Philanthropic drug development: understanding its importance, mechanisms, and future prospects.

Philanthropic drug development (PDD) addresses gaps in traditional pharmaceutical innovation, particularly for rare and underserved diseases. Cost and timeline challenges discourage new investments, especially in niche therapeutic areas. Patient organizations (POs) are uniquely positioned to help to reduce development challenges by providing expertise, supporting early research, fostering collaborations, and driving patient-centered clinical trials.

Towards a common terminology of ventilation during cardiopulmonary resuscitation.

Manual and mechanical ventilation during cardiopulmonary resuscitation are critical yet poorly understood components of resuscitation care. In recent years, intra-arrest ventilation has been the subject of a growing number of laboratory and clinical investigations. Essential components to accurately interpret or reproduce original investigations are the exact measurement and transparent reporting of key ventilation parameters, such as volumes and airway pressures obtained during ongoing cardiopulmonary resuscitation.

A health economic evaluation of the multinational, randomized controlled CONVINCE trial - cost-utility of high-dose online hemodiafiltration compared to high-flux hemodialysis.

High-flux hemodialysis (HD) and high-dose hemodiafiltration (HDF) are established treatments for patients with kidney failure. Since HDF has been associated with improved survival rates compared to HD, we evaluated the cost-effectiveness of HDF compared to HD. Cost-utility analyses were performed from a societal perspective alongside the multinational randomized controlled CONVINCE trial.

Design of pH-responsive and amphiphilic pullulan-based biological macromolecule for gene delivery.

Nanomedicine, particularly gene delivery, holds immense potential and offers promising therapeutic options. Non-viral systems gained attention due to their binding capacity, stability and scalability. Among these, natural polysaccharides, such as pullulan, are advantageous in terms of sustainability, biocompatibility and potential degradability.

Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials.

Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remains limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT).

Patients And Methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT.

Textbook Outcomes Among Patients Undergoing CRS+HIPEC for Peritoneal Surface Malignancies in an Eastern European Population.

Background: The preferred treatment option for patients with limited peritoneal metastasis (PM) is cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC).While the textbook outcome (TO) concept has been applied to other complex surgeries, its prevalence, determinants, and impact in patients with PM remain unclear. This study sought to identify factors influencing TO among individuals with PM undergoing CRS+HIPEC in an Eastern European population.

In vitro culture of the parasitic stage larvae of hematophagous parasitic nematode Haemonchus contortus.

Current research on common parasitic nematodes is limited because their infective stages cannot be propagated in vitro. Here, we report a culture system for developing L4s of Haemonchus contortus, a blood-feeding nematode of ruminants. Our results demonstrated that a proportionate mixture of NCTC-109 to Luria-Bertini (1:2) media promoted the formation of early L4s and then into late L4s upon inclusion of 12.

Characterization of lipophilicity and blood partitioning of pyrrolizidine alkaloids and their N-oxides in vitro and in silico for toxicokinetic modeling.

Lipophilicity and blood partitioning are important determinants for predicting toxicokinetics using physiologically-based toxicokinetic (PBTK) modeling. In this study, the logarithm of the -octanol:water partition coefficient (log) and the blood-to-plasma concentration ratio ( ) were for the first time experimentally determined for the pyrrolizidine alkaloids (PAs) intermedine, lasiocarpine, monocrotaline, retrorsine and their -oxides (PANOs). Validated assays for log (miniaturized shake-flask method) and (LC-MS/MS-based depletion assay) determination were compared to an ensemble of models.

Nickel-Catalyzed Three-Component Carboamination/Cyclization of Alkynes To Access 2,3-Disubstituted Quinolines.

Presented herein is a nickel-catalyzed chemo- and regioselective three-component tandem carboamination and cyclization of terminal alkynes with organoboronic acids and anthranils for facile and modular access to 2,3-substituted quinolines. In this process, anthranil has dual roles: serving as an electrophilic aminating reagent and a redox buffer to suppress the generation of an off-cycle Ni(0) complex. Moreover, the anionic acetylacetonate (acac) ligand was found to be vital to ensure a productive Ni(I)-Ni(III)-Ni(I) catalytic cycle.

Cardiac Radiomics Analyses in Times of Photon-counting Computed Tomography for Personalized Risk Stratification in the Present and in the Future.

The need for effective early detection and optimal therapy monitoring of cardiovascular diseases as the leading cause of death has led to an adaptation of the guidelines with a focus on cardiac computed tomography (CCTA) in patients with a low to intermediate risk of coronary heart disease (CHD). In particular, the introduction of photon-counting computed tomography (PCCT) in CT diagnostics promises significant advances through higher temporal and spatial resolution, and also enables advanced texture analysis, known as radiomics analysis. Originally developed in oncological imaging, radiomics analysis is increasingly being used in cardiac imaging and research.

Standardized Reporting of HCC with LI-RADS and mRECIST: Update on the Situation in Germany.

Online survey about the current status of CT protocols in hepatocellular carcinoma (HCC) in the year 2023/2024. Moreover, the usage of structured reporting using LI-RADS and mRECIST was surveyed and the results were compared with a survey from 2020.Radiologists working in outpatient or inpatient care in Germany were invited.

Evaluation of Tele-Education in Malawi for Detection of Macular Features Using Optical Coherence Tomography.

Purpose: The study aimed to assess the reliability of tele-education in training a Malawian ophthalmology resident to interpret optical coherence tomography (OCT) images of patients with macular conditions.

Methods: This was a retrospective analysis of 1000 macula-centered OCT image series from 1000 eyes of 1000 consecutive patients from Malawi, which involved initial interpretation by a German retina specialist (observer 1) (T). Observer 1 then trained a Malawian resident (observer 2) via email, and observer 2 independently interpreted images at T, followed by face-to-face training in Malawi and reinterpretation at T and T (3-month intervals).

Evaluating genome-wide and targeted forensic sequencing approaches to kinship determination.

Kinship determination is a valuable tool in forensic genetics, with applications including familial searching, disaster victim identification, and investigative genetic genealogy. Conventional typing of small numbers of autosomal short tandem repeats (STRs) confidently identifies only first-degree relatives. Massively parallel sequencing (MPS) can access more STRs and resolve alleles identical by length but differing in sequence (isoalleles), which may increase the power of kinship estimation, particularly when combined with additional sequenced single nucleotide polymorphism (SNP) loci, as in the ForenSeq DNA Signature Prep kit.

The ReAct project: Analysis of data from 23 different laboratories to characterise DNA recovery given two sets of activity level propositions.

The ReAct (Recovery, Activity) project is an ENFSI (European Network of Forensic Science Institutes) supported initiative comprising a large consortium of laboratories. Here, the results from more than 23 laboratories are presented. The primary purpose was to design experiments simulating typical casework circumstances; collect data and to implement Bayesian networks to assess the value (i.

Imprint of incomplete combustion processes on the water column of the anthropogenic-pressured Baltic Sea.

This study evaluates the distribution and sources of thermogenic organic matter in the Baltic Sea water column, focusing on polycyclic aromatic hydrocarbons (PAH), dissolved black carbon (DBC), and the imprint of thermogenic organic matter on the dissolved organic matter (DOM) pool. The spatial patterns and complex interactions between land-based and atmospheric sources were assessed from Kiel Bay to Pomeranian Bight within the water column with the combined targeted and untargeted approaches. The findings emphasize the significant influence of terrestrial inputs from the Oder River and autochthonous production composing DOM.

Functional movement disorders in dopa-responsive dystonia.

Background: Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden.

Objectives: Investigating frequency and characteristics of functional movement disorders in GCH1-positive dopa-responsive dystonia patients.

A cross-country network analysis of disease infodemics: Looking through the lens of the COVID-19 pandemic.

Infodemics surrounding pandemics and epidemics have persisted for centuries and continue to impede efforts to promote high vaccination coverage. We explored the complex interplay between COVID-19 vaccination attitudes and COVID-19-related infodemics across Germany, Ghana, India, and New Zealand using the novel network analysis. We conducted an online cross-sectional survey and recruited 1822 participants from the general populations of India (n = 411), New Zealand (n = 413), Ghana (n = 523), and Germany (n = 413) to complete COVID-19 infodemic measures and demographics questions.

Comparisons of integrated slice-specific dynamic shimming EPI and single-shot EPI diffusion-weighted imaging of the liver.

Purpose: To compare the quality of DWI images, signal loss of left hepatic lobe and diagnostic performance of apparent diffusion coefficient (ADC) values between SS-EPI and iShim-EPI in liver lesions.

Methods: Totally 142 patients were involved, images using SS-EPI and the prototype iShim-EPI were acquired before injection of gadoxetic acid-enhanced liver MRI.Image quality of demarcation of liver capsule, resolution, lesion distortion, artifacts, lesion confidence score, and signal loss in left hepatic lobe was assessed by two radiologists.

Reduced monocytic IL10 expression in PD1 inhibitor-treated patients is a harbinger of severe immune-related adverse events.

Background: Despite remarkable clinical efficacy, little is known about the system-wide immunological alterations provoked by PD1 blockade. Dynamics of quantitative immune composition and functional repertoire during PD1 blockade could delineate cohort-specific patterns of treatment response and therapy-induced toxicity.

Methods: We longitudinally assessed therapy-induced effects on the immune system in fresh whole blood using flow cytometry-based cell quantifications, accompanied by analyses of effector properties of all major immune populations upon cell-type specific stimulations.

Sex differences in survival from melanoma of the skin: The role of age, anatomic location and stage at diagnosis: A CONCORD-3 study in 59 countries.

Background: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Studies showed a survival advantage in women, but the reasons are not completely understood. We aim to estimate trends in age-standardised 5-year net survival by sex and to examine the role of age, anatomic location and stage on the survival advantage for women worldwide.

Simplified Outcome Prediction in Patients Undergoing Transcatheter Tricuspid Valve Intervention by Survival Tree-Based Modelling.

Background: Patients with severe tricuspid regurgitation (TR) typically present with heterogeneity in the extent of cardiac dysfunction and extra-cardiac comorbidities, which play a decisive role for survival after transcatheter tricuspid valve intervention (TTVI).

Objectives: This aim of this study was to create a survival tree-based model to determine the cardiac and extra-cardiac features associated with 2-year survival after TTVI.

Methods: The study included 918 patients (derivation set, n = 631; validation set, n = 287) undergoing TTVI for severe TR.