Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer.

Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids.

Critical insights into data curation and label noise for accurate prediction of aerobic biodegradability of organic chemicals.

The focus of this work is to enhance state-of-the-art Machine Learning (ML) models that can predict the aerobic biodegradability of organic chemicals through a data-centric approach. To do that, an already existing dataset that was previously used to train ML models was analyzed for mismatching chemical identifiers and data leakage between test and training set and the detected errors were corrected. Chemicals with high variance between study results were removed and an XGBoost was trained on the dataset.

A laboratory pilot study on voids in flowable bulk-fill composite restorations in bovine Class-II and endodontic access cavities after sonic vibration.

This pilot study investigated whether sonic-powered application of a bulk-fill resin-based composite (RBC) in Class-II or endodontic access cavities reduces void formation. The crowns and roots of 60 bovine teeth with Class-II cavities (C) and endodontic access cavities (E) respectively, were assigned to ten groups (C1-C5, E1-E5). Cavities were filled with RBC (SDR flow + , one increment) using different application techniques: no adaptation (C1 + E1), spreading of RBC on the cavity surfaces with a dental explorer tip (C2 + E2), low (C3 + E3) or high frequency (C4 + E4) direct activation by inserting a sonic-powered tip into RBC and high frequency indirect activation with an ultrasonic insertion tip (C5 + E5).

An adverse tumor-protective effect of IDO1 inhibition.

By restoring tryptophan, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors aim to reactivate anti-tumor T cells. However, a phase III trial assessing their clinical benefit failed, prompting us to revisit the role of IDO1 in tumor cells under T cell attack. We show here that IDO1 inhibition leads to an adverse protection of melanoma cells to T cell-derived interferon-gamma (IFNγ).

Extended regimen of a levonorgestrel/ethinyl estradiol transdermal delivery system: Predicted serum hormone levels using a population pharmacokinetic model.

Objective: This study employed population pharmacokinetic (popPK) models to predict levonorgestrel (LNG) and ethinyl estradiol (EE) exposure after dosing with the transdermal contraceptive TWIRLA® (LNG/EE TDS) as a 12-week extended regimen in a healthy female population.

Methods: PopPK models were developed using data from a previously published phase 1, open-label, randomized clinical trial, ATI-CL14 (NCT01243580), in 36 healthy individuals. Models used cycle 2 data from 18 individuals who received the LNG/EE TDS, delivering LNG 120 μg/day and EE 30 μg/day, followed by a 1-week TDS-free period.

Alternative cleavage and polyadenylation generates downstream uncapped RNA isoforms with translation potential.

The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates mRNA isoforms that expand the diversity and complexity of the transcriptome. Here, we uncovered thousands of previously undescribed 5' uncapped and polyadenylated transcripts (5' UPTs). We show that these transcripts resist exonucleases due to a highly structured RNA and N6-methyladenosine modification at their 5' termini.

Effect of brushing force on the abrasive dentin wear using slurries with different abrasivity values.

Objective: The aim of this study was to investigate the resulting abrasive dentin wear using abrasive slurries with different RDA values and applying increasing brushing forces.

Methods: Forty-five bovine incisors were randomly allocated in three groups (A, B, C, n = 15). One hundred and eighty dentin samples were prepared from these incisors and allocated to twelve groups (A1-A4, B1-B4, C1-C4; n = 15).

Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers.

Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12-15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options.

Suppression of heparan sulfation re-sensitizes YAP1-driven melanoma to MAPK pathway inhibitors.

Accumulating evidence identifies non-genetic mechanisms substantially contributing to drug resistance in cancer patients. Preclinical and clinical data implicate the transcriptional co-activators YAP1 and its paralog TAZ in resistance to multiple targeted therapies, highlighting the strong need for therapeutic strategies overcoming YAP1/TAZ-mediated resistance across tumor entities. Here, we show particularly high YAP1/TAZ activity in MITF/AXL melanomas characterized by resistance to MAPK pathway inhibition and broad receptor tyrosine kinase activity.

Effect of tapered-end and round-end bristles on the abrasive dentine wear applying increasing brushing forces.

Objective: To investigate the effect of toothbrush bristles end configuration on the abrasive dentine wear at different brushing forces.

Material And Methods: One hundred and sixty bovine dentine samples were randomized into eight groups ( = 20). Groups (1 to 4) were brushed with tapered-end bristles at 1-, 2-, 3-, and 4-N brushing forces, respectively.

Effect of the toothbrush tuft arrangement and bristle stiffness on the abrasive dentin wear.

The geometrical properties of toothbrushes play a role in developing abrasive tooth wear and non-carious cervical lesions. This study investigated the interplay between the toothbrush tuft arrangement (crossed vs. parallel) and bristle stiffness (soft vs.

OralDisk: A Chair-Side Compatible Molecular Platform Using Whole Saliva for Monitoring Oral Health at the Dental Practice.

Periodontitis and dental caries are two major bacterially induced, non-communicable diseases that cause the deterioration of oral health, with implications in patients' general health. Early, precise diagnosis and personalized monitoring are essential for the efficient prevention and management of these diseases. Here, we present a disk-shaped microfluidic platform (OralDisk) compatible with chair-side use that enables analysis of non-invasively collected whole saliva samples and molecular-based detection of ten bacteria: seven periodontitis-associated (, , , , , , ) and three caries-associated (oral , , ).

Effect of Caries Infiltrant on Margin Integrity of Composite Fillings Placed Adjacent to Demineralised Primary Enamel.

Purpose: To investigate the influence of pretreating demineralised enamel with an infiltrant on the margin integrity of Class V like composite restorations on primary teeth bonded with different adhesives.

Materials And Methods: Forty specimens from primary molars were demineralised and circular class-V-like cavities were prepared. The cavities were treated with a universal adhesive (Scotchbond Universal Adhesive, 3M Oral Care), applied either in self-etch (SE) or etch-and-rinse mode (ER) mode.

Enamel Softening Can Be Reduced by Rinsing with a Fluoride Mouthwash Before Dental Erosion but Not with a Calcium Solution.

Purpose: This in-situ-study investigated if rinsing the oral cavity with a calcium containing solution or a fluoride containing mouthwash immediately before an erosive attack leads to reduced enamel softening.

Materials And Methods: Bovine enamel samples (n = 240) with measured baseline surface microhardness (KHN) were assigned to five series (S1-5). Twelve participants carried out each series as follows: Four enamel samples of the associated test series were placed in an intraoral appliance and carried in each participants' mouth.

Green Tea Extract Reduces the Erosive Dentine Wear Caused by Energy Drinks In Vitro.

Purpose: To investigate the effect of energy drinks supplementation with green tea extract on the erosive dentine wear.

Materials And Methods: Six groups of bovine dentine samples (n = 15) were subjected to four cycles erosive attacks (10 min, 25 °C) and remineralisation (artificial saliva, 60 min, 37°C) using the following formulas: tap water; green tea extract; Red Bull; Red Bull supplemented with green tea extract; Red Bull Light; Red Bull Light supplemented with green tea extract. The erosive dentine wear - ie, the irreversible dentine loss - was measured using a stylus profilometer (µm, accuracy = 40 nm).

Erosive tooth wear among athletes.

The following article deals with various considerations concerning the frequently observed occurrence of dental erosion in athletes. It summarizes the basics of erosive tooth wear development as well as special etiologic factors for groups of athletes with increased prevalence of dental erosion and concludes with preventive advice. (Originally published (in German) in Quintessenz Zahnmed 2021;72:1008-1017).

Hydrothermal Degradation of Amino Acids.

Within the past years, hydrothermal processes have gathered much attention as promising conversion technologies for especially wet biomass. Amino acids are an integral component of biomass, zoo biomass in particular. However, what happens to them during hydrothermal treatment? Reviewing the available literature going back to the mid of the 20th century revealed an astonishing, but still fragmentary view.

Effect of toothbrush bristle stiffness and toothbrushing force on the abrasive dentine wear.

Objective: To investigate the influence of toothbrush bristle stiffness and applied brushing force on the resulting abrasive dentine wear in vitro.

Methods: One hundred sixty bovine dentine samples were randomly allocated in eight groups (n = 20). Groups one to four were brushed with a soft-bristle toothbrush with soft bristles applying 1, 2, 3 and 4 N brushing force, respectively.

Effect of a sonic toothbrush on the abrasive dentine wear using toothpastes with different abrasivity values.

Objective: This in vitro study aimed to investigate the effect of a sonic toothbrush on the resulting abrasive dentine wear using toothpastes with different abrasivities compared to the use of a manual toothbrush.

Methods: Ninety-six bovine dentine samples were divided into six groups and subjected to a brushing sequence (sonic: 20 min, 0.9 N, 10 strokes/min; manual: 20 min, 1.

Effect of dentin pretreatment on the resulting abrasive dentin wear.

Background: This study aims to investigate the influence of different dentin pretreatment procedures on the resulting abrasive dentin wear.

Methods: Two groups (A, B) of 60 dentin samples each were prepared. Group A was brushed with an abrasive slurry (RDA = 85) and group B with a different abrasive slurry (RDA = 174).

Potential of different fluoride gels to prevent erosive tooth wear caused by gastroesophageal reflux.

Background: This in-vitro-study aimed to evaluate the potential of different fluoride gels to prevent gastroesophageal reflux induced erosive tooth wear.

Methods: Surface baseline profiles of a total of 50 bovine enamel specimens [randomly assigned to five groups (G1-5)] were recorded. All specimens were positioned in a custom made artificial oral cavity and perfused with artificial saliva (0.