To assess the role of in-flight transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we investigated a cluster of cases among passengers on a 10-hour commercial flight. ...Affected persons were passengers, crew, and their close contacts. We traced 217 passengers and crew to their final destinations and interviewed, tested, and quarantined them. Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). Seating proximity was strongly associated with increased infection risk (risk ratio 7.3, 95% CI 1.2-46.2). We found no strong evidence supporting alternative transmission scenarios. In-flight transmission that probably originated from 1 symptomatic passenger caused a large cluster of cases during a long flight. Guidelines for preventing SARS-CoV-2 infection among air passengers should consider individual passengers' risk for infection, the number of passengers traveling, and flight duration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam.
This retrospective study was conducted across nine hospitals in ...Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability.
A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%).
Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Multicomponent synthesis of novel naphthoquinone-chalcone hybrids was shown.•The reaction was performed under mild and metal-free condition.•The plausible mechanisms for the ...formation of compounds 7a-m, 24a-c were discussed.
A facile and efficient synthesis of novel naphthoquinone-based chalcone hybrids (7 and 24) via the microwave-assisted one-pot three-component reactions of 2-substituted-1,4-naphthoquinones, N,N-dimethylformamide dimethyl acetal (DMF-DMA), and acetophenone derivatives has been reported. Whereas the synthesis of hybrids 7 proceeded via a condensation, 1,4-addition, rotation, elimination, and 1,3-H shift sequence of steps, the synthesis of hybrids 24 were formed through a three-step sequence including condensation, 1,4-addition, and elimination reactions.
Two different synthetic approaches to novel heterocyclic hybrid compounds of 4-azapodophyllotoxin were investigated. The obtained products were characterized by infrared spectroscopy, nuclear ...magnetic resonance spectroscopy, and high-resolution mass spectrometry. MTT protocol was then performed to examine the cytotoxic activity of these products against KB, HepG2, A549, MCF7, and Hek-293 cell lines. The cytotoxic assessment indicated that all products displayed moderate to high cytotoxicity against all tested cancer cell lines. The most active compound 13k containing the 2-methoxypyridin-4-yl group exhibited selective cytotoxicity against KB, A549, and HepG2 cell lines with the IC
values ranging from 0.23 to 0.27 μM, which were between 5- to 10-fold more potent than the positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) and 13d (HetAr = 5-bromofuran-2-yl) displayed high cytotoxic selectivity for A549 and HepG2 cancer cell lines when compared to the other cancer cell lines and low toxicity to the normal Hek-293 cell line. Molecular docking study was conducted to evaluate the interaction of new synthesized compounds with the colchicine-binding-site of tubulin. Besides that, physicochemical and pharmacokinetic properties of the most active compounds 13h,k were predicted.
In this work, role of phase composition and interstitial oxygen on the thermoelectric properties of CuCr0.85Mg0.15O2 materials prepared at different sintering temperatures (1273–1673 K) for short ...time (3 h) are reported. Interestingly, the samples sintered at 1273 K and 1673 K had the same Seebeck coefficient, despite the 1273 K sample having significantly lower conductivity, which are discussed via phase composition and interstitial oxygen induced during the CuCrO2 phase formation and its related defect (VCu, VCr, …). Besides, high conductivity of the 1673 K sample originated from the low percentage of CuO phase and the appearance of Cu2O phase. Since the 1273 K and 1673 K sintered samples have almost the same percentage of delafossite and spinel phases so the 1673 K sample still remain its high Seebeck coefficient. We suggest some reaction chemical equations for elucidating the roles of interstitial oxygen on the phase composition and thermoelectric properties CuCr0.85Mg0.15O2 delafossite material.
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•Phase composition and interstitial oxygen control thermoelectric properties of CuCr0.85Mg0.15O2.•Native interstitial oxygen is induced during the CuCrO2 phase formation.•Samples sintered at 1273 and 1673 K have the same Seebeck coefficient but different conductivity.•High conductivity of the 1673 K sample originated from the low percentage of CuO phase and the appearance of Cu2O phase.•Seebeck coefficient of samples depends on component phases but its behavior follow Heikes or Pysarenko law by defect-type.
The outage performance is a significant problem to implement the Cognitive Radio (CR) paradigm in the Vehicle to Everything (V2X) networks. Recently, more interest has focused on Non-Orthogonal ...Multiple Access (NOMA) in wireless-powered communication. In the conventional CR-enabled V2X-NOMA network, spectrum sensing and limited battery capacity at the Roadside Unit (RSU) may cause serious outage performance. In this study, RSU selection scheme is adopted. This paper presents an interesting model of a system with Simultaneous Wireless Information and Power Transfer (SWIPT) and a CR-enabled V2X-NOMA network. In the downlink, the RSU harvests wireless energy from Radio Frequency (RF) signals and senses the spectrum state at the same time. A CR-enabled V2X-NOMA system performance is presented by deriving exact expressions of outage probability of distant vehicles. In the overlay CR-enabled V2X-NOMA network, the constraints are transmit power and the number of designed RSU that make significant impacts on system performance. Simulation results show that the CR-enabled V2X-NOMA get benefits from energy harvesting and RSU selection scheme.
Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been ...suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation.BACKGROUNDSelecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation.A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022.MATERIALS AND METHODSA retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022.The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality.RESULTSThe live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality.The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.CONCLUSIONThe timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.
A series of novel naphthoquinone-fused podophyllotoxins containing fluoro and trifluoromethyl substituents were synthesized in a medium with good yields using two different synthetic approaches: ...microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, tetronic acid, fluorinated arylaldehydes, and ammonium acetate, and microwave-assisted three-component reactions of 2-amino-1,4-naphthoquinone, tetronic acid, and fluorinated arylaldehydes. The structures of all products were confirmed by spectral analysis. Together, cytotoxicity assessment of the products against four human cancer cell lines (human carcinoma KB, human hepatocellular carcinoma HepG2, lung cancer A549, breast carcinoma MCF7, and human embryonic kidney Hek-293) was performed by MTT assay. Among the obtained compounds, compound 7f turned out to be the most potent anticancer agent with significant cytotoxic activity against KB, HepG2, and MCF cancer cell lines.
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•Fifteen new 4-anilinoquinazoline-substituted triazole hybrid compounds were designed and synthesized.•Their anticancer activities against human cancer cell lines were ...evaluated.•Compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib.•Molecular docking suggests greater affinity of 13a-b and 14c than erlotinib for the ATP binding sites of the active and inactive conformations of EGFR.
In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11–14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.
A series of messagenin–based chalcones has been synthesized by Claisen‐Schmidt condensation and screened for in vitro α‐glucosidase inhibitory activity. The heterocyclization of ...30‐(3‐pyridinylidene)‐messagenin led to syn/anti N‐acetyl‐pyrazoles in a ratio of 2 : 1 that were isolated by HPLC. Messagenin chalcones act as α‐glucosidase inhibitors with IC50 range from 0.055 to 80.70 μM. The lead nanomolar level α‐glucosidase inhibitor 30‐(4‐hydroxymethyl‐benzylidene)‐messagenin 10 was studied for antihyperglycemic activity on streptozotocin–induced diabetic animal models using in vivo mechanism–based assays. In a rat model of STZ‐induced T1DM, compound 10 (20 mg/kg, orally) exhibited antihyperlipidemic activity, reducing AIP (p>0.05) and CRI (p<0.05) compared to control. Compound 10 improved diabetic nephropathy, locomotor activity in rats, and reduced diabetes–related mortality.
Messagenin–based chalcone 10 showed a pronounced hypoglycemic activity on stz–induced T1DM which involved reducing both plasma atherogenic and Castelli risk indices.
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