FDA-approved drugs featuring macrocycles or medium-sized rings.

Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more.

RADAR-AD: assessment of multiple remote monitoring technologies for early detection of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide, leading to cognitive and functional decline. Early detection and intervention are crucial for enhancing the quality of life of patients and their families. Remote Monitoring Technologies (RMTs) offer a promising solution for early detection by tracking changes in behavioral and cognitive functions, such as memory, language, and problem-solving skills.

PSMA PET/CT based multimodal deep learning model for accurate prediction of pelvic lymph-node metastases in prostate cancer patients identified as candidates for extended pelvic lymph node dissection by preoperative nomograms.

Purpose: To develop and validate a prostate-specific membrane antigen (PSMA) PET/CT based multimodal deep learning model for predicting pathological lymph node invasion (LNI) in prostate cancer (PCa) patients identified as candidates for extended pelvic lymph node dissection (ePLND) by preoperative nomograms.

Methods: [Ga]Ga-PSMA-617 PET/CT scan of 116 eligible PCa patients (82 in the training cohort and 34 in the test cohort) who underwent radical prostatectomy with ePLND were analyzed in our study. The Med3D deep learning network was utilized to extract discriminative features from the entire prostate volume of interest on the PET/CT images.

Influence of two different printing methods on the accuracy of full-guided implant insertion - a laboratory study in undergraduate dental students.

Objectives: The aim of the present study was to compare the accuracy of fully guided implant insertion in vitro achieved by two fabrication methods in a cohort of undergraduates. We hypothesized that both methods achieve a comparable accuracy.

Methods: Surface scans and cone beam computed tomography images of 48 mandibular models were matched.

Efficacy and safety of PCSK9 inhibitors in real life.

Objective: To confirm the effectiveness and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in daily clinical practice.

Methods: Retrospective observational study of patients from hospital registry of PCSK9 inhibitor treatment with a follow-up ≥ 6 months. The lipid-lowering effect and safety were evaluated.

Using Health Information Resources for People With Cognitive Impairment (digiDEM Bayern): Registry-Based Cohort Study.

Background: Dementia is a growing global health challenge with significant economic and social implications. Underdiagnosis of dementia is prevalent due to a lack of knowledge and understanding among the general population. Enhancing dementia literacy through improved health information-seeking behavior is crucial for the self-determined management of the disease by those affected.

Advances and stagnation in airway surgery: A historical perspective.

Airway pathology is a complex and incompletely mastered field. Historically, its management was rudimentary, with tracheostomies performed in ancient Egypt, and progress remained stagnant for millennia. Significant advances began in the late 19 century, followed by notable surgical and anesthetic progress in the mid-20 century.

Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.

Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.

Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.

Safety of ceftobiprole in patients with impaired renal, hepatic or immune function: a multinational retrospective hospital chart review (RETRACE study).

Ceftobiprole, an advanced-generation cephalosporin with broad bactericidal activity, is approved for community-acquired and hospital-acquired pneumonia (excluding ventilator-associated pneumonia). We aimed to evaluate, in a real-world setting, the safety profile of ceftobiprole in patients with risk conditions (severe renal impairment, hepatic impairment, and immunocompromised status), groups excluded from clinical trials. In this retrospective study (NCT04170309), 396 consecutive charts of patients treated with ceftobiprole during 2016-2022 in 15 centers in France, Italy, and Spain were analyzed: 62 had severe renal impairment, 51 had hepatic impairment, 120 were immunocompromised, and 203 had no predefined risk condition (controls).

A European Delphi Consensus on the Management of Abdominal Aortic Aneurysms in Patients with Heritable Aortic Diseases.

Objective: Abdominal aortic aneurysm (AAA) in a patient with an underlying heritable aortic disease (HAD) is rare, and evidence based recommendations for its management are lacking. This study aimed to generate a consensus from multidisciplinary specialists on the diagnosis, treatment, and surveillance of AAA associated with HAD and to define topics of interest for future research.

Methods: A Delphi consensus was designed involving European multidisciplinary specialists and reported using the ACcurate COnsensus Reporting Document (ACCORD) reporting guideline.

Infants' saccadic behavior during 2-dimensional displays of a bounce.

The study examined the saccadic behavior of 4- to 10-month-old infants when tracking a two-dimensional linear motion of a circle that occasionally bounced off a barrier constituted by the screen edges. It was investigated whether infants could anticipate the angle of the circle's direction after the bounce and the circle's displacement from the location of bounce. Seven bounce types were presented which differed in the angle of incidence.

Priors for natural image statistics inform confidence in perceptual decisions.

Decision confidence plays a critical role in humans' ability to make adaptive decisions in a noisy perceptual world. Despite its importance, there is currently little consensus about the computations underlying confidence judgements in perceptual decisions. To better understand these mechanisms, we addressed the extent to which confidence is informed by a naturalistic prior distribution.

Soft tissue-like coupling materials for in vitro acoustic emission studies in total hip arthroplasty.

In hip arthroplasty, relative movements between the femoral stem and bone can lead to implant loosening, resulting in extensive bone loss. Acoustic emission (AE) analysis is a promising technique for a nondestructive and noninvasive detection of these relative movements. To develop such a detection method, in vitro investigations using piezoelectric AE sensors on implant stems in artificial or human femora are required to characterize the AE signals induced by loosening.

The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.

Comparing answers of ChatGPT and Google Gemini to common questions on benign anal conditions.

Introduction: Chatbots have been increasingly used as a source of patient education. This study aimed to compare the answers of ChatGPT-4 and Google Gemini to common questions on benign anal conditions in terms of appropriateness, comprehensiveness, and language level.

Methods: Each chatbot was asked a set of 30 questions on hemorrhoidal disease, anal fissures, and anal fistulas.

Immunonutrition to improve the quality of life of upper gastrointestinal cancer patients undergoing neoadjuvant treatment prior to surgery (NEOIMMUNE): double-blind randomized controlled multicenter clinical trial.

Background: Malnutrition is common with esophagogastric cancers and is associated with negative outcomes. We aimed to evaluate if immunonutrition during neoadjuvant treatment improves patient's health-related quality of life (HRQOL) and reduces postoperative morbidity and toxicities during neoadjuvant treatment.

Methods: A multicenter double-blind randomized controlled trial (RCT) was undertaken.

Evaluating programmatic reactive focal drug administration impact on malaria incidence in northern Senegal: an interrupted time series analysis.

Background: The World Health Organization conditionally recommends reactive drug administration to reduce malaria transmission in settings approaching elimination. However, few studies have evaluated the impact of reactive focal drug administration (rFDA) in sub-Saharan Africa, and none have evaluated it under programmatic conditions. In 2016, Senegal's national malaria control programme introduced rFDA, the presumptive treatment of compound members of a person with confirmed malaria, and reactive mass focal drug administration (rMFDA), an expanded effort including neighbouring compounds during an outbreak, in 10 low transmission districts in the north of the country.

Syndemic, mental health and living with dependent persons in Latin America and Spain: a study with a gender perspective.

Objective: To analyze the sociostructural determinants associated with mental health problems during the lockdown period among populations residing in Brazil, Chile, Ecuador, Mexico, Peru, and Spain who lived with minors or dependents, approached from a gender perspective.

Methods: A cross-sectional study was conducted in six participating countries via an adapted, self-managed online survey. People living with minors and/or dependents were selected.

Arginine metabolism in myeloid cells in health and disease.

Metabolic flexibility is key for the function of myeloid cells. Arginine metabolism is integral to the regulation of myeloid cell responses. Nitric oxide (NO) production from arginine is vital for the antimicrobial and pro-inflammatory responses.

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia.

Background: Arginine infusion stimulates copeptin secretion, a surrogate marker of arginine vasopressin (AVP), thereby serving as a diagnostic test in the differential diagnosis of suspected AVP deficiency (AVP-D). Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.

Practice makes better? The influence of increased practice on task conflict in the Stroop task.

The Stroop task is widely used to study attentional control and cognitive flexibility. However, questions about its sensitivity to training and the impact of task conflict on attentional control remain open. We investigated the effects of practice and task conflict on attentional control in the Stroop task, with participants completing four sessions of a Stroop task over 3 weeks in low and high task-conflict conditions.

Enhanced optical properties of chitosan polymer doped with orange peel dye investigated via UV-Vis and FTIR analysis.

The current research aims to determine the impact of orange peel dye (OPD), an eco-friendly addition, on the optical properties of biodegradable polymers. This study investigates the enhancement of optical properties in solid electrolytes based on chitosan (CS) and glycerol, with varying OPD concentrations. UV-Vis-NIR spectroscopy revealed significantly enhanced UV-visible light absorption in the 200-500 nm region and effective UV light blocking.

[Formula: see text]-roaming dynamics in the formation of [Formula: see text] following two-photon double ionization of ethanol and aminoethanol.

Roaming reactions involving a neutral fragment of a molecule that transiently wanders around another fragment before forming a new bond are intriguing and peculiar pathways for molecular rearrangement. Such reactions can occur for example upon double ionization of small organic molecules, and have recently sparked much scientific interest. We have studied the dynamics of the [Formula: see text]-roaming reaction leading to the formation of [Formula: see text] after two-photon double ionization of ethanol and 2-aminoethanol, using an XUV-UV pump-probe scheme.