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Background. Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. Methods. These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated cl

Comparative Analysis of Pharmacokinetic-Pharmacodynamic Models for Propofol and Remifentanil Using Model Predictive Control

This study aims to compare the effectiveness of different Pharmacokinetic-Pharmacodynamic (PK-PD) models for administering Propofol and Remifentanil, two critical agents in anesthesia. Initially, different PK models were introduced: one for Propofol based on the Schnider model and another for Remifentanil using the Minto model. Alternatively, both drugs were modeled using the Eleveld models. The P

Estimating glomerular filtration rate in kidney transplant recipients: considerations for selecting equations

Improving the accuracy of estimated GFR (eGFR) measurement in kidney transplant recipients (KTRs) is an important goal.1 Current US and European recommendations suggest using race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based eGFR (eGFRcr) equations (2021 age and sex [AS] or 2009 age, sex, and race–non-Black [ASR-NB]) in adults, without regard to cause or treatm

Fish-hunting cone snail disrupts prey’s glucose homeostasis with weaponized mimetics of somatostatin and insulin

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, w

Targeted complement inhibition using bispecific antibodies that bind local antigens and endogenous complement regulators

Complement activation protects against infection but also contributes to pathological mechanisms in a range of clinical conditions such as autoimmune diseases and transplant rejection. Complement-inhibitory drugs, either approved or in development, usually act systemically, thereby increasing the risk for infections. We therefore envisioned a novel class of bispecific antibodies (bsAbs) which are

Prevalence of childhood cancer survivors in Europe : a scoping review

Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms refe

Palliative care services in paediatric oncology centres across Europe : A cross-sectional survey

Background: Palliative care (PC) is an integral part of cancer treatment. However, data on service availability is limited in childhood cancers. Aim: To describe the availability of PC services in paediatric oncology centres across Europe, and to identify barriers and facilitators for implementing and providing paediatric palliative care (PPC). Methods: Paediatric oncology centres across Europe we

Assembly and succession of the phyllosphere microbiome and nutrient-cycling genes during plant community development in a glacier foreland

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere m

Hobbit: Providing Fall Detection and Prevention for the Elderly in the Real World

We present the robot developed within the Hobbit project, a socially assistive service robot aiming at the challenge of enabling prolonged independent living of elderly people in their own homes. We present the second prototype (Hobbit PT2) in terms of hardware and functionality improvements following first user studies. Our main contribution lies within the description of all components developed

C3 glomerulopathy — understanding a rare complement-driven renal disease

The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — have overlapping clinical and pathologica

Association of changes in inflammation with variation in glycaemia, insulin resistance and secretion based on the KORA study

Aims: Subclinical systemic inflammation may contribute to the development of type 2 diabetes, but its association with early progression of glycaemic deterioration in persons without diabetes has not been fully investigated. Our primary aim was to assess longitudinal associations of changes in pro-inflammatory (leukocytes, high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adipone

EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies

The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR S

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Thermosensitive transient receptor potential (TRP) ion channels detect changes in ambient temperature to regulate body temperature and temperature-dependent cellular activity. Rodent orthologs of TRP vanilloid 2 (TRPV2) are activated by nonphysiological heat exceeding 50 °C, and human TRPV2 is heat-insensitive. TRPV2 is required for phagocytic activity of macrophages which are rarely exposed to ex

Seed treatment with clothianidin induces changes in plant metabolism and alters pollinator foraging preferences

Neonicotinoids, systemic insecticides that are distributed into all plant tissues and protect against pests, have become a common part of crop production, but can unintentionally also affect non-target organisms, including pollinators. Such effects can be direct effects from insecticide exposure, but neonicotinoids can affect plant physiology, and effects could therefore also be indirectly mediate

Gaia Data Release 3: Pulsations in main sequence OBAF-type stars

Context. The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M'a ¥''1.3'M') of spectral types O, B, A, or F, known as β Cep, slowly pulsating B (SP

Very high rotational frequencies and band termination in 73Br

Rotational bands in 73Br have been investigated up to spins of I = 65/2 using the EUROBALL III spectrometer. One of the negative-parity bands displays the highest rotational frequency ℏω= 1.85 MeV reported to date in nuclei with A ≥ 25. At high frequencies, the experimental J(2) dynamic moment of inertia for all bands decreases to very low values, J(2) ≤ 10ℏ2 MeV-1. The bands are described in the

Societal economic burden and determinants of costs for atopic dermatitis

Background: Atopic dermatitis (AD) is a common inflammatory skin disease while the economic burden of AD by severity is not adequately understood. Objective: To estimate the societal economic burden and to identify cost determinants of AD. Methods: In this population-based, controlled cohort study in Sweden, patients with AD were identified through diagnosis codes in primary or secondary care or b

Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma

Background: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. Methods: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Chil

Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms

Background: Immunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility. Methods: We compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell