Search Results (1,201)

The aim of this study was to compare the forces and moments exerted by thermoformed aligners (TFMs) and direct printed aligners (DPAs) on the maxillary left central incisor (21) and adjacent teeth (11, 22) during lingual bodily movement of tooth 21. Methods: An in vitro setup was used to quantify forces and moments on three incisors, which were segmented and fixed onto multi-axis force/moment transducers. TFM were fabricated using 0.76 mm-thick single-layer PET-G foils (ATMOS; American Orthodontics, Sheboygan, WI, USA) and multi-layer TPU foils (Zendura FLX; Bay Materials LLC, Fremont, CA, USA). DPAs were fabricated using TC-85 photopolymer resin (Graphy Inc., Seoul, Republic of Korea). Tooth 21 was planned for bodily displacement by 0.25 mm and 0.50 mm, and six force and moment components were measured on it and the adjacent teeth. Results: TC-85 generated lower forces and moments with fewer unintended forces and moments on the three teeth. TC-85 exerted 0.99 N and 1.53 N of mean lingual force on tooth 21 for 0.25 mm and 0.50 mm activations, respectively; ATMOS produced 3.82 N and 7.70 N, and Zendura FLX produced 3.00 N and 8.23 N of mean lingual force for the same activations, respectively. Bodily movement could not be achieved. Conclusions: The force systems generated by clear aligners are complex and unpredictable. DPA using TC-85 produced lower, more physiological force levels with fewer side effects, which may increase the predictability of tooth movement and enhance treatment outcome. The force levels generated by TFM were considered excessive and not physiologically compatible. Full article

Autumn fern, Dryopteris erythrosora, is the most marketed temperate fern in the world. The rapid increase and spread of this recently naturalized fern in North America was determined and mapped using 76 herbarium specimen records and 2553 Research Grade iNaturalist posts. In 2008, it was recorded in two states, but by 2025, it was found in 25 states in the eastern United States and Ontario, Canada. At the end of 2017, there had been only 23 iNaturalist posts, but this grew to 511 by the end of 2020 and 2553 by May 2025. The great increase in the number of iNaturalist posts is thought to be due to the real geographic spread and an actual increase in the abundance of the fern, as well as recognition of the fern by iNaturalists, and the increase in the number of iNaturalists. The spread and great increase are probably related to the high level of marketing, which introduces plants to the environment, and to biological characteristics of the fern, including apogamy and polyploidy, and possibly natural enemy release, which allows it to flourish in new environments and to displace native plants. This novel study demonstrated citizen science’s (iNaturalist’s) great value in detecting the naturalization and spread of alien plants. Full article

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

Background: Pancreas and pancreas–kidney transplantation are well-established therapeutic options for patients with type 1 diabetes mellitus (T1DM) and end-stage kidney disease (ESKD), offering the potential to restore endogenous insulin production and kidney function. It improves metabolic control, quality of life, and long-term survival. While surgical techniques and immunosuppressive strategies have advanced considerably, graft rejection and limited long-term graft survival remain significant clinical challenges. Method: To better understand these risks, the genetic and immunological factors that influence transplant outcomes are examined. Beyond traditional human leukocyte antigen (HLA) matching, non-HLA genetic variants such as gene deletions and single-nucleotide polymorphisms (SNPs) have emerged as contributors to alloimmune activation and graft failure. Result: Polymorphisms in cytokine genes, minor histocompatibility antigens, and immune-regulatory pathways have been implicated in transplant outcomes. However, the integration of such genomic data into clinical practice remains limited due to underexplored gene targets, variability in study results, and the lack of large, diverse, and well-characterized patient cohorts. Initiatives like the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) are addressing these limitations by aggregating genome-wide data from thousands of transplant donors and recipients across multiple centers. These large-scale collaborative efforts aim to identify clinically actionable genetic markers and support the development of personalized immunosuppressive strategies. Conclusions: Overall, genetic testing and genomics hold great promise in advancing precision medicine in pancreas and pancreas–kidney transplantation. Full article

A novel brain positron emission tomography (PET) radioligand, [¹¹C]HY-2-15, has potential for imaging alpha-synuclein aggregations in multiple system atrophy and misfolded tau proteins in tauopathies, based on its high binding affinity in disease brain tissue homogenates. Here, we demonstrate that [³H]HY-2-15 has the capability to bind to aggregated alpha-synuclein in multiple system atrophy brain and tau aggregations in progressive supranuclear palsy and corticobasal degeneration brain tissues via in vitro autoradiography study. A first-in-human pilot multicenter clinical study recruited a total of 10 subjects including healthy controls and patients with Parkinson’s disease, multiple system atrophy, or progressive supranuclear palsy. The study revealed that [¹¹C]HY-2-15 has a relatively higher specific uptake in the pallidum and midbrain of patients with progressive supranuclear palsy. Total-body scans performed on the PennPET Explorer showed the radiotracer was cleared by renal excretion. However, the rapid metabolism and low brain uptake resulted in a limited signal of [¹¹C]HY-2-15 in brain. Full article

A periodically poled LiNbO₃ (PPLN) non-resonant optical parametric oscillator injectionseeded by narrowband sub-50-mW CW radiation at the signal wavelength produces a >3 W average idler power at 2376 nm for a 20 kHz repetition rate, with a ~2 nm spectral linewidth. Seed levels as low as 5 mW are sufficient to produce the desired spectral narrowing effect, and spectral tuning is possible by changing the seed wavelength and simultaneously adjusting the crystal temperature. The spectral features are in good agreement with numerical simulations based on the plane wave approximation. Full article

Reported herein is a further expansion of the cooperatively catalyzed Koenigs–Knorr glycosylation reaction, known as “the 4K reaction”. It has been discovered that molecular iodine, along with a metal salt and an acid additive, can activate thioglycosides. Previous mechanistic studies showed the interaction of the anomeric sulfur with thiophilic iodine; this complex is stable until the halophilic metal salt and the acid additive are added. This new avenue has allowed for the investigation of halophilic promoters that would not activate thioglycosides without iodine. Presented herein is the recent discovery of iron(III) triflate as an efficient activator of thioglycosides via the 4K reaction pathway. Full article

Trichomes in cannabis (Cannabis sativa L.) are specialized structures responsible for cannabinoid and terpene biosynthesis, making their density a critical parameter for both research and industrial applications. However, consistent trichome density assessment remains challenging due to anatomical variability and the absence of standardized methodologies. This review critically examines the existing literature on trichome quantification across key floral structures—such as bracts, sugar leaves, calyxes, and the main cola—to identify the most reliable sites and practices for accurate evaluation. Evidence suggests that bracts represent the most consistent sampling unit, given their homogeneous trichome distribution and elevated cannabinoid concentration. Whilst sugar leaves and calyxes are also frequently analyzed, their morphological variability requires cautious interpretation. Furthermore, trichome shape, size, maturity, and vegetal surface expansion/shrinkage during stress must be considered when correlating density with secondary metabolite production. We also highlight the advantages of using more than only one floral structure and integrating microscopic imaging and software-assisted analysis to enhance reproducibility and accuracy. By synthesizing current methodologies and proposing pathways for standardization, this review aims to support more robust trichome assessment protocols, ultimately improving cannabinoid yield optimization, quality control, broader cannabis research frameworks, and an important aesthetic parameter for consumers. Future research efforts should focus on advancing imaging methodologies and optimizing sampling protocols to further improve the precision and reproducibility of trichome density and cannabinoid analyses. Full article

Background/Objectives: Deep brain stimulation (DBS) is an effective surgical treatment for Parkinson’s Disease (PD) and other movement disorders. Despite its benefits, DBS explantation occurs in 5.6% of cases, with costs exceeding USD 22,000 per implant. Traditional statistical methods have struggled to identify reliable risk factors for explantation. We hypothesized that supervised machine learning would more effectively capture complex interactions among perioperative factors, enabling the identification of novel risk factors. Methods: The Medical Informatics Operating Room Vitals and Events Repository was queried for patients with DBS, adequate clinical data, and at least two years of follow-up (n = 38). Fisher’s exact test assessed demographic and medical history variables. Data were analyzed using Anaconda Version 2.3.1. with pandas, numpy, sklearn, sklearn-extra, matplotlin. pyplot, and seaborn. Recursive feature elimination with cross-validation (RFECV) optimized factor selection was used. A multivariate logistic regression model was trained and evaluated using precision, recall, F1-score, and area under the curve (AUC). Results: Fisher’s exact test identified chronic pain (p = 0.0108) and tobacco use (p = 0.0026) as risk factors. RFECV selected 24 optimal features. The logistic regression model demonstrated strong performance (precision: 0.89, recall: 0.86, F1-score: 0.86, AUC: 1.0). Significant risk factors included tobacco use (OR: 3.64; CI: 3.60–3.68), primary PD (OR: 2.01; CI: 1.99–2.02), ASA score (OR: 1.91; CI: 1.90–1.92), chronic pain (OR: 1.82; CI: 1.80–1.85), and diabetes (OR: 1.63; CI: 1.62–1.65). Conclusions: Our study suggests that supervised machine learning can identify risk factors for early DBS explantation. Larger studies are needed to validate our findings. Full article

Background/Objectives: The oral cavity represents a convenient route of administration for drugs that exhibit significant hepatic first-pass extraction. In this study, the mucosal permeation properties of selected active pharmaceutical ingredients (APIs) incorporated into oral cavity drug products that are approved by the U.S. Food and Drug Administration were quantified using the human-derived sublingual HO-1-u-1 and buccal EpiOral™ in vitro tissue models. Methods: Epithelial barrier properties were monitored using propranolol and Lucifer Yellow as prototypic transcellular and paracellular markers. APIs were dissolved in artificial saliva, pH 6.7, and transepithelial flux from the apical to the basolateral compartment was quantified using HPLC. Results: Apparent permeability coefficients (Papp) calculated for these APIs in the sublingual HO-1-u-1 tissue model varied from Papp = 2.72 ± 0.06 × 10⁻⁵ cm/s for asenapine to Papp = 6.21 ± 2.60 × 10⁻⁵ cm/s for naloxone. In contrast, the buccal EpiOral™ tissue model demonstrated greater discrimination power in terms of permeation properties for the same APIs, with values ranging from Papp = 3.31 ± 0.83 × 10⁻⁷ cm/s for acyclovir to Papp = 2.56 ± 0.68 × 10⁻⁵ cm/s for sufentanil. The tissue-associated dose fraction recovered at the end of the transport experiment was significantly increased in the buccal EpiOral™ tissue model, reaching up to 8.5% for sufentanil. Conclusions: Experimental permeation data collected for selected APIs in FDA-approved oral cavity products will serve as a training set to aid the development of predictive computational models for improving algorithms that describe drug absorption from the oral cavity. Following a robust in vitro–in vivo correlation analysis, it is expected that such innovative in silico modeling strategies will the accelerate development of generic oral cavity products by facilitating the utility of model-integrated evidence to support decision making in generic drug development and regulatory approval. Full article

Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents. Full article

Background: TNBC patients respond poorly to chemotherapy, leading to high mortality rates and a worsening prognosis. Here, we investigated the effect of M-I on TNBC tumor growth suppression and its potential mechanisms. Methods: Signaling pathways were analyzed to study the effect of M-I on TNBC cells (human MDA-MB-231 and mouse 4T1). We used orthotopic mouse models to examine the anti-tumor efficacy of M-I. Tumor volume and the status of tumor-associated macrophages (TAMs) were assessed by qRT-PCR or FACS analysis. Results: We found a significant dose- and time-dependent inhibition of TNBC cell proliferation following treatment with M-I. Cell cycle analysis revealed a shortened S phase in M-I-treated cells and downregulation of AURKA, PLK1, CDC25c, CDK1, and cyclinB1. Furthermore, M-I treatment reduced the expression of pSTAT3, cyclinD1, and c-Myc in TNBC cells. To evaluate the anti-tumor efficacy of M-I, we employed orthotopic TNBC mouse models and observed a significant reduction in tumor growth without measurable toxicity. Next, we analyzed RNA from control and M-I-treated tumors to further assess the status of TAMs and observed a significant decrease in M2-like macrophages in the M-I-treated group. Immortalized bone marrow-derived mouse macrophages (iMacs) exposed to conditioned media (CM) of TNBC cells with or without M-I treatment indicated that the M-I treated CM of TNBC cells significantly reduce the M2phenotype in iMacs. Mechanistically, we found that M-I specifically targets the IL-4/MAPK signaling axis to reduce immunosuppressive M2 macrophage polarization. Conclusions: Our study reveals a novel mechanism by which M-I inhibits TNBC cell proliferation by regulating intracellular signaling and altering TAMs in the tumor microenvironment and highlights its potential as a promising candidate for TNBC therapy. Full article

Optical tactile sensing is gaining traction as a foundational technology in collaborative and human-interactive robotics, where reliable touch and pressure feedback are critical. Traditional systems based on total internal reflection (TIR) and frustrated TIR (FTIR) often require complex infrared setups and lack adaptability to curved or flexible surfaces. To overcome these limitations, we developed OptoSkin—a novel tactile platform leveraging direct time-of-flight (ToF) LiDAR principles for robust contact and pressure detection. In this extended study, we systematically evaluate how key optical properties of waveguide materials affect ToF signal behavior and sensing fidelity. We examine a diverse set of materials, characterized by varying light transmission (82–92)%, scattering coefficients (0.02–1.1) cm⁻¹, diffuse reflectance (0.17–7.40)%, and refractive indices 1.398–1.537 at the ToF emitter wavelength of 940 nm. Through systematic evaluation, we demonstrate that controlled light scattering within the material significantly enhances ToF signal quality for both direct touch and near-proximity sensing. These findings underscore the critical role of material selection in designing efficient, low-cost, and geometry-independent optical tactile systems. Full article