journal
https://read.qxmd.com/read/38226444/fetal-spina-bifida-associates-with-dysregulation-in-nutrient-sensitive-placental-gene-networks-findings-from-a-matched-case-control-study
#1
JOURNAL ARTICLE
Marina White, Jayden Arif-Pardy, Tim Van Mieghem, Kristin L Connor
To improve outcomes in fetuses with spina bifida (SB), better understanding is needed of the molecular drivers of SB and its comorbidities. Pregnant people carrying a fetus with isolated SB (cases; n=12) or a fetus with no congenital anomalies (controls; n=21) were recruited at Mount Sinai Hospital, Toronto. Clinical data and placental samples were collected. Placental transcriptome was sequenced (Clariom DTM microarray) and a nutrient-focused gene expression analysis pipeline was applied to determine whether fetal SB associates with placental dysfunction...
January 16, 2024: Clinical and Translational Science
https://read.qxmd.com/read/38226443/intestinal-p-gp-activity-is-reduced-in-postmenopausal-women-under-breast-cancer-therapy
#2
JOURNAL ARTICLE
Joao Paulo B Ximenez, Jurandyr Moreira de Andrade, Adriana Rocha, Eduardo Barbosa Coelho, Guilherme Suarez-Kurtz, Vera Lucia Lanchote
Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been employed as a P-gp probe, although it's important to note the involvement of other drug transporters like OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status...
January 16, 2024: Clinical and Translational Science
https://read.qxmd.com/read/38594824/randomized-placebo-controlled-double-blind-phase-i-trial-of-co-administered-pyronaridine-and-piperaquine-in-healthy-adults-of-sub-saharan-origin
#3
RANDOMIZED CONTROLLED TRIAL
Andrea Kuemmerle, Denis Gossen, Annick Janin, Andrew Stokes, Nada Abla, Maja Szramowska, Ulrike Lorch, Myriam El Gaaloul, Isabelle Borghini-Fuhrer, Stephan Chalon
Drug resistance to sulfadoxine-pyrimethamine and amodiaquine threatens the efficacy of malaria chemoprevention interventions in children and pregnant women. Combining pyronaridine (PYR) and piperaquine (PQP), both components of approved antimalarial therapies, has the potential to protect vulnerable populations from severe malaria. This randomized, double-blind, placebo-controlled (double-dummy), parallel-group, single site phase I study in healthy adult males or females of Black sub-Saharan African ancestry investigated the safety, tolerability, and pharmacokinetics of PYR + PQP (n = 15), PYR + placebo (n = 8), PQP + placebo (n = 8), and double placebo (n = 6) administered orally once daily for 3 days at the registered dose for the treatment of uncomplicated malaria...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38591811/pharmacokinetics-and-pharmacodynamics-of-mibavademab-a-leptin-receptor-agonist-results-from-a-first-in-human-phase-i-study
#4
RANDOMIZED CONTROLLED TRIAL
Andrew Gewitz, Jeanne Mendell, Yuhuan Wang, Charles Harris, Benjamin A Olenchock, Simona Podgrabinska, Wenjun Zheng, An Zhao, Hao Pan, Frédéric Vanhoutte, John D Davis
Mibavademab (previously known as REGN4461), a fully human monoclonal antibody, is being investigated for the treatment of conditions associated with leptin deficiency. Here, we report pharmacokinetics (PKs), pharmacodynamics, and immunogenicity from a phase I study in healthy participants (NCT03530514). In part A, lean or overweight healthy participants were randomized to single-ascending-dose cohorts of 0.3, 1.0, 3.0, 10, and 30 mg/kg intravenous (i.v.), or 300 and 600 mg subcutaneous doses of mibavademab or placebo...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38581109/the-association-of-cyp2c19-lof-alleles-with-adverse-clinical-outcomes-in-stroke-patients-taking-clopidogrel-an-updated-meta-analysis
#5
REVIEW
Mohitosh Biswas, Md Shahadat Hossain, Tahsin Ahmed Rupok, Md Sabbir Hossain, Chonlaphat Sukasem
The aggregated risk of recurrent stroke in stroke/transient ischemic attack (TIA) patients carrying CYP2C19 LoF alleles who take clopidogrel has not been investigated recently, and the available research is limited. This study aimed to perform an updated meta-analysis to assess the association between CYP2C19 LoF alleles and the risk of recurrent stroke in patients taking clopidogrel. Databases were searched for the literature on eligible studies. The end points were recurrent stroke, composite vascular events, and bleeding events...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38572980/advancing-the-utilization-of-real-world-data-and-real-world-evidence-in-clinical-pharmacology-and-translational-research-proceedings-from-the-ascpt-2023-preconference-workshop
#6
REVIEW
Jing Liu, Karen Rowland-Yeo, Almut Winterstein, Simon Dagenais, Qi Liu, Jeffrey S Barrett, Rui Zhu, Cyrus Ghobadi, Amita Datta-Mannan, Joy Hsu, Sujatha Menon, Mariam Ahmed, Pooja Manchandani, Paulien Ravenstijn
Real-world data (RWD) and real-world evidence (RWE) are now being routinely used in epidemiology, clinical practice, and post-approval regulatory decisions. Despite the increasing utility of the methodology and new regulatory guidelines in recent years, there remains a lack of awareness of how this approach can be applied in clinical pharmacology and translational research settings. Therefore, the American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a workshop on March 21st, 2023 entitled "Advancing the Utilization of Real-World Data (RWD) and Real-World Evidence (RWE) in Clinical Pharmacology and Translational Research...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38571339/predictors-of-potential-clinically-harmful-drug-drug-interactions-at-the-medical-wards-in-the-university-of-benin-teaching-hospital-benin-city
#7
JOURNAL ARTICLE
Oseremen Godstime Oriaifo, Abimbola Olubukunola Opadeyi, Tracy Oseremen Oriaifo, Ambrose Ohumagho Isah
Drug-drug interactions are preventable causes of adverse events. Different factors have been recognized as important predictors of drug-drug interactions but few studies have addressed these predictors in patients admitted into medical wards of a tertiary hospital in Nigeria hence this study. This was a retrospective study conducted using case records of patients admitted into the medical wards between January 1 and December 31, 2020. Patients were selected using a systematic random sampling method. Socio-demographic details including age, gender, number of comorbidities, and number of medications prescribed and diagnosis were collected on days 1, 3, and at discharge...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38563414/pharmacokinetics-pharmacodynamics-and-safety-of-fesomersen-a-novel-antisense-inhibitor-of-factor-xi-in-healthy-chinese-japanese-and-caucasian-volunteers
#8
JOURNAL ARTICLE
Tianxing Liu, Kensei Hashizume, Eva Krieg, Huijun Chen, Yuki Mukaida, Kirstin Thelen, Frauke Friedrichs, Stefan Willmann, Stephan Schwers, Alexander Solms, Rosie Yu
The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38561923/correction-to-safety-tolerability-pharmacokinetic-pharmacodynamic-characteristics-of-bersiporocin-a-novel-prolyl-trna-synthetase-inhibitor-in-healthy-subjects
#9
(no author information available yet)
No abstract text is available yet for this article.
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38561910/differential-expression-and-clinical-significance-of-igf2bp3-in-peritoneal-dialysate-of-patients-with-varying-duration-of-peritoneal-dialysis
#10
JOURNAL ARTICLE
Xiaoqi Shao, Ling Yao, Jiao Fu, Mengmeng He, Pei Zhang
This study aims to investigate the differential expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the peritoneal dialysate among patients with different durations of peritoneal dialysis and its association with the angiogenic marker vascular* endothelial growth factor (VEGF), the fibronectin (FN), and various clinical indicators. A cohort of 122 peritoneal dialysis patients was categorized into short-term (≤1 year, n = 33), mid-term (>1 and ≤5 years, n = 55), and long-term (>5 years, n = 34) groups based on dialysis duration...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38561908/modeling-the-subcutaneous-pharmacokinetics-of-antibodies-co-administered-with-rhuph20
#11
JOURNAL ARTICLE
Ryan P Nolan, Marie A Printz
Predicting the subcutaneous (SC) pharmacokinetics (PK) of antibodies in humans is challenging, with clinical data currently being the only reliable data source for modeling SC absorption and bioavailability. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that facilitates SC delivery of high-dose, high-volume therapeutics. Numerous monoclonal antibodies have been co-administered SC with rHuPH20 in a clinical setting, establishing an extensive PK database. The goal of this work is to demonstrate how aggregated clinical data can be leveraged in a universal modeling framework for characterizing SC antibody PK, resulting in parameterization that can be used in predictive simulations of new antibodies...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38558535/pharmacokinetics-pharmacodynamics-and-safety-of-frunexian-in-healthy-chinese-volunteer-adults-a-randomized-dose-escalation-phase-i-study
#12
JOURNAL ARTICLE
Jia-Yu Zhang, Zou-Rong Ruan, Bo Jiang, Dan-Dan Yang, Jia-Ying Wang, Yin Hu, Yong-Rui Wang, Yan-Mei Wang, Yun-Fei Lin, Ling-Ling Wang, Hong-Gang Lou
The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38558534/within-individual-reproducibility-of-a-dual-sample-oral-cholate-challenge-test-duo-and-simplified-versions-of-the-hepquant-shunt-test
#13
JOURNAL ARTICLE
Michael P McRae, John Kittelson, Steve M Helmke, Gregory T Everson
Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.0) is cumbersome to administer, requiring intravenous and oral administration of cholate and six peripheral venous blood samples over 90 min. To alleviate the burden of test administration, we explored whether an oral only (DuO) version, and other simplified versions, of the test could provide reproducible measurements of liver function...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38545866/generic-substitution-of-amlodipine-is-not-associated-with-increased-risk-of-mortality-or-adverse-cardiovascular-events-an-observational-cohort-study
#14
JOURNAL ARTICLE
Boya Zhao, Jing Wu, Chengzhi Lu, Xing Lin Feng
This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population-based, matched, cohort study included users of originator amlodipine using claims data during 2018-2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume-based procurement. Non-switchers refer to those remained on originator after the policy, while pure-switchers were those who switched to and continued using generic amlodipine, and back-switchers were those switched to generic amlodipine but then back to the originator...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38545863/advancing-clinical-development-for-neuronopathic-hunter-syndrome-through-a-quantitatively-driven-reverse-translation-framework
#15
JOURNAL ARTICLE
Robert D Latzman, Olivia Campagne, Meera E Modi, Marta Karas, C J Malanga, David A H Whiteman
A quantitatively-driven evaluation of existing clinical data and associated knowledge to accelerate drug discovery and development is a highly valuable approach across therapeutic areas, but remains underutilized. This is especially the case for rare diseases for which development is particularly challenging. The current work outlines an organizational framework to support a quantitatively-based reverse translation approach to clinical development. This approach was applied to characterize predictors of the trajectory of cognition in Hunter syndrome (Mucopolysaccharidosis Type II; MPS-II), a rare X-linked lysosomal storage disorder, highly heterogeneous in its course...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38545854/safety-pharmacokinetics-and-pharmacodynamics-of-anti-il-4r%C3%AE-antibody-shr-1819-in-healthy-subjects-a-randomized-controlled-phase-i-study
#16
JOURNAL ARTICLE
Na Li, Sepehr Shakib, Weilin Qian, Xiaoyan Yao, Puyuan Li, Tsz Keung Nip, Xiaoyan Bai, Kai Shen
SHR-1819 is a novel anti-IL-4Rα monoclonal antibody currently under clinical development for use in patients with type 2 inflammatory diseases. In this randomized, double-blind, placebo-controlled, single-dose escalation phase I trial, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-1819 in healthy subjects. Subjects received a single subcutaneous injection of SHR-1819 or placebo, with dose escalation starting at 60 mg and subsequently increasing to 120, 240, 360, and 720 mg...
April 2024: Clinical and Translational Science
https://read.qxmd.com/read/38515365/ischemia-induced-cardiac-dysfunction-is-exacerbated-in-adiponectin-knockout-mice-due-to-impaired-autophagy-flux
#17
JOURNAL ARTICLE
Hye Kyoung Sung, Jialing Tang, James Won Suk Jahng, Erfei Song, Yee Kwan Chan, Abdul Hadee Lone, Jeffrey Peterson, Ali Abdul-Sater, Gary Sweeney
Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio-protective effects in adiponectin knockout (Ad-KO) compared with wild-type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin-B activatable near-infrared probe as a biomarker for autophagy and detection via noninvasive three-dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad-KO...
March 2024: Clinical and Translational Science
https://read.qxmd.com/read/38515348/clinical-dose-rationale-of-tislelizumab-in-patients-with-solid-or-hematological-advanced-tumors
#18
JOURNAL ARTICLE
Tian Yu, Xiangyu Liu, Chi-Yuan Wu, Zhiyu Tang, Hongwei Wang, Patrick Schnell, Ya Wan, Kun Wang, Lucy Liu, Yuying Gao, Srikumar Sahasranaman, Nageshwar Budha
Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w...
March 2024: Clinical and Translational Science
https://read.qxmd.com/read/38515346/new-insight-of-chemical-constituents-in-persea-americana-fruit-against-obesity-via-integrated-pharmacology
#19
JOURNAL ARTICLE
Min-Gi Cha, Su-Been Lee, Sang-Jun Yoon, Sang Youn Lee, Haripriya Gupta, Raja Ganesan, Satya Priya Sharma, Sung-Min Won, Jin-Ju Jeong, Dong Joon Kim, Ki-Kwang Oh, Ki-Tae Suk
Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets...
March 2024: Clinical and Translational Science
https://read.qxmd.com/read/38515340/non-targeted-metabolomics-for-the-identification-of-plasma-metabolites-associated-with-organic-anion-transporting-polypeptide-1b1-function
#20
JOURNAL ARTICLE
Kreetta Hämäläinen, Päivi Hirvensalo, Mikko Neuvonen, Aleksi Tornio, Janne T Backman, Marko Lehtonen, Mikko Niemi
Our aim was to evaluate biomarkers for organic anion transporting polypeptide 1B1 (OATP1B1) function using a hypothesis-free metabolomics approach. We analyzed fasting plasma samples from 356 healthy volunteers using non-targeted metabolite profiling by liquid chromatography high-resolution mass spectrometry. Based on SLCO1B1 genotypes, we stratified the volunteers to poor, decreased, normal, increased, and highly increased OATP1B1 function groups. Linear regression analysis, and random forest (RF) and gradient boosted decision tree (GBDT) regressors were used to investigate associations of plasma metabolite features with OATP1B1 function...
March 2024: Clinical and Translational Science
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