•Coffee is a prominent commodity extensively used worldwide as beverage.•Coffee green seed residue from fixed oil extraction has not been studied yet.•The antioxidant action and the chemical profile ...of this residue were assessed.•This residue can be used as raw material to obtain antioxidant compounds.•This study values green chemistry principles and the reuse of by-products.
Oil extraction from green coffee seeds generates residual mass that is discarded by agribusiness and has not been previously studied. Bioactive secondary metabolites in coffee include antioxidant phenolic compounds, such as chlorogenic acids. Coffee seeds also contain caffeine, a pharmaceutically important methylxanthine. Here, we report the chemical profile, antioxidant activity, and cytotoxicity of hydroethanolic extracts of green Coffea arabica L. seed residue. The extracts of the green seeds and the residue have similar chemical profiles, containing the phenolic compounds chlorogenic acid and caffeine. Five monoacyl and three diacyl esters of trans-cinnamic acids and quinic acid were identified by ultra-performance liquid chromatography/electrospray ionization-quadruple time of flight mass spectrometry. The residue extract showed antioxidant potential in DPPH, ABTS, and pyranine assays and low cytotoxicity. Thus, coffee oil residue has great potential for use as a raw material in dietary supplements, cosmetic and pharmaceutical products, or as a source of bioactive compounds.
In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
In high-Tc superconductors the magnetic and electronic properties are determined by the probability that valence electrons jump virtually from site to site in the CuO2 planes, a mechanism opposed by ...on-site Coulomb repulsion and favoured by hopping integrals. The spatial extent of the latter is related to transport properties, including superconductivity, and to the dispersion relation of spin excitations (magnons). Here, for three antiferromagnetic parent compounds (single-layer Bi2 Sr0.9 La1.1 CuO6+δ , double-layer Nd1.2 Ba1.8 Cu3 O6 and infinite-layer CaCuO2 ) differing by the number of apical atoms, we compare the magnetic spectra measured by resonant inelastic X-ray scattering over a significant portion of the reciprocal space and with unprecedented accuracy. We observe that the absence of apical oxygens increases the in-plane hopping range and, in CaCuO2 , it leads to a genuine three-dimensional (3D) exchange-bond network. These results establish a corresponding relation between the exchange interactions and the crystal structure, and provide fresh insight into the materials dependence of the superconducting transition temperature.
Preoperative biliary drainage is often performed in patients with obstructive jaundice caused by cancer of the pancreatic head, but the benefit of the procedure is unclear. This randomized trial ...compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications.
This randomized trial compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications.
Obstructive jaundice is the most common symptom in patients with periampullary cancer (located near the ampulla of Vater) or cancer of the pancreatic head. For patients with a resectable tumor who have no radiologic evidence of metastasis, surgical resection is the only option for cure.
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Since surgery in patients with jaundice is thought to increase the risk of postoperative complications, preoperative biliary drainage was introduced to improve the postoperative outcome.
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In several experimental studies and retrospective case series, preoperative biliary drainage reduced morbidity and mortality after surgery.
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However, two meta-analyses of randomized trials and a systematic review of . . .
The merger of two neutron stars is predicted to give rise to three major detectable phenomena: a short burst of γ-rays, a gravitational-wave signal, and a transient optical-near-infrared source ...powered by the synthesis of large amounts of very heavy elements via rapid neutron capture (the r-process). Such transients, named 'macronovae' or 'kilonovae', are believed to be centres of production of rare elements such as gold and platinum. The most compelling evidence so far for a kilonova was a very faint near-infrared rebrightening in the afterglow of a short γ-ray burst at redshift z = 0.356, although findings indicating bluer events have been reported. Here we report the spectral identification and describe the physical properties of a bright kilonova associated with the gravitational-wave source GW170817 and γ-ray burst GRB 170817A associated with a galaxy at a distance of 40 megaparsecs from Earth. Using a series of spectra from ground-based observatories covering the wavelength range from the ultraviolet to the near-infrared, we find that the kilonova is characterized by rapidly expanding ejecta with spectral features similar to those predicted by current models. The ejecta is optically thick early on, with a velocity of about 0.2 times light speed, and reaches a radius of about 50 astronomical units in only 1.5 days. As the ejecta expands, broad absorption-like lines appear on the spectral continuum, indicating atomic species produced by nucleosynthesis that occurs in the post-merger fast-moving dynamical ejecta and in two slower (0.05 times light speed) wind regions. Comparison with spectral models suggests that the merger ejected 0.03 to 0.05 solar masses of material, including high-opacity lanthanides.
To provide species distribution and antifungal susceptibility profiles of 358 Trichosporon clinical isolates collected from 24 tertiary-care hospitals.
Species identification was performed by ...sequencing the IGS1 region of rDNA. Antifungal susceptibility testing for amphotericin B, fluconazole, voriconazole and posaconazole followed the Clinical and Laboratory Standards Institute reference method. Tentative epidemiologic cutoff values (97.5% ECVs) of antifungals for Trichosporon asahii were also calculated.
Isolates were cultured mostly from urine (155/358, 43.3%) and blood (82/358, 23%) samples. Trichosporon asahii was the most common species (273/358, 76.3%), followed by T. inkin (35/358, 9.7%). Isolation of non–T. asahii species increased substantially over the last 11 years 11/77 (14.2%) from 1997 to 2007 vs. 74/281, (26.3%) from 2008 to 2018, p0.03. Antifungal susceptibility testing showed high amphotericin B minimum inhibitory concentrations against Trichosporon isolates, with higher values for T. faecale. The ECV for amphotericin B and T. asahii was set at 4 μg/mL. Among the triazole derivatives, fluconazole was the least active drug. The ECVs for fluconazole and posaconazole against T. asahii were set at 8 and 0.5 μg/mL, respectively. Voriconazole showed the strongest in vitro activity against the Trichosporon isolates; its ECV for T. asahii was set at 0.25 μg/mL after 48 hours' incubation.
Trichosporon species diversity has increased over the years in human samples, and antifungal susceptibility profiles were species specific. Trichosporon asahii antifungal ECVs were proposed, which may be helpful to guide antifungal therapy.
Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and ...progression-free survival on next-line therapy (PFS2) is presented.
Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment.
The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio HR, 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes.
With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.
Background
In Sweden, social restrictions to contain SARS‐CoV‐2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially ...affecting viral dissemination. To understand the levels of past SARS‐CoV‐2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021.
Methods
In this cross‐sectional prospective study, otherwise‐healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS‐CoV‐2 spike (S) glycoprotein and the smaller receptor‐binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut‐off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time.
Setting
Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020–01807.
Participants
No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants.
Results
Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS‐CoV‐2 spike mRNA vaccination, supporting that mild infection engenders a competent B‐cell response.
Conclusions
These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.
To evaluate the effects of mechanical versus chemical cleaning protocols for cleaning the root dentin surface before cementation of fiberglass posts for their effect on the bond strength, failure ...mode, and dentinal penetration of the cementing agent using an etch-and-rinse adhesive system on dentin prepared to receive a fiberglass post.
Forty roots of bovine teeth were endodontically treated and prepared for fiber post cementation. The specimens were randomized into 4 groups of 10: Control group (CO) - irrigation with 2.5% NaOCl; DW group- irrigation with distilled water; RB group - rotating brush for cleaning root canals, and CUI group - continuous ultrasonic irrigation. The fiberglass posts were cemented, and the specimens were immersed in distilled water for 6 months. A push-out test was performed on the cervical, middle, and apical thirds of the samples. Dentinal penetration of the cementing agent and the fracture pattern were evaluated by laser confocal microscopy. Statistical analysis was performed using analysis of variance (ANOVA) and post hoc Tukey tests (α=0.05). Results: The RB and CUI groups showed significantly higher bond strength values when compared to the Control and DW groups (p<0.05). In addition, in the control and DW groups, the apical third presented lower bond strength values when compared to middle and cervical thirds.
While DW showed the highest incidence of adhesive type failure, CUI resulted in the highest dentinal penetration of the cementing agent (p<0.05). RB and CUI resulted in the highest bond strength between cementation system and root dentin. In addition, CUI favored greater dentinal penetration of fiberglass post cementing agent.
The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C–C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation ...sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population’s functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood–testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.
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