Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Trends in Physical Fitness in Children and Adolescents Within the Past 18 Years (DONALD Study).

Objective: To evaluate the trends in physical fitness in children and adolescents.

Method: The present study focusses on a longitudinal analysis of the single two-legged jump (S2LJ) from children and adolescents, who participated in the DONALD study from 2004 till 2022. P /body mass (power, surrogate for muscular performance), V (bounce speed, surrogate for coordination), F /body mass (force, surrogate for muscular strength) and (Nerve-Muscle Index, surrogate for jump efficiency) were examined by linear mixed models and propensity-score(PS)-matching analysis.

Calorimetry probe for runaway electron heat load measurement at COMPASS.

Runaway electrons, accelerated in a tokamak discharge to high energies (tens of MeV), can cause serious damage to plasma facing components. Therefore, it is important to develop effective mitigation strategies to reduce the risk of tokamak damage. To study the effects of various mitigation strategies, a dedicated diagnostic, the calorimetry probe, was developed at the COMPASS tokamak.

Senescence as a therapeutic target in cancer and age-related diseases.

Cellular senescence is a stress response that restrains the growth of aged, damaged or abnormal cells. Thus, senescence has a crucial role in development, tissue maintenance and cancer prevention. However, lingering senescent cells fuel chronic inflammation through the acquisition of a senescence-associated secretory phenotype (SASP), which contributes to cancer and age-related tissue dysfunction.

Long-term survival following anti-PD-(L)1 monotherapy in advanced urothelial cancer and an assessment of potential prognostic clinical factors: a multicentre observational study.

Background: Anti-PD-(L)1 agent are approved as first- and second-line treatment options in advanced urothelial cancer (UC), but information about long-term survival is scarce. There is a need for prognostic factors, as these may help in the decision-making concerning anti-PD-(L)1 in patients with UC. Here, we examined long-term survival following anti-PD-(L)1 in advanced UC and assessed clinical factors for their correlation with survival.

Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

Background And Purpose: Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment.

Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.

Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined.

Mid-Term Clinical and Radiological Changes in the Ankle Joint in Varus Knee Osteoarthritis Following Total Knee Arthroplasty.

In patients with varus knee osteoarthritis, compensatory changes occur in the foot and ankle joints to compensate for the varus deformity of the knee. The aim of the study was to investigate the changes in the ankle of patients whose knee alignment was corrected with total knee arthroplasty (TKA) and to explore the clinical implications of these findings. : In this retrospective observational study, we analyzed 204 knees of 179 patients who had regular follow-ups out of 431 patients who underwent TKA for varus knee osteoarthritis between January 2019 and July 2021.

Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome.

Background: Multiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24 h of traumatic injury.

Shedding Light on the Origin of ^{204}Pb, the Heaviest s-Process-Only Isotope in the Solar System.

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance.

Loss of the long form of Plod2 phenocopies contractures of Bruck syndrome-osteogenesis imperfecta.

Bruck syndrome is an autosomal recessive form of osteogenesis imperfecta caused by biallelic variants in PLOD2 or FKBP10 and is characterized by joint contractures, bone fragility, short stature, and scoliosis. PLOD2 encodes LH2, which hydroxylates type I collagen telopeptide lysines, a critical step for collagen crosslinking. The Plod2 global knockout mouse model is limited by early embryonic lethality, and thus, the role of PLOD2 in skeletogenesis is not well understood.

SEOM-GG clinical guidelines for the management of germ-cell testicular cancer (2023).

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment.

Pharmaceutical cost savings from the treatment of oncology patients in clinical trials.

Objective: The aim of this study was twofold: to assess the annual pharmaceutical savings associated with the treatment of cancer patients at Marqués de Valdecilla University Hospital and to estimate the cost of innovative antineoplastic therapies that patients receive as experimental treatment, both during clinical trials throughout 2020.

Material And Methods: An observational and financial analysis of the drug cost related to clinical trials was applied. Direct cost savings to the Regional Health System of Cantabria and the cost of innovative therapies used as an experimental treatment in clinical trials were quantified.

RENO Study: Clinical characteristics, treatment patterns and survival results in patients with metastatic renal cell carcinoma in Northern Spain.

Background: The current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an analysis describing the clinical characteristics, treatments, and health outcomes of patients with mRCC in northern Spain.

Methods: Retrospective observational study.

Measurement of the ^{140}Ce(n,γ) Cross Section at n_TOF and Its Astrophysical Implications for the Chemical Evolution of the Universe.

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values.