Significance of E-lesions in Hodgkin lymphoma and the creation of a new consensus definition: a report from SEARCH.

The International Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) seeks to provide an appropriate, universal differentiation between E-lesions and stage IV extranodal disease in Hodgkin lymphoma (HL). A literature search was performed through the PubMed and Google Scholar databases using the terms "Hodgkin disease," and "extranodal," "extralymphatic," "E lesions," "E stage," or "E disease." Publications were reviewed for the number of participants; median age and age range; diagnostic modalities used for staging; and the definition, incidence, and prognostic significance of E-lesions.

Application of Ligand- and Structure-Based Prediction Models for the Design of Alkylhydrazide-Based HDAC3 Inhibitors as Novel Anti-Cancer Compounds.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects, and in particular hydroxamic-acid-based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry.

NOXA Accentuates Apoptosis Induction by a Novel Histone Deacetylase Inhibitor.

Epigenetic modifiers of the histone deacetylase (HDAC) family are often dysregulated in cancer cells. Experiments with small molecule HDAC inhibitors (HDACi) have proven that HDACs are a vulnerability of transformed cells. We evaluated a novel hydroxamic acid-based HDACi (KH16; termed yanostat) in human pancreatic ductal adenocarcinoma (PDAC) cells, short- and long-term cultured colorectal cancer (CRC) cells, and retinal pigment epithelial cells.

Neutrophil Extracellular Traps Drive Dacryolithiasis.

Mucopeptide concretions, previously called dacryoliths, are macroscopic stones that commonly obstruct the lacrimal sac. The mechanism behind dacryolithiasis remains unclear; however, the involvement of various immune cells, including neutrophils, has been confirmed. These findings remain limited, and no information on neutrophil extracellular traps (NETs), essentially involved in the pathogenesis of other lithiases, is available yet.

Towards the optimization of drug delivery to the cochlear apex: Influence of polymer and drug selection in biodegradable intracochlear implants.

There is growing need for new drug delivery systems for intracochlear application of drugs to effectively treat inner ear disorders. In this study, we describe the development and characterization of biodegradable, triamcinolone-loaded implants based on poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) respectively, prepared by hot-melt extrusion. PEG 1500 was used as a plasticizer to improve flexibility and accelerate drug release.

Old Age and Frailty in Deceased Organ Transplantation and Allocation-A Plea for Geriatric Assessment and Prehabilitation.

Due to demographic ageing and medical progress, the number and proportion of older organ donors and recipients is increasing. At the same time, the medical and ethical significance of ageing and old age for organ transplantation needs clarification. Advanced age is associated with the frailty syndrome that has a negative impact on the success of organ transplantation.

Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells.

Introduction: Posttranslational modification of proteins by reversible acetylation regulates key biological processes. Histone deacetylases (HDACs) catalyze protein deacetylation and are frequently dysregulated in tumors. This has spurred the development of HDAC inhibitors (HDACi).

Relationship between working conditions and mental health of migrants and refugees/asylum seekers vs. natives in Europe: a systematic review.

Objective: Migrants and refugees/asylum seekers make up a significant proportion of the European workforce. They often suffer from poor working conditions, which might impact mental health. The main objective of this systematic review was to summarize and analyze existing research on working conditions of migrants and refugees/asylum seekers in European host countries and compare them to those of natives.

Mason bees and honey bees synergistically enhance fruit set in sweet cherry orchards.

Mason bees ( spp.) are efficient fruit tree pollinators that can be encouraged to occupy and breed in artificial nesting material. In sweet cherry orchards, they are occasionally used as an alternative managed pollinator as a replacement for or in addition to honey bees ().

St. Gallen/Vienna 2023: Optimization of Treatment for Patients with Primary Breast Cancer - A Brief Summary of the Consensus Discussion.

The St. Gallen Consensus Conference on early breast cancer treatment 2023 was again a live event and took place in Vienna, Austria. After 4 years and one virtual event due to the pandemic, more than 2,800 participants from over 100 countries came together in Vienna, and the 2023 St.

Northern Richness, Southern Dead End-Origin and Dispersal Events of (Sciaridae, Diptera) between New Zealand's Main Islands.

Sciaridae (Diptera) is a widespread insect family of which some species can reach high abundances in arboreal habitats. This trait, together with their (passive) mobility, enables them to quickly colonise suitable habitats. To reveal the biogeographic history of the New Zealand members of the sciarid genus , we analysed three molecular markers of selected species and populations in a Bayesian approach.

High positive end-expiratory pressure ventilation mitigates the progression from unilateral pulmonary contusion to ARDS: An animal study.

Background: Pulmonary contusion (PC) is common in severely traumatized patients and can lead to respiratory failure requiring mechanical ventilation (MV). Ventilator-induced lung injury (VILI) might aggravate lung damage. Despite underrepresentation of trauma patients in trials on lung-protective MV, results are extrapolated to these patients, potentially disregarding important pathophysiological differences.

CSF Synaptic Biomarkers in AT(N)-Based Subgroups of Lewy Body Disease.

Background And Objectives: Patients with Lewy body disease (LBD) often show a co-occurring Alzheimer disease (AD) pathology. CSF biomarkers allow the detection in vivo of AD-related pathologic hallmarks included in the amyloid-tau-neurodegeneration (AT(N)) classification system. Here, we aimed to investigate whether CSF biomarkers of synaptic and neuroaxonal damage are correlated with the presence of AD copathology in LBD and can be useful to differentiate patients with LBD with different AT(N) profiles.

Prior Movement of One Arm Facilitates Motor Adaptation in the Other.

Many movements in daily life are embedded in motion sequences that involve more than one limb, demanding the motor system to monitor and control different body parts in quick succession. During such movements, systematic changes in the environment or the body might require motor adaptation of specific segments. However, previous motor adaptation research has focused primarily on motion sequences produced by a single limb, or on simultaneous movements of several limbs.

Prolongation of Pregnancy in Patients with HELLP Syndrome Using Methylprednisolone: A Retrospective Multicentric Analysis.

Background: Immediate delivery is an established concept for preventing life-threatening complications in mothers with HELLP syndrome; however, it is associated with preterm births.

Methods: Cases of HELLP syndrome diagnosed at the university hospitals of Halle and Magdeburg (Germany) were analyzed retrospectively. Each patient of the treatment group was administered 64 mg of methylprednisolone (MP) intravenously for 10 days, with the dosage being reduced by 50% every other day in patients from Halle (n = 65).

Effect of hydrophobic extension of aryl enaminones and pyrazole-linked compounds combined with sulphonamide, sulfaguanidine, or carboxylic acid functionalities on carbonic anhydrase inhibitory potency and selectivity.

Design and synthesis of three novel series of aryl enaminones (- and -) and pyrazole () linked compounds with sulphonamides, sulfaguanidine, or carboxylic acid functionalities were reported as carbonic anhydrase inhibitors (CAIs) using the "tail approach" strategy in their design to achieve the most variable amino acids in the middle/outer rims of the hCAs active site. The synthesised compounds were assessed for their inhibitory activity against the following human (h) isoforms, hCA I, II, IX, and XII using stopped-flow CO hydrase assay. Enaminone sulphonamide derivatives (-) potently inhibited the target tumour-associated isoforms hCA IX and hCA XII (KIs 26.

Internalization or Dissociation? Negative Age Stereotypes Make You Feel Younger Now But Make You Feel Older Later.

Objectives: Negative age stereotypes have negative, assimilative effects on the subjective aging experience due to internalization processes, but sometimes positive contrast effects are reported as well, reflecting dissociation and downward comparisons. Our aim was thus to compare short-term and long-term consequences of age stereotypes on the subjective aging experience, to test the hypothesis that contrast effects are visible cross-sectionally, whereas internalization processes are observed when considering long-term changes.

Methods: We assessed age stereotypes and subjective age in a core sample of N = 459 participants (initial age range 30-80 years) from the Ageing as Future project across 3 consecutive measurement occasions spanning a longitudinal interval of 10 years.

Editorial for Special Issue-"Early-Stage Drug Discovery: Advances and Challenges".

The development of a new drug from the first hit to the launch of an approved product is a complex process that usually take around 12-15 years and costs more than USD 1-2 billion [...

RNA-binding proteins in cancer drug discovery.

RNA-binding proteins (RBPs) are crucial players in tumorigenesis and, hence, promising targets in cancer drug discovery. However, they are largely regarded as 'undruggable', because of the often noncatalytic and complex interactions between protein and RNA, which limit the discovery of specific inhibitors. Nonetheless, over the past 10 years, drug discovery efforts have uncovered RBP inhibitors with clinical relevance, highlighting the disruption of RNA-protein networks as a promising avenue for cancer therapeutics.

Higher body weight-dependent neural activation during reward processing.

Obesity is associated with alterations in brain structure and function, particularly in areas related to reward processing. Although brain structural investigations have demonstrated a continuous association between higher body weight and reduced gray matter in well-powered samples, functional neuroimaging studies have typically only contrasted individuals from the normal weight and obese body mass index (BMI) ranges with modest sample sizes. It remains unclear, whether the commonly found hyperresponsiveness of the reward circuit can (a) be replicated in well-powered studies and (b) be found as a function of higher body weight even below the threshold of clinical obesity.

With a little help from my friends? Acculturation and mental health in Arabic-speaking refugee youth living with their families.

Introduction: Refugee youth are often faced with the compounding challenges of heightened exposure to traumatic events and acculturating to a new country during a developmental period when their sense of self is still forming. This study investigated whether refugee youth's acculturation orientation (separation, integration, marginalization, and assimilation) is associated with depressive and posttraumatic stress symptoms and aimed to identify additional indicators of acculturation that may contribute to mental health.

Methods: A total of 101 Arabic-speaking refugee youths (aged 14-20 years), who were living with their families and attending school in Germany, took part in the study.

Arylidine extensions of 3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-benzenesulfonamide derivatives: Synthesis, computational simulations and biological evaluation as tumor-associated carbonic anhydrase inhibitors.

Several pyrazole-benzene sulfonamides were reported as human carbonic anhydrase inhibitors. In this research work, a design of Arylidine-extented 5-oxo-pyrazole benzenesulfonamides (4a-i), (8a-d) and (10a-e) were reported based on tail-approach design. Beside the reported synthetic procedures and confirmation by different analytical procedures, a DFT study was employed to confirm the Z- conformer of the synthesized compounds.

Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial.

Background And Hypothesis: Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications.

Study Design: Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial.

MAW: the reproducible Metabolome Annotation Workflow for untargeted tandem mass spectrometry.

Mapping the chemical space of compounds to chemical structures remains a challenge in metabolomics. Despite the advancements in untargeted liquid chromatography-mass spectrometry (LC-MS) to achieve a high-throughput profile of metabolites from complex biological resources, only a small fraction of these metabolites can be annotated with confidence. Many novel computational methods and tools have been developed to enable chemical structure annotation to known and unknown compounds such as in silico generated spectra and molecular networking.

Inhibition of the Fibrillation of Amyloid Aβ by Hybrid-Lipid-Polymer Vesicles.

The transformation of functional proteins into amyloidic plaques is responsible for the impairment of neurological functions in patients fallen victim to debilitating neurological conditions like Alzheimer's, Parkinson's, and Huntington's diseases. The nucleating role of amyloid beta (Aβ ) peptide into amyloids is well established. Herein, lipid hybrid-vesicles are generated with glycerol/cholesterol-bearing polymers aiming to alter the nucleation process and modulate the early phases of Aβ fibrillation.