Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer.

Purpose: No currently available phase III trial compared docetaxel vs. androgen receptor pathway inhibitors (ARPI) regarding cancer-control outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Moreover, few is known about the effect of sequential therapies in mHSPC and subsequent metastatic castration resistant prostate cancer (mCRPC).

Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.

Background: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.

Genomic features of lichen-associated black fungi.

Lichens are mutualistic associations consisting of a primary fungal host, and one to few primary phototrophic symbiont(s), usually a green alga and/or a cyanobacterium. They form complex thallus structures, which provide unique and stable habitats for many other microorganisms. Frequently isolated from lichens are the so-called black fungi, or black yeasts, which are mainly characterized by melanized cell walls and extremophilic lifestyles.

Three-unit posterior monolithic fixed dental prostheses made from high-translucent shade-graded zirconia: 3-Year results from a prospective clinical pilot study.

Objectives: To assess the clinical performance of tooth-supported 3-unit fixed dental prostheses (FDPs) made from shade-graded monolithic 5Y-PSZ (partly stabilized zirconia) zirconia in terms of survival rate and the quality of restorations based on modified FDI criteria over three-years.

Materials And Methods: High-translucent shade-graded monolithic zirconia (Lava Esthetic, Solventum Dental Solutions) was used to manufacture maxillary or mandibular three-unit FDPs in the posterior region (N = 22) employing subtractive milling system (Amann Girrbach). All FDPs were bonded with a universal resin cement (Rely X Universal, Solventum Dental Solutions) and evaluated 4 weeks after cementation (baseline) and after 1, 2, and 3 years.

Administration and cancer-control outcomes of bone-modifying agents in real-world patients with metastatic castration-resistant prostate cancer.

Hormonal agents administered for metastatic castration-resistant prostate cancer (mCRPC) may lead to osteoporosis, skeletal events, reduced quality of life, and even reduced overall survival (OS). Bone-modifying agents may prevent those events but their effect on cancer-control outcomes remains uncertain. Relying on our institutional tertiary-care database, we explored the effect of bone-modifying agents (bisphosphonates such as zoledronic acid and denosumab) on OS and progression-free survival in patients with mCRPC with at least 1 bone metastasis using Kaplan-Meyer estimates and Cox regression models.

In situ analysis reveals the TRiC duty cycle and PDCD5 as an open-state cofactor.

The ring-shaped chaperonin T-complex protein ring complex (TRiC; also known as chaperonin containing TCP-1, CCT) is an ATP-driven protein-folding machine that is essential for maintenance of cellular homeostasis. Its dysfunction is related to cancer and neurodegenerative disease. Despite its importance, how TRiC works in the cell remains unclear.

Triplet or Doublet Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients: An Updated Network Meta-analysis Including ARANOTE Data.

The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has been extended by another phase 3 randomized control trial (ARANOTE) demonstrating favorable outcomes of a doublet therapy combining the androgen receptor pathway inhibitor (ARPI) darolutamide with androgen deprivation therapy (ADT) over ADT monotherapy. Owing to differences in trial designs, patient enrollment, and most notably different control treatment regimens, we hereby present an updated network meta-analysis (NMA) embedding the doublet therapy with darolutamide within the current treatment regimens. In NMA-derived ranking, darolutamide and ADT showed similar oncological efficacy to the already known doublet therapies for progression-free survival (p = 0.

Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.

Purpose: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.

Materials And Methods: We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen () or tumor suppressor gene mutations (, , ).

Advanced aspects of acetogens.

Acetogens are a diverse group of anaerobic bacteria that are capable of carbon dioxide fixation and have for long fascinated scientists due to their unique metabolic prowess. Historically, acetogens have been recognized for their remarkable ability to grow and to produce acetate from different one-carbon sources, including carbon dioxide, carbon monoxide, formate, methanol, and methylated organic compounds. The key metabolic pathway in acetogens responsible for converting these one-carbon sources is ́the Wood-Ljungdahl pathway.

Novick Meets Bayes: Improving the Assessment of Individual Students in Educational Practice and Research by Capitalizing on Assessors' Prior Beliefs.

The assessment of individual students is not only crucial in the school setting but also at the core of educational research. Although classical test theory focuses on maximizing insights from student responses, the Bayesian perspective incorporates the assessor's prior belief, thereby enriching assessment with knowledge gained from previous interactions with the student or with similar students. We propose and illustrate a formal Bayesian approach that not only allows to form a stronger belief about a student's competency but also offers a more accurate assessment than classical test theory.

The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway.

The complex kinetics of disease-related amyloid aggregation of proteins such as α-Synuclein (α-Syn) in Parkinson's disease and Aβ42 in Alzheimer's disease include primary nucleation, amyloid fibril elongation and secondary nucleation. The latter can be a key accelerator of the aggregation process. It has been demonstrated that the chaperone domain BRICHOS can interfere with the secondary nucleation process of Aβ42.

Anticipating and suspending: the chronopolitics of cryopreservation.

The article brings together two disparate and so far largely disconnected bodies of research: the critical analysis of cryopreservation technologies and the debate on modes of anticipation. It starts with a short review of the state of the research on the concept of cryopolitics. In the next part I will suggest two revisions.

Mapping cellular stress and lipid dysregulation in Alzheimer-related progressive neurodegeneration using label-free Raman microscopy.

Aβ plaques are a main feature of Alzheimer's disease, and pathological alterations especially in their microenvironment have recently come into focus. However, a holistic imaging approach unveiling these changes and their biochemical nature is still lacking. In this context, we leverage confocal Raman microscopy as unbiased tool for non-destructive, label-free differentiation of progressive biomolecular changes in the Aβ plaque microenvironment in brain tissue of a murine model of cerebral amyloidosis.

Real-World Comparison of Cabazitaxel Versus Lu-PSMA Radiopharmaceutical Therapy in Metastatic Castration-Resistant Prostate Cancer.

Lu-vipivotide tetraxetan prostate-specific membrane antigen (Lu-PSMA) therapy is under current scientific investigation and aims to become established in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, real-world evidence in treatment comparison is scant. We relied on the FRAMCAP database and compared cabazitaxel versus Lu-PSMA therapy in mCRPC patients regarding progression-free survival (PFS) and overall survival (OS).

Primary tumor ablation in metastatic renal cell carcinoma.

Background: The role of primary tumor ablation (pTA) in metastatic renal cell carcinoma (mRCC) is unknown. We compared pTA-treated mRCC patients to patients who underwent no local treatment (NLT), as well as patients who underwent cytoreductive nephrectomy (CN).

Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2004-2020), we identified mRCC patients who underwent either pTA, NLT or CN.

Efficient DNA-free co-targeting of nuclear genes in Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii, a model organism for unicellular green microalgae, is widely used in basic and applied research. Nonetheless, proceeding towards synthetic biology requires a full set of manipulation techniques for inserting, removing, or editing genes. Despite recent advancements in CRISPR/Cas9, still significant limitations in producing gene knock-outs are standing, including (i) unsatisfactory genome editing (GE) efficiency and (ii) uncontrolled DNA random insertion of antibiotic resistance markers.

Gritty Parenting: The Development and Validation of the Parental Grit Scale.

In this study, we aimed to expand the domain specificity of grit by exploring it in the realm of parenting. Parental grit was defined as parents' inclination to demonstrate perseverance, sustained passion, and adaptability in pursuing long-term parenting goals. With longitudinal data from 1,373 U.

Tracking individual animals can reveal the mechanisms of species loss.

As biodiversity loss continues, targeted conservation interventions are increasingly necessary. Stemming species loss requires mechanistic understanding of the processes governing population dynamics. However, this information is unavailable for most animals because it requires data that are difficult to collect using traditional methods.

Dedicated developmental programing for group-supporting behaviors in eusocial honeybees.

The evolutionary changes from solitary to eusocial living in vertebrates and invertebrates are associated with the diversification of social interactions and the development of queen and worker castes. Despite strong innate patterns, our understanding of the mechanisms manifesting these sophisticated behaviors is still rudimentary. Here, we show that () manifests group-supporting behaviors in the honeybee () worker caste.

Mortality rates in radical cystectomy patients with bladder cancer after radiation therapy for prostate cancer.

Objective: To conduct a population-based study examining cancer-specific mortality (CSM) and other-cause mortality (OCM) differences in patients with radiation-induced secondary bladder cancer (RT-BCa) vs those with primary bladder cancer (pBCa) undergoing radical cystectomy (RC).

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with TNM bladder cancer treated with RC, who had previously been treated with external beam radiation therapy (EBRT) or brachytherapy for prostate cancer, as well as patients with TNM pBCa treated with RC. Cumulative incidence plots and multivariable competing risks regression (CRR) models were used to assess CSM after additional adjustment for OCM.

Idiosyncratic Hepatocellular Drug-Induced Liver Injury by Flucloxacillin with Evidence Based on Roussel Uclaf Causality Assessment Method and HLA B*57:01 Genotype: From Metabolic CYP 3A4/3A7 to Immune Mechanisms.

Idiosyncratic drug-induced liver injury (iDILI) by flucloxacillin presents as both cholestatic and hepatocellular injury. Its mechanistic steps are explored in the present analysis as limited data exist on the cascade of events leading to iDILI in patients with an established diagnosis assessed for causality by the Roussel Uclaf Causality Assessment Method (RUCAM). Studies with human liver microsomes showed that flucloxacillin is a substrate of cytochrome P450 (CYP) with ist preferred isoforms CYP 3A4/3A7 that toxified flucloxacillin toward 5'-hydroxymethylflucloxacillin, which was cytotoxic to human biliary epithelial cell cultures, simulating human cholestatic injury.