Oligoethylene Phosphoramidate-based Kinase Inhibitor Prodrugs - Solubility, Enzyme Inhibition, and Hydrolysis.

The efficiency of kinase inhibiting cancer therapeutics is often limited by their poor solubility in water. PEGylation is one possible strategy to improve the solubility of the drug, however, means to cleave these after reaching the target is important to make use of the therapeutic effects of the native drug. Moreover, the length of the PEG chains will have an effect on the solubility and binding.

Impact of myelodysplasia-related and additional gene mutations in intensively treated patients with -mutated AML.

This study aimed to evaluate the impact of the myelodysplasia-related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with -mutated ( ) AML. Targeted DNA sequencing of 263 genes was performed in 568 AML patients (median age: 59 years) entered into the prospective AMLSG 09-09 treatment trial. Most commonly co-mutated genes were (49.

"Double-Use" Strategy for Improving the Photoelectrochemical Performance of BiVO Photoanodes Using a Cobalt-Functionalized Polyoxotungstate.

Doping and surface-modification are well-established strategies for the performance enhancement of bismuth vanadate (BiVO) photoanodes in photoelectrochemical (PEC) water splitting devices. Herein, a "double-use" strategy for the development of high-performance BiVO photoanodes for solar water splitting is reported, where a molecular cobalt-phosphotungstate (CoPOM = Na[Co(HO)(PWO)]) is used both as a bulk doping agent as well as a surface-deposited water oxidation cocatalyst. The use of CoPOM for bulk doping of BiVO is shown to enhance the electrical conductivity and improve the charge separation efficiency, resulting in the enhancement of the maximum applied-bias photoconversion efficiency (ABPE) by a factor of ∼18 to 0.

Towards a comprehensive definition of the human fascial system.

The absence of a clear consensus on the definition and significance of fascia and the indiscriminate use of the term throughout the clinical and scientific literature has led to skepticism regarding its importance in the human body. To address this challenge, we propose that: (1) fasciae, and the fascial interstitia within them, constitute an anatomical system, defined as a layered body-wide multiscale network of connective tissue that allows tensional loading and shearing mobility along its interfaces; (2) the fascial system comprises four anatomical organs: the superficial fascia, musculoskeletal (deep) fascia, visceral fascia, and neural fascia; (3) these organs are further composed of anatomical structures, some of which are eponymous; (4) all these fascial organs and their structural components contain variable combinations and arrangements of the four classically defined tissues: epithelial, connective, muscle, and neural; (5) the overarching functions of the fascial system arise from the contrasting biomechanical properties of the two basic types of layers distributed throughout the system: one predominantly collagenous and relatively stiff, the other rich in hyaluronic acid and viscous, allowing for the free flow of fluid; (6) the topographical organization of these layers in different locations is related to local variations in function (e.g.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Unraveling the inflammation-degeneration tangle in early MS: preliminary insights from ferritin, neurogranin, TREM2, and retinal ganglion cell layer.

Background: Multiple sclerosis (MS) involves a complex interplay between immune-mediated inflammation and neurodegeneration. Recent advances in biomarker research have provided new insights into the molecular underpinnings of MS, including ferritin, neurogranin, Triggering Receptor Expressed on Myeloid cells 2 (TREM2), and neurofilaments light chain.

Objectives: This pilot study aims to investigate the levels of these biomarkers in the cerebrospinal fluid (CSF) of MS patients and explore their associations with clinical, cognitive, and optical coherence tomography (OCT) parameters.

Coronal Malalignment Is Infrequently Present in Patients With Aseptic Tibial Loosening.

Background: Coronal lower extremity malalignment and improper implant position have been described as risk factors for aseptic tibial loosening following primary total knee arthroplasty (TKA). However, several prior studies have shown no association between alignment and implant loosening. Meanwhile, there is increasing interest in kinematic alignment.

Ligand labilization gates intramolecular electron transfer in molecular photocatalyst.

Identification of rate determining steps concerning catalyst activation and catalytic turnover is key to optimize molecular photocatalysts. In this contribution, femtosecond transient absorption spectroscopy upon variation of temperature and ionic strength yields new insights into the light-driven reactivity of the benchmark molecular photocatalyst, RutpphzRhCp*.

Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain.

Tandem repeat (TR) size variation is implicated in ~50 neurological disorders, yet its impact on gene regulation in the human brain remains largely unknown. In the present study, we quantified the impact of TR size variation on brain gene regulation across distinct molecular phenotypes, based on 4,412 multi-omics samples from 1,597 donors, including 1,586 newly sequenced ones. We identified ~2.

Psychological and Social Factors Associated With Reporting Post-COVID Symptoms Among German Healthcare Workers: A Cross-Sectional Study.

Background: Health care workers (HCW) with post-COVID condition (PCC) are frequently reported to suffer from mental health impairment. Given HCW above-average risk for mental health, research is necessary and risk factors need to be assessed.

Aim: To compare mental health and health of German HCW with and without PCC and to identify associated psychological and social factors.

Acceptance, Safety, and Effect Sizes in Online Dialectical Behavior Therapy for Borderline Personality Disorder: Interventional Pilot Study.

Background: The potential of telehealth psychotherapy (ie, the online delivery of treatment via a video web-based platform) is gaining increased attention. However, there is skepticism about its acceptance, safety, and efficacy for patients with high emotional and behavioral dysregulation.

Objective: This study aims to provide initial effect size estimates of symptom change from pre- to post treatment, and the acceptance and safety of telehealth dialectical behavior therapy (DBT) for individuals diagnosed with borderline personality disorder (BPD).

Screening for anxiety in patients with cancer: Diagnostic accuracy of GAD-7 items considering lowered GAD-7 cut-offs.

Background: A standard questionnaire for generalized anxiety disorders is the GAD-7. Attempts to improve its screening capacity in oncological settings resulted in a discussion about lowering its cut-off. This study examines the diagnostic accuracy of the GAD-7 items depending on applied cut-offs and whether, similar to depressive symptoms, a distinction between somatic-emotional and cognitive items might be relevant.

Supraglottoplasty outcomes and peri-operative care in congenital laryngomalacia.

Objectives: This study aimed to identify factors predicting postoperative ICU admission, the need for orotracheal intubation (OTI), and the occurrence of supraglottic stenosis in children undergoing supraglottoplasty for laryngomalacia.

Methods: A retrospective analysis was conducted on 31 children (Dear Reviewer, we would have greatly preferred to include a larger sample size. However, as you know, this type of management is rare, and we deliberately selected a 7-year period to ensure a minimum of 30 children while avoiding significant differences in management guidelines over time.

[Coding of child abuse and neglect in hospitals in Germany: overview and classification of administrative data].

Background: Child maltreatment is a significant problem in Germany. Hospital data on child maltreatment serve as a crucial foundation for planning effective prevention measures. These data enable an assessment of the extent to which at-risk children and adolescents are identified, supported, and protected.

PET/CT-based target volume definition in involved-site radiotherapy for treatment of early-stage nodal follicular lymphoma.

Purpose: Recent advancements in imaging, particularly 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET/CT), have improved the detection of involved lymph nodes, thus influencing staging accuracy and potentially treatment outcomes. This study is a post hoc analysis of the GAZAI trial data to evaluate the impact of FDG-PET/CT versus computed tomography (CT) alone on radiation target volumes for involved-site radiotherapy (IS-RT) in early-stage follicular lymphoma (FL).

Methods: All patients in the GAZAI trial underwent pretherapeutic FDG-PET/CT examinations, which were subject to central quality control.

Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse.

Redox-Mediated Pyrene Electrolytes for Enhancing the Reversibility of Vertically Arranged Tin Electrodes in Seawater Batteries.

Seawater batteries (SWBs) have emerged as a next-generation battery technology that does not rely on lithium, a limited resource essential for lithium-ion batteries. Instead, SWBs utilize abundant sodium from seawater, offering a sustainable alternative to conventional battery technologies. Previous studies have demonstrated the feasibility of achieving high energy densities in SWB anodes using vertically aligned electrodes.

Type 1 diabetes incidence curves differ by age for girls and boys between 1996 and 2022: Results from the North Rhine-Westphalia Diabetes Registry, Germany.

The type 1 diabetes incidence was analyzed in 0- to 14-year-old children in North Rhine-Westphalia, Germany, from 1996 to 2022. The data revealed an overall increasing trend, with variations by age and sex. The incidence increased in boys across age groups but peaked in girls in the 5-9-year age group.

Preparatory Switches of Auditory Spatial and Non-Spatial Attention Among Simultaneous Voices.

Can one shift attention among voices at a cocktail party during a silent pause? Researchers have required participants to attend to one of two simultaneous voices - cued by its gender or location. Switching the target gender or location has resulted in a performance 'switch cost' - which was recently shown to reduce with preparation when a gender cue was presented in advance. The current study asks if preparation for a switch is also effective when a voice is selected by location.

A multimodal neural signature of face processing in autism within the fusiform gyrus.

Atypical face processing is commonly reported in autism. Its neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how variation in brain anatomy and function jointly impacts face processing and social functioning.

Regulation of Dendrite and Dendritic Spine Formation by TCF20.

Mutations in the Transcription Factor 20 (TCF20) have been identified in patients with autism spectrum disorders (ASDs), intellectual disabilities (IDs), and other neurological issues. Recently, a new syndrome called TCF20-associated neurodevelopmental disorders (TAND) has been described, with specific clinical features. While TCF20's role in the neurogenesis of mouse embryos has been reported, little is known about its molecular function in neurons.

Latest Developments in Targeted Biological Therapies in the Management of Chordoma and Chondrosarcoma.

Study Design: Systematic review.

Objectives: The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment.

Methods: A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours.

What is the Optimal Management of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate or Not to Operate?

Study Design: Systematic review.

Objective: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

Methods: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery.

A Low-Symmetry Copper Benzenehexathiol Coordination Polymer with In-Plane Electrical Anisotropy.

Electrically conductive coordination polymers (ECCPs), particularly those incorporating benzenehexathiol (BHT) ligands, are emerging as a distinctive class of electronic materials with tunable semiconducting and metallic properties. However, the exploration of novel ECCPs with low-symmetry structures and electrical anisotropy remains under development. Here, we report the on-water surface synthesis of a novel ECCP, namely CuBHT, which exhibits a low-symmetry structure and unique in-plane electrical anisotropy that differs from the well-known CuBHT phase.