Weal and woe of interleukin-18 in the T cell therapy of cancer.

Chimeric antigen receptor (CAR) T cell therapy of solid cancer remains below expectations; adding cytokine help through IL-18 has shown remarkable efficacy in first clinical trials. As IL-18 is also a powerful driver of hyperinflammatory conditions, we discuss to what extent unleashing IL-18 is a double-edged sword in CAR T cell therapies.

Water Activity as an Indicator for Antibody Storage Stability in Lyophilized Formulations.

Lyophilization remains a key method for preserving sensitive biopharmaceuticals such as monoclonal antibodies. Traditionally, stabilization mechanisms have been explained by vitrification, which minimizes molecular mobility in the lyophilized cake, and water replacement, which restores molecular interactions disrupted by water removal. This study proposes a novel design strategy that combines water activity and glass-transition temperature as the main indicators to predict long-term stability in lyophilized formulations.

Best Practice Guidelines - DEGUM Recommendations on Breast Ultrasound.

Breast ultrasound has been established for many years as an important method in addition to mammography for clarifying breast findings. The goal of the Best Practice Guidelines Part III of the DEGUM breast ultrasound working group is to provide colleagues working in senology with information regarding the specific medical indications for breast ultrasound in addition to the current ultrasound criteria and assessment categories published in part I and the additional and optional sonographic diagnostic methods described in part II. The value of breast ultrasound for specific indications including follow-up, evaluation of breast implants, diagnostic workup of dense breast tissue, diagnostic workup during pregnancy and lactation, and the diagnostic workup of breast findings in men is discussed.

Best Practice Guidelines - DEGUM Recommendations on Breast Ultrasound.

Breast ultrasound has been established for many years as an important method in addition to mammography for clarifying breast findings. The goal of the Best Practice Guidelines Part III of the DEGUM breast ultrasound working group is to provide colleagues working in senology with information regarding the specific medical indications for breast ultrasound in addition to the current ultrasound criteria and assessment categories published in part I and the additional and optional sonographic diagnostic methods described in part II. The value of breast ultrasound for specific indications including follow-up, evaluation of breast implants, diagnostic workup of dense breast tissue, diagnostic workup during pregnancy and lactation, and the diagnostic workup of breast findings in men is discussed.

3D Printing as an Aid in Acetabular Defects Compared to Established Diagnostics - a Survey.

The treatment of acetabular defects in revision arthroplasty is an increasing challenge. Different classifications have been introduced for preoperative planning to achieve the best possible result. 3D printing is a way to better visualize and understand these defects.

[Arthropathy as the first manifestation of undiagnosed hemochromatosis: a case report on an unusual course].

A 54-year-old man presented with increasing arthralgia and swelling of the metacarpophalangeal (MCP) joints II and III for approximately 2 years. He also reported morning stiffness and joint pain in both knees and feet.Both MCP joints II and III and the proximal interphalangeal joints II and III were tender without visible swelling.

[Renal replacement therapy in Germany: An overview with a clinical focus].

In Germany, around 80000 people are currently dependent on permanent renal replacement therapy (RRT). Due to demographic developments and improvements in life expectancy, the prevalence will continue to increase even if the effects of newer pharmacological substances such as SGLT2 inhibitors and GLP1 agonists are promising in inhibiting progression. There are basically three different methods of renal replacement therapy and their variants: Kidney transplantation (KTX), peritoneal dialysis (PD), hemodialysis (HD)/hemodiafiltration (HDF).

[Chronic Kidney Disease: epidemiology, implications for clinical practice and equations for diagnosis].

The article is based, among other things, on the updated KDIGO guideline for the evaluation and management of chronic kidney disease, which was published in Kidney International in March 2024. Chronic kidney disease is one of the most common chronic diseases, with a prevalence of around 10%, not least due to demographic ageing. The incidence of chronic kidney disease is approximately twice that of diabetes and approximately 20 times higher than that of cancer.

Protein abundance of drug transporters and drug-metabolizing enzymes in paired healthy and tumor tissue from colorectal cancer patients.

The widespread prevalence of colorectal cancer and its high mortality rate emphasize the urgent need for more effective therapies. When developing new drug products, a key aspect is ensuring that sufficiently high concentrations of the active drug are reached at the site of action. Drug transporters and drug-metabolizing enzymes can significantly influence the absorption and local accumulation of drugs in intestinal tissue.

Investigation of the suitability of confocal Raman spectroscopy for the demonstration of bioequivalence of topical products.

Bioequivalence studies of topical formulations have attracted increased interest as the European Medicines Agencies "Guideline on quality and equivalence on locally applied, locally acting cutaneous products" describes them in the context of the approval of generics. Since the guideline only proposes tape stripping as a destructive method for bioequivalence testing in in vitro skin penetration, the aim of this study was to investigate the suitability of confocal Raman spectroscopy (CRS) as a non-destructive alternative. To validate the CRS results, tape stripping and CRS experiments using ketoprofen as a model API were performed consecutively on the same samples of ex vivo porcine skin after frozen storage and compared.

RNA splicing: a split consensus reveals two major 5' splice site classes.

The established consensus sequence for human 5' splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5' splice site classes are separable in genome sequences, sensitized by specific genotypes and associated with splicing complexity. The two classes reflect the commitment to 5' splice site usage occurring primarily during 5' splice site transfer to U6 snRNA.

Distinct retinal ganglion cell types in strictly subterranean, naturally microphthalmic mammals.

African mole-rats (Bathyergidae, Rodentia) are subterranean rodents that live in extensive dark underground tunnel systems and rarely emerge aboveground. They can discriminate between light and dark but show no overt visually driven behaviours except for light-avoidance responses. Their eyes and central visual system are strongly reduced but not degenerated.

Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing.

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.

Supported Mindfulness-Based Self-Help Intervention as an Adjunctive Treatment for Rapid Symptom Change in Emotional Disorders: A Practice-Oriented Multicenter Randomized Controlled Trial.

Introduction: Rapid symptom relief is crucial for individuals with emotional disorders. The current study aimed to determine whether facilitator-supported mindfulness-based self-help (MBSH) intervention as an adjunctive treatment could provide rapid improvement for individuals with emotional disorders.

Methods: A practice-oriented randomized controlled trial was conducted on a sample of 302 patients with emotional disorders from four centers.

Phantom evaluation of feasibility and applicability of artificial intelligence based pulmonary nodule detection in chest radiographs.

The aim of our study was to evaluate the specific performance of an artificial intelligence (AI) algorithm for lung nodule detection in chest radiography for a larger number of nodules of different sizes and densities using a standardized phantom approach. A total of 450 nodules with varying density (d1 to d3) and size (3, 5, 8, 10 and 12 mm) were inserted in a Lungman phantom at various locations. Radiographic images with varying projections were acquired and processed using the AI algorithm for nodule detection.

Global trends and current research in post-traumatic osteoarthritis: A bibliometric and visualization analysis from 2010 to 2024.

Background: To investigate global trends and current research on post-traumatic osteoarthritis (PTOA) from 2010 to 2024 using bibliometric and visualization techniques.

Methods: A bibliometric analysis was conducted using data from the Web of Science Core Collection. The study examined publication trends, author contributions, institutional collaborations, keyword co-occurrence, and citation patterns, employing CiteSpace software to analyze key metrics such as publication frequency, centrality, and clustering.

Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment.

Soluble guanylate cyclase (sGC) stands as a pivotal regulatory element in intracellular signalling pathways, mediating the formation of cyclic guanosine monophosphate (cGMP) and impacting diverse physiological processes across tissues. Increased formation of reactive oxygen species (ROS) is widely recognized to modulate cGMP signalling. Indeed, oxidatively damaged, and therefore inactive sGC, contributes to poor vascular reactivity and more severe neurological damage upon stroke.

Diketopiperazine/piperidine alkaloid as a potential broad-spectrum coronaviral entry inhibitor identified by supercomputer-based virtual screening from a large natural product-based library.

The COVID-19 pandemic has underscored the urgent need for antiviral agents capable of targeting a broad range of coronaviruses, including emerging variants of SARS-CoV-2. While vaccines have been pivotal, the search for drugs that can prevent viral entry into host cells remains crucial, especially against evolving viral forms and other coronaviruses. In this study, we investigated natural products as a source of antiviral agents, focusing on their potential to block the spike protein's receptor-binding domain (RBD).

Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy.

Objective: To report patient-reported quality-of-life (QOL) outcomes in the DAYLIGHT study.

Study Design: DAYLIGHT was a phase 3b, randomized, double-blind, 24-week, placebo-controlled study. Participants were women aged ≥40 to ≤65 years with moderate to severe vasomotor symptoms (VMS) considered unsuitable for hormone therapy (HT) (contraindications, caution, stoppers, or averse) randomized 1:1 to placebo or fezolinetant 45 mg once daily.

SD-LayerNet: Robust and label-efficient retinal layer segmentation via anatomical priors.

Background And Objectives: Automated, anatomically coherent retinal layer segmentation in optical coherence tomography (OCT) is one of the most important components of retinal disease management. However, current methods rely on large amounts of labeled data, which can be difficult and expensive to obtain. In addition, these systems tend often propose anatomically impossible results, which undermines their clinical reliability.

Quantitative prediction of toxicological points of departure using two-stage machine learning models: A new approach methodology (NAM) for chemical risk assessment.

Point of departure (POD) is a concept used in risk assessment to calculate the reference dose of exposure that is likely to have no appreciable risk on health. POD can be directly utilized from no observed adverse effect levels (NOAEL) which is the dose or exposure level at which there is little or no risk of adverse effects. However, NOAEL values are unavailable for most of the chemicals due to inconsistent animal toxicity data.

Engineering organoids as cerebral disease models.

Cerebral organoids pioneered in replicating complex brain tissue architectures in vitro, offering a vast potential for human disease modeling. They enable the in vitro study of human physiological and pathophysiological mechanisms of various neurological diseases and disorders. The trajectory of technological advancements in brain organoid generation and engineering over the past decade indicates that the technology might, in the future, mature into indispensable solutions at the horizon of personalized and regenerative medicine.

Relation between Electrostatic Charge Density and Spin Hamiltonian Models of Ligand Field in Lanthanide Complexes.

Understanding the ligand field interactions in lanthanide-containing magnetic molecular complexes is of paramount importance for understanding their magnetic properties, and simple models for rationalizing their effects are much desired. In this work, the equivalence between electrostatic models, which derive their results from calculating the electrostatic interaction energy of the charge density of the 4f electrons in an electrostatic potential representing the ligands, and the common quantum mechanical effective spin Hamiltonian in the space of the ground multiplet is formulated in detail. This enables the construction of an electrostatic potential for any given ligand field Hamiltonian and discusses the effects of the ligand field interactions in terms of an interaction of a generalized 4f charge density with the electrostatic potential.