How to Design an Inhaled Drug: CHF-6523.

Inhalation provides an opportunity to target drugs to the lung, potentially improving efficacy and safety margins for the treatment of respiratory conditions. The discovery of inhaled medicines is a specialized endeavor and has different challenges to medicinal chemistry for oral drugs. The appearance of a successful campaign delivering an inhaled PI3Kδ inhibitor is therefore an opportunity to highlight how a team can address the challenges involved in the identification of such a compound.

Computational Characterization of the Interaction of CARD Domains in the Apoptosome.

The apoptosome, a critical protein complex in apoptosis regulation, relies on intricate interactions between its components, particularly the proteins containing the Caspase Activation and Recruitment Domain (CARD). This work presents a thorough computational analysis of the stability and specificity of CARD-CARD interactions within the apoptosome. Departing from available crystal structures, we identify important residues for the interaction between the CARD domains of Apaf-1 and Caspase-9.

Infectious disease hospitalization after receipt of human papillomavirus vaccine: a nationwide register-based cohort study among Danish, Finnish, Norwegian, and Swedish girls.

It has been suggested that non-live vaccines may increase susceptibility to non-targeted infections and that such deleterious non-specific effects are more pronounced in girls. We investigated whether receipt of non-live vaccine against human papillomavirus (HPV) was associated with increased risk of infectious disease hospitalization. A nationwide cohort study based on detailed individual-level data from national registries was performed in Denmark, Finland, Norway, and Sweden.

Cytotoxicity and Oxidative Stress Induced by Technology-Critical Elements Traditional Metal Contaminants: An Bioassay Study.

Technology-critical elements (TCEs), essential in emerging technologies, are increasingly finding their way into our environment, raising concerns about their sparsely studied behavior and toxicity. To contribute insights into the toxicological aspects, we employed bioassays to investigate the possible cytotoxic effects in four representative cell lines (AR-EcoScreen GR-KO-M1, DR-EcoScreen, MCF7AREc32, VM7Luc4E2) and the potential to induce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway for a number of these elements. Nine TCEs, three rare-earth elements (REEs: Gd, Nd, Yb) and six less-studied TCEs (LSTCEs: Ga, Ge, In, Ta, Te, Tl), were selected for this study, along with three well-studied traditional metal contaminants (TMCs: As, Cd, Pb) for comparison.

No Biased Attention to Threat, Incompleteness, and Disgust in Youth with OCD and Anxiety Disorders.

Obsessive-compulsive disorder (OCD) and anxiety disorders are early-onset mental disorders characterized by selective attention and strong emotional reactions. Attentional bias has been proposed to play a role in the development, onset, and maintenance of the disorders, but few studies have included youth with mental disorders, and no study has included more than one clinical group, making it unclear whether biased attention is disorder-specific or transdiagnostic in nature. In the present study, 65 youths with OCD (M = 13.

NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.

Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action.

Immigrant Background and Rape Conviction: A 21-Year Follow-Up Study in Sweden.

While extensive research exists on the severe consequences among rape victims, little is known about specific predictors in relation to rape convictions among immigrants to Europe. This study from Sweden (having one of Europe's highest per capita rates of rape) investigates individuals convicted of rape, aggravated rape, attempted rape, or attempted aggravated rape, collectively termed as rape+, against women 18 years or older, from 2000 to 2020. In this case-control study, we analyzed data from Swedish population-based registers.

Atypical development of sequential manual motor planning and visuomotor integration in children with autism at early school-age: A longitudinal kinematic study.

Many children with autism struggle with movement difficulties, yet the causes of these difficulties remain unclear. One possible explanation is atypical motor planning and integration of visual and motoric information. Before performing a goal-directed movement, the brain creates a prediction of the movement based on visual and sensory information and previous experience, forming a "blueprint" of the motor steps needed to achieve the goal.

Solvatochromic charge model of isonitrile probes for investigating hydrogen-bond dynamics with 2DIR spectroscopy.

Isonitrile-derivatized amino acids are emerging as highly effective infrared (IR) probes for investigating the structures and dynamics of hydrogen (H)-bonds. These probes enable the quantification of chemical exchange processes in solute-solvent complexes via two-dimensional IR spectroscopy and hold significant promise for site-specific dynamic studies within proteins. Despite their potential, theoretical models that elucidate the solvatochromism of isonitriles remain underdeveloped.

Design and characterization of novel graphene-enhanced vapor chambers for lightweight and high-performance electronics cooling.

The trend towards miniaturization of electronics and increasing transistor density in semiconductors requires more efficient cooling solutions. Vapor chambers are well established passive cooling devices that are used in a wide variety of electronics. Commercial vapor chambers are often made of high-density metals such as copper which can be a downside in lightweight applications such as laptops, smartphones, and tablets.

Clot signature in patients with large vessel occlusion stroke and concomitant active cancer.

Background And Purpose: Patients with active cancer face an increased risk of ischemic stroke. Also, stroke may be an initial indicator of cancer. In patients with large vessel occlusion (LVO) stroke treated with thrombectomy, analysis of the clot composition may contribute new insights into the pathological connections between these two conditions.

Identification of cellular signatures associated with chinese hamster ovary cell adaptation for secretion of antibodies.

The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell.

Healthcare Professionals' Ratings and Views of Person-Centred Care in the Context of Allogeneic Hematopoietic Stem Cell Transplantation.

Introduction: Allogeneic stem cell transplantation (allo-HCT) involves a long trajectory with high risk of complications. In person-centred care (PCC), patients' needs, resources and the care relationship are central to the care process. Healthcare professionals' (HCPs) ratings of PCC have not previously been investigated in this context.

Achievements, priorities and strategies in pediatric nephrology in Europe: need for unifying approaches or acceptance of differences?

Background: There is a lack of information on the current healthcare systems for children with kidney diseases across Europe. The aim of this study was to explore the different national approaches to the organization and delivery of pediatric nephrology services within Europe.

Methods: In 2020, the European society for Paediatric Nephrology (ESPN) conducted a cross-sectional survey to identify the existing pediatric nephrology healthcare systems in 48 European countries covering a population of more than 200 million children.

Polysaccharide-based biomaterials for regenerative therapy in intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration represents a significant cause of chronic back pain and disability, with a substantial impact on the quality of life. Conventional therapeutic modalities frequently address the symptoms rather than the underlying etiology, underscoring the necessity for regenerative therapies that restore disc function. Polysaccharide-based materials, such as hyaluronic acid, alginate, chitosan, and chondroitin sulfate, have emerged as promising candidates for intervertebral disc degeneration (IVDD) therapy due to their biocompatibility, biodegradability, and ability to mimic the native extracellular matrix (ECM) of the nucleus pulposus (NP).

Association between cardiometabolic diseases and the risk and progression of motor neuron diseases in Sweden: a population-based case-control study.

Background: The evidence on the link between cardiometabolic diseases (CMDs) and motor neuron diseases (MNDs) remains inconsistent. We aimed to determine whether there is an association of CMDs, namely, any cardiovascular disease, cardiac arrhythmia, heart failure, thromboembolic disease, hypertension, cerebrovascular disease, ischemic heart disease, diabetes mellitus type 2, and hypercholesterolemia with the risk and progression of MNDs.

Methods: We included 1463 MND patients (amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive spinal muscular atrophy (PSMA), and unspecified MND) diagnosed from January 1, 2015, to July 1, 2023, in Sweden according to the Swedish Motor Neuron Disease Quality Registry (i.

Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer - implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils.

Introduction: Ovarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is involved in different immune processes and has been associated with poor outcome in various cancer diagnoses.

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles.

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

Taguchi-based optimisation of FSW parameters for advancement in aerospace materials: Al-Li 2060 alloy.

Aluminium-lithium (Al-Li) 2060 alloy, a 3rd generation Al-Li alloy, is considered a structural material for aircraft components. This study employs the Friction Stir Welding (FSW) process with a kinematic 5-axis robotic arm to weld 4-mm-thick plates of 2060-T8E30 Al-Li alloy. The focus is on the impact of tool axial force and speeds on the microstructural evolution, mechanical properties, and surface integrity of the welded joints.

Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults.

In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup.

Prevalence of polycystic ovary syndrome among infertile women in the Gulf Cooperation Council (GCC) countries: A systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a significant contributor to female infertility and other various metabolic disorders. This systematic review estimates the prevalence of PCOS among infertile women in the Gulf Cooperation Council (GCC) countries.

Methods: The study searched five databases (PubMed, Embase, CINAHL, Web of Science, and SCOPUS), from their inception to 2022 for observational studies conducted in GCC countries.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.

Prolonged SARS-CoV-2 Viremia in an Immunocompromised Patient.

Immunocompromised patients, especially those receiving B-cell depleting therapies, are at risk for developing atypical presentation with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with the potential for diagnostic delay and adverse outcomes if such delay occurs. A 66-year-old female with history of granulomatosis with polyangiitis (GPA) with previous pulmonary involvement, treated with rituximab and low-dose prednisolone, presented with prolonged fever and cough after having been treated at home for a mild SARS-CoV-2 infection in early July 2023. The patient had a prolonged course over several months with constitutional symptoms such as fever, cough and malaise.

Exploring the potential of electrical bioimpedance technique for analyzing physical activity.

Introduction: Exercise physiology investigates the complex and multifaceted human body responses to physical activity (PA). The integration of electrical bioimpedance (EBI) has emerged as a valuable tool for deepening our understanding of muscle activity during exercise.

Method: In this study, we investigate the potential of using the EBI technique for human motion recognition.

Varus alignment of the hip and knee 2 years after anterior cruciate ligament injury is associated with medial tibiofemoral osteoarthritis 3 years later.

Purpose: To investigate if hip and knee alignment assessed 2 years after anterior cruciate ligament (ACL) injury is associated with compartment-specific radiographic knee osteoarthritis (OA) 3 years later.

Methods: An exploratory analysis was conducted in the knee ACL, nonsurgical versus surgical treatment (KANON) trial (ISRCTN84752559); 115 subjects with acute ACL injury were assessed at the 2-year follow-up; full-limb images of the injured leg were acquired, and the neck-shaft angle (NSA) and hip-knee-ankle angle (HKA) were measured. At the 5-year follow-up, weight-bearing tibiofemoral and patellofemoral radiographs were obtained.