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  • Sara Errani and Andrea Vavassori reaffirm supremacy to win US Open mixed doubles final | US Open Tennis 2025

    Sara Errani and Andrea Vavassori reaffirm supremacy to win US Open mixed doubles final | US Open Tennis 2025

    Across two frantic days in New York, Andrea Vavassori and Sara Errani repeatedly made their intentions clear. As the only doubles specialist team in a tournament that had banished the rest of their kind, they were on a mission to prove their worth by succeeding on the court.

    Shortly before midnight on an Arthur Ashe Stadium still filled with raucous spectators, the mission was complete. They triumphed in spectacular fashion at the reimagined US Open mixed doubles championship by closing out the star singles pairing of Iga Swiatek and Casper Ruud, the third seeds, 6-3 5-7 (10-6) in a supreme, intense tussle to defend their title.

    Ever since the US Open announced its transformed mixed doubles tournament six months ago, which has been moved forward to the US Open’s qualifying week and rebranded as a shortened format with an entry criteria that overwhelmingly favours singles players, Vavassori and Errani have been two of its biggest critics.

    A wildcard pairing due to their victory last year, they entered this tournament determined to back up those criticisms by proving the value of doubles players on the court. As they have marched through the draw, many of their doubles specialist peers have offered their full support. “I think this one is also for the doubles players that couldn’t play this tournament,” said Errani afterwards.

    In a draw filled with many of the best tennis players in the world, Errani and Vavassori made a decisive case for the importance of teamwork in this discipline. They demonstrated the value of sharp, decisive netplay, strategy, formations and intelligence by on the court. They were always one step ahead of the opponent and they imposed relentless pressure with their suffocating brilliance at the net.

    After blazing through to the final without dropping a set, the title was decided in an incredible match defined by sharp contrasts, the teamwork, tactical nous and shifting formations of the Italian pair against the baseline supremacy of Swiatek and Ruud, who spent the night eviscerating forehands as they tried to pierce the Italian wall at the net. They then launched a spectacular comeback to force a final set match tiebreak before the Italians closed out the match. “You proved that mixed doubles players are smarter tactically than singles players, I guess,” said Swiatek.

    While the victors made their points clear, in many ways the US Open organisers also did. This event has generated criticism for a wide variety of reasons, from the way it disposed of the doubles specialists to the changes imposed by the US Open without any input from the players themselves.

    This tournament’s aim, however, was to create a bigger stage for a format the organisers deemed obsolete, and the interest it has generated is undeniable. Four days before the start of the US Open, a completely full Arthur Ashe stadium was on hand to witness the climax of an event that had become little more than a footnote in recent years.

    One year on from their triumph over a field of specialists, the best mixed doubles team in the world reaffirmed their supremacy by beating the singles superstars. Photograph: Justin Lane/EPA

    The evening began with Swiatek and Ruud ousting the top seeds Jessica Pegula and Jack Draper in the first semi-final. During their warmup, the on-court MC suggested that Ruud could win his first grand slam title by the end of the night and described Draper as a two-time grand slam semi-finalist. They were extremely jarring claims that underlined another significant point of contention: should this event be categorised as a grand slam title or, considering its shortened format and restrictive entry conditions, is it simply an exhibition?

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    Perhaps neither of these definitions are suitable and this is simply a special event in its own category. While some teams, such as Carlos Alcaraz and Emma Raducanu, participated for the good vibes, this second night presented an intense, high quality evening of tennis. It is obvious that the singles players have far greater priorities, and they will not lose sleep over losing a mixed doubles event in their training week before the real tournament begins, but they are also intensely competitive and they each competed on Wednesday with determination and full effort.

    At a time when numerous global sports, such as athletics, swimming and even gymnastics, have introduced mixed-gender team events, this event is also a reminder of tennis’s failure to properly take advantage of one of its unique selling points: the fact that the top male and female players share the stage at the biggest tournaments. A distinct feature of mixed doubles, compared to those other mixed-gender events, is that the female players are more than capable of holding their own and making decisive winning plays against their male counterparts. For most of the first semi-final match, for example, Pegula was the best player on the court.

    In general, the two days of competition were great fun. This tournament included the unforgettable sight of 45-year-old Venus Williams tussling with Andrey Rublev from the baseline, acing him while trailing match point during Karolina Muchova and Rublev’s win over Williams and Reilly Opelka. A month after returning a 153mph serve at Wimbledon, Taylor Fritz at times struggled with Sara Errani’s 70mph first serves. Most notably, one year on from their triumph over a field of specialists, the best mixed doubles team in the world reaffirmed their supremacy by beating the singles superstars. For their efforts, they earned $1m prize money, a handsome pay rise of $800k in just one year.

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  • Huawei Pura 80 Pro crushed Pura 70 Pro in sales by 160% hike – Huawei Central

    1. Huawei Pura 80 Pro crushed Pura 70 Pro in sales by 160% hike  Huawei Central
    2. I loved the Huawei Pura 80 Ultra’s clever cameras – but it’s still impossible to recommend  stuff.tv
    3. Huawei Pura 80 Ultra vs. Vivo V60 5G: Which Flagship Smartphone Should You Buy?  Techloy
    4. Huawei Pura 80 Ultra Crushes iPhone 16 Pro Max In Camera Rankings  Forbes
    5. HUAWEI Pura 80 Ultra scores highest-ever DXOMARK 175 rating  Mindanao Times

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  • What you need to know as the band hit London

    What you need to know as the band hit London

    Harry Craig

    BBC News, London

    PA Media Chris Martin of Coldplay is singing on a stage, with bassist Guy Berryman playing on his right, guitarist Jonny Buckland on his left, and drummer Will Champion playing in the background. Martin is wearing an orange, blue and purple tye-dye T-shirt, with the others wearing dark-coloured jackets. The screen behind them is lit up in bright orange, pink and green patterns.PA Media

    The Music of the Spheres World Tour is the most-attended concert tour in history

    Having played to some 12 million fans across 43 countries, Coldplay are performing 10 sold-out nights at Wembley Stadium in August and September.

    The Music of the Spheres World Tour is already the most-attended concert tour in history and it is set to culminate in the city where the band formed, 25 years on from the release of their debut album.

    Organisers are encouraging fans to use public transport to get to and from the show, via Tube or National Rail services.

    Wembley has strict rules about items being brought into the venue. Bags must be smaller than A4 size and water bottles must be soft plastic, empty and without tops. Any posters must be smaller than A3 size.

    Dates and times

    Coldplay are playing 10 nights at Wembley Stadium, breaking the joint record set by Take That and Taylor Swift of performing eight shows at the venue in the same year.

    • Friday 22 August
    • Saturday 23 August
    • Tuesday 26 August
    • Wednesday 27 August
    • Saturday 30 August
    • Sunday 31 August
    • Wednesday 3 September
    • Thursday 4 September
    • Sunday 7 September
    • Monday 8 September

    Doors will open at 16:45 (16:15 on Sundays), with the band expected on-stage at 20:20 (19:50 on Sundays).

    Coldplay frontman Chris Martin is stood on the front of a stage leaning backwards and dancing, wearing a black jacket and black trousers with a purple-red tye-dye T-shirt. He is in front of a large screen, which has bright pink and blue lines radiating from the middle. Bassist Guy Berryman is playing on the right in a black jacket, with drummer Will Champion playing at the back of the stage behind Chris Martin.

    The tour began in 2022 to support Coldplay’s ninth album, Music of the Spheres, with their 10th record, Moon Music, then released in 2024

    Who are the support acts?

    All of the Wembley shows will begin with the Simón Bolívar Symphony Orchestra of Venezuela, conducted by Gustavo Dudamel. They are also expected to join Coldplay during their headline set.

    The orchestra will be followed by Palestinian-Chilean pop star Elyanna, who collaborated with Coldplay on their single We Pray last year.

    For the first two nights, the final act before Coldplay will be Nigerian Afrobeats singer Ayra Starr.

    Chloe Qisha will take her place on 26 and 27 August, followed by Beabadoobee on 30 and 31 August, and Tems for the final four dates.

    How to get there

    Coldplay are encouraging fans to travel by public transport, in line with their sustainability goals.

    • Transport for London (TfL) advises concert-goers to download the TfL app and check routes before travelling
    • The closest Tube station to Wembley Stadium is Wembley Park, which is on the Jubilee and Metropolitan lines. A queuing system will be in operation after the concert
    • National Rail links are available at Wembley Stadium station (Chiltern Railways to Marylebone), whilst Wembley Central station is on the Bakerloo and Lioness lines
    • Road closures will be in place, with people advised to avoid the area unless they have a ticket
    • Event-day parking at Wembley Stadium is limited and must be booked in advance via the official website
    • National Express is running coaches to and from the gig from towns and cities the UK
    PA Media A crowd of music fans in the dark are raising their hands in the air, all wearing bracelets that are glowing different colours. Some are waving flags, which are visible in the background.PA Media

    Fans will be glowing in the dark, with light-up wristbands being distributed on entry

    What will be on the set list?

    Soundchecks done by the band ahead of the Wembley performances have suggest there could be some surprise rarities and fan favourites in store, so expect the set list to look something like this:

    • Higher Power
    • Adventure of a Lifetime
    • Paradise
    • The Scientist
    • Viva La Vida
    • Hymn for the Weekend
    • Songbook (Chris Martin plays an audience request with a fan on-stage)
    • Charlie Brown
    • Yellow
    • Human Heart
    • People of the Pride
    • Clocks
    • We Pray
    • Infinity Sign
    • Something Just Like This (remixed with Martin Garrix’s Breakaway)
    • My Universe
    • A Sky Full of Stars
    • Sunrise
    • Sparks
    • The Jumbotron Song
    • Fix You
    • feelslikeimfallinginlove
    • All My Love
    • A Wave
    Chris Martin, lead singer of Coldplay, singing into a microphone with both arms raised in the air. He is wearing a grey shirt with 'LOVE' written in rainbow letters, and an unzipped blue jacket on top. The background is black and dark, with drummer Will Champion's head visible in the bottom left.

    Wembley marks the final stop of Coldplay’s world tour for now, before it is expected to resume in 2027

    What about sustainability?

    Back in 2019, Chris Martin told the BBC the band would stop touring until they could figure out how to do so in a more sustainable way.

    When their current tour was announced in 2021, they released a plan to cut their carbon footprint by at least 50%, including biodegradeable confetti and environmentally-friendly fireworks.

    In 2024 the band claimed their efforts had been a success, with carbon emissions down 59% on their last tour.

    Attendees at the Wembley shows can expect to play their own part in these goals, with exercise bikes to power the C-stage and the entire stadium covered in a kinetic dancefloor which generates electricity as fans dance.

    Neil Enore A set of steps leading the way up to Wembley Stadium, between two tower blocks. The steps are painted white, with different shades of yellow leading up the steps. In the bottom left, writing is painted in black reading 'And it was all yellow'.Neil Enore

    Wembley’s Spanish Steps have been turned yellow to mark 25 years since Coldplay’s breakthrough hit

    What else is happening in London?

    To coincide with their run of shows in London, Coldplay have announced a “takeover” at King’s Cross.

    This includes a pop-up merch shop at Coal Drops Yard and a free photo exhibition entitled Confetti Diaries by Anna Lee, the band’s official tour photographer, at The Lightroom.

    The Lightroom will also host screenings of A Film For The Future, a visual accompaniment to the band’s latest album, Moon Music.

    At Wembley itself, fans can take their picture with the Spanish Steps, which have been turned into a public art installation to mark 25 years since the release of Coldplay’s breakthrough hit, Yellow.

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  • Asian shares are mostly higher after a mixed finish on Wall Street

    Asian shares are mostly higher after a mixed finish on Wall Street

    MANILA, Philippines (AP) — Asian shares were mostly higher on Thursday after a mixed finish on Wall Street, where shares in Nvidia, Palantir and other superstar stocks pared their earlier steep losses.

    Traders are looking ahead for cues about U.S. monetary policy from a meeting of central bankers that begins later in the day in Jackson Hole, Wyoming. Federal Reserve chair Jerome Powell is due to speak to the conference on Friday.

    The Fed has kept its main interest rate steady this year, primarily because of the fear of the possibility that President Donald Trump’s tariffs could push inflation higher. But a surprisingly weak report on job growth across the U.S. may be superseding that.

    Still, minutes from the Fed’s July 29-30 meeting released Wednesday showed most Fed officials felt the threat of higher inflation was a greater concern than the potential for job losses, leading the central bank to keep its key rate unchanged.

    In Tokyo, the Nikkei 225 fell 0.6% to 42,636.74 after a survey showed Japan’s factory activity remained in contraction for the second month in August. The S&P Global flash Japan Manufacturing Purchasing Managers’ Index (PMI) increased to 49.9 in August from 48.9 in July, just below the 50 level that delineates between growth and decline.

    Regional manufacturers have been feeling pressure from Trump’s higher tariffs on exports to the United States.

    In Chinese markets, Hong Kong’s Hang Seng index edged 0.1% lower to 25,135.09, while the Shanghai composite index rose 0.4% to 3,779.52.

    South Korea’s Kospi jumped 1% to 3,161.74, while Australia’s S&P ASX 200 index added 1% to 9,005.00.

    Taiwan’s TAIEX climbed 1.2%, while India’s Sensex added 0.1%.

    “Asian markets walked into Thursday like a card room still heavy with last night’s smoke — muted, watchful, waiting for the next cue out of Jackson Hole,” Stephen Innes of SPI Asset Management said in a commentary.

    On Wednesday, the S&P 500 dipped 0.2% to 6,395.78 after trimming a 1.1% loss earlier in the day. It is still near its all-time high set last week.

    The Dow Jones Industrial Average added less than 0.1% to 44,938.31. The Nasdaq composite fell 0.7% to 21,172.86.

    The day’s action centered again around stocks caught up in the mania around artificial-intelligence technology.

    Nvidia, whose chips are powering much of the world’s move into AI, sank as much as 3.9% during the morning and was on track to be the heaviest weight on Wall Street following its 3.5% fall on Tuesday.

    But it clawed back nearly all of Wednesday’s drop and finished with a dip of just 0.1%. As it pared its loss, so did broad market indexes because Nvidia is Wall Street’s most influential stock by being its most valuable.

    Palantir Technologies, another AI darling, fell 1.1% to add to its 9.4% loss from the day before, but it had been down as much as 9.8% Wednesday morning.

    One possible contributor to the swoon was a study from MIT’s Nanda Initiative that warned that most corporations are not yet seeing any measurable return from their generative AI investments, according to Ulrike Hoffmann-Burchardi, global head of equities at UBS Global Wealth Management.

    But the larger factor may be the simple criticism that prices for such stock have simply shot too high, too fast amid the furor around AI and became too expensive.

    In other dealings early Thursday, US. benchmark crude gained 30 cents to $63.01 per barrel. Brent crude, the international standard added 26 cents to $67.10 per barrel.

    The U.S. dollar rose to 147.37 Japanese yen, from 147.29 yen. The euro slid to $1.1648 from $1.1659.

    ___

    AP Business Writer Stan Choe contributed.

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  • Assessment of the quality of endoscopic tympanoplasty and endoscopic myringoplasty videos on YouTube | BMC Medical Education

    Assessment of the quality of endoscopic tympanoplasty and endoscopic myringoplasty videos on YouTube | BMC Medical Education

    Surgical specialization training has evolved considerably in recent years [21]. Especially during the Covid-19 period, the number of assisted surgeries decreased along with the total number of surgeries performed by residents continuing their training, leading to gaps in resident education [22,23,24]. Recently, surgical training has become more challenging due to the rise in resident numbers and the decline in available educators. For these reasons, the use of surgical videos in training has increased more frequently. Therefore, it is crucial to evaluate these videos, which serve as educational tools, objectively. Additionally, analyzing parameters such as the number of views, likes, and the length of these videos by correlating them with IVORY and LAP-VEGaS scores can provide insights for creating new videos. In our study, we found that the quality of endoscopic type 1 tympanoplasty and myringoplasty surgery videos uploaded to YouTube was generally low in terms of education. Previous studies assessing the quality of surgical videos in otolaryngology often used grading systems that were not specific to the field. These studies typically employed general quality scales like JAMA, DISCERN, or the Global Quality Score (GQS) [25,26,27]. Recently, some studies have evaluated otologic surgical videos using the IVORY grading system for procedures such as DSR, stapedectomy, and parotidectomy [1, 2, 18]. A common finding across these studies is that the videos assessed did not meet the expected educational quality standards. Similarly, in our study, the majority of the evaluated videos were scored as low-quality according to the IVORY scale.

    In Mayer et al.‘s study, a correlation was found between the number of views and the total IVORY score videos [18]. However, in Yıldırım and Özdilek’s study, no such correlation was found [2]. In our study, the number of views was not significantly correlated with the IVORY score (p = 0.940), but there was a significant positive correlation between the number of views and the LAP-VEGaS score. (r = 0.299, p < 0.002).

    In our analysis, we found that increasing video length had a negative impact on the IVORY score in Section B (technical aspects). This section includes questions that assess the video based on its duration, so longer videos are expected to have lower scores in Section B. Conversely, scores for Section D (surgical procedure) increased significantly with video length, likely because longer videos allowed for more detailed descriptions of the surgical process. However, the total IVORY score was negatively affected by longer video length in the correlation analysis, suggesting that the extended duration of some videos may not have been used effectively. In contrast, video duration was not identified as a significant predictor in the regression model, which may indicate the influence of potential interactions or the effect of other confounding variables.

    Videos with a higher number of likes performed better in Sections B and D of the IVORY score, suggesting that providing technical details and thoroughly explaining the surgical procedure may enhance a video’s appeal. Furthermore, a significant positive correlation was observed between the number of likes and LAP-VEGaS scores, indicating that higher-quality videos tend to receive more viewer approval. This relationship was also confirmed in the linear regression model, where the number of likes emerged as a significant positive predictor of LAP-VEGaS scores (B = 0.008, p = 0.002), reinforcing the association between perceived video quality and viewer engagement.

    A significant negative correlation was found between dislikes and Section E, indicating that videos lacking critical organ-specific components (such as the demonstration of essential steps in the surgical procedure) were more likely to attract dislikes. The like rate was positively correlated with Section E, meaning that videos with well-executed organ-specific sections were associated with higher like rates and fewer dislikes.

    Older videos generally received lower quality scores, and this trend was supported by both correlation and regression analyses. In our study, the video upload date was significantly negatively associated with both IVORY and LAP-VEGaS scores (p < 0.001). Linear regression analyses further confirmed this relationship: video upload time was a significant negative predictor for both LAP-VEGaS (B = − 0.001, p < 0.001) and IVORY (B = − 0.001, p < 0.001) scores. These findings suggest that older videos may have lower technical and pedagogical quality, possibly due to limitations in recording equipment, editing capabilities, and the absence of standardized educational video guidelines at the time they were made. Interestingly, this pattern had not been consistently observed in previous IVORY-based studies, highlighting the potential impact of changing multimedia standards on perceived educational quality [1, 2, 18].

    Inter-rater reliability is essential when assessing scoring systems such as IVORY and LAP-VEGaS, especially in studies involving subjective evaluations. In our research, Cohen’s Kappa values showed good agreement for items 6, 7, and 9 of the LAP-VEGaS score, while the other items demonstrated excellent agreement. For the IVORY score, item 6 had good agreement, item 14 showed moderate agreement, and all remaining items showed excellent agreement. The variability observed in Item 14 could result from differences in how raters interpreted and segmented the videos into distinct surgical steps, which may reflect the subjective nature of the scoring criteria. Overall, both scoring systems demonstrated high inter-rater reliability, with intraclass correlation coefficients (ICCs) above 0.75. These results align with previous studies using similar video assessment tools, which have reported acceptable reliability levels when raters are properly trained and scoring criteria are well-defined [24, 28].

    A review of the literature on YouTube and otolaryngology reveals that the focus has primarily been on evaluating patient informational videos [29,30,31]. The evaluation of surgical training videos has only recently gained attention [1, 2, 18, 28, 32]. While research on surgical education videos is fairly common in urology and general surgery, there have been fewer studies in otolaryngology.

    In our study, the IVORY scoring system was modified to better suit the context of YouTube-based educational videos and the specific features of endoscopic type 1 tympanoplasty and myringoplasty procedures. For example, organ-specific criteria were adjusted to emphasize key video quality elements relevant to these surgical techniques. Similar modifications have been made in previous studies evaluating videos from various surgical fields [1, 2, 18]. Although such adjustments may reduce direct comparability with research using the original IVORY framework, they enhance the relevance and usefulness of the scoring criteria for our particular procedure. This customized approach allowed for a more detailed and context-aware assessment of video quality.

    While this study primarily centered on objectively assessing video quality, it is also crucial to consider the broader context of content creation and user behavior on platforms like YouTube. Although content creators do not disclose their specific motivations for uploading surgical videos, it can be assumed that the videos—many of which are excerpts from live surgeries—mainly target an audience of otolaryngology residents and specialist physicians rather than patients seeking general information. These videos may serve various purposes, such as educational uses, showcasing surgical techniques, or generating income or visibility through video content. Regardless of the original intent, such videos can still offer educational value by demonstrating surgical techniques, anatomical landmarks, the use of new surgical instruments, procedural tips, or aspects of training that may have been insufficiently covered during residency. In a survey of 70 surgical residents, medical students, and faculty surgeons, 95% of participants reported regularly watching surgical videos before performing surgeries, with YouTube being the most popular platform. YouTube’s widespread accessibility—available as a mobile app on nearly all smartphones, free of charge, and open to global content upload and viewing—likely explains its popularity among surgeons as an on-demand educational resource [33].

    Within the framework of widely accepted educational theories such as Bloom’s taxonomy and Miller’s pyramid of clinical competence, watching high-quality surgical videos can support lower-level cognitive objectives, including knowledge acquisition, comprehension, and recognition of procedural steps. Visually well-designed, structured, and pedagogically aligned videos help develop mental models, especially for learners in the early stages of surgical training [34,35,36]. The LAP-VEGaS and IVORY video assessment systems are valuable tools for evaluating the presentation quality of such materials and generally align with approaches like Mayer’s Cognitive Theory of Multimedia Learning. For instance, items related to the structured presentation of surgical steps and use of visual aids reflect Mayer’s segmenting and signaling principles, which facilitate learner attention and retention. Similarly, videos with minimal extraneous content and clear narration adhere to the coherence principle, reducing cognitive overload. However, these systems seem to fall short in capturing more comprehensive pedagogical dimensions, such as clearly defined learning outcomes, assessment of learners’ cognitive engagement, and measurement of educational effectiveness. Therefore, we believe that to more holistically define and evaluate educational quality, these scoring systems should be more closely integrated with advanced learning theories. Future scoring frameworks may benefit from incorporating validated educational metrics that align with broader instructional design and multimedia learning principles.

    In European countries, otolaryngology residency training is based on the core curricula and logbooks outlined by the UEMS ORL Section and Board training requirements [37]. Currently, these programs do not include educational objectives related to using videos as instructional materials, nor do they cover training in video assessment, editing, or production. However, every resident is also a potential peer educator and future trainer. Active participation in the learning process is essential for reaching higher cognitive levels of learning. Activities like producing, editing, and narrating educational videos can foster deeper understanding by encouraging learners to synthesize and organize knowledge while taking on a teaching role. Familiarity with video assessment criteria is also helpful for creating new, high-quality content. Supervised video creation integrated into surgical education curricula may effectively bridge passive observation and active development of clinical skills. We believe future research should examine the role and impact of such video-based instructional strategies within structured training programs.

    This study, to the best of our knowledge, is the first to evaluate the quality of endoscopic type 1 tympanoplasty and myringoplasty videos. Previous studies have generally focused on total IVORY scores, with little attention to section-specific analysis. We believe that analyzing videos segment by segment is essential, as viewer behaviors, view rates, likes, dislikes, and comments have been linked to specific parts of the videos. By focusing on these sections, video creators can potentially reach a larger audience and enhance video quality. We also recommend developing and widely adopting a specialized grading system for otolaryngology, instead of relying solely on general video scoring systems.

    There are some limitations to our study. One limitation is that videos were selected solely based on their English language and a minimum view count. While these criteria were chosen to ensure accessibility, relevance, and comparability of content, they may have introduced selection bias by excluding potentially high-quality videos in other languages or with limited exposure. Using only English content may especially underrepresent surgical techniques from non-English-speaking countries. Similarly, restricting inclusion to videos with over 1.000 views might exclude recently uploaded or niche instructional videos that have not yet gained widespread visibility. Our research focused only on videos from a single platform (YouTube), and other platforms were not considered. Although YouTube offers broad accessibility and convenience for learners, it also has inherent limitations as an educational platform. Content on YouTube is not peer- reviewed, and the qualifications of content creators are often not disclosed, raising concerns about the accuracy, safety, and educational quality of surgical videos. YouTube’s engagement-based algorithm tends to favor videos with high watch time or user interaction, metrics that do not necessarily reflect educational value. As a result, newly uploaded yet high-quality videos, especially those made by academic institutions or experienced educators, may be overshadowed by more popular but less pedagogically sound content. While all analyzed videos were recorded during surgeries, they are likely to be clicked, liked, and commented on by viewers who are not necessarily healthcare professionals. This cycle, where popularity is driven by engagement rather than instructional merit, may limit learners’ access to the most relevant and well-prepared material. We did not formally assess or verify the credentials of video uploaders. It is plausible that content uploaded by experienced surgeons or academic institutions may differ in quality from that shared by non-experts or laypersons. Additionally, the motivations behind uploading these videos may not always be educational. As Luu et al. noted, the likelihood of uploaders knowing the IVORY and LAP-VEGaS guidelines is quite low [24]. Video uploaders were evaluated based on criteria they probably did not consider when creating their content. Another limitation is the lack of external validation for the modified IVORY scoring system. While modifications were tailored to better reflect the characteristics of endoscopic tympanoplasty and myringoplasty videos on YouTube, the newly added or omitted items have not yet undergone independent validation. Future studies should aim to assess the construct validity, reliability, and applicability of these modifications across different datasets and surgical procedures, while also expanding to multilingual content and exploring other platforms or institutional video libraries to gain a more comprehensive understanding.

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  • GC Biopharma’s Study on Hunterase Lysosomal Delivery Mechanism Published in SCIE-Indexed Journal

    GC Biopharma’s Study on Hunterase Lysosomal Delivery Mechanism Published in SCIE-Indexed Journal

    YONGIN, South Korea, Aug. 21, 2025 /PRNewswire/ — GC Biopharma, a leading global pharmaceutical company based in South Korea, announced today that it has revealed the delivery mechanism of Hunterase (idursulfase beta), a recombinant enzyme replacement therapy for Hunter syndrome (MPS II). The research findings, detailing the role of N-glycosylation in lysosomal targeting, have been published in the International Journal of Biological Macromolecules, a prestigious SCIE-indexed journal.

    Hunter syndrome (MPS II) is a rare genetic disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene, resulting in a deficiency of the IDS enzyme, which is essential for the degradation of glycosaminoglycans (GAGs). This deficiency leads to the progressive accumulation of GAG within lysosomes, causing a range of symptoms. Thus, effective treatment relies on delivering the therapeutic enzyme to lysosomes to facilitate GAG breakdown.

    For effective lysosomal targeting, the N-glycan structures of the therapeutic enzyme must contain mannose-6-phosphate (M6P). M6P acts as a targeting signal, guiding the enzyme to bind to cells, facilitating its uptake and delivery into lysosomes to degrade GAGs.

    The research utilized high-resolution Orbitrap mass spectrometry to analyze the site-specific N-glycan structures of idursulfase beta (Hunterase). A total of 42 N-glycan structures were identified, with two sites, Asn221 and Asn255, found to be predominantly modified with bis-mannose-6-phosphate (bis-M6P), a structure containing two phosphate groups. The research team explains that this bis-M6P structure ensures the efficient and stable delivery of idursulfase beta (Hunterase) to lysosomes.

    The research team also demonstrated idursulfase beta’s high-affinity binding to the M6P receptors using surface plasmon resonance. Additionally, fluorescence-labeled cellular studies confirmed efficient uptake and lysosomal delivery of idursulfase beta (Hunterase).

    Moreover, several N-glycan structures of idursulfase beta (Hunterase) were found to be modified with sialic acid, which is known to prolong the enzyme’s circulation in the blood, extending its half-life.

    Hunterase (idursulfase beta), according to GC Biopharma, is highly effective for treating Hunter syndrome due to its targeted lysosomal delivery, driven by N-glycan structures modified with M6P and prolonged circulation enabled by sialic acid modifications.

    “This study analyzed the lysosomal delivery mechanism of Hunterase (idursulfase beta), supported by robust scientific evidence,” said Jae Uk Jeong, Head of R&D at GC Biopharma. “With clear evidence of its therapeutic effectiveness, patients with Hunter syndrome can have greater confidence in using Hunterase throughout their treatment journey.”

    About GC Biopharma

    GC Biopharma (formerly known as Green Cross Corporation) is a biopharmaceutical company headquartered in Yong-in, South Korea. The company has over half a century of experience in the development and manufacturing of plasma derivatives and vaccines, and is expanding its global presence with successful US market entry of Alyglo®(intravenous immunoglobulin G) in 2024. In line with its mission to meet the demands of future healthcare, GC Biopharma continues to drive innovation by leveraging its core R&D capabilities in engineering of proteins, mRNAs, and lipid nanoparticle (LNP) drug delivery platform to develop therapeutics for the field of rare disease as well as I&I (Immunology & Inflammation). To learn more about the company, visit https://www.gcbiopharma.com/eng/

    This press release may contain biopharmaceuticals in forward-looking statements, which express the current beliefs and expectations of GC Biopharma’s management. Such statements do not represent any guarantee by GC Biopharma or its management of future performance and involve known and unknown risks, uncertainties, and other factors. GC Biopharma undertakes no obligation to update or revise any forward-looking statement contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule.

    GC Biopharma Contacts (Media)

    Sohee Kim
    [email protected]

    Yelin Jun
    [email protected]

    Yoonjae Na
    [email protected]

    SOURCE GC Biopharma

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  • Synthesis, dyeing performance and surface finishing effects of aminoethyl methacrylate functionalized stilbene fluorescent whitening agents

    Synthesis, dyeing performance and surface finishing effects of aminoethyl methacrylate functionalized stilbene fluorescent whitening agents

    Materials and methods

    All reagents and solvents were obtained from commercial suppliers and used as supplied without further purification. Proton nuclear magnetic resonance spectra were determined on a Brucker Avance 500 spectrometer using tetramethylsilane as an internal standard in DMSO-d6 solution. The infrared spectra were determined on a FT-IR 370 infrared spectrometer with potassium bromide tablet pressing technology. The UV spectrum data were obtained using a TU-1810 UV Visible Spectrophotometer. The decomposition temperature was tested by a PerkinElmer TGA 4000 thermogravimetric analyzer. The whiteness and chromaticity index of cotton fiber were assessed using a CTPC whiteness meter. The microstructure of the sample was observed using a JSM-7610 F scanning electron microscope.

    Synthesis of compounds 6a-f

    2,4,6-Trichloro-1,3,5-triazine (1.28 mmol) and cold distilled water (5 mL) were placed in the reactor and subjected to an ice bath. The solution of 4,4’-diaminostilbene-2,2’-disulphonic acid (0.64 mmol), distilled water (20 mL), and saturated sodium carbonate was prepared, slowly dropped into the reactor within 30 min. Then the mixture continued to react for 2 h at 0–5℃. The reaction mixture was heated to 30℃, slowly added an aqueous solution (4 mL) containing 2-aminoethyl methacrylate (1.28 mmol), and small amount of antioxidant sodium sulfite. Then the reaction mixture was heated to 40–45℃, maintained the pH at 6–7 with saturated sodium carbonate, and continued to react for 6 h. The aqueous solution (5 mL) containing amino alcohol or amino acid (1.28 mmol) was dropped into the reaction mixture, raising the temperature to 90–95℃, maintaining the pH at 8–9 with saturated sodium carbonate, and continuing the reaction for 8 h. The three-step reaction process was tracked using thin-layer chromatography, with isopropanol: acetonitrile: ammonia solution = 5:2:3 as the developing agent (V/V). The reaction mixture was cooled to room temperature, and the pH was adjusted to 3–4 with dilute hydrochloric acid (10%). An appropriate amount of sodium chloride was added, stirred, and filtered. The filter cake was washed successively with ice water and ethanol to obtain aminoethyl methacrylate functionalized stilbene FWAs 6a-f, light yellow solid with yield of 85–93%.

    Synthesis of 6,6’-(ethene-1,2-diyl)bis(3-((4-(bis(2-hydroxyethyl)amino)-6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonic acid) (6a)

    Yield 87%; Light yellow solid powder; 1H NMR (500 MHz, DMSO-d6, δ): 10.35 (2 H, NH), 8.52 (2 H, NH), 8.04 (2 H, PhH), 7.62 (4 H, PhH), 7.47 (2 H, CH = CH), 6.07 (2 H, =CH2), 5.70 (2 H, =CH2), 4.25 (4 H, OH), 3.75 (20 H, CH2), 3.00 (4 H, CH2), 1.88 (6 H, CH3); IR (KBr, cm− 1): 3346 (OH and NH), 2952, 2886 (CH3 and CH2), 1718 (C = O), 1625, 1538 (C = C), 1415 (C = N), 1173 (S = O), 1020 (C‒O‒C).

    Synthesis of 2,2’-((((ethene-1,2-diylbis(3-sulfo-4,1-phenylene))bis(azanediyl))bis(6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazine-4,2-diyl))bis(azanediyl))diacetic acid (6b)

    Yield 85%; Light yellow solid powder; 1H NMR (500 MHz, DMSO-d6, δ): 10.12 (2 H, NH), 8.30 (2 H, NH), 8.01 (2 H, PhH), 7.58 (4 H, PhH), 7.55 (2 H, CH = CH), 6.06 (2 H, =CH2), 5.66 (2 H, =CH2), 4.29 (2 H, NH), 3.82 (8 H, CH2), 3.71 (4 H, CH2), 1.86 (6 H, CH3); IR (KBr, cm− 1): 3397 (OH and NH), 3086, 2941(CH3 and CH2), 1749 (C = O), 1623, 1588 (C = C), 1485 (C = N), 1181 (S = O), 1082 (C‒O‒C).

    Synthesis of 2,2’,2’’,2’’’-((((ethene-1,2-diylbis(3-sulfo-4,1-phenylene))bis(azanediyl))bis(6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazine-4,2-diyl))bis(azanetriyl))tetraacetic acid (6c)

    Yield 86%; Light yellow solid powder; 1H NMR(500 MHz, DMSO-d6, δ): 10.57 (2 H, NH), 8.04 (2 H, NH), 7.80 (2 H, PhH), 7.66 (4 H, PhH), 7.61 (2 H, CH = CH), 6.07 (2 H, =CH2), 5.70 (2 H, =CH2), 4.21 (4 H, CH2), 3.54 (8 H, CH2), 3.39 (4 H, CH2), 1.88 (6 H, CH3); IR (KBr, cm− 1): 3328 (OH and NH), 3085, 2954 (CH3 and CH2), 1717 (C = O), 1630, 1591 (C = C), 1482 (C = N), 1168 (S = O), 1084 (C‒O‒C).

    Synthesis of 3,3’-((((ethene-1,2-diylbis(3-sulfo-4,1-phenylene))bis(azanediyl))bis(6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazine-4,2-diyl))bis(azanediyl))dipropionic acid (6d)

    Yield 93%; Light yellow solid powder; 1H NMR (500 MHz, DMSO-d6, δ): 10.23 (2 H, NH), 8.38 (2 H, NH), 8.01 (4 H, PhH), 7.78 (2 H, PhH), 7.65 (2 H, CH = CH), 7.58 (2 H, NH), 6.06 (2 H, =CH2), 5.68 (2 H, =CH2), 4.24 (4 H, CH2), 3.70 (4 H, CH2), 3.56 (4 H, CH2), 2.61 (4 H, CH2), 1.86 (6 H, CH3); IR (KBr, cm− 1): 3399 (OH and NH), 3086, 2958 (CH3 and CH2), 1705 (C = O), 1621, 1584 (C = C), 1489 (C = N), 1175 (S = O), 1020 (C‒O‒C).

    Synthesis of 4,4’-((((ethene-1,2-diylbis(3-sulfo-4,1-phenylene))bis(azanediyl))bis(6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazine-4,2-diyl))bis(azanediyl))dibutyricacid (6e)

    Yield 91%; Light yellow solid powder; 1H NMR (500 MHz, DMSO-d6, δ): 10.19 (2 H, NH), 8.34 (2 H, NH), 8.01 (4 H, PhH), 7.79 (2 H, PhH), 7.65 (2 H, CH = CH), 7.58 (2 H, NH), 6.06 (2 H, =CH2), 5.67 (2 H, =CH2), 4.29 (4 H, CH2), 3.70 (4 H, CH2), 3.56 (4 H, CH2), 2.31 (4 H, CH2), 1.86 (6 H, CH3), 1.76 (4 H, CH2); IR (KBr, cm− 1): 3403 (OH and NH), 3121, 2956 (CH3 and CH2), 1701 (C = O), 1621, 1571 (C = C), 1489 (C = N), 1175 (S = O), 1025 (C‒O‒C).

    Synthesis of 2,2’-((((ethene-1,2-diylbis(3-sulfo-4,1-phenylene))bis(azanediyl))bis(6-((2-(methacryloyloxy)ethyl)amino)-1,3,5-triazine-4,2-diyl))bis(azanediyl))bis(3-phenylpropanoic acid) (
    6f
    )

    Yield 86%; Light yellow solid powder; 1H NMR (500 MHz, DMSO-d6, δ): 10.19 (2 H, NH), 8.81 (2 H, NH), 8.04 (2 H, PhH), 7.58 (4 H, PhH), 7.30 (10 H, PhH), 7.22 (2 H, CH = CH), 6.06 (2 H, =CH2), 5.66 (2 H, =CH2), 4.77 (2 H, NH), 4.29 (4 H, CH2), 3.24 (4 H, CH2), 3.03 (4 H, CH2), 1.86 (6 H, CH3); IR (KBr, cm− 1): 3397 (OH and NH), 3084, 2958 (CH3 and CH2), 1716 (C = O), 1623, 1590 (C = C), 1487 (C = N), 1177 (S = O), 1020 (C‒O‒C).

    Cotton fiber dyeing

    Dye solutions with concentrations of 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, and 0.70% of compounds 6a-f were prepared and the bath ratio was 1:50. Cotton fibers were placed in a dyeing bucket and dyed at 20℃, and the dyeing solution was heated by a rate of 2℃/min until the temperature reached 50℃, and then continued to dye for 15 min at this temperature. The stained sample was taken out, washed three times with cold distilled water, dried it naturally at room temperature, and tested for whiteness and chromaticity index.

    Whiteness and chromaticity index testing

    The whiteness value (CIE) and chromaticity index of untreated and dyed pure cotton fiber samples were investigated using a multifunctional whiteness meter with a D65 light source and a viewing angle of 10°. Each sample was tested three times at different locations and the average value was recorded.

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  • Scientists explore hookworm proteins as potential treatment for inflammation

    Scientists explore hookworm proteins as potential treatment for inflammation

    It’s been a long-accepted reality that with age comes increased inflammation – so widely accepted it’s been dubbed “inflammaging.” With this increase in age-related chronic inflammation also comes serious health concerns, such as cardiovascular disease and Alzheimer’s. But according to new research, inflammaging isn’t as universal of an experience as previously thought.

    Published today in Proceedings of Royal Society B, “Inflammaging is minimal among forager-horticulturalists in the Bolivian Amazon,” the work highlights little inflammaging in one non-industrialized community, and notably found an increase of inflammation with moderate levels of modernization in another.

    Led by Jacob Aronoff – a postdoctoral research scholar at Arizona State University’s School of Human Evolution and Social Change, affiliate with the Institute of Human Origins and a member of the Center for Evolution and Medicine – the study looked at two communities in the Bolivian Amazon: the Tsimane and Moseten. 

    The Tsimane are a community of more than 17,000 people across 90 villages in the lowlands of the Bolivian Amazon. Living a hunter-farmer lifestyle, their everyday life is very similar to human life prior to the Industrial Revolution. This offers a unique glimpse into the health and aging processes for humans before modern-day influences came into play. Previous research has shown that they have the healthiest hearts and lowest rates of Alzheimer’s and dementia in the world.

    Benjamin Trumble, senior author on the article and professor in ASU’s School of Human Evolution and Social Change, serves as the co-director of the Tsimane Health and Life History Project. The group has a longstanding relationship with the Tsimane to collect demographic and biomedical data, as well as helps to provide medical care for the community – a relationship that has been in effect for more than 20 years. 

    This latest look into our human past set out to determine if the inflammation we experience in old age is a universal, human experience. 

    To see if they develop inflammaging, we measured a collection of cytokines in a sample of older Tsimane adults to see if they increase with age – we found minimal increases with age.”


    Jacob Aronoff, postdoctoral research scholar at Arizona State University’s School of Human Evolution and Social Change

    To deepen their findings, the researchers also examined the Moseten. Although genetically very similar to the Tsimane, the Moseten underwent significant cultural change beginning 300 years ago when Jesuit missionaries settled among them.

    “They’re still the same genetic group, same language group, but the Moseten now have running water, electricity and indoor plumbing,” said Trumble, who is also a research scientist with ASU’s Institute of Human Origins and core faculty of the Center for Evolution and Medicine.

    “They’re kind of in an in-between place where they aren’t as industrialized as people living in the U.S., but they aren’t as traditional as a population like the Tsimane that’s still living much more like most of our human ancestors.”

    This in-between stage of modernization provides an interesting opportunity of comparison for the researchers.

    “We measured them together in the same lab, using the same technology, and we found clearly more pronounced inflammaging in the Moseten, suggesting that inflammaging – to a large extent – is a product of industrialized lifestyles,” Aronoff said.

    Inflammation isn’t the guarantee with age as previously thought. While more research is needed, it does appear to largely be impacted by environmental and lifestyle factors, such as diet and exercise. It also shows that even slight modernization has an impact on deviating the human body from its ancestral path. 

    “For 99% of human history we were physically active hunter gatherers. Now with sedentary urban city life we are basically operating outside the ‘manufacturer’s recommended warranty’ right now,” Trumble said. 

    “By working with populations that are living a more traditional lifestyle, we can get a better idea of what the baseline for human health is.”

    Other possibilities could be high parasitic and pathogen exposure, something lacking in industrialized communities, but common for the Tsimane. While more research is needed, the immune system response developed from parasitic exposure may play a role in the Tsimane’s lack of age-related inflammation. 

    “We’ve eliminated most of our parasites, and that’s a good thing. We should keep it that way,” said Trumble.

    But there may be a way we can harness the potential without the negative impact. 

    “One of the things that we could do in the future, potentially, is instead of, say people getting infected with hookworm, we could figure out what are the proteins on the surface of hookworm cells – and what if we could turn that into a drug that people could take and trick our immune system. Our immune system would think we had that problem, and then it would develop differently to fight that off.”

    Much like how we utilize vaccinations for viruses like the flu, where a controlled pathogenic exposure boosts an immune system response to fight off a natural exposure, the same may one day be true for our age-related inflammation.

    Ultimately, though, there is no “silver bullet,” according to Trumble, as lifestyle and diet are also likely major contributors to inflammaging. 

    “We have future studies underway to look at diets, physical activity and infectious exposures that the Tsimane are infected with that can have these anti-inflammatory effects. We’re going to have to do a lot of future studies to figure out what, exactly, are all the factors and how they work together,” explained Aronoff. 

    Source:

    Journal reference:

    Aronoff, J. E., et al. (2025). Inflammaging is minimal among forager-horticulturalists in the Bolivian Amazon. Proceedings of the Royal Society B: Biological Sciences. doi.org/10.1098/rspb.2025.1111.

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  • With eyes on re-election, Netanyahu’s fights with world leaders aim to distract from many political problems

    With eyes on re-election, Netanyahu’s fights with world leaders aim to distract from many political problems

    As the longest-serving Israeli prime minister (17 years), Benjamin Netanyahu is famous for his political wizardry and survival skills. But he is also a highly controversial figure with questionable moral standards and legacy.

    His latest term in office, beginning in late 2022, has been particularly challenging, thanks to the far-right radical elements of his governing coalition and the unprecedented national disaster Israel experienced at the hands of Hamas on October 7 2023.

    Yet, Netanyahu has managed to neutralise almost all immediate domestic threats to his power. At times, he has done this by manoeuvring rivals and partners into postponing moves that could topple his government. Other times, he has reshuffled his Likud Party ranks or realigned with bitter foes.

    Netanyahu is also facing increased criticism from the Israeli public, with hundreds of thousands of people taking part in marches in support of a hostage deal, as well as from former senior politicians and ex-security officials.

    And he has clashed with Eyal Zamir, the Israel Defence Force’s (IDF) chief of staff, who argued against the plan to expand the war into Gaza City. Zamir received clear messages to fold or resign, and chose to stay.

    Yet, Netanyahu chooses to ignore all of this noise, sending his entourage and loyalists to attack anyone with dissenting views. This week’s spray at Australian Prime Minister Anthony Albanese is just one example.

    As a long term political survivor, he does all of this with an eye on the next Israeli elections, due at the end of 2026.

    Propping up his far-right coalition

    Over the past two and a half years, Israel has faced unprecedented crises that have left society deeply divided.

    Under Netanyahu’s leadership, the government introduced a highly controversial judicial reform plan in early 2023, clashing with the Supreme Court and attorney general. This resulted in mass street protests against it.

    Then came the Hamas attack of October 7, 2023, which triggered an ongoing multi-front war with severe long-term social, economic and humanitarian consequences.

    Netanyahu has claimed credit for successes during this time, such as the 12-day war against Iran in June, while deflecting responsibility for any failures.

    Though stretched in many directions, Netanyahu is at his best in such conditions, pitting the conflicting sides around him against each other and playing them.

    His coalition relies on hard-right partners, especially National Security Minister Itamar Ben Gvir and Finance Minister Bezalel Smotrich. Despite the massive protests to agree to a hostage deal and international demands to end the war, Netanyahu has chosen to prioritise ensuring the stability of his coalition.

    He has acceded to Ben Gvir and Smotrich’s demands to reject ceasefire agreements with Hamas, and instead ordered increased military action against the terrorist group to try to achieve what he has called a “total victory”.

    Netanyahu has also indulged Ben Gvir and Smotrich’s talk of resettling Gaza and has enabled their moves to gradually expand Israeli settlements deeper into the West Bank and block any geographically feasible Palestinian state.

    Proving Henry Kissinger’s famous observation that “Israel has no foreign policy, only domestic politics,” Netanyahu has also angrily rebuked the wave of Western countries recognising, or preparing to recognise, a Palestinian state.

    His defiant letters to French President Emmanuel Macron and social media outbursts about Albanese are aimed less at diplomacy and more at cultivating his image as “a strong leader for Israel” among his base.

    Supported by the Trump administration’s sanctions against the International Criminal Court (ICC), Netanayhu has also felt confident attacking it for issuing warrants against him.

    Neutralising challenges from ultra-religious parties

    The government’s biggest domestic challenge has been passing a draft law addressing the decades-long exemption of tens of thousands of ultra-Orthodox (Haredi) men from army service.

    Following a Supreme Court ruling that the previous exemptions could not continue, religious parties in Netanyahu’s coalition demanded a bill to formally exempt the men from army service or they would bring down the government.

    In response, Netanyahu enticed old rival Gideon Sa’ar from the opposition into joining his government, shoring up the coalition’s previously tiny majority.

    Since then, he has bought time through broken promises, successfully persuading the ultra-Orthodox parties to wait until parliament’s return in October of this year. Meanwhile, he replaced Yuli Edelstein, the committee chair who had sought a strong bill with personal sanctions for draft evaders, with a more pliant loyalist, Boaz Bismuth.

    Eyes on re-election

    Now Netanyahu has his eye on the next general elections, officially set for late 2026 — though he would prefer they take place before the third anniversary of the October 7 attacks.

    For two years, polls have consistently predicted his defeat. As such, he is working to reshape his image. He wants Israelis to forget his central role in the October 7 catastrophe, as well as the questions surrounding the war’s management.

    He also hopes to continue diverting attention from his ongoing trial on bribery and breach of trust charges.

    But Netanyahu faces a dramatic dilemma over the war. On the one hand, he may decide to sign a ceasefire deal with Hamas and secure the release of the hostages. This would win the cheers of most Israelis, but risk the loss of his government, given the far-right ministers’ threats to dissolve the coalition if he accepts any deal without fully conquering the strip.

    On the other hand, he could proceed with the military operation in Gaza City, which may well result in the killing of the remaining hostages – either by Hamas or as a consequence of IDF attacks.

    A third option would be to continue negotiations while escalating preparations for the attack, in the hope of achieving a better deal. We will soon know what direction he will take – and what it will mean for his political future.

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  • Chronic kidney disease related to Loa loa microfilaremia in a rural area of the Republic of Congo: a population-based cross-sectional study | Infectious Diseases of Poverty

    Chronic kidney disease related to Loa loa microfilaremia in a rural area of the Republic of Congo: a population-based cross-sectional study | Infectious Diseases of Poverty

    Study area and population

    This cross-sectional study, nested within a cohort study, was conducted in May–June 2022 and included 990 participants aged 18 to 88 years living in 21 villages near Sibiti, Republic of Congo. Participants had been previously screened for Loa microfilaremia [20]. For the current study, individuals with blood microfilariae detected in 2021 were matched for sex and age (± 5 years) with two amicrofilaremic individuals from the same village. Detailed description of the study population has been published previously [8, 21].

    The sample size for the underlying cohort study (n = 990) was calculated to provide 80% statistical power to detect an increased risk of malaria (1.4-fold) and pneumonia (2.4-fold) among microfilaremic compared to amicrofilaremic individuals, based on the hypothesis that loiasis may impair splenic function and thereby increase susceptibility to infections. However, due to the lack of prior data, the sample size was not calculated to evaluate differences in renal outcomes.

    Participation in the study required informed consent from all individuals. The research was approved by the Ethics Committee of the Congolese Foundation for Medical Research (036/CIE/FCRM/2022) and by the National administrative authorities of Congo (376/MSP/CAB/UCPP-21).

    Sociodemographic and exposure covariables

    Data on age, sex, anthropometric measurements (weight, height, and body mass index—BMI), and tobacco use were collected from each participant. Blood pressure was measured supine after 10 min rest. High blood pressure (HBP) was classified into three stages (see Table 1) and mean arterial pressure (MAP) was defined as (frac{{{text{Systolic BP + 2 }} times {text{Diastolic BP}}}}{{3}}).

    Table 1 Study population, serum creatinine levels and estimated glomerular filtration rate according to CKD-EPI or EKFC formulas, and Dubois correction for body surface area

    Laboratory procedures for parasitic infections

    Fifty µl of capillary blood were collected by finger-prick between 10 a.m. and 4 p.m. (to take into account the day and night fluctuation of Loa MFD) to prepare thick blood smears (TBS) which were then Giemsa-stained, and examined at 100 × magnification by experienced technicians to count Loa and Mansonella perstans mf. Each TBS was read twice; the arithmetic mean was recorded. Prior exposure to Onchocerca volvulus was assessed using the antibody detecting Onchocerciasis rapid test targeting Ov16 antigen (Drugs & Diagnostics for Tropical Diseases, San Diego, USA). Two skin snips were taken from seropositive individuals using a 2 mm Holth punch, incubated in saline at room temperature for 24 h and examined microscopically to count the emerged mf. O. volvulus MFD was calculated as the arithmetic mean of the two counts, expressed per snip.

    Schistosoma haematobium infection was investigated in participants with haematuria detected by urine dipstick. Positive cases underwent urine filtration, Lugol staining, and microscopic examination for eggs. Soil-transmitted helminths (STH) were identified via microscopic examination of morning stool samples, transported within 6 h and processed immediately or after overnight storage at 6 °C. Stool smears were prepared using the Kato-Katz method and examined at 40 × magnification. For asymptomatic Plasmodium infection, thin blood films from venous blood (heparinized tube) were stained with RAL 555 (RAL Diagnostics, Martillac, France) and examined microscopically. An indirect ELISA was used to quantify the Immunoglobin G (IgG) antibodies levels against P. falciparum antigens [22].

    Biological examinations

    Creatinine levels were measured for each patient in whole blood with a point-of-care device (iSTAT-1; Abbott Point of Care, Princeton, NJ, USA). For logistic reasons, glycated haemoglobin (Hb1Ac) and fasting serum total cholesterol level, triglycerides, HDL, and LDL were only measured in a random subset of patients, using a point-of-care device (Afinion 2, Abbott Rapid Diagnostics, Bièvres, France). Eosinophilia and lymphocyte counts were conducted using the HemoCue WBC DIFF system (HemoCue AB, Ängelholm, Sweden).

    Arterial stiffness assessment

    Arterial stiffness was assessed through finger-toe pulse wave velocity (PWV) using the pOpmètre device (Axelife SAS, Paris, France), which records pulse waves via two infrared photodiode sensors at the finger and toe. This method is a validated, non-invasive alternative to carotid-femoral PWV, which requires skilled staff and femoral artery access [23].

    Outcome: chronic kidney disease

    Ultrasound examination

    The US examination of the kidneys was performed by experienced physicians (VD, LR) using a CX-50 device (Philips Medical Systems, Suresnes, France). Measurements included height, width, length. A second reading of the digital images (DICOM files) was performed to confirm and characterize kidney parenchymal or structure abnormalities (pyelocaliceal dilatation, cystic, or other description).

    Urine collection and dipstick analysis

    Each participant provided a morning midstream urine sample, following instructions from a trained nurse. Urinalysis was performed immediately using dipsticks (Reactif 10SL Urinalysis Strips, 41101-M, Nal von Minden, Moers, Germany) to detect proteinuria and haematuria. A single physician interpreted the results and did a second confirmatory dipstick if the initial result was positive. No discrepancies were observed. Haematuria was assessed as negative, traces, + , +  + , or +  +  + . Positive cases (≥ 1 +) underwent urine filtration and microscopic examination for S. haematobium eggs. Proteinuria was classified as negative, traces (< 0.3 g/l), level–1 (0.3–1 g/l), level–2 (1–3 g/l), or level–3 (> 3 g/l). Albumin-to-creatinine ratio (ACR, mg/mmol) was measured for proteinuria ≥ level–1 using the Afinion 2 device.

    Estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) classification

    Given limited data on creatinine distribution and CKD in our population, we applied two formulas. First, the 2009 CKD-EPI equation without ethnicity factor, as current recommendation [24, 25]. Second, the EKFC equation, a newer formula more robust across all ages [26, 27]. Only one published Q-value (median normal creatininemia) exists for Central Africa [28], based on 494 urban individuals [25]. Therefore, we estimated our own Q-values by calculating median creatinine levels in individuals without HBP or renal abnormalities (proteinuria or haematuria). CKD-EPI and EKFC eGFRs were expressed in ml/min per 1.73 m2, and classified per KDIGO (Kidney Disease: Improving Global Outcomes Guidelines) categories [29]. Renal abnormalities (RAb) were defined as ACR > 3 mg/mmol or ≥ 1 + haematuria, excluding ultrasound-confirmed causes (9 cases of pyelocaliceal dilatation suggestive of lithiasis were excluded, as the associated haematuria was most likely of urological rather than nephrological origin and thus not indicative of intrinsic renal disease).

    Statistical analysis

    Continuous variables with normal distribution were presented as mean ± standard deviation (SD); non-normal variables were reported as median (interquartile range). Explanatory variables included: age (continuous), sex (male/female), tobacco use (yes/no), MAP (continuous), PWV (≥ 12 vs. < 12 m/sec), lymphopenia (< 1200/µl), hypereosinophilia (> 1500/µl), Ascaris lumbricoides and/or Trichuris trichiura (present/absent), Loa MFD (0, 1–7999, 8000–19 999, ≥ 20 000 mf/ml), anti-Plasmodium falciparum IgG (quartiles), and Plasmodium smears (negative/positive). BMI was not included since anthropometric parameters are integrated into eGFR estimations. Lipid profiles and diabetes were not included due to substantial missing data (see Results). The PWV cutoff (12 m/sec) reflects its established association with organ damage [30]. HIV status was unknown, but lymphopenia < 1200/µl was used as a proxy.

    In our study, 25% weighed < 50 kg (10% < 45 kg, range: 30–120 kg), 25% had a height < 157 cm (10% < 152 cm, range: 141–190 cm), and 25% had a BMI < 18.9 kg/m2 (10% < 17.8, range: 13.2–47.7). Given this heterogeneity, we chose to apply Dubois body surface area (BSA) correction to both CKD-EPI and EKFC equations to better assess associations. eGFR was calculated with CKD-EPI and then de-indexed using individual BSA via the Dubois formula: BSA = 0.007184 × Weight(kg)0.425 × Height(cm)0.725, resulting in CKD-Dubois and EKFC-Dubois values (ml/min).

    First, a saturated linear regression model on eGFR was performed. Because KDIGO-CKD staging could not be used directly in the regression analysis—due to the necessity of adjusting for BSA and the small number of participants in advanced CKD stages, which limited statistical power—we defined three alternative severity thresholds based on the distribution of eGFR values in our study population to investigate a potential gradient effect of CKD severity. These were the median (Cutoff-1), the 10th percentile (Cutoff-2) – corresponding to the global prevalence of CKD –, and the 2nd percentile (Cutoff-3) –reflecting the prevalence of advanced CKD. Thresholds were calculated separately for each equation. Given that the presence of RAb is an essential component of CKD staging, it was incorporated in the categorization and thus the categories were: “ ≥ Cutoff-1 & no RAb”, “ ≥ Cutoff-1 & RAb”, “Cutoff-1 – Cutoff-2 & no RAb”, “Cutoff-1 – Cutoff-2 & RAb”, “Cutoff-2 – Cutoff-3 & no RAb”, “Cutoff-2 – Cutoff-3 & RAb”, “ < Cutoff-3 & no RAb”, “ < Cutoff-3 & RAb”.

    Due to the ordered nature of outcome variables, ordinal logistic models were initially considered. However, they were rejected after a Brant test indicated a proportional odds violation. Instead, multinomial logistic regression was used. A manual stepwise backward selection (P < 0.100) was applied to the saturated model via the likelihood ratio test. To prevent convergence failure, Loa MFD was re-categorized into three groups (0, 1–19 999, ≥ 20 000 mf/ml). Finally, potential interactions between Loa MFD, age, sex, and eosinophilia were assessed using the likelihood ratio test. After finalizing the model, we extracted risk probabilities. We then estimated the population attributable fraction (PAF) from a logistic model including the final significant variables identified (age, sex, and Loa microfilaremia as a binary variable) using the KDIGO CKD classification with the EKFC formula.

    All statistical analyses were performed using Stata 18 (StataCorps LP, College Station, Texas, USA).

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