Background

Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ~85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection.

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of ¹⁸F-labeled fibroblast activation protein inhibitor ([¹⁸F]AlF-NOTA-FAPI-04, denoted as ¹⁸F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent ¹⁸F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On ¹⁸F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUV_max (area under the curve [AUC], 0.87; P = 0.0026), SUV_peak (AUC, 0.89; P = 0.0017), SUV_mean (AUC, 0.88; P = 0.0021), TBR_max (AUC, 0.86; P = 0.0031), and TBR_mean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%–81.82% and specificities of 83.33%–100%. Changes in SUV_max (AUC, 0.81; P = 0.0116), SUV_peak (AUC, 0.82; P = 0.0097), SUV_mean (AUC, 0.81; P = 0.0116), and TBR_mean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: ¹⁸F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

The current growth and consumption based economy is not sustainable. The world must move towards a circular economy and sustainability.

The post Degrowth, green energy, social equity, and circular economy appeared first on rabble.ca.

PM Malcolm Turnbull says Australians should vote to keep a stable majority government in uncertain economic times, as the fallout from Brexit continues.

It’s a slightly more potty mouthed cast than usual, as Alice joins Peter, Kelley, Anna Marie and Chris to discuss what the cast has been playing for the week. Anna Marie’s 5-hour rule resurfaces and we explore what crazy black holes Chris has been down this week, alongside the news and your feedback.

The post RPG Cast – Episode 543: “Go Find Gnome, Dumb***” appeared first on RPGamer.

A collective gasp echoed like a thunderclap in a valley in our Daily Beast newsroom late Wednesday afternoon at the news that singer Liam Payne, who became famous as a member of the group One Direction, died at age 31.

TMZ reports that Payne fell from a hotel balcony in Argentina, where he had reunited with bandmates at 1D-er Niall Horan’s concert. He had, according to the site, been behaving “erratically,” earlier in the day, and was spotted smashing a laptop in the hotel lobby and having to be carried back to his room. He had been in headlines on gossip blogs over tension with his ex-fiancée Maya Henry, who, TMZ says, alleged “he'd left her after asking her to get an abortion.”

In the shock of his death, fans couldn’t ignore the eerie nature that Payne had just connected with his One Direction bandmates. Dark questions emerge when a celebrity dies so young: What role did the often horrific toll of fame have on a person like Payne, who has been open about addiction and suicidal ideation? But there’s also an impulse to go back to the roots of a person’s talent, to revisit what it was that we all fell in love with—and was their passion—in the first place.

Read more at The Daily Beast.

Chancellor Rachel Reeves has torpedoed the UK's economic recovery with her tax-and-spend Budget but Ed Miliband is the one who worries me.

A radio signal detected in 1977, sometimes claimed as evidence for aliens, may have been caused by a laser-like beam of microwave radiation

Radio astronomers teamed up with SpaceX to find a promising solution for helping expensive telescopes avoid interference from thousands of Starlink satellites

‘Little red dot’ galaxies seen by JWST appear to be much more tightly packed with stars than other galaxies, raising big questions about how they came to be this way

Five satellites due to launch this week could be brighter than most stars, and astronomers fear the growth of such constellations could have a catastrophic impact

See the world's best space images from the Astronomy Photographer of the Year 2024 award

The first 18 satellites of a planned Chinese mega constellation are brighter than all but 500 stars in the sky, raising fears of a huge impact on astronomy

The books, TV, games and more that New Scientist staff have enjoyed this week

In a basement beneath City St George's, University of London, senior NATO leaders watch on as four research teams demonstrate the latest in AI-controlled, autonomous drone technolo0gy

The election is over and the economy had a huge impact. An AP analysis said 96% of those surveyed admitted that prices of gas and groceries had an influence on their vote.

EA FC 25 players can snag some big freebies this week, with EA Sports celebrating the Ballon d'Or in style for all Ultimate Team players with some of the best players around.

Venomous Blue Sea Dragons are washing up on the sandy shores of the Outer Banks in North Carolina, and National Park officials advise to admire them from a distance.

When NASA’s Voyager 2 spacecraft flew by Uranus in 1986, it provided scientists’ first close glimpse of this ice-giant planet.

The post Voyager 2’s Flyby of Uranus in 1986 was During Anomalous Solar Event, New Study Suggests appeared first on Sci.News: Breaking Science News.

Robert F. Kennedy Jr. launched a "Nominees for the People" forum to crowdsource 4,000 positions in the Trump administration to Make America Healthy Again.

President-elect Trump is nominating former Arkansas Gov. Mike Huckabee to be the U.S. ambassador to Israel, he announced Tuesday in a social media post.

Former Fox News host Pete Hegseth has been selected by President-elect Trump to serve as his secretary of defense. Hegseth served in the U.S. Army.

Harris has made history multiple times over.

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The comedian is more than ready to reprise her Emmy-nominated 'SNL' guest role.

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The former president thinks Joe Biden 'nailed this decision.'

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Demand for observing time on Webb outpaces supply by a factor of nine.

Donald Trump and the Republicans have a mandate for new economic policy.

The post Breitbart Business Digest: The Trump Economic Mandate appeared first on Breitbart.

Trump nominated Republican South Dakota Gov. Kristi Noem to serve as his Secretary of the Department of Homeland Security (DHS).

The post Trump Nominates Kristi Noem for Secretary of Department of Homeland Security appeared first on Breitbart.

President-elect Donald Trump nominated Fox News host Pete Hegseth to serve as his Secretary of Defense, hailing him as a champion of his "peace through strength" policy.

The post Trump Nominates Fox News Host Pete Hegseth for Secretary of Defense: ‘Nobody Fights Harder for the Troops’ appeared first on Breitbart.

1. Trump Tracker: Fox News Anchor Nominated To Lead Pentagon  NDTV
2. Trump nominates Army veteran and Fox News host Pete Hegseth for defence secretary  The Hindu
3. Trump's defense choice stuns the Pentagon, raises questions about the Fox News host's experience  Hindustan Times
4. 'We are in a new place': Bernstein reacts to Hegseth's comments about women in combat roles  CNN
5. Pete Hegseth: Ex-Army man, Fox News host, is US's 2nd youngest Defence Secretary  India Today

President-elect Donald Trump has announced he will nominate Fox News host Pete Hegseth to serve as secretary of defense. Hegseth is a combat veteran who has long advocated for veterans.

The two-term governor of South Dakota has been a loyal Trump ally. In her new role, Noem would oversee immigration, an issue Trump campaigned heavily on.

Hours after the ruling, the UK home secretary approved Lynch's extradition to the US.

Top Democrats on Tuesday evening filed a compromise economic development bill containing state support for the life sciences and climate technology industries, ticket sales regulations, a new live theater tax credit, educator diversity reforms and more.

While reading through the list of Grammy nominees earlier I came across quite a surprise. There, competing for record of the year alongside the likes of Beyoncé's Texas Hold 'Em and Chappell Roan's Good Luck Babe, was Now and Then by The Beatles. No, to my dismay, this isn't a time travel situation, but the result of AI. 

So, here's the story of how The Beatles got nominated for two Grammys — they also snagged a best rock performance nod — 50 years after formally breaking up. It starts with a demo John Lennon recorded in the 1970s that was given to Paul McCartney, Ringo Starr and George Harrison for inclusion on the The Beatles Anthology, released in 1995. While other tracks like Free as a Bird and Real Love made it on, technology wasn't advanced enough to separate Lennon's vocals and piano without reducing the recording's quality. 

But, last year McCartney and Starr used modern machine learning technology to pull Lennon's vocals for a new track. Now and Then, released in November 2023, includes McCartney on bass, Starr on the drums, Lennon's vocals and a guitar in Harrison's style (a 1995 recording of him makes up some of the background rhythm guitar. You can watch a documentary about making the track here. 

Unsurprisingly, the song is said to be the last from the Beatles. We'll have to wait until the awards show in February to see whether or not AI will help them win another Grammy. 

Carey Price aura vraisemblablement la faveur du comité qui est appelé à décider qui sera intronisé chaque année.

Jeremy Roenick nous a offert le moment le plus touchant de l’intronisation des membres de la cuvée 2024 du Temple de la renommée du hockey.

Voyez ce que l’ancien défenseur avait à dire sur son passage dans la Belle Province!

Sydney, Australia (SPX) Nov 04, 2024
In a recent study led by Professor Xin Li and Dr. Yanlong Guo of the Institute of Tibetan Plateau Research, Chinese Academy of Sciences, researchers analyze how scientific research is evolving through the power of big data and artificial intelligence (AI). The paper discusses how the traditional "correlation supersedes causation" model is being increasingly challenged by new "data-intensive scie

Beyoncé leads the 2025 Grammy Award nominations with 11, bringing her career total to 99 nominations. That makes her the most-nominated artist in Grammy history.

Donald Trump a indiqué mardi qu’il comptait nommer Elon Musk à la tête d’un ministère nouvellement créé de l’«efficacité gouvernementale»