Finds of Siboglinids (Annelida, Siboglinidae) in the Estuaries of the Largest Arctic Rivers Are Associated with Permafrost Gas Hydrates.

Gutless marine worms of the family Siboglinidae have been found in the estuaries of the largest Arctic rivers Yenisei, Lena, and Mackenzie. Siboglinid metabolism is provided by symbiotic chemoautotrophic bacteria. Strong salinity stratification is characteristic of the estuaries of the largest Arctic rivers and ensures a high salinity at depths of 25-36 m, where siboglinids were found. High methane concentrations, which are necessary for siboglinid metabolism, result from dissociation of permafrost gas hydrates under the influence of river runoff in the conditions of Arctic warming.

Distribution of Siboglinids (Annelida, Siboglinidae) in the Laptev Sea and Adjacent Areas of the Arctic Basin.

Biodiversity in the Laptev Sea was assessed for gutless marine worms of the family Siboglinidae (Annelida), whose metabolism is provided by symbiotic bacteria that oxidize hydrogen sulfide and methane. Seven siboglinid species were found within the geographical boundaries of the Laptev Sea, and another species was found in an adjacent sector of the Arctic Basin. The largest number of finds and the greatest biological diversity of siboglinids were observed in the eastern part of the Laptev Sea in a field of numerous methane flares. One find was made in the estuary area of the Lena River at a depth of 25 m. A possible association of siboglinids with methane seepage areas is discussed.

The Finding of Pogonophorans (Annelida, Siboglinidae) in the St. Anna Trough (Kara Sea) in an Area of Gas Hydrate Dissociation.

Representatives of pogonophorans (Annelida, Siboglinidae), whose vital activity is provided by symbiotic chemoautotrophic bacteria that oxidize methane and hydrogen sulfide, were found in the St. Anna Trough at depths of 539 and 437 m. The finding of pogonophorans suggests high concentrations of methane, which might result from dissociation of bottom gas hydrates under the influence of the influx of warm Atlantic water into the Kara Sea along the St. Anna Trough.

First Experience of Keeping Pogonophorans (Annelida: Siboglinidae) in Laboratory Conditions.

The article describes the parameters of maintaining the gutless symbiotrophic annelid Siboglinum fiordicum in laboratory conditions outside the marine environment for 64 days.

New Data on Distribution of Nereilinum murmanicum (Annelida, Siboglinidae) in the Barents Sea.

The article presents a report on the findings of representatives of frenulate pogonophorans Nereilinum murmanicum in the northern and central parts of the Barents Sea, which significantly expands the range of this species and provides guidance on its distribution in this basin. Here we present the coordinates of new finds with an indication of the depth. Find points were associated with data on known and potential hydrocarbon deposits.

The First Discovery of Pogonophora (Annelida, Siboglinidae) in the East Siberian Sea Coincides with the Areas of Methane Seeps.

Pogonophora or siboglinid tubeworms (Annelida, Siboglinidae) have been found in the East Siberian Sea for the first time. On the basis of the results of molecular phylogenetic analysis, the found specimens are presumably assigned to the genus Oligobrachia. The stations where the siboglinid tubeworms have been found are located in the area of methane seeps. This confirms the previously stated hypothesis about relationship of siboglinid tubeworm distribution with the areas of underwater methane seeps.

Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study.

BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. PATIENTS AND METHODS: Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m2 or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m2 every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m2 Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib-chemotherapy combination. RESULTS: Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib-carboplatin-pemetrexed, 100%; osimertinib-cisplatin-pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib-carboplatin-pemetrexed and nausea (60%) with osimertinib-cisplatin-pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. CONCLUSIONS: Osimertinib-chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase.

Correlation of the siboglinid (Annelida: Siboglinidae) distribution to higher concentrations of hydrocarbons in the Sea of Okhotsk.

Siboglinids are a characteristic feature of reducing environments. More than 75% of all siboglinids were found in the Sea of Okhotsk at a depth of less than 400 m, while some species are known to inhabit the abyssal depth in other regions. Among the six species of siboglinids encountered in the Sea of Okhotsk, only two are widespread: Siboglinum caulleryi and Oligobrachia dogieli. A significant number of all findings belong to the area where, according to geological data, the methane concentration varies between 0.22 and 4.46*109 nmol/kg. There is a vast territory in the central part of the Sea of Okhotsk that is not inhabited by siboglinids and is characterized by minimum methane concentration values. Thus, data on the Sea of Okhotsk indicate that siboglinids are related to sites of methane seepage.

Obturacula of Vestimentifera (Annelida, Siboglinidae) Are Homological to the Dorsal Lips of the Polychaete of the Family Sabellidae.

We have conducted comparative analysis of the structure of the dorsal lips of the polychaete Eudistylia polymorpha from the family Sabellidae and the obturacula of Oasisia alvinae (Vestimentifera). It has been concluded that the obturacula of Vestimentifera are homologs of the dorsal lips of Polychaete from the family Sabellidae. It has been suggested that the head lobe of siboglinids of the subfamily Frenulata is homologous to the fused obturacula of Vestimentifera.

First Discovery of Pogonophora (Annelida, Siboglinidae) in the Kara Sea Coincide with the Area of High Methane Concentration.

Here we report the first finding of a frenulate pogonophoran (Annelida, Siboglinidae) in the southern part of the Kara Sea. This finding was made in the Yenisei Gulf in the region of the highest methane concentrations, resulting from the degradation of permafrost under the influence of river flow. It has been suggested that pogonophorans are indicators of hydrocarbon manifestations of various genesis.

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial.

BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.

Siboglinids (Annelida, Siboglinidae) as Possible Hydrocarbon Indicators as Exemplified by the Sea of Okhotsk.

The geographic and bathymetric distribution of siboglinids in the Sea of Okhotsk was studied. At least 75% of all siboglinid findings were at a depth up to 400 m. Most of them were concentrated in the northwestern part of the shelf. Comparison of the data on siboglinid distribution in the Sea of Okhotsk and the aggregate geological data on hydrocarbon distribution showed that, in the Sea of Okhotsk, siboglinids were mostly in the regions of hydrocarbon manifestations, but they were absent in the central areas with the minimum methane and hydrocarbon concentrations in both benthic sediments and the uppermost water layers.

Changes in Body Proportions during Growth of the Hydrothermal Vestimentiferan Oasisia alvinae Jones 1985 (Annelida, Siboglinidae).

During the growth of hydrothermal vestimentiferan Oasisia alvinae the trunk part of body was found to be elongated (from 51 to 83.4% of the overall body length), while the relative dimensions of all other body regions decreased. This was related to the enhanced trophosome and gonad development in the trunk part. We suppose that predominant trunk growth is a common feature of all vestimentiferans.

Protonephridial Excretory System in Vestimentifera (Siboglinidae, Annelida).

Ultrastructural study of the excretory tree of vestimentifera Ridgeia piscesae has shown that it consists of tubules that are blind at their distal ends. The tubules are lined with ciliated cells and have one or two multiciliated terminal cell(s) at the distal ends. In the tubule walls, there are putative ultrafiltration sites. The excretory tree tubules are interpreted as the secondary protonephridia.

[Analysis of one-year mortality of radically operated patients over 70 years with nonsmall cell lung cancer].

One-year lethality was studied in 613 patients older than 70 years who underwent surgery for lung cancer for the period of 1970-2002. During the first year after surgery 166 patients died (27.1%) and besides from the generalization of the disease - 92.2%, from other causes - 7.8%. The highest rate of one-year lethality was observed after pneumonectomy (39.4%), the lowest one - after lung margins resection (16.5%). It was found that the most important factor in one-year lethality rate was N2 lymph node status. Risk of dying from the generalization of the disease during the first year sharply increased in group of patients underwent extended and combined pneumonectomy (one-year lethality of 52.6% and 57.1%, respectively), pneumonectomy with N2 (56,0%), lobectomy in peripheral cancer with metastases of N2 level (63,6%), especially when the amount of the tumor was more than 5 cm (83.3%).

Piezoelectric immunosensors for the detection of individual antibiotics and the total content of penicillin antibiotics in foodstuffs.

Piezoelectric immunosensors on the basis of homologous and group-specificantibodies have been developed for detecting penicillin G, ampicillin, and the total content of penicillin antibiotics. The receptor coating of the sensor was obtained by the immobilization of penicillin G or ampicillin hapten-protein conjugates on the polypyrrole film obtained by electropolymerization and activated by glutaraldehyde. The affinity constants and the cross reactivity coefficients have been calculated. This made it possible to estimate the affinity and specificity of the polyclonal and monoclonal antibodies used. The calibration curves are linear in the range of concentrations 2.5-250.0 ng ml(-1) (penicillin G), 2.5-500.0 ng ml(-1) (ampicillin), and 1-500 ng ml(-1) (group of penicillin). The limits of detection are 0.8 ng ml(-1), 3.9 ng ml(-1), which are lower than MRL, established for penicillin antibiotics. The sensors were tested in detecting penicillins in milk, pork, beef, liver.

A piezoelectric immunosensor for chloramphenicol detection in food.

A piezoelectric immunosensor on the basis of electrogenerated polymer for detecting trace quantities of chloramphenicol, a drug which is used in veterinary for treatment and prevention of infectious diseases, was developed. The detection was conducted in a competitive format with the use of hapten-protein conjugate and monoclonal antibodies. The limit of detection is 0.2 ng ml(-1), the calibration curve is linear in the range of concentrations 0.5-100.0 ng ml(-1). Chloramphenicol was detected in food (meat, milk, egg, honey).

Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer.

BACKGROUND: Clinical results of a randomized phase III trial comparing pemetrexed-carboplatin (PC) with etoposide-carboplatin (EC) in chemonaive patients with extensive-stage disease small-cell lung cancer (ED-SCLC) resulted in trial closure for futility; biomarker analyses using immunohistochemistry (IHC) and single-nucleotide polymorphisms (SNPs) are described herein. PATIENTS AND METHODS: Thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyltransferase (GARFT), and folylpolyglutamate synthetase (FPGS) were investigated using IHC (n=395). SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), folate receptor-α FR-α, and solute carrier 19A1 (SLC19A1; n=611). RESULTS: None of the IHC biomarkers (folate pathway or ERCC1) were found to be predictive or prognostic in this setting. rs2838952 (adjacent to SLC19A1) had significant treatment-independent association with overall survival (OS; hazard ratio 0.590, P=0.01). Nine GGH-associated SNPs interacted with rs3788205 (SLC19A1) for OS on the PC arm. rs12379987 (FPGS) interacted with treatment for OS (interaction P=0.036). CONCLUSION: Potential ERCC1 and folate pathway IHC biomarkers failed to predict outcome in either study arm in ED-SCLC. SNPs in regions including FPGS and SLC19A1 and interacting SNPs in GGH and SLC19A1 were associated with differences in OS; however, none of these SNPs predicted for greater survival with PC over EC.

[Rationale for surgical treatment of octogenarians with lung cancer].

Lung cancer was treated by surgery in 17 patients (males--13, females--4) aged more than 80 years, i.e. 2% of surgical patients older than 70 (n-870). The chief death-causing factors were cardiovascular insufficiency and thromboembolism of the pulmonary artery.