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1.
Nature ; 611(7934): 81-87, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36224391

RESUMO

To meet the growing food demand while addressing the multiple challenges of exacerbating phosphorus (P) pollution and depleting P rock reserves1-15, P use efficiency (PUE, the ratio of productive P output to P input in a defined system) in crop production needs to be improved. Although many efforts have been devoted to improving nutrient management practices on farms, few studies have examined the historical trajectories of PUE and their socioeconomic and agronomic drivers on a national scale1,2,6,7,11,16,17. Here we present a database of the P budget (the input and output of the crop production system) and PUE by country and by crop type for 1961-2019, and examine the substantial contribution of several drivers for PUE, such as economic development stages and crop portfolios. To address the P management challenges, we found that global PUE in crop production must increase to 68-81%, and recent trends indicate some meaningful progress towards this goal. However, P management challenges and opportunities in croplands vary widely among countries.


Assuntos
Produção Agrícola , Produtos Agrícolas , Fósforo , Desenvolvimento Sustentável , Produção Agrícola/métodos , Produção Agrícola/tendências , Produtos Agrícolas/classificação , Produtos Agrícolas/metabolismo , Fazendas , Nutrientes/metabolismo , Fósforo/metabolismo , Desenvolvimento Sustentável/tendências , Internacionalidade , Fatores Socioeconômicos , Bases de Dados Factuais
2.
Nature ; 601(7894): 526-530, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35082416

RESUMO

The high-frequency radio sky is bursting with synchrotron transients from massive stellar explosions and accretion events, but the low-frequency radio sky has, so far, been quiet beyond the Galactic pulsar population and the long-term scintillation of active galactic nuclei. The low-frequency band, however, is sensitive to exotic coherent and polarized radio-emission processes, such as electron-cyclotron maser emission from flaring M dwarfs1, stellar magnetospheric plasma interactions with exoplanets2 and a population of steep-spectrum pulsars3, making Galactic-plane searches a prospect for blind-transient discovery. Here we report an analysis of archival low-frequency radio data that reveals a periodic, low-frequency radio transient. We find that the source pulses every 18.18 min, an unusual periodicity that has, to our knowledge, not been observed previously. The emission is highly linearly polarized, bright, persists for 30-60 s on each occurrence and is visible across a broad frequency range. At times, the pulses comprise short-duration (<0.5 s) bursts; at others, a smoother profile is observed. These profiles evolve on timescales of hours. By measuring the dispersion of the radio pulses with respect to frequency, we have localized the source to within our own Galaxy and suggest that it could be an ultra-long-period magnetar.

3.
Nature ; 606(7916): 873-877, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676486

RESUMO

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

4.
Nature ; 598(7880): 267-271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34645999

RESUMO

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

5.
Nature ; 589(7841): 211-213, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33442039

RESUMO

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.

6.
Blood ; 141(10): 1221-1232, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36580664

RESUMO

Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder in which a subset of point mutations in the von Willebrand factor (VWF) A1 domain and recently identified autoinhibitory module (AIM) cause spontaneous binding to glycoprotein Ibα (GPIbα) on the platelet surface. All reported type 2B VWD mutations share this enhanced binding; however, type 2B VWD manifests as variable bleeding complications and platelet levels in patients, depending on the underlying mutation. Understanding how these mutations localizing to a similar region can result in such disparate patient outcomes is essential for detailing our understanding of VWF regulatory and activation mechanisms. In this study, we produced recombinant glycosylated AIM-A1 fragments bearing type 2B VWD mutations and examined how each mutation affects the A1 domain's thermodynamic stability, conformational dynamics, and biomechanical regulation of the AIM. We found that the A1 domain with mutations associated with severe bleeding occupy a higher affinity state correlating with enhanced flexibility in the secondary GPIbα-binding sites. Conversely, mutation P1266L, associated with normal platelet levels, has similar proportions of high-affinity molecules to wild-type (WT) but shares regions of solvent accessibility with both WT and other type 2B VWD mutations. V1316M exhibited exceptional instability and solvent exposure compared with all variants. Lastly, examination of the mechanical stability of each variant revealed variable AIM unfolding. Together, these studies illustrate that the heterogeneity among type 2B VWD mutations is evident in AIM-A1 fragments.


Assuntos
Doença de von Willebrand Tipo 2 , Fator de von Willebrand , Humanos , Sítios de Ligação , Plaquetas/metabolismo , Mutação , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Doença de von Willebrand Tipo 2/genética , Fator de von Willebrand/química , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismo
7.
Neurobiol Dis ; 199: 106593, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971480

RESUMO

Impaired lipid metabolism is a risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and can shift the physiological α-synuclein (αS) tetramer-monomer (T:M) ratio toward aggregation prone monomers. A resultant increase in phospho-serine 129+ αS monomers associating with excess mono- and polyunsaturated fatty acids contributes to the αS aggregation. We previously reported that decreasing the release of monounsaturated fatty acids (MUFAs) by reducing or inhibiting the hormone sensitive lipase (LIPE) reversed pathologic αS phosphorylation and improved soluble αS homeostasis in cultured αS triplication PD neurons and reduced DAergic neurodegeneration in a C.elegans αS model. However, assessing LIPE as a potential therapeutic target for progressive PD motor phenotypes has not been investigated. 3K αS mice, representing a biochemical and neuropathological amplification of the E46K fPD-causing mutation, have decreased αS T:M ratios, lipidic aggregates, and a L-DOPA responsive PD-like motor syndrome. Here, we reduced LIPE by crossings of 3K mice with LIPE null mice, which attenuated motor deficits in male LIPE+/- knockdown (LKD)-3K mice. Heterozygous LIPE reduction was associated with an improved αS T:M ratio, and dopaminergic neurotransmitter levels and fiber densities. In female 3K-LKD mice, an increase in pS129+ and larger lipid droplets (LDs) likely decreased the benefits seen in males. Reducing LIPE decreased MUFA release from neutral lipid storage, thereby reducing MUFA in phospholipid membranes with which αS interacts. Our study highlights fatty acid turnover as a therapeutic target for Lewy body diseases and support LIPE as a promising target in males. LIPE regulation represents a novel approach to mitigate PD and DLB risk and treat disease.

8.
BMC Immunol ; 25(1): 18, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378441

RESUMO

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.


Assuntos
Imunoglobulina G , Síndromes de Imunodeficiência , Humanos , Embalagem de Medicamentos , Infusões Subcutâneas , Síndromes de Imunodeficiência/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Imunoglobulinas Intravenosas/uso terapêutico
9.
Ann Oncol ; 35(2): 190-199, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37872020

RESUMO

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Sunitinibe/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
10.
J Synchrotron Radiat ; 31(Pt 1): 35-41, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38084592

RESUMO

In X-ray diffraction measurements, the angular resolution has a detection limit due to the receiving size of the detector. In many cases this detection limit is too large and must be breached to obtain the desired information. A novel method is proposed here by making the detector simultaneously measuring and moving. Using the deconvolution algorithm to remove the convolution effect, the pixel size limitation is finally broken. The algorithm used is not a common one, and suppresses signals at high frequencies, ensuring the reliability of the peak shape after restoration. The feasibility of this method is verified by successfully measuring the crystal truncation rod signal of SrTiO3 single crystal, and the resolution is nearly ten times higher than that of a single pixel. Moreover, this method greatly reduces the noise and improves the signal-to-noise ratio.

11.
Opt Lett ; 49(12): 3348-3351, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875617

RESUMO

We report on observations of coherent, sustained oscillations in the absorption of continuous-wave light at 388 nm that excites the 6S1/2 → 8P3/2 transition in cesium (Cs) vapor. The oscillation frequency is close to the spacing of hyperfine levels of the 8P3/2 level that are excited simultaneously by the 388 nm field. We observe a threshold behavior of the oscillation amplitude with pump power and suggest that the effect is associated with infrared directional emission due to amplified spontaneous emission (ASE) from the 8P3/2 → 8S1/2 transition that is assisted by retro-reflections from cell windows. The effect may be used to probe a lasing process in an atomic vapor, by checking the temporal properties of the pump field transmitted through the vapor.

12.
Opt Lett ; 49(7): 1737-1740, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560850

RESUMO

Inference of joule-class THz radiation sources from microchannel targets driven with hundreds of joule, picosecond lasers is reported. THz sources of this magnitude are useful for nonlinear pumping of matter and for charged-particle acceleration and manipulation. Microchannel targets demonstrate increased laser-THz conversion efficiency compared to planar foil targets, with laser energy to THz energy conversion up to ∼0.9% in the best cases.

13.
Phys Rev Lett ; 132(13): 133201, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613284

RESUMO

We implement coherent delocalization as a tool for improving the two primary metrics of atomic clock performance: systematic uncertainty and instability. By decreasing atomic density with coherent delocalization, we suppress cold-collision shifts and two-body losses. Atom loss attributed to Landau-Zener tunneling in the ground lattice band would compromise coherent delocalization at low trap depths for our ^{171}Yb atoms; hence, we implement for the first time delocalization in excited lattice bands. Doing so increases the spatial distribution of atoms trapped in the vertically oriented optical lattice by ∼7 times. At the same time, we observe a reduction of the cold-collision shift by 6.5(8) times, while also making inelastic two-body loss negligible. With these advantages, we measure the trap-light-induced quenching rate and natural lifetime of the ^{3}P_{0} excited state as 5.7(7)×10^{-4} E_{r}^{-1} s^{-1} and 19(2) s, respectively.

14.
Phys Rev Lett ; 132(18): 182502, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38759198

RESUMO

The observation of neutrinoless double-beta (0νßß) decay would offer proof of lepton number violation, demonstrating that neutrinos are Majorana particles, while also helping us understand why there is more matter than antimatter in the Universe. If the decay is driven by the exchange of the three known light neutrinos, a discovery would, in addition, link the observed decay rate to the neutrino mass scale through a theoretical quantity known as the nuclear matrix element (NME). Accurate values of the NMEs for all nuclei considered for use in 0νßß experiments are therefore crucial for designing and interpreting those experiments. Here, we report the first comprehensive ab initio uncertainty quantification of the 0νßß-decay NME, in the key nucleus ^{76}Ge. Our method employs nuclear strong and weak interactions derived within chiral effective field theory and recently developed many-body emulators. Our result, with a conservative treatment of uncertainty, is an NME of 2.60_{-1.36}^{+1.28}, which, together with the best-existing half-life sensitivity and phase-space factor, sets an upper limit for effective neutrino mass of 187_{-62}^{+205} meV. The result is important for designing next-generation germanium detectors aiming to cover the entire inverted hierarchy region of neutrino masses.

15.
Phys Rev Lett ; 132(7): 072502, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38427897

RESUMO

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.

16.
Nature ; 559(7713): 241-245, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29995862

RESUMO

There is compelling evidence that episodic deposition of large volumes of freshwater into the oceans strongly influenced global ocean circulation and climate variability during glacial periods1,2. In the North Atlantic region, episodes of massive freshwater discharge to the North Atlantic Ocean were related to distinct cold periods known as Heinrich Stadials1-3. By contrast, the freshwater history of the North Pacific region remains unclear, giving rise to persistent debates about the existence and possible magnitude of climate links between the North Pacific and North Atlantic oceans during Heinrich Stadials4,5. Here we find that there was a strong connection between changes in North Atlantic circulation during Heinrich Stadials and injections of freshwater from the North American Cordilleran Ice Sheet to the northeastern North Pacific. Our record of diatom δ18O (a measure of the ratio of the stable oxygen isotopes 18O and 16O) over the past 50,000 years shows a decrease in surface seawater δ18O of two to three per thousand, corresponding to a decline in salinity of roughly two to four practical salinity units. This coincided with enhanced deposition of ice-rafted debris and a slight cooling of the sea surface in the northeastern North Pacific during Heinrich Stadials 1 and 4, but not during Heinrich Stadial 3. Furthermore, results from our isotope-enabled model6 suggest that warming of the eastern Equatorial Pacific during Heinrich Stadials was crucial for transmitting the North Atlantic signal to the northeastern North Pacific, where the associated subsurface warming resulted in a discernible freshwater discharge from the Cordilleran Ice Sheet during Heinrich Stadials 1 and 4. However, enhanced background cooling across the northern high latitudes during Heinrich Stadial 3-the coldest period in the past 50,000 years7-prevented subsurface warming of the northeastern North Pacific and thus increased freshwater discharge from the Cordilleran Ice Sheet. In combination, our results show that nonlinear ocean-atmosphere background interactions played a complex role in the dynamics linking the freshwater discharge responses of the North Atlantic and North Pacific during glacial periods.


Assuntos
Congelamento , Água Doce/análise , Camada de Gelo , Água do Mar/análise , Movimentos da Água , Diatomáceas/química , Foraminíferos/química , Isótopos de Oxigênio/análise , Oceano Pacífico , Salinidade , Temperatura
17.
Nature ; 564(7734): 87-90, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30487601

RESUMO

The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.

18.
Clin Radiol ; 79(4): e582-e591, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310058

RESUMO

AIM: To identify clinical and magnetic resonance imaging (MRI) radiomics predictors specialised for intracranial progression (IP) after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). MATERIALS AND METHODS: Seventy EGFR-mutated NSCLC patients with a total of 212 BMs who received first-line EGFR-TKI therapy were enrolled. Radiomics features were extracted from the BM regions on the pretreatment contrast-enhanced T1-weighted images, and the radiomics score (rad-score) of each BM was established based on the selected features. Furthermore, the mean rad-score derived from the average rad-score of all included BMs in each patient was calculated. Univariate and multivariate logistic regression analyses were performed to identify potential predictors of IP. Prediction models based on different predictors and their combinations were constructed, and nomogram based on the optimal prediction model was evaluated. RESULTS: Thirty-three (47.1 %) patients developed IP, and the remaining 37 (52.9 %) patients were IP-free. EGFR-19del mutation (OR 0.19, 95 % CI 0.05-0.69), third-generation TKI treatment (OR 0.33, 95 % CI 0.16-0.67) and mean rad-score (OR 5.71, 95 % CI 1.65-19.68) were found to be independent predictive factors. Models based on these three predictors alone and in combination (combined model) achieved AUCs of 0.64, 0.64, 0.74, and 0.86 and 0.64, 0.64, 0.75, and 0.84 in the training and validation sets, respectively, and the combined model demonstrated optimal performance for predicting IP. CONCLUSIONS: The model integrating EGFR-19del mutation, third-generation TKI treatment and mean rad-score had good predictive value for IP after EGFR-TKI treatment in NSCLC patients with BM.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Radiômica , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Imageamento por Ressonância Magnética , Mutação , Estudos Retrospectivos
19.
Clin Radiol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944542

RESUMO

AIM: Radiomics involves the extraction of quantitative data from medical images to facilitate the diagnosis, prognosis, and staging of tumors. This study provides a comprehensive overview of the efficacy of radiomics in prognostic applications for head and neck cancer (HNC) in recent years. It undertakes a systematic review of prognostic models specific to HNC and conducts a meta-analysis to evaluate their predictive performance. MATERIALS AND METHODS: This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature searches. The literature databases, including PubMed, Embase, Cochrane, and Scopus were systematically searched individually. The methodological quality of the incorporated studies underwent assessment utilizing the radiomics quality score (RQS) tool. A random-effects meta-analysis employing the Harrell concordance index (C-index) was conducted to evaluate the performance of all radiomics models. RESULTS: Among the 388 studies retrieved, 24 studies encompassing a total of 6,978 cases were incorporated into the systematic review. Furthermore, eight studies, focusing on overall survival as an endpoint, were included in the meta-analysis. The meta-analysis revealed that the estimated random effect of the C-index for all studies utilizing radiomics alone was 0.77 (0.71-0.82), with a substantial degree of heterogeneity indicated by an I2 of 80.17%. CONCLUSIONS: Based on this review, prognostic modeling utilizing radiomics has demonstrated enhanced efficacy for head and neck cancers; however, there remains room for improvement in this approach. In the future, advancements are warranted in the integration of clinical parameters and multimodal features, balancing multicenter data, as well as in feature screening and model construction within this field.

20.
Clin Radiol ; 79(3): 230-236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092646

RESUMO

AIM: To assess the accuracy of Magnetic Resonance Index of Activity (MaRIA) in evaluating therapeutic efficacy in Crohn's disease (CD) patients with different activity levels using ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Forty-eight patients underwent magnetic resonance enterography (MRE) and ileocolonoscopy at baseline, week 26, and week 52, along with the Simple Endoscopic Score for Crohn's Disease (SES-CD) and MaRIA scores. According to the SES-CD score at baseline, all patients were subdivided into mild, moderate, and severe activity subgroups. The identification of endoscopic mucosal healing (MH) was explored primarily. Moreover, the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) levels were collected and analysed. RESULTS: MaRIA correlated significantly with SES-CD and CRP at baseline, week 26, and week 52. The discrepancies in MaRIA and SES-CD were statistically significant before and after treatment. MaRIA = 24.43 and ΔMaRIA = 12.77 as the cut-off points were found to have high diagnostic accuracy for predicting MH. MaRIA (p<0.001), SES-CD (p<0.001), CRP (p<0.05), ESR (p<0.05), and CDAI score (p<0.05) in patients with MH were considerably decreased compared to those in patients without MH. CONCLUSIONS: MRE has good application value in evaluating the therapeutic response of CD patients treated with biological agents. MaRIA is a reliable indicator in the follow-up of CD patients, which is strongly correlated with SES-CD, and it has high accuracy in predicting endoscopic MH.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Índice de Gravidade de Doença
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