bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical Activity of SAR408701: A Novel Anti-CEACAM5–maytansinoid Antibody–drug Conjugate for the Treatment of CEACAM5-positive Epithelial Tumors
Authors: Decary Stéphanie , Berne Pierre-François , Nicolazzi Céline , Lefebvre Anne-Marie , Dabdoubi Tarik , Cameron Béatrice , Rival Pierrick , Devaud Catherine , Prades Catherine , Bouchard Hervé , Cassé Alhassan , Henry Christophe , Amara Céline , Brillac Claire , Ferrari Paul , Maçon Laetitia , Lacoste Eric , Combeau Cecile , Beys Eric , Naimi Souad , García-Echeverría Carlos , Mayaux Jean-François , Blanc Véronique
Published: October 2020

Purpose:

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a glycoprotein that has limited expression in normal adult tissues, but is overexpressed in carcinomas of the gastrointestinal tract, the genitourinary and respiratory systems, and breast cancer. As such, CEACAM5 is an attractive target for antibody-based therapies designed to selectively deliver cytotoxic drugs to certain epithelial tumors. Here, we describe preclinical data for a novel antibody–drug conjugate (ADC), SAR408701, which consists of an anti-CEACAM5 antibody (SAR408377) coupled to a maytansinoid agent DM4 via a cleavable linker.

Experimental Design:

The specificity and binding affinity of SAR408701 to human and cynomolgus monkey CEACAM5 were tested in vitro. The cytotoxic activity of SAR408701 was assessed in CEACAM5-expressing tumor cell lines and using patient-derived xenograft mouse models of CEACAM5-positive tumors. Pharmacokinetic-pharmacodynamic and pharmacokinetic-efficacy relationships were established. SAR408701 toxicity was evaluated in cynomolgus monkey.

Results:

SAR408701 bound selectively to human and cynomolgus monkey CEACAM5 with similar apparent Kd values (0.017 nmol/L and 0.024 nmol/L, respectively). Both in vitro and in vivo evaluations showed that SAR408701 has cytotoxic activity, leading to in vivo efficacy in single and repeated dosing. Single doses of SAR408701 induced significant increases in the tumor expression of phosphorylated histone H3, confirming the tubulin-targeting mechanism of action. The overall toxicity profile of SAR408701 in cynomolgus monkey was similar to that observed after intravenous administration of DM4 alone.

Conclusions:

On the basis of these preclinical data, the ADC SAR408701 is a promising candidate for development as a potential treatment for patients with CEACAM5-positive tumors.
Phase I Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-positive EGFR-mutant Non–small Cell Lung Cancer
Authors: Yu Helena A. , Paz-Ares Luis G. , Yang James Chih-Hsin , Lee Ki Hyeong , Garrido Pilar , Park Keunchil , Kim Joo-Hang , Lee Dae Ho , Mao Huzhang , Wijayawardana Sameera R. , Gao Ling , Hozak Rebecca R. , Chao Bo H. , Planchard David
Published: October 2020

Purpose:

We report the final analysis of JVDL (NCT02789345), which examined the combination of the EGFR tyrosine kinase inhibitor (TKI) osimertinib plus the VEGFR2-directed antibody ramucirumab in patients with T790M-positive EGFR-mutant non–small cell lung cancer (NSCLC).

Patients and Methods:

This open-label, single-arm phase I study enrolled patients with EGFR T790M-positive NSCLC, who had progressed following EGFR TKI but were third-generation EGFR TKI-naïve. A dose-limiting toxicity (DLT) period with as-needed dose deescalation was followed by an expansion cohort. Patients received daily oral osimertinib and intravenous ramucirumab every 2 weeks until progression or discontinuation.

Results:

Twenty-five patients were enrolled. No DLTs were observed. Median follow-up time was 25.0 months. Common grade 3 or higher treatment-related adverse events (TRAE) were hypertension (8%) and platelet count decreased (16%); grade 5 TRAE (subdural hemorrhage) occurred in 1 patient. Patients with (N = 10) and without central nervous system (CNS) metastasis (N = 15) had similar safety outcomes. Five patients remain on treatment. Objective response rate (ORR) was 76%. Median duration of response was 13.4 months [90% confidence interval (CI): 9.6–21.2]. Median progression-free survival (PFS) was 11.0 months (90% CI: 5.5–19.3). Efficacy was observed in patients with and without CNS metastasis (ORR 60% and 87%; median PFS 10.9 and 14.7 months, respectively). Exploratory biomarker analyses in circulating tumor DNA suggested that on-treatment loss of EGFR Exon 19 deletion or L858R mutations, detectable at baseline, correlated with longer PFS, but on-treatment loss of T790M did not. Emergent genetic alterations postprogression included C797S, MET amplification, and EGFR amplification.

Conclusions:

Ramucirumab plus osimertinib demonstrated encouraging safety and antitumor activity in T790M-positive EGFR-mutant NSCLC.

See related commentary by Garon, p. 905
Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors
Authors: Janku Filip , Zhang Halle Huihong , Pezeshki Abdulmohammad , Goel Sanjay , Murthy Ravi , Wang-Gillam Andrea , Shepard Dale R. , Helgason Thorunn , Masters Tyler , Hong David S. , Piha-Paul Sarina A. , Karp Daniel D. , Klang Mark , Huang Steven Y. , Sakamuri Divya , Raina Anjali , Torrisi Jean , Solomon Stephen B. , Weissfeld Alice , Trevino Ernest , DeCrescenzo Gary , Collins Amanda , Miller Maria , Salstrom Jennifer L. , Korn Ronald L. , Zhang Linping , Saha Saurabh , Leontovich Alexey A. , Tung David , Kreider Brent , Varterasian Mary , Khazaie Khashayarsha , Gounder Mrinal M.
Published: October 2020

Purpose:

Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation.

Patients and Methods:

This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose.

Results:

Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses.

Conclusions:

Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.
A Cyclin D1–Dependent Transcriptional Program Predicts Clinical Outcome in Mantle Cell Lymphoma
Authors: Demajo Santiago , Albero Robert , Clot Guillem , Castellano Giancarlo , Navarro Alba , Capdevila Cristina , Enjuanes Anna , Nadeu Ferran , Giné Eva , Pinyol Magda , Jaffe Elaine S. , Ott German , Staudt Louis M. , Rosenwald Andreas , Scott David W. , Rimsza Lisa M. , López-Guillermo Armando , Beà Sílvia , Campo Elias , Jares Pedro
Published: October 2020

Purpose:

Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression. Cyclin D1 is a major cell-cycle regulator and also regulates transcription, but the impact of cyclin D1–mediated transcriptional dysregulation on MCL pathogenesis remains poorly understood. The aim of this study was to define a cyclin D1–dependent gene expression program and analyze its prognostic value.

Experimental Design:

We integrated genome-wide expression analysis of cyclin D1–silenced and overexpressing cells with cyclin D1 chromatin-binding profiles to identify a cyclin D1–dependent transcriptional program in MCL cells. We analyzed this gene program in two MCL series of peripheral blood samples (n = 53) and lymphoid tissues (n = 106) to determine its biological and clinical relevance. We then obtained a simplified signature of this program and evaluated a third series of peripheral blood MCL samples (n = 81) by NanoString gene expression profiling to validate our findings.

Results:

We identified a cyclin D1–dependent transcriptional program composed of 295 genes that were mainly involved in cell-cycle control. The cyclin D1–dependent gene program was overexpressed in MCL tumors directly proportional to cyclin D1 levels. High expression of this program conferred an adverse prognosis with significant shorter overall survival of the patients. These observations were validated in an independent cohort of patients using a simplified 37-gene cyclin D1 signature. The cyclin D1–dependent transcriptional program was also present in multiple myeloma and breast tumors with cyclin D1 overexpression.

Conclusions:

We identified a cyclin D1–dependent transcriptional program that is overexpressed in MCL and predicts clinical outcome.
Pregnancy-Onset Acute Severe Colitis after in vitro Fertilization Embryo Transfer
Authors: Grgić Dora , Čuković Čavka Silvija , Elveđi Gašparović Vesna , Turk Nikša , Brinar Marko , Marušić Zlatko , Krznarić Željko
Published: October 2020

Inflammatory bowel diseases (IBD) usually affect women in their fertile years and, therefore, have implications for their fertility and pregnancy. The presence of IBD during pregnancy has been shown to adversely affect pregnancy outcomes, and increased rates of preterm delivery and of spontaneous abortion have been reported. An onset of acute severe colitis in pregnancy has rarely been seen. We present the case of a 42-year-old woman who conceived after 9 attempts of in vitro fertilization and whose pregnancy was the result of a donated oocyte. Shortly after conception, she was diagnosed with severe active ulcerative colitis, and biologic therapy was introduced in the 28th week of pregnancy. Although therapy for IBD in pregnancy is considered safe for most drugs, this was not very well known in 2015. We also consider our case exceptional because we now have a 5-year follow-up of our patient and her child after having begun biologic therapy during late pregnancy.
Tobacco Use, Knowledge about Smoking-Associated Risks, and Cessation Programs among Dental Students in Germany – ToDent
Authors: Bauer-Kemeny Claudia , Lis Ilona Verena , Raupach Tobias , Kreuter Michael
Published: October 2020

Background: Professional and consistent smoking prevention and cessation may avoid many smoking-associated deaths worldwide. Dentists can exert a decisive influence on smoking behavior, as most people regularly visit a dentist. However, only if dentists have been trained sufficiently about the consequences of smoking and of smoking cessation methods might they fulfill this task appropriately. Objectives: The aim of our study was therefore to examine the prevalence of smokers among dental students in Germany, their attitude toward smoking in general, and their knowledge about tobacco-related diseases and smoking cessation programs. Methods: A cross-sectional survey among dental students in Germany was conducted in 2016. Students of the first and tenth semesters were asked to participate in this anonymous survey. The questionnaire included items concerning their own smoking habits, their knowledge about effects of smoking on health, and their attitude toward prevention and cessation in a dental setting. Results: Seven hundred and thirty dental students participated in this survey; 21% of the participating students were smokers. Their knowledge about smoking-related diseases was widespread. Some diseases were rarely known (only in 34% of students) and others were well known (in 99% of the students). Knowledge about health risks of e-cigarettes was low. About 30% of the participating students felt competent to encourage and support patients in cessation strategies; 2 out of 3 students were willing to improve their knowledge in that area. More than 85% confirmed that advice for smoking cessation should be one of the tasks of a dentist. Conclusions: Smoking is common among dental students, their knowledge about smoking-related health risks is moderate, and self-perceived smoking cessation skills are poor. More emphasis should be placed on education regarding smoking prevention and cessation methods.
Experimental Study of Mechanical Integrity Testing in Stapled Large Bowel: Methylene Blue Leak Test Is Not Inferior to Air Leak Test
Authors: Kryzauskas Marius , Degutyte Austeja Elzbieta , Abeciunas Vilius , Lukenaite Beatrice , Jasiunas Eugenijus , Poskus Eligijus , Strupas Kestutis , Poskus Tomas
Published: October 2020

Background/Objectives: Anastomotic leakage remains the most devastating postoperative complication in colorectal surgery. The mechanical integrity of the newly formed colorectal anastomosis can be evaluated by visual inspection intraoperatively; both air leak and liquid leak tests are also used to evaluate the integrity of stapled colorectal anastomoses. It is not clear whether double-stapled anastomoses are more prone to leaks than single-stapled anastomoses. The aim of our study was to compare the methylene blue and the air leak test in the experimental setting of single-stapled and double-stapled porcine bowels. Methods: Twenty-four distal colons were excised from slaughtered pigs without delay. The proximal bowel end was closed with a linear stapler using blue cartridges. The bowels were randomly divided into single-stapled or double-stapled groups. Air leak and methylene blue leak tests were performed. A digital pressure monitor with a gradual pressure increase function was used to both gradually increase pressure within the bowel and to determine the pressure at which the stapler line disintegrated. Results: Air leakage occurred at a mean pressure of 51.62 (±16.60) mm Hg and methylene blue leakage occurred at 46.54 (±16.78) mm Hg (p = 0.31). The air and methylene blue leaks occurred at comparable pressures in single-stapled bowels and in double-stapled bowels (47.21 [±14.02] mm Hg vs. 50.96 [±19.15] mm Hg, p = 0.6). Conclusions: The methylene blue solution leak test is not inferior to the air leak test. There is no significant difference in bursting pressure between single-stapled and double-stapled anastomoses.
The Milan System for Reporting Salivary Gland Cytopathology: Assessment of Cytohistological Concordance and Risk of Malignancy
Authors: Jha Shilpy , Mitra Suvradeep , Purkait Suvendu , Adhya Amit Kumar
Published: October 2020

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was proposed by the American Society of Cytopathology and the International Academy of Cytology to bring uniformity in the reporting system and the treatment protocol. A wide range of risk of malignancy for each category has been reported by various authors by applying the system. Aim: We intend to study the cytohistological concordance and the ROM for each of the diagnostic categories of the Milan system. Materials and Methods: The study included 292 cases of fine-needle aspiration cytology (FNAC) of salivary gland lesions over a period of 3 years. The diagnosis of these cases was reclassified into the 6 categories of the Milan system. The cytohistological concordance and ROM for each category of the Milan system were calculated based on the clinical and histopathological follow-up. Results: The patients’ age ranged from 3 to 81 years with the mean of 42.65 ± 16.3 years. The cases included 189 (64.7%) parotid, 82 (28.1%) submandibular, and 21 (7.2%) cases of minor salivary gland swellings. Follow-up histopathological diagnosis for 102 cases was available. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to be 64.28, 97.01, 90, 86.67, and 87.37%, respectively. After reclassification, the number of cases in each category was as follows: category I: 31 (10.62%), category II: 80 (27.4%), category III: 2 (0.68%), category IVA: 143 (48.97%), category IVB: 1 (0.34%), category V: 13 (4.45%), and category VI: 22 (7.53%). The calculated ROM was as follows: category I: 42.86%, category II: 26.67%, category III: 100% category IVA: 10.17%, category IVB: 0%, category V: 71.42%, category VI: 100%. Conclusion: FNAC is an excellent procedure to differentiate benign from malignant tumors, and MSRSGC is a useful system for risk assessment and deciding the further treatment protocol. Our findings also suggest that in addition to the surgical follow-up, inclusion of the clinical and radiological follow-up may be a better strategy for calculation of ROM, especially for categories I and II.
Cirugía de metástasis pulmonar mejora la supervivencia de los pacientes con condrosarcoma
Authors: Hekmat Khosro
Published: October 2020

Aims: The aim of this retrospective study is to evaluate the role of pulmonary metastasectomy (PM) in patients affected by lung metastasis (LM) of grade 2 and 3 chondrosarcoma (CS). Patients and Methods: The study included 61 patients affected by LM. Patients unfit for PM were treated with chemotherapy and radiotherapy. Results: The patients' mean age was 51 years, ranging from 17 to 84 years; 44 (66.7%) patients had grade 2 CS, while 17 (25.8%) patients had grade 3 CS. Fifty-one patients presented multiple nodules: 44 of those cases were bilateral LM (72.1%). Twenty-nine (47.5%) patients underwent PM, whereas 32 (52.5%) patients underwent chemotherapy and stereotactic radiotherapy alone. At the final follow-up (average of 83 months, range 13-298), 47 (77.0%) patients had died of the disease. A better post-relapse survival rate was observed in patients who underwent PM (55.1 vs. 13.1% at 5-year follow-up, p < 0.001) and in patients with unilateral LM (60.4 vs. 25.6% at 5-year follow-up, p = 0.016). The number of LM also played a prognostic role. Conclusions: Until significant improvements in chemotherapy can be made, PM can be a valid option in the attempt to improve post-metastatic survival.
Trends of Metastasis-Directed Treatments in Patients with Renal Cell Carcinoma: A Total Population-Based Analysis in Germany in the Era of Targeted Therapies
Authors: Meyer Christian P. , Groeben Christer , Marks Phillip , Koch Rainer , Huber Johannes
Published: October 2020

Introduction: We characterize trends of metastasis-directed treatments in patients with metastatic renal cell carcinoma (mRCC) in Germany in the targeted therapy era. Methods: We identified all cases with a diagnosis of renal cell carcinoma (ICD-10: C.64) and site-specific codes for secondary malignant neoplasms (C79.x) in combination with procedural codes for resection and radiation from the Institute of Hospital Remuneration and the German Federal Statistical Office (Destatis) between 2006 and 2014. We assessed site-specific temporal trends using estimated annual percent change (EAPC) linear regression. Results: Overall, 15,742 resections and 21,224 radiation treatments were recorded. These targeted lung (44.1% resections; 22.0% radiations), lymph node (14.0% resections; 12% radiations), bone (21% resections; 38% radiations), liver (9% resections; 7% radiations), adrenal (11% resections; 3% radiations), and CNS metastases (2% resections; 19% radiations). There was a significantly increasing trend for resection of lung (EAPC +1.33, p = 0.011), bone (EAPC +2.48, p = 0.014), and adrenal (EAPC +3.4, p = 0.003) metastases, while trends for resection of CNS metastases significantly decreased (EAPC –7.93, p = 0.005). Between Western and Eastern Germany linear trends of resection (EAPC +2.75, p < 0.001; EAPC –0.44, p = 0.54) and radiation (EAPC +1.08, p = 0.15; –3.41, p = 0.03) differed significantly. Conclusion: We observed an increasing trend for metastasis-directed resections and slightly declining numbers for radiation therapy in Germany for mRCC in the targeted therapy era. Treatment differed by geography. These findings suggest more aggressive treatment algorithms following the availability of targeted therapies and a yet diverging treatment landscape needing further exploration.
Hybrid Coronary Revascularization Versus Conventional Coronary Artery Bypass Surgery
Authors: Hannan Edward L. , Wu Yifeng , Cozzens Kimberly , Sundt Thoralf M. , Girardi Leonard , Chikwe Joanna , Wechsler Andrew , Smith Craig R. , Gold Jeffrey P. , Lahey Stephen J. , Jordan Desmond
Published: October 2020

Background:

Hybrid coronary revascularization (HCR) treats multivessel coronary artery disease by combining a minimally invasive surgical approach to the left anterior descending artery with percutaneous coronary intervention for non–left anterior descending diseased coronary arteries. The objective of this study is to compare HCR and conventional coronary artery bypass graft (CABG) surgery medium-term outcomes.

Methods:

Data from multivessel disease patients in New York’s cardiac surgery and percutaneous coronary intervention registries in 2010 to 2016 were used to compare mortality and repeat revascularization rates for HCR and conventional CABG after using propensity matching to reduce selection bias.

Results:

There was a total of 303 HCR (0.80%) patients and 37 556 conventional CABG patients after exclusions. After propensity matching, the respective median follow-up times were 3.72 years and 3.76 years. There was no difference between HCR and conventional CABG in survival at 6 years (80.9% versus 85.8%%, adjusted hazard ratio, 1.44 [0.90–2.31]), but HCR had higher mortality excluding deaths during the first year (adjusted hazard ratio, 1.88 [1.10–3.23]). Conventional CABG patients were more likely to be free from repeat revascularization at 6 years than HCR patients (88.2% versus 76.6%; hazard ratio, 2.22 [1.44–3.42]).

Conclusions:

HCR is rarely performed for patients with multivessel coronary artery disease. HCR and conventional CABG had no different 6-year mortality rates, but HCR had higher mortality after 1 year and higher rates of subsequent revascularization that were caused by both the need for repeat revascularization in the left anterior descending artery where minimally invasive CABG was performed, and in the coronary arteries where percutaneous coronary intervention was performed.

Graphic Abstract:

A
graphic abstract
is available for this article.
A description of the tadpole of the Critically Endangered Botsford’s leaf-litter frog (Leptobrachella botsfordi) with comments on the distribution and conservation status of the species
Authors: NGUYEN LUAN THANH , TAPLEY BENJAMIN , CUTAJAR TIMOTHY , NGUYEN CHUNG THANH , PORTWAY CHRISTOPHER , HARDING LUKE , VAN LUONG HAO , ROWLEY JODI J. L.
Published: October 2020

We describe the tadpole of the Botsford’s leaf-litter frog Leptobrachella botsfordi, a species endemic to Mount Fansipan in northwest Vietnam, for the first time. Tadpoles of this species were found in steep, fast-flowing streams at elevations between 2500–2600 m asl. We also report a previously unknown locality for this species on Mount Fansipan, which increases the species’ known Extent of Occurrence from 8 km2 to 36 km2. Our findings will inform subsequent conservation initiatives for this poorly known and highly threatened species.
Taxonomic assessment of the inquiline fauna (Hymenoptera: Cynipidae: Synergini, Ceroptresini) reared from cynipid galls on oaks (Quercus spp.) from South Korea
Authors: LOBATO-VILA IRENE , KANG MINJOON , ROCA-CUSACHS MARCOS , KIM ILKWON , JUNG SUNGHOON , PUJADE-VILLAR JULI
Published: October 2020

A complete taxonomic assessment of the inquiline fauna (Hymenoptera: Cynipidae: Synergini, Ceroptresini) reared from cynipid oak galls collected in South Korea is conducted for the first time. Previously, six species were known from this country (Ceroptres kovalevi Belizin, 1973; Synergus chinensis Melika, Ács & Bechtold, 2004; Synergus japonicus Walker, 1874; Ufo koreanus Melika, Pujade-Villar & Choi, 2007; and presumably, Saphonecrus chaodongzhui Melika, Ács & Bechtold, 2004 and Ufo cerroneuroteri Tang & Melika, 2012). The study of new material reared from cynipid galls collected from oaks (Quercus spp.) from various locations throughout South Korea has increased the total number of inquiline species known from this country to 14, of which seven are new country records (Saphonecrus shirakashii (Shinji, 1940); Sa. symbioticus Melika & Schwéger, 2015; Synergus abei Melika & Schwéger, 2015; S. belizinellus Schwéger & Melika 2015; S. formosanus Schwéger & Melika, 2015; S. ishikarii Melika & Schwéger, 2015; and S. symbioticus Schwéger & Melika, 2015), and one is a new species: Synergus minutus Lobato-Vila & Pujade-Villar, sp. nov. The new species is formally described and illustrated. New biological and distribution data are provided for both the newly recorded species and the other reared species. The Korean fauna is compared with that from other countries within the Eastern Palearctic and the Oriental regions.
Four new species of Psychomyia (Trichoptera: Psychomyiidae) from China, with re-descriptions of two species
Authors: PENG LANG , WANG BEI-XIN , SUN CHANG-HAI
Published: October 2020

Four new species of the genus Psychomyia from China are described, illustrated and diagnosed: P. complexa n. sp. (Zhe-jiang), P. conoidea n. sp. (Zhe-jiang), P. obtorta n. sp. (Jiang-xi), and P. tripetala n. sp. (Jiang-xi). Two known species, P. martynovi Hwang 1957 and P. extensa Li, Sun & Yang 1999 are re-described and re-illustrated, with new distributional data.
Large-Aspect-Ratio Structures in Simulated Ocean Surface Boundary Layer Turbulence under a Hurricane
Authors: Watkins Clifford , Whitt Daniel B.
Published: October 2020

A large-eddy simulation (LES) initialized and forced using observations is used to conduct a process study of ocean surface boundary layer (OSBL) turbulence in a 2-km box of ocean nominally under Hurricane Irene (2011) in 35 m of water on the New Jersey shelf. The LES captures the observed deepening, cooling, and persistent stratification of the OSBL as the storm approaches and passes. As the storm approaches, surface-intensified Ekman-layer rolls, with horizontal wavelengths of about 200 m and horizontal-to-vertical aspect and velocity magnitude ratios of about 20, dominate the kinetic energy and increase the turbulent Prandtl number from about 1 to 1.5 due partially to their restratifying vertical buoyancy flux. However, as the storm passes, these rolls are washed away in a few hours due to the rapid rotation of the wind. In the bulk OSBL, the gradient Richardson number of the mean profiles remains just above (just below) 1/4 as the storm approaches (passes). At the base of the OSBL, large-aspect-ratio Kelvin–Helmholtz billows, with Prandtl number below 1, intermittently dominate the kinetic energy. Overall, large-aspect-ratio covariance modifies the net vertical fluxes of buoyancy and momentum by about 10%, but these fluxes and the analogous diffusivity and viscosity still approximately collapse to time-independent dimensionless profiles, despite rapid changes in the forcing and the large structures. That is, the evolutions of the mean temperature and momentum profiles, which are driven by the net vertical flux convergences, mainly reflect the evolution of the wind and the initial ocean temperature profile.
Rapid Scan Visible Imagery from the Geostationary Lightning Mapper (GLM) at 2.5-Minute Intervals
Authors: Cecil Daniel J. , Buechler Dennis E. , Mecikalski John R. , Li Xuanli
Published: October 2020

The Geostationary Lightning Mapper (GLM) is an instrument designed to continuously monitor lightning. It is on the GOES-16 and GOES-17 satellites, viewing much of the Western Hemisphere equatorward of 55°. Besides recording lightning-flash information, it transmits background visible-band images of its field of view every 2.5 min. The background images are not calibrated or geolocated, and they only have ~10-km grid spacing, but their 2.5-min sampling can potentially fill temporal gaps between full-disk imagery from the GOES satellites’ Advanced Baseline Imager. This paper applies an initial calibration and geolocation of the GLM background images and focuses on animations for two cases: a volcanic eruption in Guatemala and a severe thunderstorm complex in Argentina. Those locations typically have 10-min intervals between full-disk scans. Prior to April 2019, the interval was 15 min. Despite coarse horizontal resolution, the rapid updates from GLM background images appear to be useful in these cases. The 3 June 2018 eruption of Fuego Volcano appears in the GLM background imagery as an initial darkening of the pixels very near the volcano and then an outward expansion of the dark ash cloud. The GLM background imagery lacks horizontal textural detail but compensates for this lack with temporal detail. The ash cloud resembles a dark blob steadily expanding from frame to frame. Animation of the severe thunderstorm scene reveals vertical wind shear, with northerly low-level flow across a growing cumulus field and west-northwesterly upper-level flow at anvil level. Convective initiation is seen, as are propagating outflow boundaries and overshooting convective cloud tops.
Quantum dot-modified titanium dioxide nanoparticles as an energy-band tunable electron-transporting layer for open air-fabricated planar perovskite solar cells
Authors: Sanglee Kanyanee , Chuangchote Surawut , Krajangsang Taweewat , Sritharathikhun Jaran , Sriprapha Kobsak , Sagawa Takashi
Published: October 2020

Perovskite solar cells have been attracted as new representatives for the third-generation photovoltaic devices. Simple strategies for high efficiency with the long-term stability of solar cells are the challenges for commercial solar cell technology. Another challenge of the development toward industrial scale in perovskite solar cells is the production under the ambient and high humidity. In this sense, we successfully fabricated perovskite solar cells via solution depositions of all layers under ambient air with a relative humidity above 50%. Titanium dioxide (TiO2) nanoparticles with the roles for efficient charge extraction and electron transportation properties were used as an electron-transporting layer in the cell fabrication. The modification of TiO2 nanoparticles for energy band adjustment was done by doping with nontoxic cadmium sulfide (CdS) quantum dots. With the variation of CdS concentrations, energy band is not only changeable, but the enhancement of the perovskite solar cells efficiency could be achieved compared with the conventional cells made of pristine-TiO2 film and TiO2 nanoparticles.
Gene expression profiling reveals the effects of light on adventitious root formation in lotus seedlings (Nelumbo nucifera Gaertn.)
Authors: Libao Cheng , Yuyan Han , Minrong Zhao , Xiaoyong Xu , Zhiguang Shen , Chunfei Wang , Shuyan Li , Zhubing Hu
Published: October 2020

Background

Lotus is an aquatic horticultural crop that is widely cultivated in most regions of China and is used as an important off-season vegetable. The principal root of lotus is degenerated, and adventitious roots (ARs) are irreplaceable for plant growth. We found that no ARs formed under darkness and that exposure to high-intensity light significantly promoted the development of root primordia. Four differential expression libraries based on three light intensities were constructed to monitor metabolic changes, especially in indole-3-acetic acid (IAA) and sugar metabolism.

Results

AR formation was significantly affected by light, and high light intensity accelerated AR development. Metabolic changes during AR formation under different light intensities were evaluated using gene expression profiling by high-throughput tag-sequencing. More than 2.2 × 104 genes were obtained in each library; the expression level of most genes was between 0.01 and 100 (FPKF value). Libraries constructed from plants grown under darkness (D/CK), under 5000 lx (E/CK), and under 20,000 lx (F/CK) contained 1739, 1683, and 1462 upregulated genes and 1533, 995, and 834 downregulated genes, respectively, when compared to those in the initial state (CK). Additionally, we found that 1454 and 478 genes had altered expression in a comparison of libraries D/CK and F/CK. Gene transcription between libraries D/F ranged from a 5-fold decrease to a 5-fold increase. Twenty differentially expressed genes (DEGs) were involved in the signal transduction pathway, 28 DEGs were related to the IAA response, and 35 DEGs were involved in sugar metabolism. We observed that the IAA content was enhanced after seed germination, even in darkness; this was responsible for AR formation. We also observed that sucrose could eliminate the negative effect of 150 μMol IAA during AR development.

Conclusions

AR formation was regulated by IAA, even in the dark, where induction and developmental processes could also be completed. In addition, 36 genes displayed altered expression in carbohydrate metabolism and ucrose metabolism was involved in AR development (expressed stage) according to gene expression and content change characteristics.
Exogenous polyunsaturated fatty acids (PUFAs) promote changes in growth, phospholipid composition, membrane permeability and virulence phenotypes in Escherichia coli
Authors: Herndon Joshua L. , Peters Rachel E. , Hofer Rachel N. , Simmons Timothy B. , Symes Steven J. , Giles David K.
Published: October 2020

Background

The utilization of exogenous fatty acids by Gram-negative bacteria has been linked to many cellular processes, including fatty acid oxidation for metabolic gain, assimilation into membrane phospholipids, and control of phenotypes associated with virulence. The expanded fatty acid handling capabilities have been demonstrated in several bacteria of medical importance; however, a survey of the polyunsaturated fatty acid responses in the model organism Escherichia coli has not been performed. The current study examined the impacts of exogenous fatty acids on E. coli.

Results

All PUFAs elicited higher overall growth, with several fatty acids supporting growth as sole carbon sources. Most PUFAs were incorporated into membrane phospholipids as determined by Ultra performance liquid chromatography-mass spectrometry, whereas membrane permeability was variably affected as measured by two separate dye uptake assays. Biofilm formation, swimming motility and antimicrobial peptide resistance were altered in the presence of PUFAs, with arachidonic and docosahexaenoic acids eliciting strong alteration to these phenotypes.

Conclusions

The findings herein add E. coli to the growing list of Gram-negative bacteria with broader capabilities for utilizing and responding to exogenous fatty acids. Understanding bacterial responses to PUFAs may lead to microbial behavioral control regimens for disease prevention.
Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance
Authors: Liu Li , Yu Jingyi , Shen Xiaofei , Cao Xingwei , Zhan Qing , Guo Yinjuan , Yu Fangyou
Published: October 2020

Background

Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect.

Results

MIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria.

Conclusions

Our in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.
“One-stop shop”: safety and efficacy of combining atrial septal defect occlusion and left atrial appendage closure for patients with atrial septal defect and atrial fibrillation
Authors: Zhang Zhi-hui , Yao Qing , Huang Hai-yun , Zhu Ping , Xu Xiang , Song Zhi-Yuan , Li Hua-kang
Published: October 2020

Background

One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF.

Methods

Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45–60 days, followed with regular evaluation of TTE and TEE.

Results

Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45–60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45–60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation.

Conclusion

One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.
Pooling for SARS-CoV-2 control in care institutions
Authors: Cabrera Alvargonzalez Jorge Julio , Rey Cao Sonia , Pérez Castro Sonia , Martinez Lamas Lucía , Cores Calvo Olaia , Torres Piñon Julio , Porteiro Fresco Jacobo , Garcia Comesaña Julio , Regueiro Garcia Benito
Published: October 2020

Background

Workers and residents in Care Homes are considered at special risk for the acquisition of SARS-CoV-2 infection, due to the infectivity and high mortality rate in the case of residents, compared to other containment areas. The role of presymptomatic people in transmission has been shown to be important and the early detection of these people is critical for the control of new outbreaks. Pooling strategies have proven to preserve SARS-CoV-2 testing resources.

The aims of the present study, based in our local experience, were (a) to describe SARS-CoV-2 prevalence in institutionalized people in Galicia (Spain) during the Coronavirus pandemic and (b) to evaluate the expected performance of a pooling strategy using RT-PCR for the next rounds of screening of institutionalized people.

Methods

A total of 25,386 Nasopharyngeal swab samples from the total of the residents and workers at Care Homes in Galicia (March to May 2020) were individually tested using RT-PCR. Prevalence and quantification cycle (Cq) value distribution of positives was calculated. Besides, 26 pools of 20 samples and 14 pools of 5 samples were tested using RT-PCR as well (1 positive/pool). Pooling proof of concept was performed in two populations with 1.7 and 2% prevalence.

Results

Distribution of SARS-CoV-2 infection at Care Homes was uneven (0–60%). As the virus circulation global rate was low in our area (3.32%), the number of people at risk of acquiring the infection continues to be very high. In this work, we have successfully demonstrated that pooling of different groups of samples at low prevalence clusters, can be done with a small average delay on Cq values (5 and 2.85 cycles for pools of 20 and 5 samples, respectively).

Conclusions

A new screening system with guaranteed protection is required for small clusters, previously covered with individual testing. Our proposal for Care Homes, once prevalence zero is achieved, would include successive rounds of testing using a pooling solution for transmission control preserving testing resources. Scale-up of this method may be of utility to confront larger clusters to avoid the viral circulation and keeping them operative.
Thrombotic thrombocytopenic purpura developed during the conservative treatment of anti-phospholipase A2 receptor antibody-positive idiopathic membranous nephropathy: a case report
Authors: Iio Rei , Akiyama Shin’ichi , Mitsumoto Kensuke , Iwata Yukimasa , Okushima Hiroki , Shimada Karin , Ota Naomi , Tomida Kodo , Fushimi Hiroaki , Shoji Tatsuya , Matsumoto Masanori , Hayashi Terumasa
Published: October 2020

Background

Idiopathic membranous nephropathy (MN) is one of the major glomerulonephritis that cause nephrotic syndrome. The phospholipase A2 receptor (PLA2R) has recently been identified as an endogenous antigen of idiopathic MN. Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by schistocytes, hemolytic anemia, thrombocytopenia, and organ dysfunction which occurs as a result of thrombi. Patients with acquired TTP have autoantibodies against a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13). These autoantibodies act as an inhibitor and cause ADAMTS13 deficiency. Idiopathic MN and acquired TTP are usually considered as independent autoimmune diseases. We experienced a patient who developed TTP during the conservative treatment of idiopathic MN, with the coexistence of ADAMTS13 inhibitor and anti-PLA2R antibody.

Case presentation

A 73-year-old man presented with thrombocytopenia, hemolytic anemia, disturbance of consciousness, and acute kidney injury after 4-year course of biopsy-proven idiopathic MN. ADAMTS13 activity was undetectable and the ADAMTS13 inhibitor was identified. Additionally, he was positive for anti-PLA2R antibody. The patient did not have any diseases that could cause secondary thrombotic microangiopathy, and he was diagnosed with acquired TTP. Steroid therapy and plasma exchange were initiated and the acquired TTP resolved. MN achieved remission 3 months after the anti-PLA2R antibody disappeared.

Conclusions

This is the first reported case of acquired TTP developed during conservative treatment of idiopathic MN, with both ADAMTS13 inhibitor and anti-PLA2R antibody positive at the onset of the TTP. The present case suggests that idiopathic MN might be associated with the development of some cases of acquired TTP.
Endometrial scratch vs no intervention in egg donation cycles: the ENDOSCRATCH trial protocol
Authors: Izquierdo Alexandra , de la Fuente Laura , Spies Katharina , Rayward Jennifer , López Lourdes , Lora David , Galindo Alberto
Published: October 2020

Background

The effects of endometrial scratching (ES) on embryo implantation have been studied for many years. Several studies have shown better outcomes when performed on patients undergoing intrauterine insemination and in vitro fertilization (IVF) cycles, but many other reports have not been able to find these differences. As far as cycles with donor eggs are concerned, reported evidence is scarce. Our aim in this trial is to determine if ES is useful for those patients undergoing IVF cycles with donor eggs, in order to assure a greater homogeneity in embryo quality and endometrial preparation.

Methods

This single centre randomized controlled trial will include patients undergoing an egg donation cycle, meeting the inclusion criteria and who accept to participate in the study. Once informed consent is signed, patients will be randomly allocated to the study arm (group A) and then receive ES in the luteal phase of the cycle prior to embryo transfer, or the control arm (group B) without any intervention. All cycle data will be collected and analyzed to obtain the clinical pregnancy and the live birth rates in the two groups.

Discussion

Several studies have tried to determine the effectiveness of an ES in IVF cycles, but it is still unclear due to the heterogeneity of these reports. The aim of this study is to determine if there are differences in clinical pregnancy rate and live birth rate in egg donor cycles, when comparing an ES performed in the preceding luteal phase versus no intervention, given that embryo quality and endometrial preparation protocols will be comparable.

Trial registration

Ethical approval of version 2.0 of this trial was obtained on the 13th January 2017. It was retrospectively registered on the 5th April 2017 as the ENDOSCRATCH Trial (NCT03108157) in ClinicalTrials.gov.