bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO076: Development of a CD137 (4-1BB) receptor occupancy assay using fluorescently labelled Bicycles®
Authors: Kanakia Drasti N. , Upadhyaya Punit , Lahdenranta Johanna , Repash Elizabeth , Haines Eric , McDonnell Kevin , Hurov Kristen , Brandish Philip , Keen Nicholas
Published: February 2021

Receptor occupancy (RO) assays are designed to quantify the binding of therapeutics to their cell surface targets and are frequently used to generate both pre-clinical and clinical pharmacodynamic biomarker data. Flow cytometry is a commonly used technique to measure receptor occupancy on immune cell populations within fresh blood specimens. Yet, receptor occupancy assays are subject to numerous technical and logistical challenges. To ensure that reliable and high-quality results are generated from receptor occupancy assays, careful assay design and key reagent selection, characterization, and utilization are of critical importance. Antibodies are commonly conjugated with fluorophores and used in receptor occupancy assays for related therapeutics. Bicycles® are a new therapeutic modality - fully synthetic, constrained bicyclic peptides with high affinity and excellent target selectivity. Here, we describe a novel utility for fluorescently-labeled Bicycles in the development of a CD137 (4-1BB) receptor occupancy assay. CD137 is a member of the TNFR superfamily involved in stimulation of several immune cell types, including T cells and NK cells. CD137 is well validated pre-clinically, as agonism with anti-CD137 antibodies is effective in vivo, however, clinical utility to date has been limited by dose dependent hepatotoxicity. We have demonstrated that tumor-targeted immune cell agonists (TICAsTM) comprised of CD137 binding Bicycles coupled to tumor antigen binding Bicycles exert anti tumoral properties with a favorable safety profile. Here, we demonstrate another functionality for the Bicycle platform, as a measurement of CD137 TICA target engagement and receptor occupancy. Using fluorescently-labeled CD137 Bicycles, we measured RO on immune populations in isolated human peripheral blood mononuclear cells (PBMCs), as well as in whole blood. The assay shows high specificity as no Bicycle binding was observed in CD137 negative cell populations. Additionally, RO was shown to be dependent on the presence of CD137-binding Bicycles. Together, this novel approach of measuring receptor occupancy may be used to inform on both the pre-clinical and clinical therapeutic properties of Bicycle TICAs.

Citation Format: Drasti N. Kanakia, Punit Upadhyaya, Johanna Lahdenranta, Elizabeth Repash, Eric Haines, Kevin McDonnell, Kristen Hurov, Philip Brandish, Nicholas Keen. Development of a CD137 (4-1BB) receptor occupancy assay using fluorescently labelled Bicycles® [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO076.
Abstract PR004: Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation
Authors: Wu Bogang , Chiang Huai-Chin , Sun Xiujie , Yuan Bin , Mitra Payal , Hu Yanfen , Curiel Tyler J. , Li Rong
Published: February 2021

The programmed death-ligand 1 (PD-L1)-dependent immune checkpoint attenuates host immunity and maintains self-tolerance. Imbalance between protective immunity and immunopathology due to altered PD-L1 signaling can lead to autoimmunity or tumor immunosuppression. The role of the PD-L1-dependent checkpoint in non-immune system is less reported. We previously found that white adipocytes highly express PD-L1. Here we show that adipocyte-specific PD-L1 knockout mice exhibit enhanced host anti-tumor immunity against mammary tumors and melanoma with low or no tumor PD-L1. However, adipocyte PD-L1 ablation in tumor-free mice also exacerbates diet-induced body weight gain, pro-inflammatory macrophage infiltration into adipose tissue, and insulin resistance. Low PD-L1 mRNA levels in human adipose tissue correlate with high body mass index and presence of type 2 diabetes. Therefore, our mouse genetic approach unequivocally demonstrates a cell-autonomous function of adipocyte PD-L1 in promoting tumor growth and inhibiting anti-tumor immunity. In addition, our work uncovers a previously unrecognized role of adipocyte PD-L1 in mitigating obesity-related inflammation and metabolic dysfunction.

This abstract is also being presented as PO031.

Citation Format: Bogang Wu, Huai-Chin Chiang, Xiujie Sun, Bin Yuan, Payal Mitra, Yanfen Hu, Tyler J. Curiel, Rong Li. Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PR004.
Abstract PR013: Microfluidic purification of T lymphocytes separated from blood for chimeric antigen receptor T-cell manufacturing
Authors: Elsemary Mona T. , Maritz Michelle F. , Smith Louise , Warkiani Majid , Thierry Benjamin
Published: February 2021

The CAR T cell manufacturing process is complex and expensive. In addition, the quality of the final product suffers from great variability, which is in part due to the personalized nature of the therapy. An important source of variability of final CAR T cells products is the starting cellular material for manufacture. The percentage of T-cells separated from a patient’s blood used for CAR T cell manufacture is highly variable and influenced by many factors. The percentage of ‘other’ cells typically range anywhere from 10 to 90%, and these cells interfere with the downstream T-cell modification and expansion processes, potentially preventing the production of high-quality end products. Microfluidic technologies which separate cells based on their physical attributes have previously shown great success in separating circulating cancer cells from blood but have not yet been applied in the CAR T cell manufacturing process. Early research has shown the possibility of depleting red blood cells and platelets, however little has been done in the specific purification of T-cells and depletion of other lymphocytic cells. This research therefore aimed to investigate the use of microfluidics in the separation and purification of T-cells towards addressing known bottlenecks/issues in the CAR T cells manufacturing process. We have designed and optimized microfluidic devices of various dimensions with enrichment and depletion outlets. We will report on the successful utilization of these devices in various critical steps of the manufacturing process.

This abstract is also being presented as PO080.

Citation Format: Mona T. Elsemary, Michelle F. Maritz, Louise Smith, Majid Warkiani, Benjamin Thierry. Microfluidic purification of T lymphocytes separated from blood for chimeric antigen receptor T-cell manufacturing [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PR013.
Expression and Significance of MicroRNA-126 and MicroRNA-21 in Peripheral Blood Mononuclear Cells in Patients with Myasthenia Gravis
Authors: Huang Pan , He Xiao-ying , Xu Min
Published: February 2021

Objective: The aim of the study was to investigate the expression and significance of microRNA-126, microRNA-21, FOXP3mRNA, acetylcholine receptor antibody (AChR-Ab), and interleukin 6 (IL-6) in peripheral blood of patients with myasthenia gravis (MG). Methods: From September 2015 to March 2018, 60 patients with MG who were first diagnosed as MG were selected as the MG group, and 50 healthy people in the same period were selected as the normal group. RT-PCR technology was used to detect the relative expression of microRNA-126, microRNA-21, and FOXP3mRNA in peripheral blood mononuclear cells of the MG group and the control group. The EILISA and IPA technique was used to detect the expression levels of IL-6 and AChR-Ab in the peripheral serum of the 2 groups. Results: There were no differences between groups regarding patient’s characteristics and baseline data. microRNA-21 and microRNA-126 are highly conserved in the human genome. microRNA-21, microRNA-126, FOXP3mRNA, AChR-Ab, and IL-6 are differentially expressed in the MG group and the control group (p < 0.05). microRNA-21 is positively correlated with AChR-Ab and IL-6 in MG patients (r = 0.746, 0.789, p < 0.05), but has no correlation with FOXP3mRNA (r = −0.249 p = 0.055), while micro­RNA-126 is positively correlated with FOXP3mRNA and negatively correlated with AChR-Ab and IL-6 (r = 0.526, −0.797, −0.801, p < 0.05). Conclusion: Patients with MG have differential expression of microRNA-21 and microRNA-126 and may participate in the pathogenesis of MG by regulating pathways related to inflammatory immune response.
Reciprocal Antagonism between MicroRNA-138 and SIRT1 and Its Implications for the Angiogenesis of Endothelial Cells
Authors: Wang Shangyu , Shao Zengwu , Tang Xin , Wang Kaijie , Zhao Jinping , Dong Zhe
Published: February 2021

MicroRNAs and sirtuins are important epigenetic regulators of gene expression and both contribute significantly to postnatal vascular development. However, the crosstalk between miRNAs and sirtuins in the modulation of angiogenesis has rarely been discussed. Here, we investigated the interactions between miR-138 and sirtuins in the process of angiogenesis. We found that overexpression of miR-138 markedly suppressed the proliferation, migration, and tube-forming capacities of the endothelial cells. And, miR-138 inhibitor-treated endothelial cells showed a reversed phenotype. Furthermore, miR-138 plays a negative role in vascular development in vivo. Western blot and qPCR assays demonstrated that SIRT1 was silenced by miR-138, and a luciferase reporter assay showed that miR-138 bound to the 3′-UTR of SIRT1. The re-expression of SIRT1 alleviated miR-138-mediated suppression of angiogenesis. Furthermore, silencing SIRT1 could boost the level of miR-138. And, upon miR-138 inhibitor treatment, SIRT1 silencing no longer reduced the angiogenic ability of endothelial cells significantly. These results demonstrated that the circuitry involving miR-138 and SIRT1 may participate in vascular homeostasis and also offered the possibility of identifying a new approach in the treatment of angiogenic diseases.
Improvements in Inflammation and Calcium Balance of Citrate versus Acetate as Dialysate Buffer in Maintenance Hemodialysis: A Unicentric, Cross-Over, Prospective Study
Authors: Broseta José Jesús , López-Romero Luis Carlos , Cerveró Alba , Devesa-Such Ramón , Soldevila Amparo , Bea-Granell Sergio , Sánchez-Pérez Pilar , Hernández-Jaras Julio
Published: February 2021

Introduction: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. Methods: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients’ treatment remained unchanged during the study period. Results: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. Conclusions: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes.
NASH/Liver Fibrosis Prevalence and Incidence of Nonliver Comorbidities among People with NAFLD and Incidence of NAFLD by Metabolic Comorbidities: Lessons from South Korea
Authors: Park Jiyoon , Lee Eunice Yewon , Li Jie , Jun Mi Jung , Yoon Eileen , Ahn Sang Bong , Liu Chuanli , Yang Hongli , Rui Fajuan , Zou Biyao , Henry Linda , Lee Dong Hyun , Jun Dae Won , Cheung Ramsey C. , Nguyen Mindie H.
Published: February 2021

Background: NAFLD incidence, NASH prevalence, NAFLD fibrosis prevalence, incidence of metabolic comorbidities, and mortality data in the NAFLD population remain limited. Aims: We used a meta-analytic approach to “stage” NAFLD among the Korean population. Methods: We searched PubMed, Embase, Cochrane Library, and KoreaMed from inception until June 29, 2019, and calculated pooled estimates via the random-effects model. Results: We screened 1,485 studies and analyzed 191 eligible studies: 179 (3,556,579 participants) for NAFLD prevalence and outcome analysis and 32 (1,089,785 participants) for NAFLD incidence analysis. NAFLD prevalence was 31.46% overall and 50–60% in those with metabolic risks. The incidence (per 1,000 person-years) of NAFLD was 42.8 overall and 70–77% in those with metabolic risk. The incidence (per 1,000 person-years) of new-onset T2DM, hypertension, cardiovascular disease, and chronic kidney disease was found to be 16.9, 47.9, 100.6, and 13.9, respectively. From biopsy data, 30.21% of the NAFLD population had moderate-to-severe steatosis (9 studies, 2,461 participants) and 52.27% had NASH (7 studies, 1,168 participants) and 85.41% had fibrosis <stage 2 (8 studies, 1,995 participants). All-cause mortality was 2.6 (1.3 if without malignancy) per 1,000 person-years. Conclusions: The overall prevalence of NAFLD was 31.46% with an incidence rate of 42.8 per 1,000 person-years. NASH prevalence was 52% but <15% had significant fibrosis. The prevalence and incidence of nonliver comorbidities was high especially for cardiovascular disease incidence. The burden of NAFLD is high in Korea. Health policy efforts need to be directed towards reversing the course of NAFLD disease.
Shared Decision-Making for Left Ventricular Assist Devices
Authors: Thompson Jocelyn S. , Fitzgerald Monica D. , Allen Larry A. , McIlvennan Colleen K. , Glasgow Russell E. , Wynia Matthew , Morris Megan A. , Beilenson John , Gherst Chris , Matlock Dan D.
Published: February 2021

Background

The left ventricular assist device (LVAD) has become a common medical option for patients with end-stage heart failure. Although patients’ chances of survival may increase with an LVAD compared with medical therapy, the LVAD poses many risks and requires major lifestyle changes, thus making it a complex medical decision. Our prior work found that a decision aid for LVADs significantly increased decision quality for both patients and caregivers and was successfully implemented at 6 LVAD programs.

Methods

In follow-up, we are conducting a nationwide dissemination and implementation project, with the goal of implementing the decision aid at as many of the 176 LVAD programs in the United States as possible. Guided by the Theory of Diffusion of Innovations, the project consists of 4 phases: (1) building a network; (2) promoting adoption; (3) supporting implementation; and (4) encouraging maintenance. Developing an LVAD network of contacts occurs by using a national baseline survey of LVAD clinicians, existing professional relationships, and an internet-based strategy. A suite of resources targeted to promote adoption and support implementation of the decision aid into standard LVAD education processes are provided to the network. Evaluation is guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework, where clinician and patient surveys and qualitative interviews determine the reach, effectiveness, adoption, implementation, and maintenance achieved.

Conclusions

This project is a true dissemination study in that it targets the entire population of LVAD programs in the United States and is unique in its use of social marketing principles to promote adoption and implementation. The implementation plan is intended to serve as a test case and model for dissemination and implementation of other evidence-based decision support aids and strategies.
Cladosporium species from submerged decayed leaves in Brazil, including a new species and new records
Authors: FREITAS MAYARA L. R. , GOMES ANDRÉ A. M. , ROSADO ANDRÉ W. C. , PEREIRA OLINTO L.
Published: February 2021

Fungi belonging to the genus Cladosporium are cosmopolitan and occur in various substrates and hosts. Nevertheless, this is the first time that we have described this genus colonizing leaf litter submerged in water. We surveyed Cladosporium spp. associated with submerged leaf litter, from three localities belonging to the Atlantic Forest biome in the State of Minas Gerais, Brazil. A multilocus DNA sequence typing approach employing ITS, Actin, and Translation elongation factor 1-α region/genes associated with morphological and cultural analyses were used to identify these species. The species C. angulosum and C. anthropophilum are reported for the first time in Brazil, and a new species for the genus is described here as C. puris.
A new species and a new record of Begonia (sect. Platycentrum, Begoniaceae) from northeastern India
Authors: KRISHNA NIKHIL , PRADEEP AYILLIATH KUTTIYERI , AMRUTHA ATHALAPPIL , JAYAKRISHNAN THACHAT
Published: February 2021

A new species of Begonia, Begonia murlenensis (sect. Platycentrum) is described and illustrated from northeastern India. The new species is compared with B. manhaoensis. Diagnostic characters are provided along with a distribution map and notes on its habitat and phenology. Begonia zhongyangiana as a new record in India is also presented here along with a distribution map.
Discovery of the chelonine tribe Adeliini Viereck, 1918 (Hymenoptera: Braconidae) from the Indian subcontinent with the description of a new genus from south India
Authors: RANJITH A.P. , VAN ACHTERBERG C. , SAMARTSEV K.G. , NASSER M.
Published: February 2021

The small chelonine tribe Adeliini is one of the derived groups with the postpectal carina absent, which is considered to be an apomorphic character for the Cheloninae. Adeliine genera generally exhibit a narrow endemism although the genus Adelius is widely distributed. Adeliini are reported from the Indian subcontinent for the first time with the description of a new genus and a new species, Carinadelius medicus Ranjith & van Achterberg gen. et sp. nov. from south India. A revised key to the genera of Adeliini is provided with the illustrations of all included genera. The genus Myriola, which was previously included under Adelius, is re-instated based on morphological characters. The New World species of the genus Paradelius are transferred to Sculptomyriola Belokobylskij: Sculptomyriola neotropicalis (Shimbori & Shaw, 2019), S. nigra (Whitfield, 1988) and S. rubra (Whitfield, 1988) are new combinations.
A striking new species of Papuan groundsnake (Stegonotus: Colubridae) from southern Papua New Guinea, with a dichotomous key to the genus in New Guinea
Authors: O’SHEA MARK , RICHARDS STEPHEN J.
Published: February 2021

We describe a new species of groundsnake of the genus Stegonotus (Colubridae) from the Purari River basin in Gulf Province, Papua New Guinea. The new species can be most readily distinguished from all other New Guinean Stegonotus by its unique dorsal colour pattern which consists of a dark head and creamy-white anterior one third to two thirds of the body, grading into increasingly dense dark pigmentation on the posterior of the body and tail. It is most similar to S. iridis from the Raja Ampat Archipelago off western New Guinea, but that species has a different pattern of pigmentation dorsally, has a lower ventral scale count (198–211 vs. 229–239), and exhibits a different temporal scale arrangement. The description of S. aplini sp. nov. brings to fourteen the number of Stegonotus species described from New Guinea. A dichotomous key to described species in the New Guinea region is provided.
Description of Bagarius vegrandis, a new species of sisorid catfish from Indochina (Actinopterygii: Siluriformes), with notes on the identity of Bagarius bagarius
Authors: NG HEOK HEE , KOTTELAT MAURICE
Published: February 2021

Bagarius vegrandis, new species, is described from the Chao Phraya and Mekong river drainages. It differs from congeners in having a small maximum body size (to 220 mm SL vs. 520–1400 mm SL) and the adipose-fin origin markedly posterior to (vs. at vertical through or very slightly posterior to) the anal-fin origin. It further differs from congeners in having the following unique combination of characters: ovoid unculiferous plaques on dorsal surface of head, lateral margin of frontal not significantly deflected dorsally, eye diameter 11–15% HL, interorbital distance 23–28% HL, head width 18.3–22.3% SL, head depth 11.1–14.1% SL, filamentous extensions to first pectoral-fin element reaching to anus, dorsal spine width 10.6–13.9 times in its length, body depth at anus 8.7–12.0% SL, neural spines of the 4–6 vertebrae immediately anterior to adipose fin distally flattened but not forming series of prominent bumps along dorsal midline, length of adipose-fin base 10.8–13.0% SL, caudal-peduncle length 19.0–22.4% SL, caudal-peduncle depth 3.2–4.2% SL, 19–20 preanal vertebrae, and 39–40 total vertebrae. Bagarius bagarius (Hamilton, 1822) is demonstrated to be a species restricted to the Indian subcontinent (with Bagrus yarrelli Sykes, 1839, Pimelodus platespogon Valenciennes, in Jacquemont, 1839 and Pimelodus carnaticus Jerdon, 1849 as junior subjective synonyms) and Bagarius lica Volz, 1903 resurrected from synonymy with B. yarrelli as a valid species from Southeast Asia.
In SituPhotoelectron Spectroscopy and Theoretical Calculation Study of Thermally Evaporated Copper Naphthalocyanine
Authors: Lee Hyunbok , Lee Younjoo , Kang Donghee , Yi Yeonjin , Cho Sang Wan
Published: February 2021

Recently, organic photovoltaics (OPVs) have attracted attention as a next-generation energy source as their power conversion efficiency (PCE) has significantly improved. To increase the PCE of OPVs further, a fundamental understanding of material properties of a new organic semiconductor
is highly important. Copper naphthalocyanine (CuNc) is composed of macrocyclic ligands with extended benzene rings of copper phthalocyanine (CuPc). Thus, it can be considered as a potential candidate for an efficient p-type organic semiconductor, similar to a well-known conventional
p-type organic semiconductor CuPc. In this study, we investigated the electronic structure of thermally evaporated CuNc on indium tin oxide (ITO) wit in situ ultraviolet and X-ray photoelectron spectroscopy (UPS and XPS) and density functional theory (DFT) calculations. DFT calculations
predict that CuNc has a lower ionization energy (IE) and band gap than CuPc. However, the IE measured by UPS and the band gap measured by UV-vis absorption of the deposited film were much higher than CuPc. Derived from the measured UPS, XPS spectra and DFT calculation results, we concluded
that CuNc could be decomposed with thermal evaporation in a vacuum and the pyrrole-based material might be deposited on ITO. The increased IE and band gap were attributed to the disappearance of the highest occupied molecular orbital originating from the macrocyclic ligands with D4h
symmetry. Therefore, the thermal evaporation method would not be a suitable method to obtain the CuNc film for device application, and the alternative solution process at low temperature would be more adequate.
Electrochemical Properties of Micro-Sized Bismuth Anode for Sodium Ion Batteries
Authors: Cha Seunghwan , Kim Changhyeon , Kim Huihun , Cho Gyu-Bong , Cho Kwon-Koo , Ryu Ho-Suk , Ahn Jou-Hyeon , Sohn Keun Yong , Ahn Hyo-Jun
Published: February 2021

Recently, sodium ion batteries have attracted considerable interest for large-scale electric energy storage as an alternative to lithium ion batteries. However, the development of anode materials with long cycle life, high rate, and high reversible capacity is necessary for the advancement
of sodium ion batteries. Bi anode is a promising candidate for sodium ion batteries due to its high theoretical capacity (385 mAh g–1 or 3800 mAh l–1) and high electrical conductivity (7.7 × 105 S m –1). Herein, we report
the preparation of Bi anode using micro-sized commercial Bi particles. DME-based electrolyte was used, which is well known for its high ionic conductivity. The Bi anode showed excellent rate-capability up to 16 C-rate, and long cycle life stability with a high reversible capacity of 354 mAh
g–1 at 16 C-rate for 50 cycles.
Effect of Solution-Treated Temperature on Microstructure in TiNixCu12 (x = 39, 40 at %) Alloys
Authors: Kim Ji-Hyun , Kim Min-Su , Nam Tae-Hyun
Published: February 2021

Ti–xNi–12Cu (at%) (x = 39, 40) alloys were prepared and then their transformation behavior and microstructures were investigated after solution treatment at various temperatures by means of scanning electron microscopy, energy dispersive X-ray spectroscopy,
and differential scanning calorimetry. Matrix (B2), Ti2 (Ni, Cu) and Ti(Ni, Cu)2 phases were observed in all specimens except the TiNi39Cu12 alloy solution treated at 1373 K in which matrix (B2) and Ti2 (Ni, Cu) were observed. Volume fraction
of Ti(Ni, Cu)2 phase decreased with increasing solution treatment temperature. All specimens showed the B2–B19 martensitic transformation behavior. Transformation temperatures and hysteresis decreased with increasing solution treatment temperature, which was ascribed to the
decrease in the volume fraction of Ti(Ni, Cu)2 phase resulting in the increase in Ni content of matrix.
An evaluation of CMIP6 historical simulations of the cold season teleconnection between tropical Indo-Pacific sea surface temperatures and precipitation in Southwest Asia, the coastal Middle East, and Northern Pakistan and India
Authors: Barlow Mathew , Hoell Andrew , Agel Laurie
Published: February 2021

The ability of six CMIP6 models to reproduce the observed cold season teleconnection between tropical Indo-Pacific sea surface temperatures (SSTs) and precipitation in Southwest Asia, the coastal Middle East (CME), and Northern Pakistan and India (NPI) is examined. The 1979-2014 period is analyzed, to maximize observations over both the tropical ocean and the regions. Nine historical simulations for the same period are examined for each model, to account for the internal variability of the coupled system. The teleconnection is examined in terms of SSTs, precipitation, 200 hPa geopotential heights, and derived quantities.

All the models capture some of the broadest features of the teleconnections, but there is a wide range in the ability of the models to reproduce the magnitude and details. The differences appear related to both the models’ ability to capture the details of the tropical variability, including the position and strength of the precipitation anomalies in the Indo-west Pacific, as well as the models’ ability to accurately propagate the tropically-forced response into the region. The teleconnections to the CME and NPI regions on the eastern and western margins, respectively, of the strongest signal are very similar in structure and have similar results, except that the models’ ability to reproduce the strength and details of the teleconnection is even more limited, consistent with their marginal locations and known influence of other modes of variability. For all three areas, the wide range in model ability to capture the leading teleconnection suggests caution in interpreting climate regional projections.
Impact of Stochastic Physics and Model Resolution on the Simulation of Tropical Cyclones in Climate GCMs
Authors: Vidale Pier Luigi , Hodges Kevin , Vannière Benoit , Davini Paolo , Roberts Malcolm J. , Strommen Kristian , Weisheimer Antje , Plesca Elina , Corti Susanna
Published: February 2021

The role of model resolution in simulating geophysical vortices with the characteristics of realistic tropical cyclones (TCs) is well established. The push for increasing resolution continues, with general circulation models (GCMs) starting to use sub-10-km grid spacing. In the same context it has been suggested that the use of stochastic physics (SP) may act as a surrogate for high resolution, providing some of the benefits at a fraction of the cost. Either technique can reduce model uncertainty, and enhance reliability, by providing a more dynamic environment for initial synoptic disturbances to be spawned and to grow into TCs. We present results from a systematic comparison of the role of model resolution and SP in the simulation of TCs, using EC-Earth simulations from project Climate-SPHINX, in large ensemble mode, spanning five different resolutions. All tropical cyclonic systems, including TCs, were tracked explicitly. As in previous studies, the number of simulated TCs increases with the use of higher resolution, but SP further enhances TC frequencies by ~30%, in a strikingly similar way. The use of SP is beneficial for removing systematic climate biases, albeit not consistently so for interannual variability; conversely, the use of SP improves the simulation of the seasonal cycle of TC frequency. An investigation of the mechanisms behind this response indicates that SP generates both higher TC (and TC seed) genesis rates, and more suitable environmental conditions, enabling a more efficient transition of TC seeds into TCs. These results were confirmed by the use of equivalent simulations with the HadGEM3-GC31 GCM.
Correction to: Year-round pesticide contamination of public sites near intensively managed agricultural areas in South Tyrol
Authors: Linhart Caroline , Panzacchi Simona , Belpoggi Fiorella , Clausing Peter , Zaller Johann G. , Hertoge Koen
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Across establishments, within firms: worker’s mobility, knowledge transfer and survival
Authors: Tavares Marisa Fernanda Figueiredo
Published: February 2021

We analyze the recruitment strategies and the survival of newly created establishments that are affiliated with pre-established _rms. For the new establishments, the existence of ports of entry as well as the importance of internal and external recruitment is assessed. Being affiliated with a pre-established firm may be a source of competitive advantage and improve the new plant’s chances of survival as the parent firm may supply the newly created unit with expertise and firm-specific knowledge. In this research we suggest a channel for knowledge transfer that has been little addressed in previous literature: within firm and across establishments mobility of workers. As firm-specific knowledge is mainly embodied and non-tradable, we suggest that it can be successfully transferred to the new unit embodied in the workers that are internally recruited. We find that internally transferred workers, particularly skilled workers hired at high-rank jobs play an important role in improving the survival of new establishments.
ACEF performed better than other risk scores in non-ST-elevation acute coronary syndrome during long term follow-up
Authors: Kristić Ivica , Crnčević Nikola , Runjić Frane , Čapkun Vesna , Polašek Ozren , Matetic Andrija , Vrsalovic Mislav
Published: February 2021

Background

Risk stratification of patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) is an important clinical method, but long-term studies on patients subjected to all-treatment strategies are lacking. Therefore, the aim was to compare several established risk scores in the all-treatment NSTE-ACS cohort during long-term follow-up.

Methods

Consecutive patients (n = 276) with NSTE-ACS undergoing coronary angiography were recruited between September 2012 and May 2015. Six risk scores for all patients were calculated, namelyGRACE 2.0, ACEF, SYNTAX, Clinical SYNTAX, SYNTAX II PCI and SYNTAX II CABG. The primary end-point was Major Adverse Cardiovascular Events (MACE) which was a composite of cardiac death, nonfatal myocardial infarction, ischemic stroke or urgent coronary revascularization.

Results

During a median follow-up of 33 months, 64 MACE outcomes were recorded (23.2%). There was no difference between risk score categories, except in the highest risk group ofACEFandSYNTAX II PCIscores which exhibited significantly more MACE (51.6%, N = 33 and 45.3%, N = 29,P = 0.024, respectively). In the multivariate Cox regression analysis of individual variables, only age and atrial fibrillation were significant predictors for MACE (HR 1.03, 95% CI 1.00–1.05,P = 0.023 and HR 2.02, 95% CI 1.04–3.89,P = 0.037, respectively). Furthermore, multivariate analysis of the risk scores showed significant prediction of MACE only withACEFscore (HR 2.16, 95% CI 1.36–3.44,P = 0.001). The overall performance ofGRACE,SYNTAX,Clinical SYNTAXandSYNTAX II CABGwas poor with AUC values of 0.596, 0.507, 0.530 and 0.582, respectively, whileACEFandSYNTAX II PCIshowed the best absolute AUC values for MACE (0.630 and 0.626, respectively).

Conclusions

ACEFrisk score showed better discrimination than other risk scores in NSTE-ACS patients undergoing all-treatment strategies over long-term follow-up and it could represent a fast and user-friendly tool to stratify NSTE-ACS patients.
The Frailty In Residential Sector over Time (FIRST) study: methods and baseline cohort description
Authors:   on behalf of the FIRST Study Collaborators, Jadczak Agathe Daria , Robson Leonie , Cooper Tina , Bell J. Simon , Visvanathan Renuka
Published: February 2021

Background

The Frailty In Residential Sector over Time (FIRST) Study is a 3-year prospective cohort study investigating the health of residents living in residential aged care services (RACS) in South Australia. The study aims to examine the change in frailty status and associated health outcomes.

Methods

This interim report presents data from March 2019–October 2020. The study setting is 12 RACS from one organisation across metropolitan and rural South Australia involving 1243 residents. All permanent (i.e. respite or transition care program excluded) residents living in the RACS for at least 8 weeks were invited to participate. Residents who were deemed to be medically unstable (e.g. experiencing delirium), have less than 3 months to live, or not fluent in English were excluded. Data collected included frailty status, medical diagnoses, medicines, pain, nutrition, sarcopenia, falls, dementia, anxiety and depression, sleep quality, quality of life, satisfaction with care, activities of daily living, and life space use at baseline and 12-months. Data Linkage will occur over the 3 years from baseline.

Results

A total of 561 permanent residents (mean age 87.69 ± 7.25) were included. The majority of residents were female (n = 411, 73.3%) with 95.3% (n = 527) being classified as either frail (n = 377, 68.2%) or most-frail (n = 150, 27.1%) according to the Frailty Index (FI). Most residents were severely impaired in their basic activities of daily living (n = 554, 98.8%), and were at-risk of malnutrition (n = 305, 55.0%) and at-risk of sarcopenia (n = 492, 89.5%). Most residents did not experience pain (n = 475, 85.4%), had normal daytime sleepiness (n = 385, 69.7%), and low anxiety and depression scores (n = 327, 58.9%).

Conclusion

This study provides valuable information on the health and frailty levels of residents living in RACS in South Australia. The results will assist in developing interventions that can help to improve the health and wellbeing of residents in aged care services.

Trial registration

Prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000500156).
Prognostic value of visual residual tumour cells (VRTC) for patients with esophageal squamous cell carcinomas after neoadjuvant therapy followed by surgery
Authors: Wang Xingxing , Wang Hao , Wang Haixing , Huang Jie , Wang Xin , Jiang Zhengzeng , Tan Lijie , Jiang Dongxian , Hou Yingyong
Published: February 2021

Background

We assessed visual residual tumour cells (VRTC) with both Becker’s tumour regression grading (TRG) system and Japanese TRG system in esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant therapy followed by surgery.

Methods

We compared Becker system and Japanese system in 175 ESCC patients treated between 2009 and 2015.

Results

According to Becker system, the 5-year DFS/DSS rates were 70.0%/89.3, 53.8%/56.7, 43.0%/49.0, and 42.4%/39.1% for TRG 1a (VRTC 0), TRG 1b (1–10%), TRG 2 (11–50%), and TRG 3 (> 50%). According to Japanese system, the rates were 38.8%/34.1, 49.5%/58.7, 50.2%/49.0 and 70.0%/89.3% for Grade 0-1a (VRTC> 66.6%), Grade 1b (33.3–66.6%), Grade 2 (1–33.3%) and Grade 3 (0). TRG according to two systems significantly discriminate the patients’ prognosis. TRG according to Becker system (HR 2.662, 95% CI 1.151–6.157), and lymph node metastasis (HR 2.567, 95% CI 1.442–4.570) were independent parameters of DSS.

Conclusions

Both Becker and Japanese system had their advantage in risk stratification of these ESCC patients. It was speculated that dividing 1–10% VRTC into a group might contribute to independently prognostic significance of Becker’s TRG system. Therefore, in addition to TRG of different systems, the percentage of VRTC might be recommended in the pathologic report, which could make the results more comparable among different researches, and more understandable for oncologists in the clinical practice.
An investigation of depression, anxiety, and stress and its relating factors during COVID-19 pandemic in Iran
Authors: Khademian Fatemeh , Delavari Sajad , Koohjani Zahra , Khademian Zahra
Published: February 2021

Background

The COVID-19 (SARS-CoV-2) is an emerging epidemic caused by the new Coronavirus. It has affected more than 200 countries, infected 5,939,234 people, and killed 367,255 in the world until 1 June 2020. While the disease epidemic could affect population mental health, this study aimed to investigate stress, anxiety, and depression during the Corona pandemic in Iran.

Methods

An online survey was designed using the depression, anxiety, and stress scale (DASS-21) questionnaire. The questionnaire was available for all Iranian population from 18 to 28 April 2020. Finally, 1498 participants filled the questionnaire using snowball sampling. Data were analyzed using multivariate regression models.

Results

Findings showed that most participants had experienced a normal level of stress (36.6%), anxiety (57.9%) and depression (47.9%). About 2.5% of respondents report an extremely severe level of stress. This amount of anxiety and depression was 6.3 and 7.9%, respectively. Regression model showed being female (CI: − 1.299; − 0.248), living with a high risk family member (CI: 0.325; 1.400), health status (CI: − 0.857; − 0.595), economic status (CI: − 0.396; − 0.141), social capital (CI: − 0.475; − 0.244), risk of disease (CI: 0.081; 0.729), and following COVID-19 news (CI: 0.111; 0.551) have a relation with stress level. Education level (CI: − 0.252; − 0.017), living with a high risk family member (CI: 0.0301; 1.160), health status (CI: − 0.682; − 0.471), social capital (CI: − 0.236; − 0.048), risk of disease (CI: 0.154; 0.674), and following COVID-19 news (CI: 0.046; 0.401) have a relation with anxiety score. Depression score was in relation with education level (CI: − 0.263; − 0.022), having a high-risk family member (CI: 0.292; 1.155), health status (CI: − 0.687; − 0.476), social capital (CI: − 0.235; − 0.048), risk of disease (CI: 0.144; 0.667), and following Covid-19 news (CI: 0.053; 0.408).

Conclusions

Most of the factors related to depression, anxiety, and stress are related to COVID-19, such as having a vulnerable person in the family, risk of disease, and following COVID-19 news. The findings suggest the factors that should be taken into consideration for improving population mental health during pandemics.
Guidelines and best practice recommendations on reproductive health services provision amid COVID-19 pandemic: scoping review
Authors: Tolu Lemi Belay , Feyissa Garumma Tolu , Jeldu Wondimu Gudu
Published: February 2021

Background

Policymakers and health professionals prefer to use summarized evidence of practice recommendations. The aim of this scoping review is therefore to identify available guidelines, consensus statements, the standard of practice, and practice recommendations on reproductive health service provision during the COVID-19 pandemics.

Methods

We searched guideline databases and websites of professional associations and international organizations working on sexual and reproductive health. We looked for practice recommendations on sexual reproductive health services (SRH) during COVID-19 pandemics. Additionally, we searched: MEDLINE, EMBASE, and Google Scholar. Data extraction was done by two independent reviewers using a customized tool that was developed to record the key information of the source that’s relevant to the review question. The difference between the two authors on data extraction was resolved by discussion.

Results

A total of 21 records were included in the review. Identified recommendations were classified into thematic areas. The records addressed approaches to antenatal care, labour and delivery, postnatal care, safe abortion, contraception, gender-based violence, and artificial reproduction.

Conclusions

There were consistent consensus statements and recommendations that there should be access to sexual and reproductive health services like antenatal care (ANC), postnatal care (PNC), contraception service, safe abortion care, and clinical management of rape survivors during the COVID-19 pandemics with the concerted effort of service re-organization. The practice recommendations focus on innovative ways of service provision to minimize patient and staff exposure to COVID-19 as well as alleviate the burden on the health care system. These include utilizing telemedicine and community/home-based care or self-care.
Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack
Authors: Ma Tian-Tian , Wong Ian C. K. , Whittlesea Cate , Man Kenneth K. C. , Lau Wallis , Wang Zixuan , Brauer Ruth , MacDonald Thomas M. , Mackenzie Isla S. , Wei Li
Published: February 2021

Background

To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)).

Methods

This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model.

Results

During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75–0.89) for two medications, 0.65 (0.59–0.70) for three medications, 0.61 (0.56–0.67) for four medications, 0.60 (0.54–0.66) for five medications and 0.66 (0.59–0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46–0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53–68%) lower risk of mortality compared with APAs alone.

Conclusion

Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study.
The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya
Authors:   LSHTM CMMID COVID-19 Working Group, Mburu C. N. , Ojal J. , Chebet R. , Akech D. , Karia B. , Tuju J. , Sigilai A. , Abbas K. , Jit M. , Funk S. , Smits G. , van Gageldonk P. G. M. , van der Klis F. R. M. , Tabu C. , Nokes D. J. , Scott JAG , Flasche S. , Adetifa IMO
Published: February 2021

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Results

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8–54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19–54), 46% (30–59), and 54% (43–64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25–56), 54% (43–63), and 67% (59–72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.

Conclusion

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.