keyword
https://read.qxmd.com/read/38698408/mechanism-of-action-potency-and-efficacy-considerations-for-cell-therapies
#1
REVIEW
Carl G Simon, Erich H Bozenhardt, Christina M Celluzzi, David Dobnik, Melanie L Grant, Uma Lakshmipathy, Thiana Nebel, Linda Peltier, Anthony Ratcliffe, James L Sherley, Glyn N Stacey, Rouzbeh R Taghizadeh, Eddie H P Tan, Sandrine Vessillier
One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective...
May 2, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38697808/association-of-blood-pressure-and-outcomes-differs-upon-cerebral-perfusion-post-thrombectomy-in-patients-with-acute-ischemic-stroke
#2
JOURNAL ARTICLE
Jinjie Liu, Ximing Nie, Zhe Zhang, Wanying Duan, Xin Liu, Hongyi Yan, Lina Zheng, Changgeng Fang, Jiaping Chen, Yuyi Wang, Zhixuan Wen, Shuning Cai, Miao Wen, Zhonghua Yang, Yuesong Pan, Sibo Liu, Liping Liu
BACKGROUND: The relationship between post-endovascular thrombectomy (EVT) blood pressure (BP) and outcomes in patients with acute ischemic stroke (AIS) remains contentious. We aimed to explore whether this association differs with different cerebral perfusion statuses post-EVT. METHODS: In a multicenter observational study of patients with AIS with large vessel occlusion who underwent EVT, we enrolled those who accepted CT perfusion (CTP) imaging within 24 hours post-EVT...
May 2, 2024: Journal of Neurointerventional Surgery
https://read.qxmd.com/read/38697793/association-between-ct-perfusion-parameters-and-hemorrhagic-transformation-after-endovascular-treatment-in-acute-ischemic-stroke-results-from-the-escape-na1-trial
#3
JOURNAL ARTICLE
Rosalie V McDonough, Nathaniel B Rex, Johanna M Ospel, Nima Kashani, Leon A Rinkel, Arshia Sehgal, Joachim C Fladt, Ryan A McTaggart, Raul Nogueira, Bijoy Menon, Andrew M Demchuk, Alexandre Poppe, Michael D Hill, Mayank Goyal
BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds...
May 2, 2024: AJNR. American Journal of Neuroradiology
https://read.qxmd.com/read/38692571/longitudinal-imaging-of-tumor-perfusion-after-preoperative-endovascular-embolization-in-meningiomas-surgical-time-window-selecting-clinical-consideration-and-outcomes
#4
JOURNAL ARTICLE
FuMing Yang, Yi Chen, Chao Chen, YaNan Li, LaiXing Wang, GuoSheng Han
OBJECTIVE: To quantitatively investigate the longitudinal computed tomography perfusion (CTP) imaging in meningiomas preoperatively embolized using microcatheters. METHODS: This retrospective monocentric study included 27 patients with symptomatic supratentorial meningiomas. Quantitative CTP images before and post-embolization were evaluated and correlated with angiographic, immunohistochemical, and clinical data. RESULTS: The mean age of the patients was 45±18 years, with a female-to-male ratio of 1...
April 29, 2024: World Neurosurgery
https://read.qxmd.com/read/38690787/octupolar-cyclotriphosphazene-cored-self-standing-covalent-organic-framework-membranes-as-nonlinear-optical-materials-impact-of-linkage-types-and-material-forms
#5
JOURNAL ARTICLE
Suresh Bommakanti, Satyapriya Nath, Rudrashish Panda, Sankalpa N Panda, Jeebanjyoti Mohapatra, Adithyan Puthukkudi, Chetan V Rajput, Sharmistha Anwar, Ritwick Das, Bishnu P Biswal
Conjugated and processable self-standing vinylene-linked covalent organic framework membranes (COFMs) are highly demanding for photonics and optoelectronics. In this work, we have fabricated the first cyclotriphosphazene (CTP) cored vinylene-linked self-standing COFM (CTP-PDAN). For comparison purposes, we have successfully fabricated the imine-linked congener (CTP-PDA). Leveraging the inherent nonlinear optical (NLO) response of the CTP core, both membranes were directly mounted to evaluate NLO parameters using the open-aperture (OA) Z-scan technique...
May 1, 2024: Journal of Physical Chemistry Letters
https://read.qxmd.com/read/38687161/applicability-of-child-turcotte-pugh-score-in-anticipating-post-ercp-adverse-events-in-patients-with-cirrhosis-a-systematic-review-and-meta-analysis
#6
JOURNAL ARTICLE
Saqr Alsakarneh, Fouad Jaber, Willie Mohammed, Mohammad Almeqdadi, Abdallah Al-Ani, Yassine Kilani, Saeed Abughazaleh, Laith Momani, Muhammad Shah Miran, Hassan Ghoz, John Helzberg, Wendell Clarkston, Mohamed Othman
Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score...
May 1, 2024: Journal of Clinical Gastroenterology
https://read.qxmd.com/read/38685917/incidence-of-acute-kidney-injury-in-patients-with-acute-ischaemic-stroke-undergoing-ct-angiography-cta-and-ct-perfusion-ctp-a-systematic-review-and-meta-analysis
#7
JOURNAL ARTICLE
Alishba Kamran, Neha Saleem Paryani, Noor Fatima Suri, Javeria Khan, Fahad Amir, Marium Mehmood, Sehan Siraj Lashkerwala, Javeria Hayat, Shayan Marsia
BACKGROUND AND PURPOSE: We conducted a systematic review and meta-analysis to assess the incidence of acute kidney injury (AKI) in patients undergoing CT angiography (CTA) and CT perfusion (CTP) for acute ischaemic stroke (AIS). Concerns over contrast-induced nephropathy (CIN) often lead medical centres to mandate pre-imaging serum creatinine level assessments, causing unnecessary delays. We aim to confirm further the practice of conducting CTA/CTP without first testing creatinine. METHODS: We searched PubMed, Cochrane Central and Scopus from inception until March 2023 for studies reporting on AKI in patients with AIS receiving CTA/CTP...
2024: BMJ neurology open
https://read.qxmd.com/read/38676500/to-explore-potential-inhibitors-against-various-enzymatic-targets-of-human-african-trypanosomiasis
#8
JOURNAL ARTICLE
Sayandeep Brahma, Susmita Moitra, Soumya Ranjan Bagchi, Asmita Samadder, Sisir Nandi
Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis (HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing risk of drug resistance is another major problem to be addressed. Cysteine protease, Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase, Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase are potential enzymatic targets for the development of novel inhibitors against HAT which are the main focus of this review...
April 25, 2024: Combinatorial Chemistry & High Throughput Screening
https://read.qxmd.com/read/38667490/ct-perfusion-derived-rcbv-42-lesion-volume-is-independently-associated-with-followup-flair-infarct-volume-in-anterior-circulation-large-vessel-occlusion
#9
JOURNAL ARTICLE
Dhairya A Lakhani, Aneri B Balar, Hamza Salim, Manisha Koneru, Sijin Wen, Burak Ozkara, Hanzhang Lu, Richard Wang, Meisam Hoseinyazdi, Risheng Xu, Mehreen Nabi, Ishan Mazumdar, Andrew Cho, Kevin Chen, Sadra Sepehri, Nathan Hyson, Victor Urrutia, Licia Luna, Argye E Hillis, Jeremy J Heit, Greg W Albers, Ansaar T Rai, Adam A Dmytriw, Tobias D Faizy, Max Wintermark, Kambiz Nael, Vivek S Yedavalli
Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023...
April 19, 2024: Diagnostics
https://read.qxmd.com/read/38666480/thrombectomy-in-ischemic-stroke-patients-with-large-core-but-minor-ischemic-changes-on-non-enhanced-computed-tomography
#10
JOURNAL ARTICLE
Gabriel Broocks, Helge Kniep, Rosalie McDonough, Matthias Bechstein, Christian Heitkamp, Laurens Winkelmeier, Susan Klapproth, Tobias Djamsched Faizy, Maximilian Schell, Gerhard Schön, Uta Hanning, Susanne Gellißen, André Kemmling, Panagiotis Papanagiotou, Jens Fiehler, Lukas Meyer
PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is regularly used to guide patient selection for mechanical thrombectomy (MT). Similarly, penumbral imaging based on computed tomography perfusion (CTP) may serve as neuroimaging tool to guide treatment. Yet, patients with a large ischemic core on CTP may show only minor ischemic changes resulting in a high ASPECTS. AIM: We hypothesized twofold: 1) the treatment effect of vessel recanalization in patients with core volume >50ml but ASPECTS≥6 is not different compared to high ASPECTS patients with core volume <50ml, and 2) recanalization is associated with core overestimation...
April 26, 2024: International Journal of Stroke: Official Journal of the International Stroke Society
https://read.qxmd.com/read/38666150/target-controlled-infusion-a-comparative-prospective-observational-study-of-the-conventional-tci-pump-and-the-novel-smartphone-based-application-itiva
#11
JOURNAL ARTICLE
Shagun B Shah, Rajiv Chawla, Manish Gupta
BACKGROUND AND AIMS: Empirically adjusted, standard drug doses fail to address interindividual pharmacokinetic and pharmacodynamics variability. Target-controlled infusion (TCI) delivers drugs in calibrated boluses to achieve and maintain a selected target plateau drug level (plasma or effect site). Interactive total intravenous anesthesia (iTIVA™ ) smartphone software simulates TCI and employs 31 established pharmacokinetic models for 11 different intravenous agents and is coupled with standard volumetric infusion pumps for administering TCI...
2024: Journal of Anaesthesiology, Clinical Pharmacology
https://read.qxmd.com/read/38665995/application-of-imaging-modalities-for-endovascular-thrombectomy-of-large-core-infarcts-in-clinical-practice
#12
REVIEW
Hai Zeng, Qingfeng Zhu
Four randomized controlled trials of large infarct core volume (LICV) included three imaging modalities: non-contrast CT (NCCT)-Alberta Stroke Program Early CT Score (ASPECTS), diffusion-weighted imaging (DWI)-ASPECTS, and NCCT-ASPECTS combined with CTP (CT perfusion). However, there is no clear consensus on the optimal imaging modality for endovascular thrombectomy (EVT) trials of large core infarcts. The variety and complexity of imaging modalities make it difficult to apply them in clinical practice. By familiarizing ourselves with these imaging modalities, we can better apply them in the clinic and correctly screen patients with large core infarcts in the anterior circulation who can benefit from EVT therapy...
2024: Frontiers in Neurology
https://read.qxmd.com/read/38665468/measuring-the-effect-of-ayushman-bharat-pradhan-mantri-jan-aarogya-yojna-ab-pmjay-on-health-expenditure-among-poor-admitted-in-a-tertiary-care-hospital-in-the-northern-state-of-india
#13
JOURNAL ARTICLE
Shweta Kanwal, Dinesh Kumar, Raman Chauhan, Sunil Kumar Raina
BACKGROUND: Ayushman Bharat - Pradhan Mantri Jan Aarogya Yojna (AB-PMJAY) as a financial risk protection scheme intends to reduce catastrophic health expenditure (CHE), especially among poor. The current study was carried out to assess the utility of AB-PMJAY in terms of reduction in CHE from before and after admission in a tertiary hospital in the northern state of India. METHODOLOGY: It was a hospital-based cross-sectional study carried out from August 2020 to October 2021 at a public tertiary hospital of Himachal Pradesh, India...
2024: Indian Journal of Community Medicine
https://read.qxmd.com/read/38664433/a-dynamic-nomogram-for-predict-individual-risk-of-malignant-brain-edema-after-endovascular-thrombectomy-in-acute-ischemic-stroke
#14
JOURNAL ARTICLE
Huiyuan Wang, Chenghua Xu, Yu Xiao, Panpan Shen, Shunyuan Guo, Yafei Shang, Xinyi Chen, Jie Xu, Chunrong Li, Mingming Tan, Sheng Zhang, Yu Geng
The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT...
April 25, 2024: Scientific Reports
https://read.qxmd.com/read/38664278/is-salvage-plug-assisted-retrograde-transvenous-obliteration-parto-safe-and-effective-for-bleeding-gastric-varices-a-preliminary-single-center-experience
#15
JOURNAL ARTICLE
Ranjan Kumar Patel, Taraprasad Tripathy, Manas Kumar Panigrahi, Hemant Kumar Nayak, Subash Chandra Samal, Bramhadatta Pattnaik, Tanmay Dutta, Sunita Gupta, Sudipta Mohakud, Suprava Naik, Nerbadyeswari Deep Bag
BACKGROUND: Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy. AIMS: To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months. MATERIALS AND METHODS: Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database...
April 25, 2024: Emergency Radiology
https://read.qxmd.com/read/38658605/risk-factors-and-predictive-nomograms-for-bedside-emergency-endoscopic-treatment-following-endotracheal-intubation-in-cirrhotic-patients-with-esophagogastric-variceal-bleeding
#16
JOURNAL ARTICLE
Ajuan Zeng, Yangjie Li, Lingna Lyu, Shibin Zhang, Yuening Zhang, Huiguo Ding, Lei Li
Data on emergency endoscopic treatment following endotracheal intubation in patients with esophagogastric variceal bleeding (EGVB) remain limited. This retrospective study aimed to explore the efficacy and risk factors of bedside emergency endoscopic treatment following endotracheal intubation in severe EGVB patients admitted in Intensive Care Unit. A total of 165 EGVB patients were enrolled and allocated to training and validation sets in a randomly stratified manner. Univariate and multivariate logistic regression analyses were used to identify independent risk factors to construct nomograms for predicting the prognosis related to endoscopic hemostasis failure rate and 6-week mortality...
April 24, 2024: Scientific Reports
https://read.qxmd.com/read/38649539/long-term-outcome-after-endovascular-treatment-for-large-ischemic-core-acute-stroke-is-associated-with-hypoperfusion-intensity-ratio-and-onset-to-reperfusion-time
#17
JOURNAL ARTICLE
Zhengyang Wang, Ling Li
BACKGROUND: Endovascular treatment (EVT) is effective for large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined core. However, the influence of perfusion imaging during thrombectomy on the functional outcomes of patients with large ischemic core (LIC) stroke at both early and late time windows is uncertain in real-world practice. METHOD: A retrospective analysis was performed on 99 patients who underwent computed tomography angiography (CTA) and CT perfusion (CTP)-Rapid Processing of Perfusion and Diffusion (RAPID) before EVT and had a baseline ischemic core ≥ 50 mL and/or Alberta Stroke Program Early CT Score (ASPECTS) score of 0-5...
April 23, 2024: Neurosurgical Review
https://read.qxmd.com/read/38648489/protein-engineering-a-photornr-chimera-based-on-a-unifying-evolutionary-apparatus-among-the-natural-classes-of-ribonucleotide-reductases
#18
JOURNAL ARTICLE
David Y Song, JoAnne Stubbe, Daniel G Nocera
Ribonucleotide reductases (RNRs) are essential enzymes that catalyze the de novo transformation of nucleoside 5'-di(tri)phosphates [ND(T)Ps, where N is A, U, C, or G] to their corresponding deoxynucleotides. Despite the diversity of factors required for function and the low sequence conservation across RNRs, a unifying apparatus consolidating RNR activity is explored. We combine aspects of the protein subunit simplicity of class II RNR with a modified version of Escherichia coli class la photoRNRs that initiate radical chemistry with light to engineer a mimic of a class II enzyme...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38647971/a-circuitous-route-for-in-vitro-multi-enzyme-cascade-production-of-cytidine-triphosphate-to-overcome-the-thermodynamic-bottleneck
#19
JOURNAL ARTICLE
Zonglin Li, Yahui Zhong, Zhoulei Qing, Zhimin Li
Cytidine triphosphate (CTP), as a substance involved in the metabolism of phospholipids, proteins and nucleic acids, has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline. In this study, we established an in vitro six-enzyme cascade system to generate CTP. To avoid thermodynamic bottlenecks, we employed a circuitous and two-stage reaction strategy. Using cytidine as the key substrate, the final product CTP is obtained via the deamination and uridine phosphorylation pathways, relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate...
January 4, 2024: Bioresources and Bioprocessing
https://read.qxmd.com/read/38645360/universal-glycosyltransferase-continuous-assay-for-uniform-kinetics-and-inhibition-database-development-and-mechanistic-studies-illustrated-on-st3gal1-c1galt1-and-fut1
#20
JOURNAL ARTICLE
Abdullateef Nashed, Kevin J Naidoo
Chemical systems glycobiology requires experimental and computational tools to make possible big data analytics benefiting genomics and proteomics. The impediment to tool development is that the nature of glycan construction and mutation is not template driven but rests on cooperative glycosyltransferase (GT) catalytic synthesis. What is needed is the collation of kinetics and inhibition data in a standardized form to make possible analytics of glycan and glycoconjugate synthesis, mechanism extraction, and pattern recognition...
April 16, 2024: ACS Omega
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