Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
Más filtros

Base de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Wellcome Open Res ; 9: 466, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39364081

RESUMEN

We present a genome assembly from a female Hawthorn Fruit Fly, Anomoia purmunda (Arthropoda; Insecta; Diptera; Tephritidae). The genome sequence has a length of 798.30 megabases. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.48 kilobases in length.

2.
Med Dosim ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39266380

RESUMEN

To assess the impact of Strut Adjusted Volume Implant (SAVI) catheter digitization variability on dosimetric evaluation parameters of HDR breast brachytherapy treatment plans. Four clinically approved SAVI cases were chosen for this digitization variability analysis. All patients were implanted with 6-1 SAVI device. Six experienced physicists independently digitized SAVI catheters. Plans utilizing significant peripheral loading were used for this study where SAVI catheters were near the chest wall and/or skin. After digitization was completed for each case by each physicist, the original clinical dwell times were copied over for comparison. This ensured that only variability among plans is the digitization of SAVI catheters by different users. The original plan that went through two physicists' checks and one physician's review was considered the "ground truth" plan to which all other plans were compared. Plans were evaluated on planning parameters for lumpectomy cavity's PTV_Eval D90, V150, V200 and for the OARs (Chest-Wall/Ribs and Skin), on D0.03cc, D0.1cc, D1cc, D2cc. Additionally, a visualization window setting-based uncertainty test was performed on the same 4 cases. Our results showed that the average and maximum dwell positional digitization uncertainties were 0.36 and 0.75 mm, respectively. Average PTV_Eval D90 was 97.11+/-2.93 %, V150 was 23.10+/-4.25 cc, V200 was 11.88+/-1.93 cc. All OAR constraints were met on all plans - Chest-Wall/Ribs (CW/Ribs) and Skin D0.03cc was 103.40+/-9.23 % and 93.60+/-6.14 %, respectively. Aggregate analysis across all plans shows a clinically nonsignificant spread around the mean for all parameters considered. The robustness of SAVI treatment plans to minor variation in catheter digitization was proved through our multiuser study. Our study showed that SAVI planning constraints are stable within reasonable variation of digitization differences. Such uncertainty analysis is useful in standardization of digitization practices in a department and in defining action levels on digitization fixing request during a 2nd check.

3.
Wellcome Open Res ; 9: 59, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114489

RESUMEN

We present a genome assembly from an individual female Tuberolachnus salignus (the giant willow aphid; Arthropoda; Insecta; Hemiptera; Aphididae). The genome sequence is 456.8 megabases in span. Most of the assembly is scaffolded into 10 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 22.43 kilobases in length.

4.
Wellcome Open Res ; 9: 211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139614

RESUMEN

We present a genome assembly from an individual male Carpatolechia fugitivella (the Elm Groundling; Arthropoda; Insecta; Lepidoptera; Gelechiidae). The genome sequence is 493.1 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.26 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,721 protein coding genes.

6.
Med Dosim ; 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38001010

RESUMEN

Advances in radiotherapy (RT) technologies permit significant decreases in the dose delivered to organs at risk (OARs) for patients with esophageal cancer (EC). Novel RT modalities such as proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT), as well as motion management techniques including breath hold (BH) are expected to further improve the therapeutic ratio. However, to our knowledge, the dosimetric benefits of PBT vs MRgRT vs volumetric-modulated arc therapy (VMAT) have not been directly compared for EC. We performed a retrospective in silico evaluation using the images and datasets of nine distal EC patients who were treated at our institution with a 0.35-Tesla MR linac to 50.4 Gy in 28 fractions in mid-inspiration BH (BH-MRgRT). Comparison free-breathing (FB) intensity-modulated PBT (FB-IMPT) and FB-VMAT plans were retrospectively created using the same prescription dose, target volume coverage goals, and OAR constraints. A 5 mm setup margin was used for all plans. BH-IMPT and BH-VMAT plans were not evaluated as they would not reflect our institutional practice. Planners were blinded to the results of the treatment plans created using different radiation modalities. The primary objective was to compare plan quality, target volume coverage, and OAR doses. All treatment plans met pre-defined target volume coverage and OAR constraints. The median conformity and homogeneity indices between FB-IMPT, BH-MRgRT and FB-VMAT were 1.13, 1.25, and 1.43 (PITV) and 1.04, 1.15, 1.04 (HI), respectively. For FB-IMPT, BH-MRgRT and FB-VMAT the median heart dose metrics were 52.8, 79.3, 146.8 (V30Gy, cc), 35.5, 43.8, 77.5 (V40Gy, cc), 16.9, 16.9, 32.5 (V50Gy, cc) and 6.5, 14.9, 17.3 (mean, Gy), respectively. Lung dose metrics were 8.6, 7.9, 18.5 (V20Gy, %), and 4.3, 6.3, 11.2 (mean, Gy), respectively. The mean liver dose (Gy) was 6.5, 19.6, 22.2 respectively. Both FB-IMPT and BH-MRgRT achieve substantial reductions in heart, lung, and liver dose compared to FB-VMAT. We plan to evaluate dosimetric outcomes across these RT modalities assuming consistent use of BH.

7.
Med Dosim ; 48(4): 238-244, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37330328

RESUMEN

Given the positive results from recent randomized controlled trials in patients with oligometastatic, oligoprogressive, or oligoresidual disease, the role of radiotherapy has expanded in patients with metastatic non-small cell lung cancer (NSCLC). While small metastatic lesions are commonly treated with stereotactic body radiotherapy (SBRT), treatment of the primary tumor and involved regional lymph nodes may require prolonged fractionation schedules to ensure safety especially when treating larger volumes in proximity to critical organs-at-risk (OARs). We have developed an institutional MR-guided adaptive radiotherapy (MRgRT) workflow for these patients. We present a 71-year-old patient with stage IV NSCLC with oligoprogression of the primary tumor and associated regional lymph nodes in which MR-guided, online adaptive radiotherapy was performed, prescribing 60 Gy in 15 fractions. We describe our workflow, dosimetric constraints, and daily dosimetric comparisons for the critical OARs (esophagus, trachea, and proximal bronchial tree [PBT] maximum doses [D0.03cc]), in comparison to the original treatment plan recalculated on the anatomy of the day (i.e., predicted doses). During MRgRT, few fractions met the original dosimetric objectives: 6.6% for esophagus, 6.6% for PBT, and 6.6% for trachea. Online adaptive radiotherapy reduced the cumulative doses to the structures by 11.34%, 4.2%, and 5.62% when comparing predicted plan summations to the final delivered summation. Therefore, this case study presets a workflow and treatment paradigm for accelerated hypofractionated MRgRT due to the significant variations in daily dose to the central thoracic OARs to reduce treatment-related toxicity associated with radiotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Radioterapia Guiada por Imagen , Humanos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Radiocirugia/métodos , Espectroscopía de Resonancia Magnética
8.
Med Dosim ; 48(3): 127-133, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36966049

RESUMEN

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes.

9.
Adv Radiat Oncol ; 8(1): 101084, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36483070

RESUMEN

Purpose: Nearly all patients with pancreatic ductal adenocarcinoma (PDAC) eventually die of progressive cancer after exhausting treatment options. Although distant metastases (DMs) are a common cause of death, autopsy studies have shown that locoregional progression may be directly responsible for up to one-third of PDAC-related deaths. Ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) is a novel treatment strategy that appears to improve locoregional control compared with nonablative radiation therapy, potentially leading to improved overall survival. Methods and Materials: A single-institution retrospective analysis was performed of patients with nonmetastatic inoperable PDAC treated between 2018 to 2020 using the MRIdian Linac with induction chemotherapy, followed by 5-fraction A-SMART. We identified causes of death that occurred after A-SMART. Results: A total of 62 patients were evaluated, of whom 42 (67.7%) had died. The median follow-up time was 18.6 months from diagnosis and 11.0 months from A-SMART. Patients had locally advanced (72.6%), borderline resectable (22.6%), or resectable but medically inoperable PDAC (4.8%). All patients received induction chemotherapy, typically leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (69.4%) or gemcitabine/nab-paclitaxel (24.2%). The median prescribed dose was 50 Gy (range, 40-50), corresponding to a median biologically effective dose of 100 Gy10. Post-SMART therapy included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%). Death was attributed to locoregional progression, DMs, cancer-related cachexia/malnutrition, surgery/irreversible electroporation complications, other reasons not due to cancer progression, or unknown causes in 7.1%, 45.2%, 11.9%, 9.5%, 11.9%, and 14.3% of patients, respectively. Intra-abdominal metastases of the liver and peritoneum were responsible for 84.2% of deaths from DMs. Conclusions: To our knowledge, this is the first contemporary evaluation of causes of death in patients with PDAC receiving dose-escalated radiation therapy. We demonstrated that the predominant cause of PDAC-related death was from liver and peritoneal metastases; therefore novel treatment strategies are indicated to address occult micrometastatic disease at these sites.

10.
Wellcome Open Res ; 8: 519, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38779053

RESUMEN

We present a genome assembly from an individual female Othius punctulatus (a rove beetle; Arthropoda; Insecta; Coleoptera; Staphylinidae). The genome sequence is 870.5 megabases in span. Most of the assembly is scaffolded into 10 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 20.71 kilobases in length.

11.
Wellcome Open Res ; 8: 511, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38855724

RESUMEN

We present a genome assembly from an individual female Sisyra nigra (the Black Spongefly; Arthropoda; Insecta; Neuroptera; Sisyridae). The genome sequence is 372.6 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.34 kilobases in length.

12.
Wellcome Open Res ; 8: 527, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38803349

RESUMEN

We present a genome assembly from an individual female Beris morrisii (the yellow-legged black legionnaire; Arthropoda; Insecta; Diptera; Stratiomyidae). The genome sequence is 613.3 megabases in span. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.69 kilobases in length.

13.
Wellcome Open Res ; 8: 560, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38779042

RESUMEN

We present a genome assembly from an individual female Limnephilus auricula (a caddisfly; Arthropoda; Insecta; Trichoptera; Limnephilidae). The genome sequence is 971.3 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 18.29 kilobases in length.

14.
Front Oncol ; 12: 888462, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35814383

RESUMEN

Background: Radiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood. Methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021. Results: Sixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively. Conclusions: To our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.

15.
Adv Radiat Oncol ; 7(6): 100978, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35647412

RESUMEN

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

16.
Adv Radiat Oncol ; 7(2): 100840, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35146215

RESUMEN

PURPOSE: Compared with computed tomography, magnetic resonance (MR) image guidance offers significant advantages for radiation therapy (RT) that may be particularly beneficial for reirradiation (reRT). However, clinical outcomes of MR-guided reRT are not well described in the published literature. METHODS AND MATERIALS: We performed a single-institution retrospective safety and efficacy analysis of reRT patients treated on the MRIdian Linac to targets within the abdomen or pelvis using continuous intrafraction MR-based motion management with automatic beam triggering. Fiducial markers were not used. RESULTS: We evaluated 11 patients who received prior RT to a median of 50 Gy (range, 30-58.8 Gy) in 25 fractions (range, 5-28 fractions). The median interval to reRT was 26.8 months. The most frequently retreated sites were nodal metastases (36.4%) and pancreatic cancer (27.3%). The median reRT dose was 40 Gy (range, 25-54 Gy) in 6 fractions (range, 5-36 fractions); ultrahypofractionation (63.6%) was more common than hyperfractionation (36.4%). Daily on-table adaptive replanning was used for 3 patients (27.3%). With a median of 14 months' follow-up from reRT completion (range, 6-32 months), the median and 1-year freedom from local progression were 29 months and 88.9%, respectively, and the median and 1-year overall survival were 17.5 months and 70.0%, respectively. One patient (9.1%) experienced acute grade 2 toxic effects; there were no acute or late treatment-related toxic effects of grade 3 or greater. CONCLUSIONS: Magnetic resonance-guided reRT appeared to be feasible and may facilitate safe dose escalation. Additional follow-up is needed to better assess long-term efficacy and late toxic effects. Prospective evaluation of this novel treatment strategy is warranted.

17.
Front Oncol ; 12: 1037674, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36713501

RESUMEN

Purpose/Objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. Materials/Methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.

18.
Radiother Oncol ; 166: 101-109, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34843842

RESUMEN

BACKGROUND AND PURPOSE: To quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRTBH) versus BH or free-breathing (FB) CT-based image-guided radiotherapy (CT-IGRT) for the ablative treatment of adrenal malignancies. MATERIALS AND METHODS: Twenty adrenal patients underwent adaptive IMRT MRgRTBH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRTBH and CT-IGRTFB on a c-arm linac. Only CT-IGRTFB used an ITV, summed from GTVs of all phases of the 4DCT respiratory evaluation. All used the same 5 mm GTV/ITV to PTV expansion. Metrics evaluated included: target volume and coverage, conformality, mean ipsilateral kidney and 0.5 cc gastrointestinal organ-at-risk (OAR) doses (D0.5cc). Adaptive dose for MRgRTBH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRTBH and MRgRTBH to assess frequency of OAR violations and coverage reductions for each fraction. RESULTS: The more common VMAT CT-IGRTFB, with its significantly larger target volumes, proved inferior to MRgRTBH in mean PTV and ITV/GTV coverage, as well as small bowel D0.5cc. Conversely, VMAT CT-IGRTBH delivered a dosimetrically superior initial plan in terms of statistically significant (p ≤ 0.02) improvements in target coverage, conformality and D0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRTBH. However, non-adaptive CT-IGRTBH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D95% than predicted for MRgRTBH. CONCLUSION: Breath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRTBH, but the ability of MRgRTBH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched.


Asunto(s)
Radiocirugia , Radioterapia Guiada por Imagen , Radioterapia de Intensidad Modulada , Humanos , Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Tomografía Computarizada por Rayos X
19.
J Med Chem ; 64(22): 16450-16463, 2021 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-34748707

RESUMEN

The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others.


Asunto(s)
Antimaláricos/química , Antimaláricos/farmacología , ATPasas Transportadoras de Calcio/antagonistas & inhibidores , Descubrimiento de Drogas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Modelos Biológicos , Humanos , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Relación Estructura-Actividad
20.
J Appl Clin Med Phys ; 22(10): 36-44, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34432944

RESUMEN

PURPOSE: To develop a simplified aluminum compensator system for total body irradiation (TBI) that is easy to assemble and modify in a short period of time for customized patient treatments. METHODS: The compensator is composed of a combination of 0.3 cm thick aluminum bars, two aluminum T-tracks, spacers, and metal bolts. The system is mounted onto a plexiglass block tray. The design consists of 11 fixed sectors spanning from the patient's head to feet. The outermost sectors utilize 7.6 cm wide aluminum bars, while the remaining sectors use 2.5 cm wide aluminum bars. There is a magnification factor of 5 from the compensator to the patient treatment plane. Each bar of aluminum is interconnected at each adjacent sector with a tongue and groove arrangement and fastened to the T-track using a metal washer, bolt, and nut. Inter-bar leakage of the compensator was tested using a water tank and diode. End-to-end measurements were performed with an ion chamber in a solid water phantom and also with a RANDO phantom using internal and external optically stimulated luminescent detectors (OSLDs). In-vivo patient measurements from the first 20 patients treated with this aluminum compensator were compared to those from 20 patients treated with our previously used lead compensator system. RESULTS: The compensator assembly time was reduced to 20-30 min compared to the 2-4 h it would take with the previous lead design. All end-to-end measurements were within 10% of that expected. The median absolute in-vivo error for the aluminum compensator was 3.7%, with 93.8% of measurements being within 10% of that expected. The median error for the lead compensator system was 5.3%, with 85.1% being within 10% of that expected. CONCLUSION: This design has become the standard compensator at our clinic. It allows for quick assembly and customization along with meeting the Task Group 29 recommendations for dose uniformity.


Asunto(s)
Aluminio , Irradiación Corporal Total , Humanos , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA