Search Results (198,310)

Vaginitis is a widespread issue for women worldwide, yet current diagnostic tools are lacking. Bacterial vaginosis (BV) is the most prevalent type of vaginitis, found in 10–50% of reproductive-aged women. Current diagnostic methods for BV rely on clinical criteria, microscopy, or the detection of a few microbes by qPCR. However, many vaginal infections lack a single etiological agent and are characterized by changes in the vaginal microbiome community structure (e.g., BV is defined as a loss of protective lactobacilli resulting in an overgrowth of anaerobic bacteria). Shotgun metagenomic sequencing provides a comprehensive view of all the organisms present in the vaginal microbiome (VMB), allowing for a better understanding of all potential etiologies. Here, we describe a robust VMB metagenomics sequencing test with a sensitivity of 93.1%, a specificity of 90%, a negative predictive value of 93.4%, and a positive predictive value of 89.6% certified by Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologist (CAP), and the Clinical Laboratory Evaluation Program (CLEP). We sequenced over 7000 human vaginal samples with this pipeline and described general findings and comparisons to US census data. Full article

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates’ ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay’s effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel^® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay’s potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations. Full article

The Mississippi River Delta Front (MRDF) is a subaqueous apron of rapidly deposited and weakly consolidated sediment extending from the subaerial portions of the Birdsfoot Delta of the Mississippi River, long characterized by mass-wasting sediment transport. Four (4) depositional environments dominate regionally (an undisturbed topset apron, mudflow gully, mudflow lobe, and prodelta), centering around mudflow distribution initiated by a variety of factors (hurricanes, storms, and fluid pressure). To better understand the spatiotemporal scales of the events as well as the controlling processes, eight cores (5.8–8.0 m long) taken offshore from the South Pass (SP) and the Southwest Pass (SWP) were analyzed for gamma density, grain size, sediment fabric (X-radiography), and geochronology (²¹⁰Pb/¹³⁷Cs radionuclides). Previous work has focused on the deposition of individual passes and has been restricted to <3 m core penetration, limiting its geochronologic completeness. Building on other recent studies, within the mudflow gully and lobe cores, the homogeneous stepped profiles of ²¹⁰Pb activities and the corresponding decreased gamma density indicate the presence of gravity-driven mass failures. ²¹⁰Pb/¹³⁷Cs indicates that gully sedimentary sediment accumulation since 1953 is greater than 580 cm (sediment accumulation rate [SAR] of 12.8 cm/y) in the southwest pass site, and a lower SAR of the South Pass gully sites (2.6 cm/y). This study shows that (1) recent dated mudflow deposits are identifiable in both the SWP and SP; (2) SWP mudflows have return periods of 10.7 y, six times more frequent than at the SP (66.7 y); (3) ²¹⁰Pb inventories display higher levels in the SWP area, with the highest focusing factors in proximal/gully sedimentation, and (4) submarine landslides in both study areas remain important for sediment transport despite the differences in sediment delivery and discharge source proximity. Full article

Abstract: Metamaterials have emerged as a focal point in contemporary science and technology due to their ability to drive significant innovations. These engineered materials are specifically designed to couple the phenomena of different physical natures, thereby influencing processes through mechanical or thermal effects. While much of the recent research has concentrated on frequency conversion into electromagnetic waves, the field of acoustic frequency conversion still faces considerable technical challenges. To overcome these hurdles, researchers are developing metamaterials with customized acoustic properties. A key equation for modeling nonlinear acoustic wave phenomena is the dissipative Westervelt equation. This study investigates analytical solutions using ansatz-based methods combined with Lie symmetries. The approach presented here provides a versatile framework that is applicable to a wide range of fields in metamaterial design. Full article

Pancreatic cancer presents formidable challenges due to rapid progression and resistance to conventional treatments. Oncolytic viruses (OVs) selectively infect cancer cells and cause cancer cells to lyse, releasing molecules that can be identified by the host’s immune system. Moreover, OV can carry immune-stimulatory payloads such as interleukin-12, which when delivered locally can enhance immune system-mediated tumor killing. OVs are very well tolerated by cancer patients due to their ability to selectively target tumors without affecting surrounding normal tissues. OVs have recently been combined with other therapies, including chemotherapy and immunotherapy, to improve clinical outcomes. Several OVs including adenovirus, herpes simplex viruses (HSVs), vaccinia virus, parvovirus, reovirus, and measles virus have been evaluated in preclinical and clinical settings for the treatment of pancreatic cancer. We evaluated the safety and tolerability of a replication-competent oncolytic adenoviral vector carrying two suicide genes (thymidine kinase, TK; and cytosine deaminase, CD) and human interleukin-12 (hIL12) in metastatic pancreatic cancer patients in a phase 1 trial. This vector was found to be safe and well-tolerated at the highest doses tested without causing any significant adverse events (SAEs). Moreover, long-term follow-up studies indicated an increase in the overall survival (OS) in subjects receiving the highest dose of the OV. Our encouraging long-term survival data provide hope for patients with advanced pancreatic cancer, a disease that has not seen a meaningful increase in OS in the last five decades. In this review article, we highlight several preclinical and clinical studies and discuss future directions for optimizing OV therapy in pancreatic cancer. We envision OV-based gene therapy to be a game changer in the near future with the advent of newer generation OVs that have higher specificity and selectivity combined with personalized treatment plans developed under AI guidance. Full article

The friction/adhesion between the tool and chip is generally large in metal cutting, and it causes many problems such as high cutting energy/rough surface finish. To suppress this, cutting fluid and tool coating are used in practice, but they are high in energy/cost and environmentally unfriendly. Therefore, this paper investigates the extraordinarily high-speed cutting (EHS cutting) mechanics of mainly soft and highly heat-conductive materials and proposes their application to solve the friction/adhesion problem in an environmentally friendly manner. In order to clarify the EHS cutting mechanics, a simple analytical model is constructed and experiments are conducted with measurement of the cutting temperature and forces. As a result, the following points are clarified/found: (1) heat softening at the secondary plastic deformation zone rather than the primary plastic deformation zone, (2) friction coefficient drop to 0.170 in EHS cutting, and (3) gradually increasing trend of cutting temperature in EHS cutting. Finally, EHS cutting is applied to dry cutting of aluminum alloys with a non-coated carbide tool and compared to conventional wet cutting with a DLC-coated carbide tool, and it is shown that a coating/coolant can be omitted in this region to achieve environmentally friendly cutting. Full article

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease’s pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which—upon effective drug delivery to their target cells—allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease. Full article

Colorectal cancer (CRC) is a significant public health issue, particularly in low- and middle-income countries like Thailand. While numerous studies advocate for regular screenings and health promotion programs to mitigate CRC risk, there is a notable lack of tailored health promotion models specifically designed for high-risk groups in Thailand. This research aims to develop a health promotion model to prevent CRC in high-risk groups through a quasi-experimental design. The study involved 68 Thai participants aged 40–70 years, divided equally into experimental and comparison groups. Independent-Samples t-test, Paired-Samples t-test, and one-way variance test (F-test) were employed to analyze the data. The comparison of baseline average scores for physical health, mental health, social health, and knowledge on health-promoting behaviors between the experimental and comparison groups revealed no significant differences. However, following the experiment, the average scores in physical health (t = −2.81, p = 0.01) and mental health (t = −10.30, p < 0.001) were significantly higher compared to pre-experiment levels, with the exception of social health (t = 0.07, p = 0.94). Furthermore, the average knowledge scores related to promoting physical, mental, and social health in the experimental group also showed a significant increase after the experiment (t = −4.53, p < 0.001). The findings suggest that health personnel should advocate for annual CRC screening and the implementation of health promotion programs, especially focusing on physical, mental, and social aspects for at-risk populations. This study underscores the need for long-term health promotion models to achieve continuous and sustainable health improvements in these groups. Full article

Smart dental materials refer to materials used in dentistry with additional functionality to enhance treatment outcomes, which may improve oral health. Smart materials for dental restorations can react to stimuli such as a specific temperature, a different pH, or mechanical stress, repair small cracks or damage by themselves, and interact beneficially with biological surroundings. For example, they might release ions and promote tooth remineralization or have antibacterial properties to prevent bacterial growth. Others can have enhanced mechanical properties like strength and wear resistance to ensure these materials can withstand daily masticatory forces. This review presents our current comprehension of smart dental materials designed for tooth restoration. We focused on what these materials need to be effective, like durability, biocompatibility, and aesthetic requests, besides identifying new ideas for their design. A detailed analysis of the current challenges in formulating these materials, such as the balance between enough ions released with proper physicochemical properties and achieving the desired biological response, was discussed. We also discussed how these cutting-edge technologies are leveraged to overcome existing limitations, creating more dental materials with potential clinical translation. The review also discusses the practical challenges in implementation and the prospects for these materials in dentistry. Full article

The present study analyzes two potential therapeutic approaches for Alzheimer’s disease (AD). One is the suppression of the neuronal integrated stress response (ISR). Another is the targeted degradation of intraneuronal amyloid-beta (iAβ) via the activation of BACE1 (Beta-site Aβ-protein-precursor Cleaving Enzyme) and/or BACE2. Both approaches are rational. Both are promising. Both have substantial intrinsic limitations. However, when combined in a carefully orchestrated manner into a composite therapy they display a prototypical synergy and constitute the apparently optimal, potentially most effective therapeutic strategy for AD. Full article

Poor oral health can impact overall health. This study assessed the association between dental factors (dentate status and dental utilization) and self-rated health (S-RH) among older adults in two cross-sectional datasets: (1) NIH “All of Us (AoU) Research Program” (May 2018—July 2022 release) and (2) U.S. nationally representative “Health and Retirement Study” (HRS) 2018 wave. Participants aged ≥ 51 years were included in these analyses if (1) from AoU, they had clinical dental and medical data from electronic health records (EHRs) and surveys (n = 5480), and (2) from HRS, they had dental and socio-demographic survey data (n = 14,358). S-RH was dichotomized (fair/poor vs. better) and analyzed with logistic regression. Sample survey weights for HRS and stratification and averaging AoU results used the weighted HRS race–ethnicity and age distribution standardized respective analyses to the U.S. population. Fair/poor S-RH was reported by 32.6% in AoU and 28.6% in HRS. Dentate status information was available from 7.7% of AoU EHRs. In population-standardized analyses, lack of dental service use increased odds of fair/poor S-RH in AoU, OR (95% CI) = 1.28 (1.11–1.48), and in HRS = 1.45 (1.09–1.94), as did having diabetes, less education, and ever being a smoker. Having no natural teeth was not statistically associated with fair/poor S-RH. Lack of dental service was positively associated with fair/poor S-RH in both datasets. More and better oral health information in AoU and HRS are needed. Full article

Biunivalent holomorphic functions form an interesting class in geometric function theory and are connected with special functions and solutions of complex differential equations. This class has been investigated by many authors, mainly to find the coefficient estimates. The assumption of biunivalence is rigid; this rigidity means that, for example, only the initial Taylor coefficients have been estimated. The aim of this paper is to develop a variational technique for biunivalent functions, which provides a power tool for solving the general extremal problems on the classes of such functions. It involves quasiconformal analysis. Full article

In the field of wound care, the prescription of antibiotics and antimicrobials is haphazard and irrational, which has led to unchecked overprescribing. Recent Joint Commission guidelines mandate that hospital outpatient clinics develop and implement antimicrobial stewardship programs (ASPs). Yet few ASPs exist in wound clinics across the United States (US). Understanding baseline prescribing practices and rates in the US is a critical first step toward rational antimicrobial use and effective ASPs. This prospective study was conducted across eight outpatient wound clinics from January–December 2022. Data from consecutive patients attending single-time-point initial visits were recorded, including clinical findings, antimicrobial prescribing trends, and sampling practices. A total of 1438 wounds were included; 964 were assessed by clinical examination (standard of care, SoC), and 474 by clinical examination plus fluorescence imaging. SoC patients were prescribed more concurrent medications on average than fluorescence patients (1.4 vs. 1 per patient). Prescriptions were preferentially topical in the fluorescence group (92% vs. 64%, p > 0.0001), and systemic antibiotics represented 36% of the single items prescribed under SoC (vs. 8% in fluorescence group p < 0.0001). Fluorescence imaging provided objective and actionable information at the bedside, which led to a decrease in the use of antibiotics. Real-time diagnostic technologies are essential in establishing a meaningful ASP. Full article

Language loss hinders the expression of Indigenous Peoples and their unique worldviews, impairing the intergenerational transfer of knowledge. In Hawai‘i, where a vast majority of the population was fluent and “universally literate” in ‘Ōlelo Hawai‘i from the mid to late 1800s, colonial impositions drastically reduced the number of fluent speakers to roughly 2000 by the 1970s. Efforts to revitalize the language since then have greatly increased the number of current ‘Ōlelo Hawai‘i speakers and resources. Building upon this great work, the Hā Kūpuna National Resource Center for Native Hawaiian Elders at the University of Hawai‘i has initiated projects to contribute to the reclamation of ‘Ōlelo Hawai‘i by increasing our contemporary understanding of ancestral Hawaiian perspectives on elders. To support these projects, significant changes in power structures within our organization were necessary. Insights gained from these projects include gaining clarity on the evolution of the usage of the word “kupuna”, identifying more nuanced perspectives on elders, understanding the importance of family relationships on caregiving outcomes, and understanding the importance of carefully translating English words into ‘Ōlelo Hawai‘i. Full article

Moringa oleifera Lam. (moringa) is a plant native to India, used as a nutritional and medicinal supplement in many cultures around the world. Moringa has been linked to maintaining metabolic homeostasis and is often marketed as a weight loss supplement and a potential remedy for diseases such as diabetes. Here, we investigate how moringa, a ‘superfood’ with predicted protective effects against chronic diseases such as diabetes, influences the nutritional physiology and microbiome composition of the fruit fly Drosophila melanogaster. We administered moringa as a dietary supplement to Drosophila, and quantified key nutritional indices: glucose, triacylglyceride, and protein levels, and fly weight. We showed that dietary moringa supplementation significantly reduced fly glucose levels by up to ~30% and resulted in substantial restructuring of Drosophila microbiota composition, altering both gut and intracellular bacterial populations. The effect of moringa on fly glucose levels is specific because other nutritional indices, namely, triacylglyceride and protein levels and fly weight, were not significantly affected by dietary moringa supplementation. This study highlights the importance of moringa as a modulator of host glucose metabolism. Full article