Biology (Basel). 2024 Dec 7;13(12):1025. doi: 10.3390/biology13121025.

ABSTRACT

The journal Biology was launched in 2012 [...].

PMID:39765692 | DOI:10.3390/biology13121025

Pharmaceuticals (Basel). 2024 Nov 26;17(12):1592. doi: 10.3390/ph17121592.

ABSTRACT

Background: Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used during pregnancy. Due to their fetotoxicity, NSAIDs are contraindicated during the third trimester. There is ongoing controversy about the extent to which NSAIDs may cause cardiovascular and renal impairment in the fetus earlier in the second trimester. Paracetamol, used as an effective treatment for closure of patent ductus arteriosus (PDA) after birth, is suspected to cause similar but unwanted effects during the third trimester of pregnancy. Methods: Three major pharmacovigilance databases (VigilanceCentral, EudraVigilance, and VigiBase) were searched for Individual Case Safety Reports (ICSRs; n = 1288) on fetotoxic effects that have been shown to result from NSAID exposure in late pregnancy. Results: In 219/1288 cases, an NSAID and/or paracetamol was taken after the first trimester, and the ICSR was not related to other reported risk factors. Out of these 219 ICSRs, 48 were exposed to NSAIDs in the second but not the third trimester or to paracetamol in the third trimester. Causality assessment was "probable or likely" in four NSAID reports and none of the paracetamol reports. Conclusions: The scarcity of adverse drug reactions (ADRs) in our study and in the literature, despite decades of pharmaceutical marketing and worldwide use of paracetamol as an analgesic of choice in the third trimester and the absence of formal contraindications against NSAIDs in the second trimester, speaks against a substantial cardiovascular and nephrotoxic risk of temporary use of NSAIDs in the second trimester or paracetamol in the third trimester. NSAIDs continue to be contraindicated in the third trimester.

PMID:39770434 | DOI:10.3390/ph17121592

Funding Opportunity PAR-24-329 from the NIH Guide for Grants and Contracts. This notice of funding opportunity (NOFO) encourages formative research, intervention development, and pilot-testing of interventions. Primary scientific areas of focus include the feasibility, tolerability, acceptability and safety of novel or adapted interventions that target HIV prevention, treatment or services research for people who use drugs. For the purposes of this NOFO, "intervention" may include behavioral, social, or structural approaches, as well as combination biomedical and behavioral approaches that prevent the acquisition and transmission of HIV infection, or improve clinical outcomes for persons living with HIV.

Funding Opportunity RFA-AT-25-002 from the NIH Guide for Grants and Contracts. This notice of funding opportunity (NOFO) invites investigators currently funded through the NIH Implementing a Maternal Health and Pregnancy Outcomes Vision for Everyone (IMPROVE) Initiative to develop applications to test the feasibility of complementary and integrative approaches with psychological and/or physical inputs (often called mind and body interventions) to promote healthy pregnancies and enhance maternal health outcomes. Currently funded IMPROVE investigators- particularly the Maternal Health Centers of Excellence- are encouraged to partner with investigators with complementary and integrative health expertise. Eligibility is limited to currently funded investigators of the IMPROVE initiative. Applications submitted under this NOFO are expected to propose a multisite feasibility clinical trial that will provide new information that is scientifically necessary for the planning and conduct of a subsequent clinical efficacy or effectiveness study, pragmatic trial, or dissemination and implementation trial on a mind and body intervention to enhance maternal health. It is expected that applications to this NOFO will describe the planned future clinical trial and in so doing demonstrate that the proposed (R01) research is scientifically necessary to design or plan the subsequent fully powered, full-scale clinical trial. Under this R01, the data collected should be used to fill gaps in scientific knowledge, including, but not limited to the following: assessing whether the intervention can be delivered with fidelity across sites; demonstrating feasibility of recruitment, accrual, and randomization of participants across sites; demonstrating participant adherence to the intervention, as well as retention of participants throughout the study across sites; refining and assessing the feasibility of protocolized multimodal interventions, and/or demonstrating feasibility of data collection across sites in preparation for a future fully powered, multisite efficac

Funding Opportunity RFA-NR-25-004 from the NIH Guide for Grants and Contracts. Research shows that intersecting systems of privilege and oppression produce and sustain wide and unjust variations in health. The Axes Initiative will support research to understand health at the intersections of social statuses such as race, ethnicity, socioeconomic status, sexual orientation, and ability, by examining contributions of social and other determinants of health.

Funding Opportunity RFA-AT-25-003 from the NIH Guide for Grants and Contracts. The purpose of this initiative is to: (1) support the efforts by R15-eligible Principal Investigators (PIs) to conduct rigorous basic and/or mechanistic pain research projects; (2) promote integrated, interdisciplinary research partnerships between R15-eligible PIs and additional investigators from U.S. domestic institutions, and (3) enhance the pain research environment at the R15-eligible institution for health professional trainees or undergraduate and/or graduate students by actively engaging them in the proposed pain research projects.

Funding Opportunity PAS-25-102 from the NIH Guide for Grants and Contracts. This Notice of Funding Announcement (NOFO) encourages the submission ofpilot and feasibilityclinical trialsconducted in humans that will lay the foundation for larger clinical trials related to the prevention and/or treatment of diseases and conditions within the mission of NIDDK. The program will support small, short-term proof-of-concept clinical trials in humans to acquire preliminary data regarding the effects of the intervention, as well as feasibility data related to recruitment and retention, and study conduct. Applications for clinical trials submitted under this NOFO should have clearly described aims and objectives and have a high likelihood that the trial findings will lead to more definitive, hypothesis-driven trials to improve understanding, diagnosis, prevention or treatment of the diseases studied and have the potential to impact clinical practice and/or public health.Preliminary data regarding intervention efficacy are not required.

Funding Opportunity PAR-25-377 from the NIH Guide for Grants and Contracts. This Notice of Funding Opportunity (NOFO) will support innovative, collaborative, and multi-disciplinary research focused on clinical epidemiology, evaluation of public and/or health care policies, and validation of measurements that address health and health care disparities related to non-communicable and chronic diseases (NCDs) with the highest disease burden and mortality in Latin America and among U.S. Hispanics/Latinos. Multi-disciplinary research teams would be expected to meaningfully collaborate with key partners that must include at least one PI or MPI from institutions in Latin America.

Funding Opportunity PAS-25-073 from the NIH Guide for Grants and Contracts. This Notice of Funding Opportunity (NOFO) seeks to stimulate HIV/AIDS research within the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that align with the HIV/AIDS research priorities outlined by the NIH Office of AIDS Research (OAR). These priorities were most recently described in NOT-OD-20-018 UPDATE: NIH HIV/AIDS Research Priorities and Guidelines for Determining HIV/AIDS Funding.

Funding Opportunity PAR-25-048 from the NIH Guide for Grants and Contracts. The purpose of this announcement is to encourage grant applications for investigator-initiated prospective observational comparative effectiveness research (CER) to the National Institute of Neurological Disorders and Stroke (NINDS). The study must address questions within the mission and research interests of the NINDS and may evaluate preventive strategies, diagnostic approaches, or interventions including drugs, biologics, and devices, or surgical, behavioral, and rehabilitation therapies. Information about the mission and research interests of the NINDS can be found at the NINDS website (https://www.ninds.nih.gov/). Studies proposed should provide a cost-effective means of collecting data with a meaningful bearing on current clinical practice. Awards made under this FOA will initially support a milestone-driven planning phase (UG3) for up to 2 years, with possible transition to a observational study phase of up to five years (UH3). Only UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA. The UG3 phase for observational studies will permit both scientific and operational planning activities. Scientific planning activities include small-scale data collection to assess the feasibility and/or acceptability of data collection, storage, and planned analyses. Operational planning activities include, at a minimum, development of recruitment and retention strategies, case report forms, data management system and other tools for data and quality management. The UH3 phase of the award will support the conduct of investigator-initiated observational study.

Notice NOT-LM-24-008 from the NIH Guide for Grants and Contracts

Notice NOT-RM-25-002 from the NIH Guide for Grants and Contracts

Notice NOT-OD-25-055 from the NIH Guide for Grants and Contracts

Notice NOT-OD-25-042 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-25-363 from the NIH Guide for Grants and Contracts. The purpose of this NOFO is the rapid and efficient translation of innovative laboratory research findings into therapeutics for use by clinicians to treat visual system diseases or disorders. Multidisciplinary teams of scientists and clinicians must focus on generating preclinical data that will lead to the development of biological, pharmacological, medical device and/or combination product interventions. The ultimate goal of this program is to make new technological, biological and pharmacological resources available to clinicians and their patients. The steps towards this goal should be clearly delineated in a series of milestones that support the development of a therapeutic or device that will lead to an Investigational New Drug (IND) or Investigational Device Exception (IDE) application to the U.S. Food and Drug Administration (FDA) and/or testing in a clinical trial. The R33 is to focus on advancing a single therapeutic candidate through IND/IDE -enabling studies, filing an IND package with the FDA, and designing future clinical trials. Applicants pursuing early stage applied research should consider the companion (R61/R33) NOFO PA-23-XXX.

Funding Opportunity PAR-25-335 from the NIH Guide for Grants and Contracts. The purpose of this Notice of Funding Opportunity (NOFO) is the rapid and efficient translation of innovative laboratory research findings into therapeutics for use by clinicians to treat visual system diseases or disorders. Multidisciplinary teams of scientists and clinicians must focus on generating preclinical data that will lead to the development of biological, pharmacological, medical device and/or combination product interventions. The ultimate goal of this program is to make new technological, biological and pharmacological resources available to clinicians and their patients. The steps towards this goal should be clearly delineated in a series of milestones that support the development of a therapeutic or device that will lead to an Investigational New Drug (IND) or Investigational Device Exception (IDE) application to the U.S. Food and Drug Administration (FDA) and/or testing in a clinical trial. This NOFO will utilize a bi-phasic, milestone-driven mechanism of award. The R61 phase will support research that has demonstrated significant preliminary data but has not advanced to the level of clinical translation. The R33 phase will support research that is in the final states of preclinical development with potential for near-term clinical development. Support for a single phased award that does not need the R61 Exploratory phase is available in the companion R33, PAR-23-205.

Funding Opportunity RFA-RM-24-013 from the NIH Guide for Grants and Contracts. This notice of funding opportunity (NOFO) invites applications from eligible organizations to establish the New Approach Methodologies (NAMs) Data Hub and Coordinating Center (NDHCC) for the NIH Common Fund Complement Animal Research In Experimentation (Complement-ARIE) program. The goal of Complement-ARIE is to implement better models for understanding human health and disease outcomes across diverse populations that complement traditional models and make biomedical research more efficient and effective. The award made through this announcement will support Complement-ARIE by providing a centralized data hub, building a searchable repository for various NAMs data types, establishing standards for data reporting and model credibility, developing and implementing an Integrated Testing Strategies (ITS), developing strategies for interoperability, sustainability data reuse, and developing tools for data analytics, dissemination, and sharing. The awardee will also serve as the coordinating center for the overall Complement-ARIE program.

Res Sq [Preprint]. 2024 Dec 23:rs.3.rs-5418279. doi: 10.21203/rs.3.rs-5418279/v1.

ABSTRACT

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization. We identified two novel loci (rs1106260 and rs60847828) associated with non-response to antidepressants and showed significant polygenic prediction in independent samples. Genetic correlation analyses show positive associations between non-response to antidepressants and most psychiatric traits, and negative associations with cognitive traits and subjective well-being. In addition, we investigated drugs that target proteins likely involved in mechanisms underlying antidepressant non-response, and shortlisted drugs that warrant further replication and validation of their potential to reduce depressive symptoms in individuals who do not respond to first-line antidepressant medications. These results suggest that meta-analyses of GWAS utilizing real-world measures of treatment outcomes can increase sample sizes to improve the discovery of variants associated with non-response to antidepressants.

PMID:39764137 | PMC:PMC11703334 | DOI:10.21203/rs.3.rs-5418279/v1

Phytomedicine. 2024 Dec 21;136:156343. doi: 10.1016/j.phymed.2024.156343. Online ahead of print.

ABSTRACT

BACKGROUND: Among all gynecological cancers, ovarian cancer is the leading cause of death. Epithelial ovarian cancer (EOC) accounts for over 85 % of ovarian cancer cases and is characterized by insidious onset, early metastasis, and a high recurrence rate. Alterations in gut microbiota, often as a consequence of chemotherapy, can promote cancer development and exacerbate the disease. The m6A reader IGF2BP3 is a regulator in the occurrence and progression of various tumors and is associated with angiogenesis. Enterolactone (ENL) has demonstrated significant anti-tumor activity against various human cancers, including EOC. However, whether ENL could interact with IGF2BP3 to suppress EOC remains unclear.

PURPOSE: This study aims to investigate suppressive effects of ENL upon combining with IGF2BP3 on EOC and elucidates the underlying mechanism.

METHODS: The Cell Counting Kit-8 and crystal violet assays were used to assess tumor cell proliferation. Scratch and Transwell assays were employed to evaluate tumor cell migration, while tube formation assays were utilized to examine angiogenesis. Western blotting was used to measure the expression levels of IGF2BP3, VEGF, PI3K, AKT1, p-PI3K, and p-AKT1. An in vivo xenograft nude mouse model was established, fecal samples were collected, and 16S rDNA sequencing was performed to analyze gut microbiota in association with the suppressive effects of ENL and its interactions with IGF2BP3.

RESULTS: IGF2BP3 is highly expressed in EOC and is positively correlated with poor survival in EOC patients. ENL reduces IGF2BP3 expression in EOC, thereby inhibiting the IGF2BP3-mediated VEGF/PI3K/AKT signaling pathway and suppressing the proliferation, migration, invasion, and angiogenesis of EOC. Additionally, ENL ameliorates gut microbiome, especially in conjunction with shIGF2BP3.

CONCLUSION: ENL interacts with IGF2BP3 and suppresses its expression in EOC, leading to the deactivation of the IGF2BP3-mediated VEGF/PI3K/AKT signaling pathway and the subsequent inhibition of angiogenesis. The combination of ENL and shIGF2BP3 demonstrates a synergistic effect on EOC. ENL also ameliorates the gut microbiome, especially in conjunction with shIGF2BP3, to suppress EOC.

PMID:39765033 | DOI:10.1016/j.phymed.2024.156343

Clin Imaging. 2025 Jan 2;119:110400. doi: 10.1016/j.clinimag.2024.110400. Online ahead of print.

ABSTRACT

PURPOSE: To develop an educational, interactive, ultra-high resolution, in vivo magnetic resonance (MR) neurography atlas for direct visualization of the brachial plexus and upper extremity.

METHODS: A total of 16 adult volunteers without known peripheral neuropathy underwent magnetic resonance (MR) neurography of the brachial plexus and upper extremity. To improve vascular suppression, subjects received an intravenous infusion of ferumoxytol. To improve image quality, MR neurography datasets were reconstructed using a deep learning algorithm. The atlas was then developed using a web-based user-interface software, which allowed for labeling of peripheral nerves and muscles, and mapping of muscles to their respective innervation. The user interface was optimized to maximize interactivity and user-friendliness.

RESULTS: Fifteen subjects completed at least one scan with no reported adverse reactions from the ferumoxytol infusions. Adequate vascular suppression was observed in all MR neurography datasets. The images of the brachial plexus and upper extremity included in this atlas allowed for identification and labeling of 177 unique anatomical structures from the neck to the wrist. The atlas was made freely accessible on the internet.

CONCLUSION: A detailed and interactive MR neurography atlas of the brachial plexus and upper extremity was successfully developed to depict small nerves and fascicular detail with unprecedented spatial and contrast resolution. This freely available online resource (https://www.hss.edu/MRNatlas) can be used as an educational tool and clinical reference. The techniques utilized in this project serve as a framework for continued work in expanding the atlas to cover other peripheral nerve territories.

PMID:39765207 | DOI:10.1016/j.clinimag.2024.110400