TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.

Intratumoural expression of dihydropyrimidine dehydrogenase is an independent prognostic factor in resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydrogenase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019.

The Development of Algorithms for Individual Ranges of Body Temperature and Oxygen Saturation in Healthy and Frail Individuals.

Background/objectives: Individual habitual conditions entail a risk during the interpretation of vital parameters. We developed algorithms for calculating, validating, and interpreting individual normal ranges of body temperature and oxygen saturation.

Methods: In total, 70 healthy individuals aged 27 to 80 and 52 frail individuals aged 60 to 100 were included.

A DNA methylation signature identified in the buccal mucosa reflecting active tuberculosis is changing during tuberculosis treatment.

Tuberculosis (TB) poses a significant global health threat, with high mortality rates if left untreated. Current sputum-based TB treatment monitoring methods face numerous challenges, particularly in relation to sample collection and analysis. This pilot study explores the potential of TB status assessment using DNA methylation (DNAm) signatures, which are gaining recognition as diagnostic and predictive tools for various diseases.

Evaluating binaural hearing capabilities in individuals with sensorineural hearing loss through bilateral bone conduction stimulation.

This study investigated the impact of bilateral bone conduction (BC) stimulation and sensorineural hearing loss on spatial release from masking, binaural intelligibility level difference, and lateralization. The study involved two groups of adults with mild to moderate sensorineural hearing loss: one group of 21 participants with symmetric hearing loss and another group of nine participants with asymmetric hearing loss. All tests were conducted through BC and air conduction (AC) headsets with non-individualized virtual positions of the sound sources and linear amplification based on individual hearing thresholds.

Finite element analysis on the human and guinea pig cochlear vibration patterns under bone conduction stimulations.

To compare the vibrational patterns of human and guinea pig cochleae accurately, we developed and validated a novel finite element model of the guinea pig, leveraging it to analyze vibrational patterns in the cochlea. This approach is mirrored in our examination of the human cochlear model, providing granular insights into the nuances of human bone conduction hearing. The comparative analysis reveals that the guinea pig cochlea mirrors human cochlear vibrational patterns, thus serving as an efficient proxy for exploring human cochlear function.

A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers.

Background: Most women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown.

Challenges and Facilitation Approaches for the Participatory Design of AI-Based Clinical Decision Support Systems: Protocol for a Scoping Review.

Background: In the last few years, there has been an increasing interest in the development of artificial intelligence (AI)-based clinical decision support systems (CDSS). However, there are barriers to the successful implementation of such systems in practice, including the lack of acceptance of these systems. Participatory approaches aim to involve future users in designing applications such as CDSS to be more acceptable, feasible, and fundamentally more relevant for practice.

Parents in the Driver's Seat-Experiences of Parent-Delivered Baby-mCIMT Coached Remotely.

: Recent guidelines on early intervention in children at high risk of cerebral palsy (CP) recommend parental involvement and family-centered home-based interventions with parents as primary trainers. Therapist coaching by home visitation is resource demanding, and telerehabilitation is a viable option for remote intervention and coaching. This study aims to describe parents' experiences of engaging in Baby-mCIMT coached remotely.

Sensory symptoms associated with autistic traits and anxiety levels in children aged 6-11 years.

Background: Autism spectrum conditions (ASC) and quantitative autistic traits (QATs) are associated with sensory symptoms, which may contribute to anxiety and adversely affect social and cognitive development. Although sensory symptoms can occur across all senses, the relative roles of specific sensory modalities as contributors to the autistic phenotype and to anxiety are not well understood. The objective of this study was to examine which sensory symptoms were most predictive of high anxiety.

Patient Weight and Chemoprophylaxis in Abdominoplasty: Does It Result in More Bleeding Events?

Background: Bariatric surgery has gained popularity in recent decades as an effective treatment for obesity. Abdominoplasty is one of the most often performed aesthetic procedures all over the world. In post-bariatric patients undergoing abdominoplasty, the diameter size and number of the abdominal wall perforators increase proportionally with increased body weight.

Vitrification of pig embryos dysregulates the microRNA transcriptome profile.

This study examined how the vitrification of pig blastocysts using either the superfine open pulled straw (SOPS) or Cryotop method affects the expression profile of embryonic microRNA (miRNA) transcriptomes, as well as its relation to changes in the expression of target genes (TGs). Surgically collected pig blastocysts were vitrified using either the SOPS method (n = 60; 4-6 embryos/device) or the Cryotop system (n = 60; 20 embryos/device). Embryos were cultured in vitro for 24 h after warming.

Social transmission of inflammation in mice.

The ability to detect and respond to sickness in others promotes survival. Here we show that mouse dams respond to immune challenged pups by mirroring their inflammatory response. Dams with pups subjected to immune challenge displayed a marked induction of inflammatory mediators in both the brain and the periphery, accompanied by an increase in maternal behaviors and corticosterone levels.

Slow touch and ultrafast pain fibres: Revisiting peripheral nerve classification.

One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification.

Automated region growing-based segmentation for trabecular bone structure in fresh-frozen human wrist specimens.

Bone strength depends on both mineral content and bone structure. Measurements of bone microstructure on specimens can be performed by micro-CT. In vivo measurements are reliably performed by high-resolution peripheral computed tomography (HR-pQCT) using dedicated software.

Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.

Voltage-gated potassium (Kv) channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels share similar structures but have opposite gating polarity. Kv channels have a strong coupling (>10) between the voltage sensor (S4) and the activation gate: when S4s are activated, the gate is open to >80% but, when S4s are deactivated, the gate is open <10 of the time. Using noise analysis, we show that the coupling between S4 and the gate is <200 in HCN channels.

Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young-FGF-21 Highly Associated with Overt Disease.

Any difference in biomarkers between genotype-positive individuals with overt hypertrophic cardiomyopathy (HCM), and genotype-positive but phenotype-negative individuals (G+P-) in HCM-associated pathways might shed light on pathophysiological mechanisms. We studied this in young HCM patients. 29 HCM patients, 17 G+P--individuals, and age- and sex-matched controls were prospectively included.