Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT.

Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids.

Safety differences across androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer.

Approval of apalutamide, enzalutamide and darolutamide has transformed the treatment landscape and guideline recommendations for patients with nonmetastatic castration-resistant prostate cancer but now raises the issue of decision-making regarding treatment selection. In this perspective, we discuss the efficacy and safety of these second-generation androgen receptor inhibitors and propose that for patients with nonmetastatic castration-resistant prostate cancer, safety considerations for these treatments are especially important. We examine these considerations in the context of patient and caregiver preferences as well as patient clinical characteristics.

The Hospitalization-Related Costs of Adverse Events for Novel Androgen Receptor Inhibitors in Non-Metastatic Castration-Resistant Prostate Cancer: An Indirect Comparison.

Introduction: Three novel androgen receptor inhibitors are approved in the USA for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC): apalutamide, enzalutamide, and darolutamide. All three therapies have demonstrated prolonged metastasis-free survival in their respective phase III trials, with differing safety profiles. The objective of this study was to compare the mean per-patient costs of all-cause adverse events (AEs) requiring hospitalization between darolutamide versus apalutamide and enzalutamide for nmCRPC in the USA.

The triple oxygen isotope composition of marine sulfate and 130 million years of microbial control.

The triple oxygen isotope composition (Δ'O) of sulfate minerals is widely used to constrain ancient atmospheric O/CO and rates of gross primary production. The utility of this tool is based on a model that sulfate oxygen carries an isotope fingerprint of tropospheric O incorporated through oxidative weathering of reduced sulfur minerals, particularly pyrite. Work to date has targeted Proterozoic environments (2.

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

Purpose: No published head-to-head randomized trials have compared the safety and efficacy of darolutamide vs apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares prespecified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.

Materials And Methods: Individual patient data from the phase III ARAMIS trial (N=553; N=943) were selected and reweighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (N=401; N=806) and PROSPER (N=468; N=933) trials.

Volcanic controls on seawater sulfate over the past 120 million years.

Changes in the geological sulfur cycle are inferred from the sulfur isotopic composition of marine barite. The structure of the S/S record from the Mesozoic to present, which includes ∼50- and 100-Ma stepwise increases, has been interpreted as the result of microbial isotope effects or abrupt changes to tectonics and associated pyrite burial. Untangling the physical processes that govern the marine sulfur cycle and associated isotopic change is critical to understanding how climate, atmospheric oxygenation, and marine ecology have coevolved over geologic time.

Patient and caregiver benefit-risk preferences for nonmetastatic castration-resistant prostate cancer treatment.

Background: Recently approved second-generation androgen receptor inhibitors (SGARIs) for non-metastatic castration-resistant prostate cancer (nmCRPC) have similar efficacy but differ in safety profiles. We used a discrete choice experiment (DCE) to examine how nmCRPC patients and caregivers perceive the benefits versus risks of these new treatments.

Methods: An online DCE survey with 14 treatment choice questions was administered to nmCRPC patients and caregivers.

Physician preferences for non-metastatic castration-resistant prostate cancer treatment.

Background: Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. We used a discrete choice experiment to explore how United States physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC, a largely asymptomatic disease.

Oxygen isotope effects during microbial sulfate reduction: applications to sediment cell abundances.

The majority of anaerobic biogeochemical cycling occurs within marine sediments. To understand these processes, quantifying the distribution of active cells and gross metabolic activity is essential. We present an isotope model rooted in thermodynamics to draw quantitative links between cell-specific sulfate reduction rates and active sedimentary cell abundances.

Metabolic Capability and Phylogenetic Diversity of Mono Lake during a Bloom of the Eukaryotic Phototroph Picocystis sp. Strain ML.

Algal blooms in lakes are often associated with anthropogenic eutrophication; however, they can occur without the human introduction of nutrients to a lake. A rare bloom of the alga sp. strain ML occurred in the spring of 2016 at Mono Lake, a hyperalkaline lake in California, which was also at the apex of a multiyear-long drought.

Direct medical costs of treatment in newly-diagnosed high-grade glioma among commercially insured US patients.

Aim: This analysis assessed the direct medical costs of newly-diagnosed, temozolomide (TMZ)-treated glioblastoma (GBM) from the perspective of a US commercial setting.

Materials And Methods: The analysis included subjects identified from the IMS PharMetrics LifeLink Plus™ claims database from January 1, 2008 to August 31, 2014 who were ≥18 years of age, had ≥1 malignant brain cancer diagnosis, had brain surgery ≤90 days prior to TMZ initiation, had TMZ treatment, and were continuously enrolled for ≥12 months pre-diagnosis and ≥1 month post-diagnosis. Per-patient per-month (PPPM) and cumulative costs from 3 months pre-diagnosis to various post-diagnosis follow-up time points were calculated.

The Importance of Economic Perspective and Quantitative Approaches in Oncology Value Frameworks of Drug Selection and Shared Decision Making.

Unlabelled: The debate around value in oncology drug selection has been prominent in recent years, and several professional bodies have furthered this debate by advocating for so-called value frameworks. Herein, we provide a viewpoint on these value frameworks, emphasizing the need to consider 4 key aspects: (1) the economic underpinnings of value; (2) the importance of the perspective adopted in the valuation; (3) the importance of the difference between absolute and relative measures of risk and measuring patient preferences; and (4) the recognition of multiple quality-of-life (QoL) domains, and the aggregation and valuation of those domains, through utilities within a multicriteria decision analysis, may allow prioritization of QoL above the tallying of safety events, particularly in a value framework focusing on the individual patient. While several frameworks exist, they incorporate different attributes and-importantly-assess value from alternative perspectives, including those of patients, regulators, payers, and society.

Total Synthesis of Cryptocaryol A by Enantioselective Iridium-Catalyzed Alcohol C-H Allylation.

The polyketide natural product cryptocaryol A is prepared in 8 steps via iridium catalyzed enantioselective diol double C-H allylation, which directly generates an acetate-based triketide stereodiad. In 4 previously reported total syntheses, 17-28 steps were required.

Ruthenium-catalyzed hydrohydroxyalkylation of acrylates with diols and α-hydroxycarbonyl compounds to form spiro- and α-methylene-γ-butyrolactones.

Under the conditions of ruthenium(0)-catalyzed hydrohydroxyalkylation, vicinal diols 1a-1l and methyl acrylate 2a are converted to the corresponding lactones 3a-3l in good to excellent yield. The reactions of methyl acrylate 2a with hydrobenzoin 1f, benzoin didehydro-1f, and benzil tetradehydro-1f form the same lactone 3f product, demonstrating that this process may be deployed in a redox level-independent manner. A variety of substituted acrylic esters 2a-2h participate in spirolactone formation, as illustrated in the conversion of N-benzyl-3-hydroxyoxindole 1o to cycloadducts 4a-4h.

Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognition.

Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn(2+), Ni(2+), Cu(2+), and the biologically relevant Mg(2+) and Zn(2+) efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.

[Anomalies of the skull in cleidocranial dysplasia].

Background: The description of the otorhinolaryngeal and craniofacial anomalies in patients with cleidocranial dysplasia.

Methods: For this study, 26 patients with cleidocranial dysplasia were examined after their medical history had been recorded. The main focus was placed on otorhinolaryngological and orthodontic findings.

Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage.

Gene expression profiling of matched colorectal carcinomas and metastases could reveal key molecular events involved in tumour progression and metastasis. Expression profiles have been created from 25 colorectal carcinomas (CRCs, pT1-4), corresponding normal colonic mucosa, and 14 liver metastases using cDNA arrays containing 1176 cancer-related genes (Clontech). Hierarchical clustering clearly distinguished carcinomas from non-cancerous tissues, separated tumours into high-stage (pT4 and extensive lymph node or distant metastases) and low-stage (< or =pT3) groups, and correlated with the histopathological classification in 87% (33/38 cases).

[How do metallic middle ear implants behave in the MRI?].

Background: Magnetic resonance imaging (MRI) has gained in frequency and importance as a diagnostic procedure. In respect to the close anatomical relationship in the temporal bone it is necessary to know whether it is hazardous to patients with metallic middle ear implants regarding displacement and rise in temperature. For the MR image quality artefacts caused by metallic prostheses should be low.

Value of high-resolution MR in patients scheduled for cochlear implantation.

Objective: To determine sensitivity and specificity of high-resolution MR imaging and of high-resolution axial CT (HRCT) and to compare the two modalities in predicting the surgical and functional success of cochlear implantation.

Material And Methods: The presurgical MR images (2D T2W TSE, 3D T2*W CISS, plain and contrast-enhanced 3D T1W MP-RAGE) and axial HRCT findings of 26 patients were evaluated with regard to the predictive value concerning the success of cochlear implantation.

Results: We found a high correlation between MR and HRCT and the success of cochlear implantation.

Comparison of a T2* w. 3D CISS and a T2 w. 3D turbo spin echo sequence for the anatomical study of facial and vestibulocochlear nerves.

Thirty healthy volunteers were examined with a T2* w. 3D CISS and a T2 w. 3D turbo spin echo (TSE) sequence in order to compare the facial and vestibulocochlear nerve detectability in the cerebellopontine angle and the internal auditory canal.

ESEEM studies of succinate:ubiquinone reductase from Paracoccus denitrificans.

Electron spin-echo envelope modulation (ESEEM) spectroscopy has been performed in order to obtain structural information about the environment of the reduced [2Fe-2S] cluster (S-1 center), the oxidized [3Fe-4S] cluster (S-3 center), and the flavin semiquinone radical in purified succinate:ubiquinone reductase from Paracoccus denitrificans. Spectral simulations of the ESEEM data from the reduced [2Fe-2S] yielded nuclear quadrupole interaction parameters that are indicative of peptide nitrogens. We also observed a weak interaction between the oxidized [3Fe-4S] cluster and a peptide 14N.