Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery.

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing.

Management of nausea and vomiting induced by antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are an emerging class of anticancer therapy that combines the specificity and long circulation half-life of monoclonal antibodies with the cytotoxic potency of the payload connected through a chemical linker. The optimal management of toxicities is crucial for improving quality of life in patients undergoing ADCs and for avoiding improper dose reductions or discontinuations. This article focuses on the characteristics and management of nausea and vomiting (NV) induced by three ADCs: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd).

The influence of familiarity between the surgeon and their assistant on patient outcomes: a prospective observational cohort study.

Background: The inverse relationship between increased surgical team familiarity and reduced operative time is established, but its effect on patient outcomes remains uncertain.

Materials And Methods: A prospective cohort study including operations by attending surgeons between 1 November 2020 and 31 December 2021 across fourteen surgical departments from four French university hospitals. Surgical team familiarity was measured as the cumulative number of previous operations performed by the same dyad of attending and assisting surgeons.

A protein corona modulates the function of mineralization-competent matrix vesicles.

Mineralizing cells release a special class of extracellular vesicles known as matrix vesicles (MV), crucial for bone mineralization. Following their release, MV anchor to the extracellular matrix (ECM), where their highly specialized enzymatic machinery facilitates the formation of seed mineral within the MV's lumen, subsequently releasing it onto the ECM. However, how MV propagate mineral onto the collagenous ECM remains unclear.

Specific modulation of 28S_Um2402 rRNA 2'--ribose methylation as a novel epitranscriptomic marker of ZEB1-induced epithelial-mesenchymal transition in different mammary cell contexts.

The epithelial-mesenchymal transition (EMT) is a dynamic transdifferentiation of epithelial cells into mesenchymal cells. EMT programs exhibit great diversity, based primarily on the distinct impact of molecular activities of the EMT transcription factors. Using a panel of cancer cell lines and a series of 71 triple-negative primary breast tumors, we report that the EMT transcription factor ZEB1 modulates site-specific chemical modifications of ribosomal RNA (rRNA).

Self-assembly processes of 2D Au(I)-S(CH)COOH lamellae.

Solving the assembled structure of Au(I)-thiolate linear coordination polymers has been a challenging task as they generally lack good crystallinity. This has prevented the elucidation of their assembly processes at the molecular level. In this paper, selected area electron diffraction (SAED) patterns of two-dimensional (2D) Au(I)-S(CH)COOH (Au(I)-MPA) lamellae are obtained by applying cryogenic transmission electron microscopy.

SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes: Choriocarcinoma From Other Trophoblastic Lesions and Early Complete Hydatidiform Mole From Partial Mole and NonMolar Villi.

The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included.

Mixed Comparative Evaluation of a Training Program Dedicated to Cystic Fibrosis Reference Centers: Protocol for the Pilot Implementation of Shared Decision-Making in the Treatment of Diabetes in Adult Patients With Cystic Fibrosis.

Background: Diabetes affects half of the patients with cystic fibrosis who are aged 30 years and older. Diabetes progresses asymptomatically over a long period of time. Two treatment options are possible: start insulin as soon as cystic fibrosis diagnosis is made with the additional constraints of cystic fibrosis or wait while monitoring the patient's clinical condition and start insulin when diabetes symptoms develop and therefore later.

Methodologies and characteristics of studies investigating the cost of the palliative phase of cancer: a systematic review.

Purpose: Improvements in the treatment of advanced cancer have increased life expectancy but have also increased the costs to healthcare systems, patients and their families. A systematic review is needed to summarize research work on the cost of cancer. The primary objective was to describe the characteristics and methodology of studies investigating the cost of cancer during the palliative phase.

Catalytic H/D exchange of (hetero)arenes with early-late polyhydride heterobimetallic complexes: impact of transition metal pairs.

Metal-catalyzed hydrogen isotope exchange (HIE) has become a valuable method for incorporating deuterium and tritium into organic molecules, with applications in a wide range of scientific fields. This study explores the role of transition metal cooperativity in enhancing catalytic hydrogen/deuterium (H/D) exchange using early-late heterobimetallic polyhydride (ELHB) complexes. A series of four ELHB complexes, of general formula [M(CHBu)(H)M'Cp*], combining early transition metals (M = Hf, Ta) with late metals (M' = Ir, Os), were synthesized and evaluated for their catalytic activity in HIE of (hetero)arenes.

Reshaping computational neuropsychiatry beyond synaptopathy.

Computational neuropsychiatry is a leading discipline to explain psychopathology in terms of neuronal message passing, distributed processing, and belief propagation in neuronal networks. Active Inference (AI) has been one of the ways of representing this dysfunctional signal processing. It involves that all neuronal processing and action selection can be explained by maximizing Bayesian model evidence, or minimizing variational free energy.

Prevention of refeeding syndrome: Evaluation of an enteral refeeding protocol for severely undernourished children.

Objectives: Refeeding syndrome (RS) defines the deleterious clinical and metabolic changes occurring during nutritional support of severely malnourished patients. Pediatric guidelines to prevent and treat RS are scarce and highly variable. This study aimed to evaluate the effectiveness and safety of an enteral refeeding protocol in severely undernourished hospitalized children with anorexia nervosa (AN) or organic diseases (OD).

Distinct phenotypes of patients and healthcare resource utilization after hospitalization for COVID-19: an observational study.

Background: Little is known about postdischarge healthcare resource use (HCU) among patients hospitalized for coronavirus disease 2019 (COVID-19). The objective was to identify distinct profiles of patients based on postdischarge cares.

Methods: This was a retrospective cohort study using the French National Health System claims database.

Exposure to Rifampicin and its Metabolite 25-Deacetylrifampicin Rapidly Decreases During Tuberculosis Therapy.

Background And Objective: Limited information is available on the pharmacokinetics of rifampicin (RIF) along with that of its active metabolite, 25-deacetylrifampicin (25-dRIF). This study aimed to analyse the pharmacokinetic data of RIF and 25-dRIF collected in adult patients treated for tuberculosis.

Methods: In adult patients receiving 10 mg/kg of RIF as part of a standard regimen for drug-susceptible pulmonary tuberculosis enrolled in the Opti-4TB study, plasma RIF and 25-dRIF concentrations were measured at various occasions.

Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection.

Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain.

IFN-γ licenses normal and pathogenic ALPK1/TIFA pathway in human monocytes.

Alpha-kinase 1 (ALPK1) is an immune receptor sensing the bacterial nucleotide sugar ADP-heptose. ALPK1 phosphorylates TIFA leading to its oligomerization and downstream NF-κB activation. Specific mutations in are associated with an autoinflammatory syndrome termed ROSAH and with spiradenoma (skin cancers with sweat gland differentiation).

What is the origin of the normal ranges of blood cell counts? An evolutionary perspective.

Background: The normal values of the complete blood count are part of the foundational medical knowledge that is seldom questioned due to their well-established nature. These normal values are critical for optimal physiological function while minimizing the harmful consequences of an excessive number of blood cells. Thus, they represent an evolutionary trade-off likely shaped by natural selection if they significantly influence individual fitness and exhibit heritability.

[Cancer and nutritional management of overweight and obesity: Practice evaluation].

Context: The aim of this practice evaluation was to assess weight trends during and after a nutritional intervention in cancer patients and survivors.

Methods: This retrospective study was conducted between January 2014 and October 2020 in adults with different cancer types managed at the Léon-Bérard Cancer Center, undergoing treatment or during post-treatment follow-up, with a BMI≥25kg/m and who had at least 3 consultations with a nutrition physician. Nutritional management focused on behavioral, metabolic and nutritional aspects.

Clinical significance criteria in the ICSD and DSM sleep disorder classifications: a content overlap analysis using the Jaccard index.

Study Objectives: Both the (ICSD) and the sleep-wake disorders section of the (DSM) emphasize the importance of clinical judgment in distinguishing the normal from the pathological in sleep medicine. The fourth edition of the DSM (DSM-IV, 1994) introduced the clinical significance criterion (CSC) to standardize this judgment and enhance diagnostic reliability.

Methods: This review conducts a theoretical and historical content analysis of CSC presence, frequency, and formulation in the diagnostic criteria of sleep disorders.

Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections.

Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis.

Synthesis of Resorcinol and Chlorophenol from Irradiation of 1,3-Dichlorobenzene in a Water Ice Environment by Low-Energy Electrons.

Dichlorobenzene is beneficial to industries, however, the release of this compound into the environment causes significant damage to ecosystems and human health, as it exhibits resistance to biodegradation. Here, we show that chlorophenol and resorcinol are synthesized from 1,3-dichlorobenzene in a water ice environment (1) directly on a poly-crystalline gold surface and (2) after low-energy (<12 eV) electron irradiation of admixture films. For the latter, at energies below 5.