is at 1 p.m. Sunday. Both races will air live on FOX, the FOX Sports app and the INDYCAR Radio Network.


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  • First round of Pak-Afghan talks concludes, focusing on trade, security

    First round of Pak-Afghan talks concludes, focusing on trade, security

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    ISLAMABAD:

    The first round of additional secretary-level talks between Pakistan and Afghanistan has been completed, focusing on the implementation of decisions made during Deputy Prime Minister and Foreign Minister Ishaq Dar’s visit to Kabul on April 19.

    The discussions centered around key areas of mutual interest, including trade, transit cooperation, security, and connectivity.

    According to a statement from the Ministry of Foreign Affairs, the Pakistani delegation was led by Additional Secretary for Afghanistan and Western Asia Ali Asad Gilani while the Afghan delegation was headed by Moti Noor Ahmad Noor, Director-General of the Political Division of the Afghan Ministry of Foreign Affairs.

    During the talks, both sides recognised terrorism as a significant threat to regional peace and security. Pakistan emphasised the need for decisive actions against terrorist groups operating from Afghan territory, stressing that such groups undermine Pakistan’s security and hinder regional development.

    The two delegations also reviewed the progress of various agreements, including the removal of the 10% processing fee in Afghan transit trade, the provision of insurance guarantees, reductions in scanning procedures, and the activation of the track-and-trace system.

    Additionally, the discussions covered the Uzbekistan-Afghanistan-Pakistan railway framework agreement, with both sides agreeing to finalise it soon. The return of Afghan citizens to their homeland was also a key topic of discussion.

    The briefing revealed that since January 2024, Pakistan has issued over 500,000 visas for medical, tourism, business, and educational purposes. Both sides reiterated their commitment to facilitating legal movement of individuals across borders and enhancing bilateral ties.

    The next round of talks will be scheduled at mutually agreed-upon dates, with both countries reaffirming their support for strengthening sustainable cooperation to address shared challenges.


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  • Investigating the Pathological Relevance of N-acylsphingosine Amidohydrolase 2 (ASAH2) and Related Proteins in Alzheimer’s Disease

    Investigating the Pathological Relevance of N-acylsphingosine Amidohydrolase 2 (ASAH2) and Related Proteins in Alzheimer’s Disease


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  • Epic Games Settles App Store Antitrust Claims With Samsung

    Epic Games Settles App Store Antitrust Claims With Samsung

    Epic Games Inc. settled its antitrust case against Samsung Electronics Co. that alleged the company was conspiring with Alphabet Inc.’s Google to block rival app marketplaces through default settings on mobile devices sold by the electronics giant.

    In a brief court filing Monday, the maker of the blockbuster shooter game Fortnite dismissed all of the antitrust claims against Samsung and Google. Google remains a defendant on several non-antitrust claims.

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  • Sinner advances to Wimbledon QFs after Dimitrov retires – ATP Tour

    1. Sinner advances to Wimbledon QFs after Dimitrov retires  ATP Tour
    2. Wimbledon 2025: Sinner gets reprieve as Dimitrov retires injured; Djokovic, Swiatek and Andreeva through – live  The Guardian
    3. ‘Pain-free’ Dimitrov ready for Sinner clash following retirement nightmare  ATP Tour
    4. What happened to Grigori Dimitrov? Injury update as Bulgarian star retires hurt at Wimbledon  Hindustan Times
    5. Jannik Sinner sent bleak message by Grigor Dimitrov before Wimbledon showdown  Daily Express

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  • Over Half of Middle-Aged Adults With HIV Experience Physical Function Decline

    Over Half of Middle-Aged Adults With HIV Experience Physical Function Decline

    Grace Kulik (née Ditzenberger), PT, DPT

    Image credits: LinkedIn

    Kristine M Erlandson, MD, MS

    Image credits: LinkedIn

    A new analysis from the PREPARE (Pitavastatin to REduce Physical Function Impairment and FRailty in HIV) trial found that 52% of middle-aged adults with HIV experienced measurable declines in physical function over time. Published in the June 2025 issue of Open Forum Infectious Diseases, the study highlights the importance of identifying individuals at risk for functional decline to support aging with HIV and prevent disability.

    The analysis included 569 participants with HIV (median age 51 years; interquartile range, 47–55), 81% of whom were male and 52% White. Physical function was assessed annually using gait speed, chair rise rate, grip strength, and a modified Short Physical Performance Battery (SPPB), which also included balance time. Decline was defined as falling below the 20th percentile on at least one measure. While overall declines were modest, variability among individuals was considerable.

    Demographic and clinical risk factors for decline included female sex (RR, 1.32; 95% CI, 1.12–1.55), non-White race (RR, 1.23; 95% CI, 1.05–1.45), and older age. In multivariable analyses adjusting for age, sex, and race, additional independent predictors included history of depression treatment, elevated body mass index (BMI), baseline frailty, and elevated inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6).

    To contextualize these findings, Contagion spoke with study authors Grace Kulik, PT, DPT, PhD candidate at the University of Colorado (UCD) Anschutz Medical Campus, and Kristine M Erlandson, MD, MS, professor of infectious diseases at UCD Anschutz about the clinical implications of functional decline in people with HIV (PWH), including the roles of inflammation, ART exposure, and screening in mitigating long-term impairment.

    Contagion: How do systemic inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) specifically contribute to physical function decline in people with HIV, given the immune dysregulation associated with the infection?

    Kulik: Higher levels of inflammatory markers are thought to contribute to muscle wasting, which in turn is thought to reduce physical function. Chronic inflammation has also been linked with reduced levels of overall physical activity, and low physical activity is strongly associated with poor physical function.

    Contagion: Which infectious complications or HIV-related comorbidities most significantly exacerbate functional impairment, and what early monitoring strategies do you recommend?

    What You need To Know

    The PREPARE trial found that 52% of adults with HIV showed measurable declines in physical function, based on standard mobility and strength assessments.

    Risk factors for decline included elevated hsCRP and IL-6, higher BMI, prior depression treatment, female sex, and non-White race.

    Routine clinical screening using chair rise or gait speed tests can help identify early functional decline and guide timely interventions.

    Kulik: Prior studies by Dr. Erlandson have demonstrated that physical function is negatively associated with the immune response to cytomegalovirus, which is a common co-infection among people with HIV, even if they have a suppressed viral load. HIV is associated with a greater risk for other comorbidities, such as cardiovascular disease and diabetes, which have also been linked to physical function impairment. Performing annual or semi-annual tests such as 4-meter gait speed, time to complete 5 or 10 chair rises, and grip strength tests are the most commonly used strategies to screen for physical function impairment. Personally, I think that the 4-meter gait speed or chair rise assessments are the most feasible to incorporate for clinical screening because grip strength requires additional equipment and calibration.

    Contagion: From your clinical experience, how do antiretroviral therapy (ART) regimens impact physical function trajectories in aging individuals with HIV?

    Erlandson: Some of the older therapies (AZT, DDI, D4T) can have a negative impact on skeletal muscle, mitochondrial function (in fat or skeletal muscle), and/or contribute to neuropathy. Efavirenz has also been linked to greater physical function decline, possibly through some of the neurocognitive or weight-suppressive effects. Obesity contributes to physical function decline, so we ultimately may see greater physical function declines in people with greater weight gain, regardless of the regimen.

    Contagion: What role do you see for infectious disease specialists in multidisciplinary interventions aimed at preventing or mitigating physical decline in this population?

    Erlandson: Many infectious disease specialists serve as the primary care providers for patients living with HIV. Infectious disease providers may see people with HIV frequently—especially older adults or those with more comorbidities—and have the opportunity to recognize early declines and to provide counseling on preventive measures to mitigate physical function declines. Infectious disease specialists may also recognize important side effects or drug interactions with HIV medications that might contribute to physical function impairments, such as protease inhibitors with some statins.

    Reference
    Kulik GL, Umbleja T, Brown TT, et al. Prognostic factors of physical function decline among middle-aged adults with HIV. Open Forum Infect Dis. 2025;12(6):ofaf311. doi:10.1093/ofid/ofaf311

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  • 7 Sneaky Signs You Could Have Cognitive Decline

    7 Sneaky Signs You Could Have Cognitive Decline

    • Cognitive lapses aren’t always linked to aging or dementia. Factors like stress, anxiety, and multitasking can mimic or contribute. 
    • Incorporating brain-healthy foods, staying physically active and engaging in mentally stimulating activities are ways to slow cognitive decline. 
    • Early consultation with a healthcare professional is crucial for proper diagnosis and intervention.

    It happens from time to time: You start telling a story, only to lose your train of thought halfway through. Or you walk into a room and can’t remember what you went in there to do. Mental glitches like these happen to everyone and are understandably scary, but aren’t necessarily a sign of cognitive decline. “The feeling of your brain short-circuiting is often more likely due to psychological processes,” says Sarah Garcia-Beaumier, Ph.D. Increases in stress, distractions, multitasking, anxiety or depression can be contributors. “A common consideration we have to make clinically is whether cognitive symptoms are due to early dementia, or rather due to a depressive or anxiety disorder,” Garcia-Beaumier says.

    Cognitive Lapses vs. Cognitive Decline 

    Cognitive decline typically involves a worsening of performance in areas such as memory, attention or language. Common signs include forgetting to call someone or struggling to recall the right word. When those symptoms appear much more than they did previously, so much so that others are starting to notice, “that’s typically an early red flag for cognitive decline beyond what we expect for the normal aging process,” says Garcia-Beaumier. Normal aging may cause minor delays in memory retrieval, like struggling to remember a name but recalling it later. These are not signs of dementia or cognitive impairment, per Thomas Hammond, M.D. “Forgetting conversations or important appointments, or feeling lost in familiar places, are more worrisome and concerning for significant early cognitive impairment,” Hammond explained.

    Garcia-Beaumier notes that some individuals with mild cognitive impairment may stabilize or improve over time. Still, unresolved psychological distress or untreated health issues could increase the risk of dementia, making it crucial to address potential warning signs early.

    Common Signs of Cognitive Decline 

    1. You struggle to stay on top of things. 

    The corticolimbic system of the brain modulates the experience of anxiety. “It also happens to be the same area of the brain that helps with processing speed, attention, planning, judgment, organization and lots of thinking skills,” says Garcia-Beaumier. “So if there’s a change in this area of the brain due to stress or anxiety, these cognitive skills are also affected.”

    This overlap in brain pathways, along with the larger amount of resources devoted to modulating your stress and anxiety due to your body constantly shifting between survival and recuperation mode, will lead to a varying array of cognitive deficits.

    These pathways are also crucial in processing information—if you can no longer pay attention to things, your brain isn’t going to be able to encode them and retain them for later memory.

    2. You can’t find the words you’re looking for. 

    Cognitive decline manifests itself in almost all aspects of complex daily tasks, especially our language. “Even a simple undertaking, like naming a kitchen appliance, engages our brain networks extensively, making it a sensitive indicator of early decline,” says Aubry Alvarez-Bakker, Ph.D..

    A strong sign can be found in moments when you might forget a simple, specific word you’re looking for, so you try to describe it instead. Over time, you might also start having difficulty keeping up with conversations, which can lead to anxiety in social situations.

    The specific mechanism behind why this happens isn’t fully known, but research shows that language decline often originates in the left side of the brain. “We also know that low BDNF production (a protein produced by our nervous system that’s crucial for the production of new brain cells) means fewer new cells to help us carry on activity across our brain,” says Alvarez-Bakker.

    As we age, production of this protein naturally declines, so our body relies heavily on our environment to create BDNF to “fertilize” our brain and allow new cells to form. “Among the best foods to consume to boost BDNF in our body—and subsequently ward off cognitive decline—are blueberries, turmeric, green tea and dark chocolate,” says Alvarez-Bakker.

    3. You feel blasé about things you used to enjoy. 

    Because apathy is a common symptom of severe burnout, it’s easy to pay no mind that it can also be a symptom of cognitive decline. “It’s actually the most common symptom and perhaps the most overlooked,” says Alvarez-Bakker.

    A sudden loss of interest in activities you used to love, or a willingness to throw in the towel easily, is a common symptom of dementia. You might lose interest in reading books, gardening or many other activities you used to enjoy. You might also find things that used to be easy for you to accomplish are now overwhelming, or that you avoid complex tasks or projects entirely.

    “This is unfortunate because withdrawing from stimulation is known to speed up the decline process,” says Alvarez-Bakker. “Luckily, our lifestyle can help counteract this symptom to an extent.” When apathy creeps in, the best step to take is to get personal by integrating things you deeply enjoy—music, art, sports, reminiscing—into daily activities that will boost your participation in life, and in turn, stimulation.

    4. You’ve been acting out of character. 

    Subtle personality changes are an often-missed sign of cognitive decline, primarily because of how easily they can be blamed on chronic stress (say, becoming easily angered or swearing when that isn’t a regular part of your vocabulary).

    You might also find yourself withdrawing from social interactions and activities—and when you are around others, you may not participate in discussions, but instead stay quiet. “These are symptoms which are often written off as an individual being shy,” says Hammond. “However, the person who was once talkative and garrulous will often become quiet and a wallflower as an early sign of developing cognitive decline.”

    Regardless if stress is the cause or a variable that’s augmenting the cognitive decline, “any treatment hoping to prevent or reduce cognitive decline needs to incorporate stress management,” says, Isaac Tourgeman, Ph.D.

    5. You’re always ruminating and worrying. 

    Incessantly ruminating and worrying keeps your fight-or-flight response in overdrive, and symptoms of chronic stress can mimic cognitive decline, such as forgetfulness and inattention.

    “Uncontrolled, toxic thinking has the potential to create a state of low-grade inflammation across the brain and body over time, which can impact our cognitive health and ability to remember or recall information,” says Caroline Leaf, Ph.D. “If left unmanaged, this kind of chronic cognitive upset can progress into varying levels of cognitive decline.”

    Resolution of the underlying causes of your rumination and worry is paramount to improving current and preventing future symptoms of cognitive decline.

    6. You’ve recently been sick or have a chronic condition. 

    “Cognitive dulling is a common feature associated with general medical illnesses, such as the flu, urinary tract infection and gastroenteritis,” says Hammond. “Metabolic stress caused by minor infection will often lead to a transient cognitive decline,” Hammond added.

    Other conditions can also lead to cognitive decline, including sleep disorders (such as sleep apnea). “Similar to psychological distress, sometimes symptoms can be resolved if it’s due to one of these conditions,” says Garcia-Beaumier. “But if left untreated, it does increase a person’s risk of dementia down the line.”

    Depression can result in what’s called pseudodementia, where depression essentially masquerades as cognitive impairment. “Symptoms present as forgetfulness, difficulty with attention and lowered energy and motivation,” says Tourgeman. This is when it’s especially important to consult with your doctor to ensure the right diagnosis is made and proper treatment given.

    7. Other people are noticing your mental glitches. 

    “We all experience cognitive glitches to a certain extent when going through the pressures of life, but a good rule of thumb is if anyone who knows you has noticed a consistent increase of these symptoms over time, it may be a sign that you’re experiencing cognitive decline,” says Leaf. Usually the person experiencing symptoms is the last to be aware of the decline, so it’s important to be open to feedback and proactive about taking action.

    How to Help Prevent or Slow Cognitive Decline 

    “While we currently aren’t able to change our genes, we can influence how our environment impacts them,” says Tourgeman. “A healthy lifestyle—eating a brain-healthy diet (like the MIND Diet), exercising regularly, reducing stress and distractions, maintaining a sense of utility and connectedness—can all go a long way.”

    And no healthy lifestyle with the goal of avoiding or improving cognitive decline would be complete without a wide range of activities that keep your brain engaged. “Playing brain games on your phone will only go so far, though, mostly because you’ll only get really good at that one thing,” says Garcia-Beaumier. “Doing lots of activities that you enjoy and that challenge you is best.” Things like reading, playing games, learning new skills and dancing can all contribute to optimal cognitive health when done in conjunction with other healthy habits.

    How to Know When It’s Time to See a Healthcare Provider 

    “Any time someone notices cognitive changes, such as memory not being as good or the brain feeling slower or foggy, they should check in with their doctor,” says Garcia-Beaumier. “But it’s especially important if family or friends are also noticing issues or if the issues make it hard to fulfill daily responsibilities.”

    You can try to work on decreasing stress and improving how you take care of any other health conditions to see if that also clears up any cognitive issues, but there isn’t a definitive way to know whether your symptoms are due to stress, psychological issues, another health condition or cognitive decline without talking to a healthcare provider and possibly seeing specialists for further testing.

    “Even getting some basic tests, early before any issues arise, can allow your doctor to compare your current cognitive performance to possible cognitive issues in the future,” says Garcia-Beaumier.

    Our Expert Take

    The occasional mental lapse, like misplacing your keys or forgetting the name of a person you just met, is a normal part of life and not necessarily a cause for concern. These fleeting moments of forgetfulness are often tied to stress, lack of sleep, or even simply being preoccupied with too many things at once. However, when these cognitive issues become consistent, noticeable to others and begin to interfere with daily life, they may signal something more significant, such as cognitive decline. Taking proactive steps to manage stress, maintain overall health, and engage in stimulating mental and physical activities can help you protect your brain’s function and resilience.

    Understanding the difference between normal cognitive aging and more concerning symptoms is key to addressing issues early on. Consult a healthcare professional if you or those close to you observe persistent changes in memory, attention, or overall behavior. Seeking support and adopting lifestyle habits that prioritize brain health can not only slow potential decline but also improve your quality of life. By staying informed and proactive, you give yourself the best chance at maintaining your cognitive health and vitality for years to come.

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  • Wojciech Szczęsny contract extension until 2027

    Wojciech Szczęsny contract extension until 2027

    FC Barcelona and the player Wojciech Szczęsny have reached an agreement for the extension his contract which will tie him to the Club until 30 June 2027.  

    The deal comes after a great season from the goalkeeper following his unexpected arrival to cover the unfortunate long term injury to Marc ter Stegen. Barça needed a keeper and chose  Szczęsny, who came out of retirement to accept the challenge after having hung up his gloves in the summer. The Pole responded by showing he is still one of the best goalkeepers in European Football. 

    Stats that speak for themselves  

    In 30 appearances for Barça in the 2024/25 season, Szczęsny kept 14 clean sheets and was never on the losing side in La Liga. The Polish player’s experience and maturity was a great help for coach Hansi Flick in a young and inexperienced Barça squad.  

    Impressive CV  

    The goalkeeper’s time at Barça is another addition to his impressive career. Szczęsny announced his retirement in August 2024. However, Barça’s call brought him back to football after an admirable career and many achievements. After leaving his hometown of Warsaw at the age of 16 years old, he went on to play for major European sides such as Arsenal, Roma and Juventus, giving him great experience in the continent’s top leagues.  

    More trophies  

    With the domestic treble at Barça in 2024/25, Szczęsny has now claimed 14 trophies during his career with more than 500 appearances, 83 of which have come in the Champions League, the last eight of which came last season in a Barça shirt. They may well not be his last with the goalkeeper remaining a blaugrana now until 2027.  

     

     

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