bluuebunny/crossref_metadata_2025 huggingface dataset:
The Birth of the Psychedelic Industry: Capitalising on the Psychedelic Renaissance
Authors: Yoo Minsu , Sakopoulos Sofia
Published: December 2024

The resurgence of psychedelic medicine, often termed ‘the psychedelic renaissance,’ marks a profound shift from decades of repressed research to a burgeoning field characterised by significant scientific, regulatory, and economic transformations. Once marginalised, psychedelics are now experiencing widespread interest and investment, spurred by changes in legal frameworks, public attitudes, and an influx of venture capital (VC). This article explores the interplay between scientific innovation and capital investment within the psychedelic sector, highlighting how private funding shapes the form of research and its financialization. The study investigates the roles of VC and private interests in driving the psychedelic renaissance, examining how these financial forces influence ethical considerations and broader socio‐political implications. Through in‐depth interviews with key stakeholders in the industry, including in‐house scientists and investors, the research uncovers how market‐driven imperatives and financial conflicts of interest shape both scientific practices and public perceptions of psychedelic medicine—and how these perceptions, in turn, influence the industry. The analysis underscores the tension between the idealistic and capitalist narratives surrounding psychedelic medicine, suggesting that the psychedelic industry reflects broader trends in biotech and pharmaceutical industries, where innovation is closely tied to financial investment and market dynamics. At the same time, it highlights the paradox of psychedelic mysticism, which remains elusive to the rigid criteria of evidence‐based medicine, thereby challenging the prevailing paradigm of psychopharmacological research. The findings call for a critical examination, through continuous public engagement, of the ethical dimensions of integrating psychedelics into mainstream medicine, highlighting the need to focus on the emergence of grey areas within capital networks where cultural and political values are constantly rearranged and restructured.
Cryopreservation of ovarian cortex as fertility preservation in transgender men: A case report and literature review
Authors: Sanches Marcos Paulo Ribeiro , de Carvalho Renata Cristina , Camillo Jacqueline , Monteiro Amanda Begatti Victorino , Dias‐da‐Silva Magnus Régios , Ruano José Maria Cordeiro , Sartori Marair Gracio Ferreira , Fraietta Renato
Published: December 2024

Transgender people have been experiencing significant advancements in their social visibility, although they continue to face frequent discrimination and exclusion. Among the issues encompassing transgender individuals' health care, the right to reproductive and sexual health have gained traction in the study landscape, necessitating an exploration of fertility preservation options for these patients. This report sheds light on the process of cryopreserving gametes and ovarian tissue after total hysterectomy with bilateral salpingo‐oophorectomy for gender reassignment in a transgender man in hormonal masculinization. The procedure resulted in the cryopreservation of three immature oocytes and ovarian tissue fragments. The objective of this study is to contribute to the promotion of knowledge and the sharing of experiences, aiming to gradually enhance the attention on reproductive health among transgender individuals.
Evaluation of pharmacist‐initiated glycemic control in adult medicine patients with diabetes
Authors: Wells Drew A. , Sakaan Sami , Shaver Jacob , Cutshall B. Tate , Twilla Jennifer
Published: December 2024

Introduction

Historically, clinical pharmacists' management of inpatient glycemic control has been driven by institutional protocols or the collaboration of multi‐disciplinary glycemic control teams.

Objectives

The purpose of this study was to describe the impact of a pharmacist's expanded scope of practice (ESOP) on glycemic control in hospitalized patients with diabetes.

Methods

This was a single‐center, descriptive, retrospective cohort study of adult hospitalized patients with diabetes who had active, scheduled insulin orders initiated or titrated for more than 48 hours by an internal medicine pharmacist. The primary outcome was to determine the mean daily blood glucose (BG) levels for patients started on scheduled insulin therapy between Provider‐initiated and Pharmacist‐initiated groups. Other outcomes included the percentage of Level 1 hypoglycemia (BG 54–70 mg/dL), Level 2 hypoglycemia (BG <54 mg/dL), hyperglycemia (BG 181–239 mg/dL), and severe hyperglycemia (BG ≥240 mg/dL).

Results

A total of 111 patients were included: 50 in the Pharmacist‐initiated group and 61 in the Provider‐initiated group. There were similar outcomes between Pharmacist‐initiated and Provider‐initiated groups when comparing time within goal BG range (45% vs. 38%, p = 0.104) and percentage of hypoglycemia (1% vs. 4%, p = 0.175). The Pharmacist‐initiated group had significantly less percentage of Level 2 hypoglycemia compared with the Provider‐initiated group (0.1% vs. 1.2%, p = 0.004). Severe hyperglycemia occurred more frequently in the Provider‐initiated group (19% vs. 33%, p = 0.005), but there was more hyperglycemia seen in the Pharmacist‐initiated group (34% vs. 26%, p = 0.005).

Conclusion

Pharmacist glycemic management for hospitalized adult medicine patients can be achieved through a pharmacist's ESOP in collaboration with providers and can have similar efficacy and improved safety. Further changes to the ESOP, including early identification and initiation of glycemic therapy, can enhance the effectiveness of this service.
Modulation of cationic surfactant micellization by imidazolium‐based ionic liquids: A thermodynamic study
Authors: Patiño‐Agudelo Álvaro Javier , Ferreira Gabriel Max Dias , Ferreira Guilherme Max Dias , Coelho Yara Luiza , Marques Isabela A. , Moreau Pedro dos Santos , Ribera Ruben Ramallo , dos Santos Pires Ana Clarissa , da Silva Luis Henrique Mendes
Published: December 2024

Understanding the modulation of ionic surfactant properties in the presence of ionic liquids (ILs) is fundamental for expanding the application of that class of compounds. Although the effect of ILs on the micellization process of anionic surfactant has gained broad attention, its effect on cationic surfactants aggregation processes has been underexplored. This work investigated the effect of 1‐alkyl‐3‐methylimidazolium chlorides (CnmimCl, with n = 2 or 4) and NaCl on the micellization of alkylpyridinium chlorides (CnPyCl, with n = 12 or 16) cationic surfactants using Isothermal Titration Calorimetry (ITC) and electrical conductivity. The reduction in the critical micellar concentration (CMC) in the presence of the electrolytes depends similarly on the stoichiometry between the surfactant and the electrolyte in the solution before micellization, independent of the electrolyte nature. However, the more hydrophobic the ionic liquid and the surfactant, the more intense the effects of electrolyte concentration on the micellar dissociation degree (α) and the micellization parameters (, and ). The presence of C2mimCl or C4mimCl made the micellization process of both surfactants more exothermic, associated mainly with the maximization of non‐dispersive interactions among monomers within the micelles and reduction of repulsive electrostatic interactions among surfactant head groups. Additionally, kosmotropic effects and preferential solvation of the surfactant, more intense for C4mimCl, actuate at high concentrations of this ionic liquid, intensifying the decrease of . This underscores that, despite both the imidazolium cation and the surfactant being positively charged, dispersive interactions between them play an important role in efficiently modulating the aggregation process.
Integrated Optical Spectrometers on Silicon Photonics Platforms
Authors: Zhang Zunyue , Zhang Shujiao , Liu Xingyu , Wei Zhijie , Sharma Tarun , Murugan Ganapathy Senthil , Tsang Hon Ki , Liu Tiegen , Cheng Zhenzhou
Published: December 2024

Spectroscopy plays a pivotal role in discerning the chemical and biochemical compositions of analytes, significantly impacting chemical and material analysis, disease diagnosis, environmental monitoring, and space exploration. Despite the widespread demand for optical spectrometers in both industry and academia, their deployment in many practical applications is hindered by the high costs, large footprints, and mechanical vibration sensitivity of conventional spectrometers. These problems are addressed by integrated optical spectrometers. Silicon photonics offers a potentially low‐cost platform for ultracompact integrated optical spectrometers, leveraging the complementary metal‐oxide‐semiconductor (CMOS) compatible fabrication technology and high flexibility in on‐chip light manipulation of high‐index waveguides. The integrated optical spectrometers on silicon photonics platforms provide promising solutions for developing ultra‐compact and cost‐effective spectral analyzers in various applications. This review paper overviews recent advancements in integrated optical spectrometers on silicon photonics platforms over the past decades, focusing on their fundamental principles, design methodologies, spectral performances, and potential applications. By blending foundational knowledge with cutting‐edge research, this review aims to involve researchers from different fields, including spectroscopy, materials science, astronomy, environmental engineering, and beyond.
Improving Stability and Mechanical Strength of Electrospun Chitosan‐Polycaprolactone Scaffolds Using Genipin Cross‐linking for Biomedical Applications
Authors: Uma Thanu Krishnan Neela Nagalekshmi , Szewczyk Piotr K. , Karbowniczek Joanna E. , Polak Martyna , Knapczyk‐Korczak Joanna , Stachewicz Urszula
Published: December 2024

Electrospun nanofiber scaffolds have become vital in biomedical applications due to their high surface area and tunable properties. Chitosan (CS) is widely used, but its rapid degradation limits its effectiveness. This study addresses this limitation by blending CS with polycaprolactone (PCL) and applying genipin cross‐linking to enhance its stability and mechanical properties. Scanning electron microscopy indicated a uniform morphology of the electrospun fibers, and further, the crystallinity of the scaffolds before and after cross‐linking is verified. Fourier‐transform infrared spectroscopy is used to analyze the chemical structure, identifying the presence of trifluoroacetic acid residues in the as‐spun fibers. These residues are successfully eliminated through neutralization and cross‐linking, which are critical for enhancing stability and cell viability in in‐vitro studies. Mechanical testing revealed that cross‐linked CS+PCL scaffolds exhibit a 350% increase in tensile strength compared to pure CS, and zeta potential reaches the favorable for cell development ‐26.27 mV. The cytotoxicity assay results with murine NIH 3T3 fibroblast cells indicate the suitability of CS+PCL scaffolds for targeted tissue engineering and wound healing. This work establishes the potential for fine‐tuning scaffold properties to create stable, functional, and biocompatible substrates for extended biomedical use.
Patient‐Reported Experience Measures for In‐ and Outpatients in Mental Health and Substance Use Services: Psychometric Properties and Results From a Nationwide Survey in Finland
Authors: Viertiö Satu , Therman Sebastian , Kuussaari Kristiina , Suvisaari Jaana
Published: December 2024

Objectives

We implemented the first national patient experience survey, with novel patient‐reported experience measures (PREMs), in out‐ and inpatient mental health and substance use services in Finland.

Methods

The Outpatient Experience Scale (OPES) and the Inpatient Experience Scale (IPES) were co‐designed with experts by experience and professionals. The survey was carried out in 2021 in 435 treatment facilities. We applied bi‐factor analysis of ordinal indicators to prespecified and exploratory models.

Results

We received 8794 outpatient and 1112 inpatient responses. Both the OPES and the IPES were essentially unidimensional, with high internal consistency (omega 0.98 in both) and strong factor loadings. The Net Promoter Score item was a fairly poor indicator of overall satisfaction. The most positive experiences were related to respect and acceptance, while statements related to receiving information and inclusion of significant others in the treatment process received more critical feedback. The best experience was in integrated mental health and substance use services. Involuntarily admitted patients had the most negative patient experiences.

Conclusions

The new PREMs proved to work well in measuring patient experience. Service users generally reported positive experiences. The primary service development need is sharing information with patients.
Effect of Zr Doping on Structure and Ferroelectric Properties of Nanostructured Barium Titanate
Authors: Salem Mohamed M. , Altarawneh Aseel M. , Alibwaini Yamen A. , Ghazy Ryad , Hemeda Osama M. , Zhou Di , Darwish Moustafa A. , Hossain M. Khalid , Tishkevich Daria I. , Zubar Tatiana I. , Trukhanova Ekaterina L. , Trukhanov Alex V. , Trukhanov Sergei V. , Mostafa Maha
Published: December 2024

Using soft chemistry methods, solid solutions of BaTi1‐xZrxO3 with 0 ≤ x ≤ 1 were obtained. The phase nature and features of the perovskite crystalline structure were established by x‐ray analysis and Fourier transform infrared (FTIR) spectroscopy. It was found that the average particle size increases with increasing content of zirconium cations. The average size of the crystallites, which are mostly irregular in shape and closely connected, is ∼43 nm. The d33 piezoelectric coefficient decreases while the concentration of zirconium cations increases. It is interesting to note that the residual polarization very strongly depends on the average crystallite size and, on the contrary, increases with increasing concentration of zirconium cations. The discovered behavior can be used in the design and production of electrostatic read‐only memory devices.
Regularized X‐FEM Modeling of Arbitrary 3D Interacting Crack Networks
Authors: Iarve Endel V. , Zhou Eric , Ballard M. Keith , Gao Zhenjia , Adluru Hari K. , Mollenhauer David
Published: December 2024

An extension to the Regularized eXtended Finite Element Method (RX‐FEM) is proposed that allows arbitrary 3D cracks through a novel hierarchical enrichment algorithm. The technique avoids geometric consideration of how a crack cuts elements or intersects other cracks. Each crack is described separately in terms of its sign distance function and regularized step function, which are only recorded for nodes in the region where the gradient of the regularized step function is non‐zero. The algorithm creates a set of superimposed nodes, referred to as node twins, and elements, referred to as twinned elements, for each crack and determines the connectivity of the element twins using the involved crack indices. The displacement jump is calculated between each pair of element twins corresponding to the same crack, and a cohesive zone model (CZM) is formulated for each pair of twins to model crack opening. Following the theory for the novel method, several examples are presented that illustrate capabilities of the new method that the traditional RX‐FEM formulation lacked. A quasi‐2D example of offset crack propagation is considered and successfully compared with published results. Additionally, two 3D examples involving perpendicularly intersecting cracks are considered, illustrating the intersection of two crack fronts and correct partitioning of the domain into eight fragments due to three crossing cracks, respectively.
Innovative Progress of LSPR‐Based Dark‐Field Scattering Spectral Imaging in the Biomedical Assay at the Single‐Particle Level
Authors: Shi Yang , Wang Lixiang , Li Lingling , Feng Chen , Cao Yue
Published: December 2024

The growing demand for detection and sensing in the biomedical field is placing higher demands on technology. In clinical testing, it is expected to be able to realize both rapid large‐field imaging and analysis of single particles (or single molecules or single cells), and it is expected to be able to grasp both the unique individuality of single particles in time and space during the complex reaction process, as well as the regular correlation between single particles in the same population distribution. Supported and promoted by the theory of localized surface plasmon resonance (LSPR), dark‐field microscopy, as a single‐particle optical imaging technique with a very high signal‐to‐noise ratio, provides a powerful new means to address the above clinical detection needs. This review will focus on the innovative applications of dark‐field microscopy in biomedical‐related assays in the past five years, introducing the basic principles and listing the impressing works. We also summarize how dark‐field microscopy has been combined with other techniques, including surface‐enhanced Raman scattering, fluorescence, colorimetry, electrochemistry, etc., to witness the joint progress and promotion of detection methods in the future. It also provides an outlook on the current challenges and future trends in this field.
Tensile failure strain mechanism of stitched composites with z‐stitch method: Influence of stitch pattern and density
Authors: Mei Ming , Zeng Tai , Wang Wenjie , He Yujia , Jiang Shengqiang , Wen Lei , Huang Jielin , Li Xu
Published: December 2024

The tensile failure mechanism of standard composites has been extensively investigated, but is not clear for stitched composites with z‐stitch method. This work systematically explored the tensile performance of the stitched composites with z‐stitch method under different stitch patterns and densities. The tensile strength and Poisson's ratio of stitched composites are reduced especially under high stitch density and 45° and 90° stitch patterns due to the induced defects and suppression effect on the crimp of load‐bearing yarn. Most importantly, the strain at failure moment is meticulously characterized to elucidate the failure strain mechanism by digital image correlation. For the stitched composite with 0° stitch pattern, obvious strain concentration only occurs in high stitch density specimen. In contrast, the strain concentration occurs in any stitch density for stitched composites with 45° and 90° stitch patterns, and is located around the stitch thread, especially becomes small with the increase of stitch density.

Highlights

High stitch density, 45° and 90°patterns reduce strength and Poisson's ratio.

Strain concentration occurs at failure moment in high stitch density specimen.

Strain concentration is located around stitch thread.
Engineered Polystyrene‐Zirconium Dioxide Nanocomposite With Enhanced Optical Properties
Authors: James Jemy , Thomas Martin George , Joseph Tomy Muringayil , Maria Hanna J. , Vignaud Guillaume , Grohens Yves , Penkova Anastasia , Rouxel Didier , Kalarikkal Nandakumar , Thomas Sabu
Published: December 2024

The demand for transparent polymers with high‐refractive indices (RIs) is increasing due to their versatility; however, low RIs also hold significance. Engineering the RI of polymer nanocomposites is crucial which benefits industry and research. The study investigates the influence of ZrO2 nanoparticles on the optical and surface properties of the polystyrene matrix. UV–Vis spectroscopy confirms that transparency is maintained with a light transmittance of 90 even with a ZrO2 loading of 16 wt%, while ellipsometry shows a steady increase in the RI due to the incorporation of nanoparticles. The RI of composites exceeds that of pure polystyrene (RI: 1.3–1.7) and utilizes the RI of ZrO2 (> 2.00) without altering the sample thickness. The microscopic image shows uniform distribution of particles up to 8 wt%, with slight agglomeration at higher contents. Scanning electron microscopy examination shows that the ZrO2 nanoparticles (20–150 nm) form loose agglomerated structures, while atomic force microscopy examination shows aggregate formation at 16 wt%. The addition of ZrO2 increases the surface roughness and water contact angle up to 4 wt%, which is related to the concentration of the nanofiller and the minimal interaction between ZrO2 and water. The results demonstrate the potential of ZrO2‐loaded nanocomposites for applications requiring high RIs and optical transparency.
First‐Principles Investigation of the Valley Splitting of Si Quantum Slabs
Authors: Hayashi Toshiaki , Kageshima Hiroyuki , Tokura Yasuhiro , Noborisaka Jin‐Ichiro , Nishiguchi Katsuhiko
Published: December 2024

First‐principles calculations based on density functional theory are performed on silicon (Si) quantum slabs to investigate the valley splitting of the lowest sub‐bands at the Γ point in the conduction band. The calculations show that strong strain in the [110] direction of the slab largely enhances the valley splitting, which may be related to the giant valley splitting observed in a device consisting of silicon‐on‐insulator and buried oxide layers. The relation between the valley splitting and the atomic configuration of the slabs is also examined.
Optimizing Surplus Food Redistribution: Leveraging Digital Platforms to Advance Sustainable Consumption
Authors: Agmapisarn Charoenchai , Seetha Prapakorn , Fakfare Pipatpong
Published: December 2024

Reducing food waste is a critical global challenge, intertwined with broader goals of sustainable consumption and sustainable development. This challenge is addressed by surplus food mobile applications that connect restaurants with consumers to minimize waste and promote sustainability. This study employs the Attitude‐Behavior‐Context (ABC) theory to investigate the key features of these platforms that influence consumer attitudes and food waste reduction behaviors, contributing to sustainability. Utilizing Integrated Generalized Structured Component Analysis (IGSCA) alongside single Necessary Condition Analysis (NCA), we examined features such as real‐time listings, sustainability messaging, accessibility, discounted pricing, and charitable collaborations. Results indicate that real‐time listings, sustainability messaging, accessibility, and charitable collaborations are crucial for fostering positive consumer attitudes and driving effective food waste reduction, while discounted pricing did not significantly impact attitudes. Complemented by necessity logic, these findings extend the ABC theory by emphasizing the essential role of specific contextual factors in promoting sustainable behaviors. Practically, the study offers actionable insights for platform developers to prioritize essential features, enhancing consumer engagement and contributing to the reduction of food waste in alignment with sustainability objectives.
Exploring the Antiaging Properties of Curcumin, Flaxseed, and Collagen: A Comprehensive Review
Authors: Varma Payal , Kandasubramanian Balasubramanian
Published: December 2024

Aging is a progressive and irreversible pathophysiological process. It manifests as a reduction in the functioning of tissues and cells as well as a marked increase in the risk of several aging‐related diseases, including metabolic, immune system diseases, and cardiovascular disorders. Therefore, the search for potent antiaging agents is crucial. Curcumin, collagen, and flaxseed are considered antiaging agents due to their unique properties and mechanisms that help combat the signs of aging. Curcumin, a potent phytochemical exhibits strong antioxidant and anti‐inflammatory properties, Collagen, an essential protein for skin elasticity and strength, flaxseed rich in lignans, antioxidants, and omega‐3 fatty acids offers a nutrient‐dense profile that helps to shield the skin from oxidative stress and inflammation. This review focuses on the antiaging properties of curcumin, collagen, and flaxseed, highlighting their unique structures as well as their molecular and cellular mechanisms of aging. Various extrinsic and intrinsic factors lead to decreases in the production of collagen, hyaluronic acid, and elastin making the skin prone to wrinkles, and damage. These factors and their impacts are discussed in this article. By examining the current research, this review sheds light on the potential benefits and innovative uses of these substances in antiaging treatments. The article also identifies future directions for research and development in this promising field.
New Quinoxaline Linked Fused Imidazo‐oxazole Conjugates as EGFR Inhibitors: Design, Synthesis, in Vitro Anti‐Breast Cancer Evaluation, Molecular Docking Studies and in Silico ADMET
Authors: Ferazoddin Mohammad , Syeda Arshiya Banu , Palabindela Rambabu , Syeda Asra Banu , Dasari Gouthami , Bandari Srinivas
Published: December 2024

A novel series of quinoxaline‐linked fused oxazole‐imidazole conjugates (7a–n) have been synthesized. The anticancer activity of these compounds was evaluated against two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231, using Erlotinib as a reference drug, with the MTT assay method. The results showed that compounds 7g, 7f, and 7e exhibited significantly greater efficacy compared to the standard drug Erlotinib. In a cell survival test using the normal breast cell line MCF‐10A, these three potent compounds (7g, 7f, and 7e) were evaluated, and none displayed notable cytotoxicity, with IC50 values greater than 98.13 #x000B5;M. Furthermore, compounds 7g, 7f, and 7e were assessed for tyrosine kinase EGFR inhibitory activity, using Erlotinib as the reference. The in vitro tyrosine kinase EGFR inhibitory assay revealed that compounds 7g and 7f demonstrated excellent efficacy, with IC50 values of 1.52 ± 0.09 µM and 1.25 ± 0.08 µ;M, respectively. Molecular docking studies also confirmed that compounds 7g, 7f, and 7e exhibited strong binding interactions with both EGFR and ER‐α. Additionally, the most potent compounds (7g, 7f, and 7e) underwent in silico pharmacokinetic evaluation using SWISS, ADME, and pkCSM. These compounds complied with five major filters (Lipinski's rule, Ghose rule, Veber rule, Egan rule, and Muegge rule) without any violations.
Sasa veitchii extract exhibits antitumor effect against murine pancreatic adenocarcinoma in vivo and in vitro
Authors: Hamanaka Junya , Mikami Yurie , Horiuchi Ayane , Yano Aiko , Amano Fumiya , Shibata Suo , Ogata Aya , Ogata Kenichi , Nagatsu Akito , Miura Nobuhiko , Sano Makoto , Suzui Masumi , Yoshioka Hiroki
Published: December 2024

Aim

Sasa veitchii extract (SE) has been used as a traditional medicine to treat halitosis, stomatitis, gingivitis, and pressure ulcers. SE exerts various antimicrobial, antiviral, and antitumor effects. Although SE has the potential to inhibit breast, colon, and lung cancer cells, it remains unknown whether these effects can also be applied to other types of cancer. In this study, we explored the antitumor effects of SE in murine pancreatic ductal adenocarcinoma (PDAC) cells both in vivo and in vitro.

Methods

For in vitro experiments, we examined cell proliferation after 48 hours. We evaluated the apoptosis‐and cell‐cycle‐related molecules using immunocytochemistry and immunoblot analyses. For the in vivo study, we evaluated the tumor volume and weight during three weeks of SE administration using an allograft model.

Results

SE showed the antitumor effect in a dose‐ and time‐dependent manner. SE treatment induced apoptosis in higher dose (400 μg/mL) and induced the downregulation of cyclin‐dependent kinases Cdk4/Cdk6 and Cyclin D1 in lower dose (200 μg/mL). In a murine allograft model, tumor volume and weight were reduced by SE administration.

Conclusion

SE exhibits an antitumor effect against murine PDAC cells in vivo and in vitro.
Emerging Alzheimer's disease treatment paradigms: A late‐stage clinical trial review
Authors: Hlávka Jakub P. , Kinoshita Andrew T. , Jeyasingh Divya , Huang Cheng , Mirsafian Leila , Jacobson Mireille
Published: December 2024

INTRODUCTION

Without disease‐modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near‐total failure rate in clinical trials suggests that more disease‐modifying therapies are on the horizon. In this review, we assess the late‐stage pipeline of disease‐modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms—groups of candidates that share an underlying biological mechanism of action and general disease target.

METHODS

We extracted data from the National Library of Medicine clinical trials database regarding Phase 2 and 3 trials of disease‐modifying AD therapies. We categorized trials into eight unique treatment paradigms, which we defined by combinations of therapy (biologic, small molecule, cell and gene therapy, other) and target (amyloid, tau, other). We analyzed primary endpoints, eligibility criteria including clinical ratings of cognition, trial phase and length, and funding sources.

RESULTS

We identified 123 unique disease‐modifying intervention candidates in 175 late‐stage clinical trials. Biologic and small molecule drugs comprised 30% and 54% of trials, respectively. Eligibility criteria favored patients between the ages of 60 and 80 years with mild cognitive impairment. Including multi‐phase trials, 81% of studies were engaged in Phase 2 and 27% in Phase 3. Notably, within the Biologic–Amyloid paradigm, 64% of trials were engaged in Phase 3.

DISCUSSION

Current studies of disease‐modifying therapies for AD comprise a diverse set of approaches to treating the disease. However, effort is largely concentrated in a few treatment paradigms and a narrow patient population, causing varying rates of progress among treatment paradigms in the late‐stage clinical trial pipeline. Strategies may be warranted to accelerate successes in the most promising therapeutical paradigms and nurture growth within nascent areas lacking resources but not potential.

Highlights

An analysis of Alzheimer's disease trial treatment paradigms was conducted.

From April 2021 to March 2023, 175 trials of 123 unique candidates were reviewed.

Biologic and small molecule drugs comprised 30% and 54% of trials, respectively.

Eligibility criteria favored ages 60 through 80 with mild cognitive impairment.
Effect of local epidural application of methylprednisolone acetate on time to ambulation in non‐ambulatory dogs with thoracolumbar intervertebral disc disease: A prospective randomised, blinded control trial
Authors: Natsios Pavlos , Golini Lorenzo , Park Brian H. , Steffen Frank
Published: December 2024

Background

The objective of this study was to analyse the potential benefit of the epidural application of steroids on time to ambulation in non‐ambulatory dogs affected by intervertebral disc disease (IVDD) treated with decompressive surgery.

Methods

This prospective, randomised, blinded control trial involved 41 dogs with thoracolumbar disc extrusion, which were randomly allocated into two groups. In the control group, saline was locally applied after surgical decompression of the spinal cord (n = 23). In the treatment group (n = 18), local epidural application of methylprednisolone acetate (1 mg/kg) was used. Ambulation time was the primary outcome measure, defined as the ability to take 10 independent steps.

Results

The median number of days to ambulation was 7 days (range: 1‒17 days) for the control group and 3 days (range: 1‒8 days) for the treatment group. One dog from the treatment group developed discospondylitis and abscess formation.

Limitations

The study's heterogeneity in dog breeds, ages and pre‐existing health conditions could affect the generalisability of the findings.

Conclusion

Epidural methylprednisolone acetate applied locally at the time of surgery may accelerate recovery in dogs following IVDD surgery.
Next Steps in Research, Business, and Policy
Authors: Caplin Andrew
Published: December 2024

This chapter highlights important next steps in cognitive economic research in relation to the cognitive revolution. Particular topics discussed are design of human- AI interactions, ensuring that workers and students are as well informed as possible about the impact of AI on their future earnings, and how to test students in the era of Large Language Models. It also stresses business and policy applications of cognitive economic research in relation to financial planning, cognitive decline, and online consumer protection.
Listening to a Place from a Multispecies Perspective Through Aesthetic Practices in Herlev
Authors: Werner Siv , McGowan Madeleine Kate
Published: December 2024

This chapter describes the arts and urban development project “The Garden Caretaker”, an interdisciplinary project that connects artistic practice, architecture, citizen involvement, urban development, and the multispecies perspective. The project takes place in Herlev, on the outskirts of Copenhagen, Denmark. Through its activities, “The Garden Caretaker” fosters connections among humans, non-humans, and their shared local environment. The project serves as a demonstrator site for the NEB lighthouse Desire—Designing the irresistible circular society initiative, exploring how fields of aesthetics, urban planning and biodiversity contribute to a greener, more inclusive urban transition.
Co-creating a Circular Campus in Kalundborg
Authors: Bech Pernille , Overgaard Flemming
Published: December 2024

In response to pressuring challenges such as climate change and the need for sustainable building and manufacturing, the Kalundborg demonstrator aims to develop innovative solutions grounded in education, inclusion, biology, and ecology. The experimentation conducted within the Desire project calls for a transdisciplinary approach for the learning environment, ensuring that graduates can work across educational levels and engage various stakeholders in co-creating innovative solutions. The city of Kalundborg aspires to develop a robust educational campus for about 1,250 students, researchers, teachers, entrepreneurs, and future job candidates. Located near the major Kalundborg biotech industry and just outside the city center, this campus is set to become a significant educational hub within biosolutions and biomanufacturing. This transformation highlights challenges such as the development of a shared vision, plans and programs for the future of the campus. Key challenges include fostering local citizen engagement, creating a vision for the sustainable educational campus that meets diverse needs, and ensuring long-term benefits for the city and its inhabitants. The experimentation conducted within the Desire project seeks to address these issues through comprehensive and inclusive development strategies, promoting sustainable urban development and community resilience.
Literature Review
Authors: Qu Xue , Kojima Daizo , Wu Laping , Ando Mitsuyoshi
Published: December 2024

In this chapter, rice harvest losses are reviewed in terms of estimation methods, magnitudes of loss, causes of loss, impacts, and interventions.
Competing narratives in AI ethics: a defense of sociotechnical pragmatism
Authors: Watson David S. , Mökander Jakob , Floridi Luciano
Published: December 2024

Several competing narratives drive the contemporary AI ethics discourse. At the two extremes are sociotechnical dogmatism, which holds that society is full of inefficiencies and imperfections that can only be solved by better technology; and sociotechnical skepticism, which highlights the unacceptable risks AI systems pose. While both narratives have their merits, they are ultimately reductive and limiting. As a constructive synthesis, we introduce and defend sociotechnical pragmatism—a narrative that emphasizes the central role of context and human agency in designing and evaluating emerging technologies. In doing so, we offer two novel contributions. First, we demonstrate how ethical and epistemological considerations are intertwined in the AI ethics discourse by tracing the dialectical interplay between dogmatic and skeptical narratives across disciplines. Second, we show through examples how sociotechnical pragmatism does more to promote fair and transparent AI than dogmatic or skeptical alternatives. By spelling out the assumptions that underpin sociotechnical pragmatism, we articulate a robust stance for policymakers and scholars who seek to enable societies to reap the benefits of AI while managing the associated risks through feasible, effective, and proportionate governance.
Stimulation of histamine H1-receptors produces a positive inotropic effect in the human atrium
Authors: Pham Thanh Hoai , Abella Lina Maria Rayo , Hadova Katarina , Klimas Jan , Dhein Stefan , Pockes Steffen , Schlicht Jonas Manfred Albert , Hofmann Britt , Kirchhefer Uwe , Neumann Joachim , Gergs Ulrich
Published: December 2024

There is a controversy whether histamine H1-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H1-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H1-receptor in the heart (H1-TG). We detected the messenger ribonucleic acid (mRNA) expression of human histamine H1-receptors in HAP. In LA from H1-TG, each cumulatively applied concentration of histamine and a dual H1/H2-agonist called 2-(2-thiazolyl)-ethylamine (ThEA) caused a time-dependent initial negative inotropic effect followed over time by a lasting positive inotropic effect. Both effects were concentration-dependent in LA from H1-TG. After 100 µM cimetidine, 10 µM histamine exercised a positive inotropic effect in HAP that was diminished by 10 µM mepyramine, an H1-receptor antagonist. The concentrations of mepyramine and cimetidine used here are based on the work of others and our own work (e.g., Guo et al. J Cardiovasc Pharmacol. 6:1210-5 1984, Rayo Abella et al. J Pharmacol Exp Ther. 389:174-185 2024). Similarly, we observed that ThEA (10 µM, 30 µM, 100 µM cumulatively applied) induced a concentration- and time-dependent positive inotropic effect in HAP. In HAP, we detected never negative inotropic effects to either histamine or ThEA. The positive inotropic effects to ThEA in HAP were reduced by mepyramine. The positive inotropic effects of ThEA in LA from H1-TG and in HAP were not accompanied by reductions in the time of tension relaxation. We conclude that stimulation of histamine H1-receptors only increases and does not decrease force of contraction in the HAP in our patients.
Unraveling the competition between charge and energy transfer in 0D/2D nanographene-graphene heterojunctions
Authors: Wlazło Mateusz , Langer Michal , Semchuk Oleksandr Y. , Osella Silvio
Published: December 2024

The charge and energy transfer processes in photoexcited 0D/2D donor/graphene heterojunctions occur through multiple different pathways. A donor deexcitation event occurring in the most prevalent Förster energy transfer mechanism (strongly favored over Dexter transfer in van der Waals heterojunctions) prevents charge transfer from taking place, thus creating a competition between the two processes. By applying a robust computational approach, we describe the two processes from first principles and quantify their rates using Förster and Marcus theories. We consider nanojunctions where the donor are nanographenes with varying size and symmetry, and discern important trends, e.g., the symmetry-induced quenching, or the enhancement due to increased size. We observe that heterojunctions where nanographenes do not have a center of symmetry show decreased photoinduced hole and energy transfer rates, which can then be recovered by increasing the delocalization length, whereas for centrosymmetric nanographenes both hole and energy transfer processes are enhanced. Nevertheless, the hole transfer rate dominates over the energy transfer process, providing a new computation-driven design principle for obtaining a high-charge transfer junction with minimized contribution of the competing energy transfer.
Effectiveness of negative pressure wound therapy (NPWT) in preventing incisional surgical site infection after stoma closure: a single institutional retrospective study
Authors: Nakanishi Ryo , Ozawa Heita , Toyota Naoyuki , Akutsu Ritsuto , Fujita Shin
Published: December 2024

Purpose

Recent findings suggest that utilizing negative pressure wound therapy (NPWT) concurrently with stoma closure may decrease the risk of incisional surgical site infection (iSSI). However, the specific impact of NPWT on iSSI after stoma closure remains unclear. This study investigated the impact of NPWT on SSI after stoma closure.

Methods

Between January, 2010 and December, 2022, 185 patients underwent stoma closure at our hospital. Multivariate analysis was conducted to identify the risk factors for iSSI, using logistic regression analysis. Propensity score matching (PSM) was performed to balance the effect of potential co-factors of stoma closure with and without NPWT, on the incidence of superficial SSIs.

Results

Multivariate analysis identified that the absence of NPWT was an independent risk factor for iSSIs (Odds ratio [OR]: 11.1; 95% confidence interval [CI]: 1.88–64.9; P = 0.0078). Following cohort matching, the NPWT-absence and NPWT-presence groups comprised 54 patients each. The incisional SSI rate was significantly lower in the NPWT-presence group than in the NPWT-absence group (0.9%; n = 1 vs. 7.4%; n = 8, respectively; OR: 9.2; 95% CI 1.11–76.4; P = 0.04).

Conclusion

The findings of this study demonstrated that stoma closure with NPWT reduced the SSI rates remarkably. Therefore, NPWT should be considered for stoma closure procedures.
Reduced-order adaptive synchronization in a chaotic neural network with parameter mismatch: a dynamical system versus machine learning approach
Authors: Kobiolka Jan , Habermann Jens , Yamakou Marius E.
Published: December 2024

This paper addresses the reduced-order synchronization problem between two chaotic memristive Hindmarsh-Rose (HR) neurons of different orders using two distinct methods. The first method employs the Lyapunov active control technique. Through this technique, we develop appropriate control functions to synchronize a 4D chaotic HR neuron (response system) with the canonical projection of a 5D chaotic HR neuron (drive system). Numerical simulations are provided to demonstrate the effectiveness of this approach. The second method is data-driven and leverages a machine learning-based control technique. Our technique utilizes a heuristic combination of reservoir computing (RC) algorithms, incorporating reservoir observer, online control, and online predictive control algorithms. We anticipate our effective heuristic RC adaptive control algorithm to guide the development of more formally structured and systematic, data-driven RC control approaches to chaotic synchronization problems and to inspire more data-driven neuromorphic methods for controlling and achieving synchronization in chaotic neural networks in vivo.
Structural wheat trait estimation using UAV-based laser scanning data: Analysis of critical aspects and recommendations based on a case study
Authors: Dreier Ansgar , Lopez Gina , Bajracharya Rajina , Kuhlmann Heiner , Klingbeil Lasse
Published: December 2024

Purpose

The use of UAVs (Unmanned Aerial Vehicles) equipped with sensors such as laser scanners offers an alternative to conventional, labor-intensive manual measurements in agriculture, as they enable precise and non-destructive field surveys.

Methods

This paper evaluates the use of UAV-based laser scanning (RIEGL miniVUX-SYS) for estimating the crop height and the plant area index (PAI) of winter wheat. (Methods) It further introduces a novel ground classification method, enhancing early growth stage classification through sensor attributes like intensity and pulse shape deviation.

Results

The crop height estimation shows a high

$$R^2$$

R
2

score with

$$99.69~\%$$

99.69

%

but a systematically lower estimate with a mean absolute error of 7.4 cm. The potential of PAI derivation is analyzed with three different estimation strategies and provides an overview and limitations of the approach. Additional weighting based on the scan angle and the adaptation of the extinction coefficient present results with

$$R^2$$

R
2

of

$$97.66~\%$$

97.66

%

and a mean absolute error of 0.25.

Conclusion

The investigation discusses further the impact of the calculated gap fraction, which describes the ratio of laser beams penetrating through the crop canopy in comparison to the total number of measurements.
Evaluating and accelerating vision transformers on GPU-based embedded edge AI systems
Authors: Martin-Salinas Ignacio , Badia Jose M. , Valls Oscar , Leon German , del Amor Rocio , Belloch Jose A. , Amor-Martin Adrian , Naranjo Valery
Published: December 2024

Many current embedded systems comprise heterogeneous computing components including quite powerful GPUs, which enables their application across diverse sectors. This study demonstrates the efficient execution of a medium-sized self-supervised audio spectrogram transformer (SSAST) model on a low-power system-on-chip (SoC). Through comprehensive evaluation, including real time inference scenarios, we show that GPUs outperform multi-core CPUs in inference processes. Optimization techniques such as adjusting batch size, model compilation with TensorRT, and reducing data precision significantly enhance inference time, energy consumption, and memory usage. In particular, negligible accuracy degradation is observed, with post-training quantization to 8-bit integers showing less than 1% loss. This research underscores the feasibility of deploying transformer neural networks on low-power embedded devices, ensuring efficiency in time, energy, and memory, while maintaining the accuracy of the results.
Selection signatures associated with adaptation in South African Drakensberger, Nguni, and Tuli beef breeds
Authors: Maxman Gomo , van Marle-Köster Este , Lashmar Simon Frederick , Visser Carina
Published: December 2024

In the present study 1,709 cattle, including 1,118 Drakensberger (DRB), 377 Nguni (NGI), and 214 Tuli (TUL), were genotyped using the GeneSeek® Genomic Profiler™ 150 K bovine SNP panel. A genomic data set of 122,632 quality-filtered single nucleotide polymorphisms (SNPs) were used to identify selection signatures within breeds based on conserved runs of homozygosity (ROH) and heterozygosity (ROHet) estimated with the detectRUNS R package. The mean number of ROH per animal varied across breeds ranging from 36.09 ± 12.82 (NGI) to 51.82 ± 21.01 (DRB), and the mean ROH length per breed ranged between 2.31 Mb (NGI) and 3.90 Mb (DRB). The smallest length categories i.e., ROH < 4 Mb were most frequent, indicating historic inbreeding effects for all breeds. The ROH based inbreeding coefficients (FROH) ranged between 0.033 ± 0.024 (NGI) and 0.081 ± 0.046 (DRB). Genes mapped to candidate regions were associated with immunity (ADAMTS12
,
LY96, WDPCP) and adaptation (FKBP4, CBFA2T3, TUBB3) in cattle and genes previously only reported for immunity in mice and human (EXOC3L1, MYO1G). The present study contributes to the understanding of the genetic mechanisms of adaptation, providing information for potential molecular application in genetic evaluation and selection programs.