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1.
Sensors (Basel) ; 23(17)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37687931

RESUMEN

Precision medicine has emerged as a transformative approach to healthcare, aiming to deliver personalized treatments and therapies tailored to individual patients. However, the realization of precision medicine relies heavily on the availability of comprehensive and diverse medical data. In this context, blockchain-enabled federated learning, coupled with electronic medical records (EMRs), presents a groundbreaking solution to unlock revolutionary insights in precision medicine. This abstract explores the potential of blockchain technology to empower precision medicine by enabling secure and decentralized data sharing and analysis. By leveraging blockchain's immutability, transparency, and cryptographic protocols, federated learning can be conducted on distributed EMR datasets without compromising patient privacy. The integration of blockchain technology ensures data integrity, traceability, and consent management, thereby addressing critical concerns associated with data privacy and security. Through the federated learning paradigm, healthcare institutions and research organizations can collaboratively train machine learning models on locally stored EMR data, without the need for data centralization. The blockchain acts as a decentralized ledger, securely recording the training process and aggregating model updates while preserving data privacy at its source. This approach allows the discovery of patterns, correlations, and novel insights across a wide range of medical conditions and patient populations. By unlocking revolutionary insights through blockchain-enabled federated learning and EMRs, precision medicine can revolutionize healthcare delivery. This paradigm shift has the potential to improve diagnosis accuracy, optimize treatment plans, identify subpopulations for clinical trials, and expedite the development of novel therapies. Furthermore, the transparent and auditable nature of blockchain technology enhances trust among stakeholders, enabling greater collaboration, data sharing, and collective intelligence in the pursuit of advancing precision medicine. In conclusion, this abstract highlights the transformative potential of blockchain-enabled federated learning in empowering precision medicine. By unlocking revolutionary insights from diverse and distributed EMR datasets, this approach paves the way for a future where healthcare is personalized, efficient, and tailored to the unique needs of each patient.


Asunto(s)
Cadena de Bloques , Medicina de Precisión , Humanos , Registros Electrónicos de Salud , Difusión de la Información , Poder Psicológico
2.
Adv Differ Equ ; 2021(1): 354, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34759965

RESUMEN

Hahn's difference operator D q ; w f ( x ) = ( f ( q x + w ) - f ( x ) ) / ( ( q - 1 ) x + w ) , q ∈ ( 0 , 1 ) , w > 0 , x ≠ w / ( 1 - q ) is used to unify the recently established difference and q-asymptotic iteration methods (DAIM, qAIM). The technique is applied to solve the second-order linear Hahn difference equations. The necessary and sufficient conditions for polynomial solutions are derived and examined for the ( q ; w ) -hypergeometric equation.

3.
J Enzyme Inhib Med Chem ; 34(1): 1573-1589, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852269

RESUMEN

Pyridazine scaffolds are considered privileged structures pertaining to its novelty, chemical stability, and synthetic feasibility. In our quest towards the development of novel scaffolds for effective vascular endothelial growth 2 (VEGFR-2) inhibition with antiangiogenic activity, four novel series of pyridazines were designed and synthesised. Five of the synthesised compounds; namely (8c, 8f, 15, 18b, and 18c) exhibited potent VEGFR-2 inhibitory potency (>80%); with IC50 values ranging from low micromolar to nanomolar range; namely compounds 8c, 8f, 15, 18c with (1.8 µM, 1.3 µM, 1.4 µM, 107 nM), respectively. Moreover, 3-[4-{(6-oxo-1,6-dihydropyridazin-3-yl)oxy}phenyl]urea derivative (18b) exhibited nanomolar potency towards VEGFR-2 (60.7 nM). In cellular assay, the above compounds showed excellent inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells at 10 µM concentration. Finally, an extensive molecular simulation study was performed to investigate the probable interaction with VEGFR-2.


Asunto(s)
Antineoplásicos/farmacología , Descubrimiento de Drogas , Inhibidores de Proteínas Quinasas/farmacología , Piridazinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Teoría Funcional de la Densidad , Ensayos de Selección de Medicamentos Antitumorales , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Piridazinas/síntesis química , Piridazinas/química , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
4.
Expert Rev Anti Infect Ther ; 12(5): 535-44, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24694091

RESUMEN

Dolutegravir, is a second generation integrase inhibitor that had recently received United States Food and Drug Administration and European Commission approval for the treatment of adult patients with HIV-1 infection. Dolutegravir provides distinct advantages compared with first generation integrase inhibitors. Unlike raltegravir, dolutegravir can be given once daily for patients who are antiretroviral treatment naïve. Once-a-day dolutegravir dosing also does not require a pharmacokinetic booster like elvitegravir which minimizes the drug-drug interaction potential of dolutegravir. In Phase III clinical trials, dolutegravir-containing regimens have demonstrated either non-inferiority or superiority to current first line agents such as raltegravir, darunavir/ritonavir, and efavirenz containing regimens. Moreover, dolutegravir may be effective for patients with a history of raltegravir and/or elvitegravir resistance. Dolutegravir will likely play a major role in the management of patients with HIV-1 infection, and will be aided when coformulation with abacavir/lamivudine as a single pill, once-daily regimen is available.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Integrasa de VIH/metabolismo , VIH-1/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adulto , Ensayos Clínicos como Asunto , Didesoxinucleósidos/farmacocinética , Didesoxinucleósidos/uso terapéutico , Esquema de Medicación , Combinación de Medicamentos , Interacciones Farmacológicas , Farmacorresistencia Viral , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/farmacocinética , VIH-1/fisiología , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Humanos , Lamivudine/farmacocinética , Lamivudine/uso terapéutico , Oxazinas , Piperazinas , Piridonas , Pirrolidinonas/farmacocinética , Pirrolidinonas/uso terapéutico , Quinolonas/farmacocinética , Quinolonas/uso terapéutico , Raltegravir Potásico
5.
J Pharm Technol ; 30(3): 87-92, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34860885

RESUMEN

Objective: To review and critically analyze the literature for the use of tigecycline for the treatment of urinary tract infections (UTIs). Data Sources: A search of the MEDLINE database was performed (2004 to July 2013). Search terms included tigecycline, Tygacil, pyelonephritis, cystitis, and urinary tract infections in addition to a manual search of references from the articles retrieved. Study Selection and Data Exaction: All studies of humans, English-language articles, clinical studies, observational studies, and case reports were evaluated. Data Synthesis: Fourteen cases of tigecycline use for UTIs were identified. No clinical trials were identified via the search of the MEDLINE database. Twelve of the 14 cases described positive clinical outcomes with use of tigecycline for the treatment of UTI. Microbiological clearance was evaluable in 11 patients, of which 9 patients achieved documented microbiological clearance. None of the patients had mortality attributable to the use of tigecycline for the UTI. Two of the 14 cases reported had patients with subsequent cultures growing tigecycline-resistant organisms. Conclusion: Case reports have documented clinical improvement/success with the use of tigecycline for the treatment of UTIs. However, use of tigecycline for the treatment of UTIs remains controversial because of limited data and the lack of randomized control trials demonstrating efficacy. Tigecycline should be avoided for the treatment of UTIs when well-established options such as aminoglycosides and ß-lactams are available. When alternative options are nonexistent, tigecycline can be considered.

6.
Expert Opin Pharmacother ; 13(2): 175-91, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22216937

RESUMEN

INTRODUCTION: Thrombosis risk necessitates dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist, in patients who have acute coronary syndrome. Current guidelines emphasize the critical role of dual antiplatelet therapy in both medical management and invasive strategy, especially in patients undergoing percutaneous coronary intervention. With the availability of multiple ADP-receptor antagonists, it is crucial to select the most appropriate agent for each patient. AREAS COVERED: The pertinent trials were identified through a MEDLINE search, in addition to a manual search from the articles retrieved. This review examines the differences between clopidogrel, prasugrel and ticagrelor in terms of their pharmacological/pharmacokinetic properties, clinical efficacy, drug interactions and safety parameters. EXPERT OPINION: Prasugrel and ticagrelor exhibit greater platelet inhibition and superior efficacy compared with clopidogrel, at the expense of higher bleeding risk. Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding. Additionally, these two agents may offer advantage over clopidogrel in those patients who might have risk for drug resistance due to CYP2C19 polymorphism. In selecting the ideal agent for patients, clinicians should tailor the antiplatelet regimen by considering individual risk factors and medication characteristics.


Asunto(s)
Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacología , Adenosina/uso terapéutico , Clopidogrel , Interacciones Farmacológicas , Humanos , Piperazinas/farmacología , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Clorhidrato de Prasugrel , Antagonistas del Receptor Purinérgico P2Y/farmacología , Tiofenos/farmacología , Tiofenos/uso terapéutico , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Ticlopidina/uso terapéutico , Resultado del Tratamiento
7.
Int J Antimicrob Agents ; 38(3): 192-6, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21549573

RESUMEN

With a decreasing pipeline of novel antibiotics and increasing antibacterial resistance, the need to optimise the current antibiotics in our armamentarium has become vitally important. Daptomycin is a novel lipopeptide antibiotic that exhibits concentration-dependent activity. Currently, the daptomycin dosage is 4 mg/kg/day for treatment of complicated skin and soft-tissue infections and 6 mg/kg/day for Staphylococcus aureus bloodstream infections, including those with right-sided endocarditis, however higher doses (>6 mg/kg/day) have been explored as a possible alternative. A comprehensive review of published data identified through a MEDLINE search of the literature from 1967-2011 and a manual search of references was performed with the primary objective of critically evaluating the safety and efficacy of high-dose daptomycin. Search results yielded two prospective trials, three retrospective reviews, case reports and in vitro simulation studies on high-dose daptomycin. To date, clinical trials, retrospective reviews, case reports and in vitro simulation models have documented the safety and tolerability of high-dose daptomycin, even when administered for a prolonged duration. Additionally, in vitro benefits observed include suppression of the emergence of daptomycin resistance and increased rapidity of bactericidal activity.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Daptomicina/administración & dosificación , Antibacterianos/efectos adversos , Bacteriemia/tratamiento farmacológico , Daptomicina/efectos adversos , Humanos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Resultado del Tratamiento
8.
Appl Radiat Isot ; 69(1): 90-3, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20724172

RESUMEN

A simple formula for computing the generalized Hubbell radiation rectangular source integral [formula in text] is introduced. Tables are given to compare the numerical values derived from our approximation formula with those given earlier in the literature.

9.
Pharmacotherapy ; 30(4): 390-404, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20334459

RESUMEN

As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967-2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add-on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well-designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.


Asunto(s)
Arterias/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Pulmón/efectos de los fármacos , Inhibidores de Fosfodiesterasa/uso terapéutico , Prostaglandinas/uso terapéutico , American Heart Association , Arterias/fisiopatología , Cardiología , Quimioterapia Combinada , Humanos , Pulmón/fisiopatología , Estados Unidos
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