Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
Background
Non‐pharmacological interventions are effective neonatal pain reduction strategies. We aimed to study the effects of non‐nutritive sucking (NNS) and swaddling on infants' behavioural and ...physiological parameters during shallow or deep heel stick procedures.
Method
In this prospective, multi‐centred, randomized controlled clinical trial, we enrolled 671 newborns. The infants undergoing shallow or deep heel stick procedures were randomized into four groups: oral sucrose (routine care, group S), oral sucrose combined with NNS (group NS), oral sucrose combined with swaddling (group SS) and oral sucrose combined with NNS and swaddling (group NSS). The behavioural responses were evaluated by the Revised Neonatal Facial Coding System and the physiological signals were monitored by electrocardiogram monitors.
Results
A significant synergistic analgesic effect was observed between the NS and SS groups in both the shallow (F = 5.952, p = 0.015) and deep heel stick (F = 7.452, p = 0.007) procedure. NSS group exhibited the lowest pain score. For the deep heel stick procedure, the NS group had a significantly lower increase in heart rate (HR)% and decrease in SPO2% than the S group (F = 17.540, p = 0.000, F = 10.472, p = 0.001), while this difference was not observed in the shallow heel stick procedure. No difference was found between the S and SS groups, in terms of different physiological parameters.
Conclusion
Non‐nutritive sucking and swaddling had synergistic effects on pain relief when used with oral sucrose. For the deep heel stick procedure, oral sucrose combined with NNS and swaddling provided the best pain relief effect. For the shallow heel stick procedure, addition of NNS and swaddling did not improve the effects.
Photosensitizers (PSs) with multiple characteristics, including efficient singlet oxygen (
1
O
2
) generation, cancer cell-selective accumulation and subsequent mitochondrial localization as well as ...near-infrared (NIR) excitation and bright NIR emission, are promising candidates for imaging-guided photodynamic therapy (PDT) but rarely concerned. Herein, a simple rational strategy, namely modulation of donor-acceptor (D-A) strength, for molecular engineering of mitochondria-targeting aggregation-induced emission (AIE) PSs with desirable characteristics including highly improved
1
O
2
generation efficiency, NIR emission (736 nm), high specificity to mitochondria, good biocompatibility, high brightness and superior photostability is demonstrated. Impressively, upon light irradiation, the optimal NIR AIE PS (DCQu) can generate
1
O
2
with efficiency much higher than those of commercially available PSs. The excellent two-photon absorption properties of DCQu allow two-photon fluorescence imaging of mitochondria and subsequent two-photon excited PDT. DCQu can selectively differentiate cancer cells from normal cells without the aid of extra targeting ligands. Upon ultralow-power light irradiation at 4.2 mW cm
−2
,
in situ
mitochondrial photodynamic activation to specifically damage cancer cells and efficient
in vivo
melanoma ablation are demonstrated, suggesting superior potency of the AIE PS in imaging-guided PDT with minimal side effects, which is promising for future precision medicine.
Mitochondria-targeted photosensitizers with highly efficient singlet oxygen generation, bright near-infrared AIE and good two-photon absorption are obtained through ingenious molecular engineering for cancer cell-selective photodynamic therapy.
Many breakthroughs in the laboratories often do not bridge the gap between research and commercialization. However, silicon photonics bucked the trend, with industry observers estimating the ...commercial market to close in on a billion dollars in 2020 <xref ref-type="bibr" rid="ref45">45 . Silicon photonics leverages the billions of dollars and decades of research poured into silicon semiconductor device processing to enable high yield, robust processing, and most of all, low cost. Silicon is also a good optical material, with transparency in the commercially important infrared wavelength bands, and is a suitable platform for large-scale photonic integrated circuits. Silicon photonics is therefore slated to address the world's ever-increasing needs for bandwidth. It is part of an emerging ecosystem which includes designers, foundries, and integrators. In this paper, we review most of the foundries that presently enable silicon photonics integrated circuits fabrication. Some of these are pilot lines of major research institutes, and others are fully commercial pure-play foundries. Since silicon photonics has been commercially active for some years, foundries have released process design kits (PDK) that contain a standard device library. These libraries represent optimized and well-tested photonic elements, whose performance reflects the stability and maturity of the integration platforms. We will document the early works in silicon photonics, as well as its commercial status. We will provide a comprehensive review of the development of silicon photonics and the foundry services which enable the productization, including various efforts to develop and release PDK devices. In this context, we will report the long-standing efforts and contributions that previously IME/A * STAR and now AMF has dedicated to accelerating this journey.
The super τ-charm facility (STCF) is an electron−positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with ...a peak luminosity of 0.5 × 10 35 cm −2·s −1 or higher. The STCF will produce a data sample about a factor of 100 larger than that of the present τ-charm factory - the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for ...screening PA without drug washout.
We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated.
PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS
. The PAPS
model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout.
PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS
model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.
Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in ...behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1
knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1
mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1
mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.
A novel nano‐packing material with lower relative humidity, oxygen transmission rate and high longitudinal strength was synthesized by blending polyethylene with nano‐powder (nano‐Ag, kaolin, anatase ...TiO2, rutile TiO2), and its effect on preservation quality of strawberry fruits (Fragaria ananassa Duch. cv Fengxiang) was investigated during storage at 4 °C. Results showed that nano‐packaging was able to maintain the sensory, physicochemical, and physiological quality of strawberry fruits at a higher level compared with the normal packing (polyethylene bags). After a 12‐d storage, decreases in the contents of total soluble solids, titratable acidity, and ascorbic acid of nano‐packing were significantly inhibited. Meanwhile, decay rate, anthocyanin, and malondialdehyde contents were decreased to 16.7%, 26.3 mg/100g, 66.3 μmol/g for nano‐packing and 26.8%, 31.9 mg/100g, 75.4 μmol/g for normal packing; polyphenoloxidase (PPO) and pyrogallol peroxidase (POD) activities were significantly lower in nano‐packing than the control. These data indicated that the nano‐packaging might provide an attractive alternative to improve preservation quality of the strawberry fruits during extended storage.
Practical Application: Nano‐packing exhibited identified quality benefits applicable to the preservation of fresh strawberry. Furthermore, nano‐packing has the advantages of simple processing and feasibility to be industrialized in contrast with other storages. Thus, the utilization of nano‐packing will likely assist commercial producers and retailers in extending the shelf life of products over a broader range in the future.
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