Trifluorophenyl‐functionalized multi‐walled‐carbon‐nanotube/poly(vinylidene fluoride) (TFP‐MWNT/PVDF) nanocomposites are fabricated by employing a wet‐chemistry route. The modified MWNTs are observed ...to form a well‐dispersed, structurally random nanophase within the polymer matrix (see figure). The TFP‐MWNT/PVDF nanocomposite exhibits enhanced dielectric permittivity when the content of TFP‐MWNT is close to the percolation threshold.
Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) ...aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas.
A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world.
MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance.
In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.
•MCDBT-1 had a sensitivity of 69.1% and a specificity of 98.9% in detecting six cancers.•In the real world, MCDBT-1 decreased late-stage incidence by 38.7%-46.4% and increased 5-year survival rate by 33.1%-40.4%.•In parallel, MCDBT-2 was set at a lower specificity but a higher sensitivity than MCDBT-1 and had an ideal performance.
Ordovician strata of the South Mayo Trough in western Ireland contain clastic deposits that represent materials eroded from a large and diverse continental area over a time scale that spans much of ...the Earth's history. Therefore, it is a useful region to use detrital zircons to construct a continental crustal growth model. Here, we report integrated U-Pb, Lu-Hf and O isotope measurements obtained from in situ analyses of 160 zircons from the South Mayo Trough. U-Pb zircon crystallization ages define three major magmatic episodes of crustal reworking in the Archaean (Lewisian), Mesoproterozoic (Grenville), and Ordovician (Grampian). These data, together with oxygen isotope data and Hf model ages, suggest that crustal growth, recorded in the strata of the South Mayo Trough, started at c. 4 Ga and continued until 1.4 Ga, with two major growth periods at 2.3-2.1 and 2.0-1.5 Ga. We find that the crustal incubation time is decoupled from the duration of supracrustal alteration processes; some zircons with very long crustal incubation times have pristine mantle δ18O signatures suggesting minimal low-temperature surface processing in their source regions. Identifying such zircons is the key for future studies in constructing realistic net continental crustal growth models unaffected by crustal recycling.
Abstract
The electronic instabilities in CsV
3
Sb
5
are believed to originate from the V 3
d
-electrons on the kagome plane, however the role of Sb 5
p
-electrons for 3-dimensional orders is largely ...unexplored. Here, using resonant tender X-ray scattering and high-pressure X-ray scattering, we report a rare realization of conjoined charge density waves (CDWs) in CsV
3
Sb
5
, where a 2 × 2 × 1 CDW in the kagome sublattice and a Sb 5
p
-electron assisted 2 × 2 × 2 CDW coexist. At ambient pressure, we discover a resonant enhancement on Sb
L
1
-edge (2
s
→5
p
) at the 2 × 2 × 2 CDW wavevectors. The resonance, however, is absent at the 2 × 2 × 1 CDW wavevectors. Applying hydrostatic pressure, CDW transition temperatures are separated, where the 2 × 2 × 2 CDW emerges 4 K above the 2 × 2 × 1 CDW at 1 GPa. These observations demonstrate that symmetry-breaking phases in CsV
3
Sb
5
go beyond the minimal framework of kagome electronic bands near van Hove filling.
Abstract
Unconventional superconductors often feature competing orders, small superfluid density, and nodal electronic pairing. While unusual superconductivity has been proposed in the kagome metals
...A
V
3
Sb
5
, key spectroscopic evidence has remained elusive. Here we utilize pressure-tuned and ultra-low temperature muon spin spectroscopy to uncover the unconventional nature of superconductivity in RbV
3
Sb
5
and KV
3
Sb
5
. At ambient pressure, we observed time-reversal symmetry breaking charge order below
$${T}_{{{\rm{1}}}^{*}\simeq$$
T
1
*
≃
110 K in RbV
3
Sb
5
with an additional transition at
$${T}_{{{\rm{2}}}^{*}\simeq$$
T
2
*
≃
50 K. Remarkably, the superconducting state displays a nodal energy gap and a reduced superfluid density, which can be attributed to the competition with the charge order. Upon applying pressure, the charge-order transitions are suppressed, the superfluid density increases, and the superconducting state progressively evolves from nodal to nodeless. Once optimal superconductivity is achieved, we find a superconducting pairing state that is not only fully gapped, but also spontaneously breaks time-reversal symmetry. Our results point to unprecedented tunable nodal kagome superconductivity competing with time-reversal symmetry-breaking charge order and offer unique insights into the nature of the pairing state.
The black hole X-ray binary source 4U 1543–47 experienced a super-Eddington outburst in 2021, reaching a peak flux of up to ∼1.96 × 10 −7 erg cm −2 s −1 (∼8.2 Crab) in the 2−10 keV band. Soon after ...the outburst began, it rapidly transitioned into the soft state. Our goal is to understand how the accretion disk structure deviates from a standard thin disk when the accretion rate is near Eddington. To do so, we analyzed spectra obtained from quasi-simultaneous observations conducted by the Hard X-ray Modulation Telescope (Insight-HXMT), the Nuclear Spectroscopic Telescope Array ( NuSTAR ), and the Neil Gehrels Swift Observatory ( Swift ). These spectra are well fitted by a model comprising a disk, a weak corona, and a reflection component. We suggest that the reflection component is caused by disk self-irradiation, that is by photons emitted from the inner disk that return to the accretion disk surface as their trajectories are bent by the strong gravity field. In this scenario, the best-fitting parameters imply that the reflected flux represents more than half of the total flux. Using general relativistic ray-tracing simulations, we show that this scenario is viable when the disk becomes geometrically thick, with a funnel-like shape, as the accretion rate is near or above the Eddington limit. In the specific case of 4U 1543–47, an angle ≳45 deg between the disk surface and the equatorial plane can explain the required amount of self-irradiation.
Hypoxia-inducible factor 1 (HIF-1) is a crucial transcription factor for the cellular adaptive response to hypoxia, which contributes to multiple events in cancer biology. MicroRNAs (miRNAs) are ...involved in almost all cellular activities such as differentiation, proliferation, and apoptosis. In this work, we use miRNA microarrays to profile miRNA expression in acute myeloid leukemia (AML) cells with inducible HIF-1α expression, and identify 19 differentially expressed miRNAs. Our study shows that HIF-1α represses the expression of miR-17 and miR-20a by downregulating c-Myc expression. These two miRNAs alleviate hypoxia and HIF-1α-induced differentiation of AML cells. More intriguingly, miR-17 and miR-20a directly inhibit the p21 and STAT3 (signal transducer and activator of transcription 3) expression, both of which can reverse miR-17/miR-20a-mediated abrogation of HIF-1α-induced differentiation. Moreover, we show in vivo that miR-20a contributes to HIF-1α-induced differentiation of leukemic cells. Taken together, our results suggest that HIF-1α regulates the miRNA network to interfere with AML cell differentiation, representing a novel molecular mechanism for HIF-1-mediated anti-leukemic action.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
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