Placebo nonresponders: An experimental investigation on their unreliability over time.

In order to disentangle the effects of drugs from placebo responses, several approaches have been used, such as a placebo run-in phase in which only placebo nonresponders, or poor responders, are considered for further randomization to either placebo or active treatment. This study is aimed at investigating the variability of placebo nonresponders obtained through the classical placebo run-in paradigm (group RUN) and through mismatch conditioning (group MIS), as done in our previous study. To do this, we simulated a real clinical trial in the laboratory, in which the placebo responders of both groups were discarded and the remaining nonresponders of both groups RUN and MIS were randomized to either continuing on placebo (groups RUN-P and MIS-P, respectively) or receiving topical 0.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age.

Outcome of a Mix-and-Match Approach with a Monofocal Aspherical and a Bifocal Extended Depth-of-Focus Intraocular Lens to Achieve Extended Monovision in Cataract Patients.

Background: Extended monovision is a novel mix-and-match approach that has been recently introduced. It involves implanting an aspherical monofocal intraocular lens (IOL) for distance vision in the dominant eye, and a bifocal extended depth-of-focus (EDOF) IOL in the nondominant eye. The target refraction for the nondominant eye is - 1.

Precision biotic as an effective replacement of hydrolyzed yeast and butyrate in antibiotic free diets of broiler chickens raised under field conditions.

A total of 1,436,000 Ross 380 AP broiler chicks were included in the experiment, which was conducted in two cycles with 20 houses per cycle and 35,900 birds per house. The objective was to evaluate, under field conditions, the impact of a precision biotic (PB) on the growth performance and cecal microbiome of broiler chickens, in comparison to enzymatically hydrolyzed yeast (EHY) and butyrate (BT) in an antibiotic-free diet. Each cycle consisted of six (6) houses under PB supplementation, and 14 houses under the regular dietary program used by the integration.

Assessment of pandemic-related pregnancy stress from seven western countries using Rasch analyses.

Introduction: This study examined psychometric properties of the Pandemic-Related Pregnancy Stress Scale (PREPS) using a Rasch Model (RM) in a large sample of pregnant women from Germany, Israel, Italy, Poland, Spain, Switzerland and the United States of America (USA).

Material And Methods: Rasch analyses were used to analyze a sample of 7185 pregnant women who completed the PREPS during the COVID-19 pandemic onset from April to August 2020. Psychological, sociodemographic, and obstetric factors were also collected and analyzed.

Ion exchange chromatography of biotherapeutics: Fundamental principles and advanced approaches.

Ion exchange chromatography (IEX) is an important analytical technique for the characterization of biotechnology-derived products, such as monoclonal antibodies (mAbs) and more recently, cell and gene therapy products such as messenger ribonucleic acid (mRNA) and adeno-associated viruses (AAVs). This review paper first outlines the basic principles and separation mechanisms of IEX for charge variant separation of biotherapeutics, and examines the different elution modes based on salt or pH gradients. It then highlights several recent trends when applying IEX for the characterization of biotechnology-derived products, including: i) the effective use of pH gradients, ii) the improvement of selectivity by using organic solvents in the mobile phase, multi-step gradients, or by combining ion pairing and ion exchange, and iii) the increase in analytical throughput using ultra-short columns or automated screening of conditions.

AI Interventions to Alleviate Healthcare Shortages and Enhance Work Conditions in Critical Care: Qualitative Analysis.

Background: The escalating global scarcity of skilled health care professionals is a critical concern, further exacerbated by rising stress levels and clinician burnout rates. Artificial intelligence (AI) has surfaced as a potential resource to alleviate these challenges. Nevertheless, it is not taken for granted that AI will inevitably augment human performance, as ill-designed systems may inadvertently impose new burdens on health care workers, and implementation may be challenging.

Operando X-Ray Tomoscopy of Laser Beam Welding.

The phenomena occurring in a weld seam during advancement of a laser beam over a metallic component are still under dispute. The occurrence and evolution of porosity and the occasional blowout of melt need to be understood. Here, a recently developed X-ray tomoscopy setup is applied, providing one hundred 3D images per second to capture the temporal evolution of the melt pool in an AlSi9Cu3(Fe) die-casting while a laser beam advances.

Floodplain forests drive fruit-eating fish diversity at the Amazon Basin-scale.

Unlike most rivers globally, nearly all lowland Amazonian rivers have unregulated flow, supporting seasonally flooded floodplain forests. Floodplain forests harbor a unique tree species assemblage adapted to flooding and specialized fauna, including fruit-eating fish that migrate seasonally into floodplains, favoring expansive floodplain areas. Frugivorous fish are forest-dependent fauna critical to forest regeneration via seed dispersal and support commercial and artisanal fisheries.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Casein Kinases 2-dependent phosphorylation of the placental ligand VAR2CSA regulates Plasmodium falciparum-infected erythrocytes cytoadhesion.

Placental malaria is characterized by the massive accumulation and sequestration of infected erythrocytes in the placental intervillous blood spaces, causing severe birth outcomes. The variant surface antigen VAR2CSA is associated with Plasmodium falciparum sequestration in the placenta via its capacity to adhere to chondroitin sulfate A. We have previously shown that the extracellular region of VAR2CSA is phosphorylated on several residues and that the phosphorylation enhances the adhesive properties of CSA-binding infected erythrocytes.

Comparison of a non-invasive point-of-care measurement of anemia to conventionally used HemoCue devices in Gambella refugee camp, Ethiopia, 2022.

Annual surveys of refugees in Gambella, Ethiopia suggest that anemia is a persistent public health problem among non-pregnant women of reproductive age (NP-WRA, 15-49 years). Measurement of anemia in most refugee camp settings is conducted using an invasive HemoCue 301. We assessed the accuracy and precision of a non-invasive, pulse CO-oximeter in measuring anemia among NP-WRA in four Gambella refugee camps.

Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.

Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.

Geometry and dynamics of representations in a precisely balanced memory network related to olfactory cortex.

Biological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex.

An Acta Orthopaedica educational article: Treatment of pediatric spondylolysis and spondylolisthesis.

Spondylolysis is defined as a defect or elongation in the pars interarticularis of the lumbar spine, either unilateral or bilateral. Growing children with bilateral spondylolysis may develop spondylolisthesis, i.e.

Perovskite Nanocrystal Self-Assemblies in 3D Hollow Templates.

Highly ordered nanocrystal (NC) assemblies, namely, superlattices (SLs), have been investigated as materials for optical and optoelectronic devices due to their unique properties based on interactions among neighboring NCs. In particular, lead halide perovskite NC SLs have attracted significant attention owing to their extraordinary optical characteristics of individual NCs and collective emission processes like superfluorescence (SF). So far, the primary method for preparing perovskite NC SLs has been the drying-mediated self-assembly method, in which the colloidal NCs spontaneously assemble into SLs during solvent evaporation.

Selective Hydrogen Isotope Exchange Catalysed by Simple Alkali-Metal Bases in DMSO.

Isotope Exchange processes are becoming the preferred way to prepare isotopically labelled molecules, avoiding the redesign of multistep synthetic protocols. In the case of deuterium incorporation, the most used strategy has employed transition metals, that offer high reactivity under mild reaction conditions. Despite their success, the trade-off is that these metals are precious, and often exhibit high toxicity.

Porous Organic Polymers Incorporating Shape-persistent Cyclobenzoin Macrocycles for Organic Solvent Separation.

The recovery and separation of organic solvents is highly important for the chemical industry and environmental protection. In this context, porous organic polymers (POPs) have significant potential owing to the possibility of integrating shape-persistent macrocyclic units with high guest selectivity.  Here, we report the synthesis of a macrocyclic porous organic polymer (np-POP) and the corresponding model compound by reacting cyclotetrabenzil naphthalene octaketone macrocycle with 1,2,4,5-tetraaminobenzene and 1,2-diaminobenzene, respectively, under solvothermal conditions.

Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke: The POST-TNK Randomized Clinical Trial.

Importance: The impact of adjunctive intra-arterial tenecteplase administration following near-complete to complete reperfusion by endovascular thrombectomy (EVT) for acute ischemic stroke is unknown.

Objective: To assess the efficacy and adverse events of adjunctive intra-arterial tenecteplase in patients with large vessel occlusion stroke who had achieved near-complete to complete reperfusion (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2c to 3) after EVT.

Design, Setting, And Participants: Investigator-initiated, randomized, open-label, blinded outcome assessment trial implemented at 34 hospitals in China among 540 patients with stroke due to proximal intracranial large vessel occlusion within 24 hours of the time they were last known to be well, with an eTICI score of 2c to 3 after EVT, and without prior intravenous thrombolysis.

Effects of Exergaming on Physical Fitness of Youth with Overweight and Obesity: A Systematic Review with Meta-Analysis.

Due to the exponential growth in technology, exergames emerged as a potential tool to foster physical activity (PA) levels. This study provides an overall view of the literature on the effects of exergaming on physical fitness components among overweight and obese children and adolescents. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed in the PubMed, Web of Science, and Scopus databases.

Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke: The POST-UK Randomized Clinical Trial.

Importance: Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion.

Objective: To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion.

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

The interaction of structured data using openEHR and large Language models for clinical decision support in prostate cancer.

Background: Multidisciplinary teams (MDTs) are essential for cancer care but are resource-intensive. Decision-making processes within MDTs, while critical, contribute to increased healthcare costs due to the need for specialist time and coordination. The recent emergence of large language models (LLMs) offers the potential to improve the efficiency and accuracy of clinical decision-making processes, potentially reducing costs associated with traditional MDT models.