bluuebunny/crossref_metadata_2025 huggingface dataset:
Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of four multicenter clinical trials
Authors: Zhou Jian-Guo , Wong Ada Hang-Heng , Wang Haitao , Jin Su-Han , Tan Fangya , Chen Yu-Zhong , He Si-Si , Shen Gang , Frey Benjamin , Fietkau Rainer , Hecht Markus , Carr Shamus R. , Wang Ruihong , Shen Bo , Schrump David S. , Ma Hu , Gaipl Udo S.
Published: September 2022

Importance

Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment.

Objective

This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients.

Design, Setting, and Participants

This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti–PD-L1) single-agent treatment (n = 1,479) or docetaxel single-agent treatment (n = 707). BCT was conducted at three time points: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients.

Main Outcomes and Measures

Overall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points.

Results

The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLR_T3 = 5, PLR_T3 = 180, and NMR_T2 = 6 were identified as strong predictive biomarkers for atezolizumab (Ate)–treated NSCLC patients in comparison with docetaxel (Dtx)–treated patients regarding OS (BCTscore low risk: HR Ate vs. Dtx = 1.54 (95% CI: 1.04–2.27), P = 0.031; high risk: HR Ate vs. Dtx = 0.84 (95% CI: 0.62–1.12), P = 0.235). The identified BCTscore model showed better OS AUC in the OAK (AUC12month = 0.696), BIRCH (AUC12month = 0.672) and POPLAR+FIR studies (AUC12month = 0.727) than that of each of the three single BCT biomarkers.

Conclusion and Relevance

The BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients.
Costimulation blockade and Tregs in solid organ transplantation
Authors: Muckenhuber Moritz , Wekerle Thomas , Schwarz Christoph
Published: September 2022

Regulatory T cells (Tregs) play a critical role in maintaining self-tolerance and in containing allo-immune responses in the context of transplantation. Recent advances yielded the approval of the first pharmaceutical costimulation blockers (abatacept and belatacept), with more of them in the pipeline. These costimulation blockers inhibit effector cells with high clinical efficacy to control disease activity, but might inadvertently also affect Tregs. Treg homeostasis is controlled by a complex network of costimulatory and coinhibitory signals, including CD28, the main target of abatacept/belatacept, and CTLA4, PD-1 and ICOS. This review shall give an overview on what effects the therapeutic manipulation of costimulation has on Treg function in transplantation.
Effects of sex steroids on thymic epithelium and thymocyte development
Authors: Taves Matthew D. , Ashwell Jonathan D.
Published: September 2022

Sex steroid hormones have major effects on the thymus. Age-related increases in androgens and estrogens and pregnancy-induced increases in progestins all cause dramatic thymic atrophy. Atrophy can also be induced by treatment with exogenous sex steroids and reversed by ablation of endogenous sex steroids. Although these observations are frequently touted as evidence of steroid lymphotoxicity, they are often driven by steroid signaling in thymic epithelial cells (TEC), which are highly steroid responsive. Here, we outline the effects of sex steroids on the thymus and T cell development. We focus on studies that have examined steroid signalingin vivo, aiming to emphasize the actions of endogenous steroids which,viaTEC, have remarkable programming effects on the TCR repertoire. Due to the dramatic effects of steroids on TEC, especially thymic involution, the direct effects of sex steroid signaling in thymocytes are less well understood. We outline studies that could be important in addressing these possibilities, and highlight suggestive findings of sex steroid generation within the thymus itself.
Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens
Authors: de Souza Matheus Oliveira , Madan Bharat , Teng I-Ting , Huang Aric , Liu Lihong , Fahad Ahmed S. , Lopez Acevedo Sheila N. , Pan Xiaoli , Sastry Mallika , Gutierrez-Gonzalez Matias , Yin Michael T. , Zhou Tongqing , Ho David D. , Kwong Peter D. , DeKosky Brandon J.
Published: September 2022

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged continuously, challenging the effectiveness of vaccines, diagnostics, and treatments. Moreover, the possibility of the appearance of a new betacoronavirus with high transmissibility and high fatality is reason for concern. In this study, we used a natively paired yeast display technology, combined with next-generation sequencing (NGS) and massive bioinformatic analysis to perform a comprehensive study of subdomain specificity of natural human antibodies from two convalescent donors. Using this screening technology, we mapped the cross-reactive responses of antibodies generated by the two donors against SARS-CoV-2 variants and other betacoronaviruses. We tested the neutralization potency of a set of the cross-reactive antibodies generated in this study and observed that most of the antibodies produced by these patients were non-neutralizing. We performed a comparison of the specific and non-specific antibodies by somatic hypermutation in a repertoire-scale for the two individuals and observed that the degree of somatic hypermutation was unique for each patient. The data from this study provide functional insights into cross-reactive antibodies that can assist in the development of strategies against emerging SARS-CoV-2 variants and divergent betacoronaviruses.
Adipose tissue macrophage in obesity-associated metabolic diseases
Authors: Yao Jingfei , Wu Dongmei , Qiu Yifu
Published: September 2022

Adipose tissue macrophage (ATM) has been appreciated for its critical contribution to obesity-associated metabolic diseases in recent years. Here, we discuss the regulation of ATM on both metabolic homeostatsis and dysfunction. In particular, the macrophage polarization and recruitment as well as the crosstalk between ATM and adipocyte in thermogenesis, obesity, insulin resistance and adipose tissue fibrosis have been reviewed. A better understanding of how ATM regulates adipose tissue remodeling may provide novel therapeutic strategies against obesity and associated metabolic diseases.
Haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood in hematologic malignancy patients: A report of 80 cases
Authors: Zeng Cong , Chen Yan , Hua Juan , Liu Yi , Cheng Ting-ting , Ma Xia , Chen Xu , Wang Shi-yu , Xu Ya-jing
Published: September 2022

The outcomes of 80 patients with hematologic malignancies who received haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) combined with unrelated cord blood (UCB) from March 2017 to June 2020 were analyzed in this retrospective study. Anti-thymocyte globulin(ATG) was administered at a dose of 7.5 mg/kg. The median time for neutrophil and platelet engraftment was 13(range: 8-22) days and 14(range: 8-103) days, respectively. The 30-day cumulative incidence of neutrophil engraftment was 100%, and the 100-day cumulative incidence of platelet engraftment was 95%. All patients achieved complete haploidentical peripheral blood stem cell engraftment, and no cord blood chimerism was observed. The cumulative incidence of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) on 100-day was 26.3%(95%CI: 17.2%–36.3%) and 5.0%(95%CI: 1.6%–11.4%), respectively. The estimated cumulative incidence of chronic GVHD (cGVHD) and moderate-severe cGVHD at 3-year was 43.3%(95%CI: 31.6%–54.4%) and 16.0%(95%CI: 8.7%–25.2%), respectively. The estimated 3-year cumulative incidence of relapse and non-relapse mortality was 18.8%(95%CI: 10.0%–29.7%) and 17.8%(95%CI: 9.9%–27.5%), respectively. The estimated 3-year probabilities of overall survival, disease-free survival, GVHD/relapse-free survival were 77.6%(95%CI: 68.3%–88.1%), 63.4%(95%CI: 52.6%–76.5%), and 55.5%(95%CI: 44.8%–68.7%), respectively. These satisfying results suggested that haplo-PBSCT combined with UCB is an alternative transplantation protocol for hematologic malignancies.
Environmental factors influencing the risk of ANCA-associated vasculitis
Authors: Zhao Wen-Man , Wang Zhi-Juan , Shi Rui , Zhu Yu-Yu , Zhang Sen , Wang Rui-Feng , Wang De-Guang
Published: September 2022

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.
Clinical predictive value of naïve and memory T cells in advanced NSCLC
Authors: Zhang Guan , Liu Aqing , Yang Yanjie , Xia Ying , Li Wentao , Liu Yunhe , Zhang Jing , Cui Qian , Wang Dong , Liu Xu , Guo Yongtie , Chen Huayu , Yu Jianchun
Published: September 2022

Currently, there is no sensitive prognostic biomarker to screen out benefit patients from the non-benefit population in advanced non-small cell lung cancer patients (aNSCLCs). The 435 aNSCLCs and 278 normal controls (NCs) were recruited. The percentages and absolute counts (AC) of circulating naïve and memory T lymphocytes of CD4+ and CD8+ T cells (Tn/Tm) were measured by flow cytometry. The percentage of CD4+ naïve T (Tn), CD8+ Tn, CD8+ T memory stem cell (Tscm), and CD8+ terminal effector T cell decreased obviously. Still, all AC of Tn/Tm of aNSCLCs was significantly lower compared to NCs. Higher AC and percentage of CD4+ Tn, CD8+ Tn, and CD4+ Tscm showed markedly longer median PFS in aNSCLCs. Statistics demonstrated the AC of CD4+ Tn (≥ 3.7 cells/μL) was an independent protective factor for PFS. The analysis of the prognosis of immunotherapy showed the higher AC and percentage of CD4+ Tn and CD4+ Tscm and higher AC of CD8+ Tscm had significantly longer median PFS and the AC of CD4+ Tn (≥ 5.5 cells/μL) was an independent protective factor for PFS. Moreover, higher AC and percentages of Tn/Tm suggested higher disease control rate and lower progressive disease rate. The AC of Tn/Tm showed more regular patterns of impairment and was more relative with the disease progression than percentages in aNSCLCs. AC had a better predictive value than percentages in Tn/Tm for PFS. Notably, the AC of CD4+ Tn was a potential prognostic biomarker for the PFS and efficacy of immunotherapy.
Combined effects of nanoplastics and heavy metal on antioxidant parameters of juvenile tri-spine horseshoe crabs
Authors: Arif Iqra , Shang Yueyong , Zhang Caoqi , Khan Fahim Ullah , Tan Kian Ann , Waiho Khor , Wang Youji , Kwan Kit Yue , Hu Menghong
Published: September 2022

Juvenile tri-spine horseshoe crabs (Tachypleus tridentatus) were exposed to determine the effects of single and combined stresses of polystyrene nanoplastics (nano-PS) and heavy metal (Cu2+) on antioxidant enzyme parameters. The juveniles were exposed to a 21-day 100-nm polystyrene concentration (104 particles l-1) and a concentration of Cu2+ (10 µg l-1) followed by a recovery period of 7 days. The in vivo antioxidant activity for whole horseshoe crab was analyzed. The results revealed that all antioxidant parameters, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and lipid peroxidation (LPO), showed both increased and decreased levels in different experimental groups of horseshoe crabs having different experimental conditions compared to the control group at three time points, i.e., on days 7, 14, and 21. Similarly during the recovery period, SOD, CAT, and MDA showed decreased levels in all experimental groups, while GSH and LPO showed increased levels in all experimental groups of horseshoe crabs under the influence of different experimental conditions of nanoplastics and heavy metals compared to the control group on day 28. These results showed that the exposure of nano-PS and Cu2+ had precise effects on juvenile horseshoe crabs. Integrated biomarker responses showed that nano-PS and Cu2+ had adverse effects on juvenile horseshoe crabs. By principal component analysis, the potentially toxic effects of nano-PS and Cu2+ on horseshoe crabs were obtained.
Metal complexation, FT-IR characterization, and plankton abundance in the marine surface microlayer of coastal areas in the Eastern Mediterranean
Authors: Karavoltsos Sotirios , Sakellari Aikaterini , Plavšić Marta , Bekiaris Georgios , Tagkouli Dimitra , Triantafyllidis Anastasios , Giannakourou Antonia , Zervoudaki Soultana , Gkikopoulos Ioannis , Kalogeropoulos Nick
Published: September 2022

Barely any data exist on metal speciation in the marine surface microlayer (SML), a rather complex environment, the study of which contributes to enhancement of knowledge on metal speciation and its effect to the ocean. Metal speciation is significant since life requires a wide variety of trace metals that are essential for the growth of the organisms. Ligand concentrations (L) of copper (Cu), zinc (Zn), and cadmium (Cd) were studied by anodic stripping voltammetry (ASV) in the SML of coastal areas within the Aegean Sea in the Eastern Mediterranean. Complexing capacities in the SML in decreasing order ranged for Cu from 29 to 201 nM (median 101 nM), for Zn 24–149 nM (45 nM), and for Cd 1.0–1.5 nM (1.4 nM). Average enrichment factors (EFs) of SML samples compared to subsurface ones (SSW) were calculated equal to 0.9 ± 0.8, 1.2 ± 0.5, and 1.7 ± 1.6 for LZn, LCu, and LCd, respectively. In five out of the six total paired samples of SML and SSW, lower concentrations of LZn were measured in the SML, which is not the case for LCu and LCd. Due to elevated dissolved Zn concentrations in the SML, its complexation is incomplete, contrary to those of Cu and Cd, which are fully complexed. These trace metals are essential nutrients for biological functions, hence any differences on their concentration and chemical speciation may directly influence the distribution of phytoplankton species in the upper water column and neuston. EFs of SML relatively to subsurface water ranged in average between 1.2 and 2.4 for total organic carbon (TOC), chlorophyll a (Chla), and plankton, being generally >2 for most of the amino acids detected, demonstrating a relative enrichment of the SML in organic matter. A significant correlation was found between Cu ligands and dinoflagellates <20 μm, confirming older findings supporting that marine dinoflagellates of Gymnodinium genera produce Cu ligands. New insights are provided in the study and the importance of investigating bio-essential metal ions (Cu, Zn, Cd) and their organic complexes in the SML is pointed. Data on Zn and Cd complexing capacities in the SML are the first published so far.
Distinct roles of global cyclonic and anticyclonic eddies in regulating near-inertial internal waves in the ocean interior
Authors: Yuan Man , Song Zhuo , Jing Zhao , Li Zhuoran , Wu Lixin
Published: September 2022

In this study, we examine the regulation of wind-powered near-inertial internal waves (NIWs) in the ocean interior by mesoscale eddies, using an eddy-resolving global climate model. There is an enhancement (weakening) of NIW activity within anticyclonic (cyclonic) eddies from the surface boundary layer (SBL) base down to ~4,000 m, associated with a decreased (increased) wave vertical scale. The influence of anticyclonic eddies on NIW activity is more pronounced than that of cyclonic eddies, suggesting that the net effect of mesoscale eddies is to intensify the NIWs in the ocean interior. The enhanced (weakened) NIW activity under the SBL in anticyclonic (cyclonic) eddies is ascribed to both horizontal convergence (divergence) of NIW energy flux under the SBL and increased (decreased) downward NIW energy flux from the SBL base. The former is only confined to a layer within several hundred meters under the SBL, whereas the latter becomes dominant in the deeper ocean.
Marine litter in submarine canyons: A systematic review and critical synthesis
Authors: Hernandez Ivan , Davies Jaime S. , Huvenne Veerle A. I. , Dissanayake Awantha
Published: September 2022

The presence of marine litter is of concern in submarine canyons, although research in this area is still in its infancy. A critical synthesis and literature review selecting studies with primary data of benthic marine litter at depths of over 50 m revealed important gaps in the knowledge, with information on the impact of macroplastics in deep-sea environments still scarce. Less than 1% of medium to large submarine canyons mapped have been studied in any measure for marine litter, with over 91% of the canyon studies located in European waters. Imaging techniques are now the main tools used for sampling, overtaking trawling methods despite the continued growth of the latter for marine litter deep-sea research. Enumeration of litter was diverse with over 75% using abundance for quantification. Despite the existence of litter protocols available for deep-sea environments, over 73% of studies did not use any. There was no standardization in the implementation of established classification protocols, which were either not used in full or were customized in part. Fishing-related categories do not feature as a top-level category in the classification hierarchy in any of the protocols, yet over 50% of publications featured fishing materials as a main category, pointing to a more intuitive activity-based categorization of litter instead of a materials-led approach from the established protocols. Furthermore, interactions between litter and the surrounding environment and biota are very much underreported with little or no consensus between how the data are analyzed and expressed. There were no discernible patterns between litter density, composition and broad geographical location of canyons, with individual topographical characteristics, hydrodynamic regimes and anthropogenic activities being determining factors in how submarine canyons are affected by litter. Overall, there is no apparent framework to allow comparison of studies and due to the different methods of identifying, enumerating, quantifying and classifying marine litter, or lack of data on position and morphological setting within the canyon system. The evidence provided within this study highlights a ‘call to action’ for an urgent need to standardize and unify methodologies with new or established protocols to fully understand the impact of marine litter in submarine canyons.
“There and back again” - Ultrastructural changes in the gills of Bathymodiolus vent-mussels during symbiont loss: Back to a regular filter-feeding epidermis
Authors: Piquet Bérénice , Le Panse Sophie , Lallier François H. , Duperron Sébastien , Andersen Ann C.
Published: September 2022

Deep-sea mussels Bathymodiolus azoricus, from Azorean hydrothermal vents, house two types of symbionts in their fleshy gills: methane-oxidizing (MOX) and sulfide-oxidizing (SOX) Gamma-proteobacteria. As soon as the mussels are collected, their symbionts are deprived from their environmental nutrient flux, and cannot rely on their usual metabolism. Recent studies have shown that the gill cells undergo high rates of apoptosis, as well as regionalized cell proliferation. This study follows the fate of the symbionts and of the hosting bacteriocytes at the ultrastructural level, during an extended starvation period. Just upon collection, we evidenced an apico-basal journey of the symbionts in the bacteriocytes, starting with (1) apical single symbiont endocytosis, (2) symbiont division, (3) symbiont storage, (4) and symbiont digestion within lysosomes, above the basal lamina. After 4-9 days starvation, endocytosis occurred with (5) empty blebbing, (6) the lysosomes increased in size, and the bacteriocytes lost their apical membrane, resulting in (7) a baso-apical return of the symbiont-containing lysosomes outside the gills, while the nucleus showed condensed chromatin, characteristic of apoptosis/necroptosis (8). Between the bacteriocytes, narrow intercalary cells appear to divide (9). Our hypothesis is that intercalary cells are stem cells that replace lost bacteriocytes. After 61 days there was no symbiont left, and the epidermis resembled those of the non-symbiotic filter-feeding mussel Mytilus edulis.
Shallow-water hydrothermal vent system as an extreme proxy for discovery of microbiome significance in a crustacean holobiont
Authors: Chiu Ling , Wang Min-Chen , Tseng Kuang-Yu , Wei Chih-Lin , Lin Huei-Ting , Yang Shan-Hua , Tseng Yung-Che
Published: September 2022

The shallow-water hydrothermal vent (HV) system off Kueishan Island lies at the end of the Okinawa Trough to the northeast of Taiwan. Near its submarine vent openings, aperiodic vent discharges generate a dynamic acidic (pH 5.5-8.1) and sulfidic (9-3000 μM) ecosystem. The dominant metazoan in this unique environment is the brachyuran vent crab, Xenograpsus testudinatus, which has developed robust metabolic strategies and highly adaptive acid-base regulatory mechanisms to maintain its physiological homeostasis. X. testudinatus is considered a holobiont, but the symbiotic mechanisms underlying acid and sulfur tolerance in the host-microbe system remain largely unclear. In this study, we used LoopSeq long-read sequencing of the full-length 16S rRNA gene to identify the bacterial communities present in the gills and carapace surface of X. testudinatus. The alpha diversity analysis, Venn diagram, and principal coordinate analysis (PCoA) indicated that the gills and carapace surface exhibit different bacterial constituents. Further measurements of relative abundance, coupled with functional predictions and fluorescence in situ hybridization (FISH), revealed a predominance of Sulfurovum sp. NBC37-1, a key bacterium that can perform sulfur and hydrogen oxidation to support denitrification processes. Consequently, our findings suggest that the symbiotic bacteria may play a critical role in conferring the extraordinary acid and sulfur tolerances of X. testudinatus, allowing the crustacean holobiont to thrive in its ecological niche within one of the most extreme marine habitats on Earth.
Interannual variations of the North Equatorial Current/Undercurrent from mooring array observations
Authors: Huang Ying , Zhang Linlin , Wang Fujun , Wang Fan , Hu Dunxin
Published: September 2022

Interannual variability of the North Equatorial Current (NEC)/Undercurrent (NEUC) in the northwestern Pacific was investigated with the mooring array measurements at 130°E during 2014-2021, in combination with the satellite altimetry. Mooring observations indicate that the velocity of the NEC/NEUC in the upper 900 m exhibits significant variations on the interannual time scale. The westward-flowing NEC strengthens when the underlying eastward-flowing NEUC weakens, and the NEUC branch at 8.5°N is intensified during the mature phase of El Niño and reaches the maximum velocity during the decay phase of El Niño. The phase of the interannual variation of the currents delays with the increasing latitude, with the signal at 15°N lagging that at 8.5°N by about one year. Based on a 1.5 layer reduced gravity model, the interannual variation is suggested to be controlled mainly by the westward propagating baroclinic Rossby wave induced by the wind stress curl forcing in the central Pacific. Different propagating speed of the baroclinic Rossby wave at different latitudes explains the meridional phase lag of the interannual signal. Empirical Orthogonal Function and vertical mode decomposition analysis suggest that the interannual variation of the NEC/NEUC velocity in the northern part is dominated by surface-intensified signals with a vertical structure of the first baroclinic mode, while that in the southern part is dominated by subsurface-intensified signals which is associated with the combination of the first two baroclinic modes. The low-order mode baroclinic response of the ocean to the wind forcing accounts for the interannual fluctuation of the NEC/NEUC velocity observed by the mooring array.
Achieving sustainable production and consumption of virgin plastic polymers
Authors: Grabiel Tim , Gammage Tom , Perry Clare , Dixon Christina
Published: September 2022

The United Nations Environment Assembly (UNEA) recently adopted a resolution with a mandate to negotiate a new international legally binding instrument (a treaty) on plastic pollution. The mandate includes the need to ‘prevent’ as well as ‘reduce’ and ‘eliminate’ plastic pollution through a ‘comprehensive approach that addresses the full life cycle of plastic’. Unsustainable production and consumption of virgin (primary) plastic polymers represents the single greatest threat to preventing plastic pollution and risks undermining the incoming treaty. However, current discussions on a global plastics treaty overlook upstream measures that address virgin plastic production and consumption, focusing instead on midstream and downstream measures on product design and waste management. This article presents the justification for and benefits of a stepwise approach for controlling virgin plastic production and consumption internationally, inspired by the Montreal Protocol on Substances that Deplete the Ozone Layer;
Active control of dual electromagnetically induced transparency in terahertz graphene-metal hybrid metasurfaces
Authors: Li Quan , Su Hao , Zhu Jun , Wang Shuang
Published: September 2022

Active control of electromagnetically induced transparency (EIT) using metasurfaces has attracted growing interests in recent years, especially the ones that have multiple EIT windows. Here, we give out a metallic metasurface design that can achieve dual EIT (D-EIT) in the terahertz (THz) regime, and propose a strategy to individually and simultaneously control the two windows by integrating graphene structures into the design. The near-field simulations indicate that the physical mechanism lies in the composite effect of conductive graphene. The theoretical analysis reveals that the active modulation is attributed to the changes in the damping rates of the dark modes and the coupling coefficients between bright mode and dark modes. The proposed graphene-metal hybrid metasurfaces provide a way for designing compact dual-band slow-light and modulation devices, which may find potential applications in dual-frequency-channel THz wireless communications.
Advances in assembled micro- and nanoscale mechanical contact probes
Authors: Mead James L. , Klauser Waldemar , von Kleist-Retzow Fabian , Fatikow Sergej
Published: September 2022

The micro- and nanoscale characterization and mapping of surface properties and surface behaviour is critical to both physical and biological science. Mechanical contact probes are a critical tool for investigating surface and interface science, and have seen greater development and a diversification in recent years. In particular, mechanical contact probes that have been fabricated from the bottom-up by the assembly of synthesized nano- or microscale materials can provide enhanced functionality and sensitivity over traditional microcantilevers. This work provides an overview of recent developments in the field of assembled micro- and nanoscale mechanical contact probes, with a specific focus on three probe types: colloidal particle probes with high aspect ratio and a high lateral sensitivity, one-dimensional probes comprising of nanotube and/or nanowire deflection elements, and liquid metal-based probes. For each probe type, the state-of-the-art is reviewed, and their assembly, design, functionality and capabilities are discussed. An outlook on the future direction of probe development and potential applications is also given.
Seroprevalence and burden of hepatitis E viral infection among pregnant women in central Nigeria attending antenatal clinic at a Federal Medical Centre in Central Nigeria
Authors: Ehi Airiohuodion Philomena , Wartel Anh , Yako Andrew B. , Mac Peter Asaga
Published: September 2022

Introduction

HEV infection may be life threatening in pregnant women and has been linked with 20–30% mortality, especially in the third trimester of pregnancy. HEV infection leads to elevated levels of preterm labour and other immunological parameters. It is vertically transmitted and could lead to poor feto-maternal outcomes. especially in fulminating viral hepatitis where both the mother and foetus could be lost. There is currently no known treatment or vaccine for HEV. There is therefore a need to study HEV seroprevalence and burden among vulnerable groups, such as pregnant women and their newborns in Nigeria, where maternal mortality is highly significant.

Methods

A total of 200 samples were collected from pregnant women attending antenatal clinic at Federal Medical Centre (FMC) Keffi, in central Nigeria, of which (156/200) samples were from HIV-negative pregnant women and (44/200) were from HIV-positive pregnant women, using a simple random sampling method.

Results

In total, 200 pregnant women [78.0% (156/200) HIV-negative pregnant women and 22.0% (44/200) HIV-positive pregnant women] were recruited for this study. The ages of the pregnant women ranged from 15-49 years, with a mean age of 26.4 years (± 6.23). The overall HEV IgG seropositivity in the study population was 31.5% (63/200); 95% CI (30-33).

Conclusion

This study highlighted an unexpectedly high seroprevalence of HEV and poor feto-maternal outcomes in pregnant women residing in a rural and urban setting of central Nigeria. The study showed that the inherently high HEV seropositivity and poor feto-maternal outcomes may not be attributed to HEV viral hepatitis only but may be a combination of extrinsic and intrinsic factors.
Sentinel Lymph Node Biopsy in Prostate Cancer Patients: Results From an Injection Technique Targeting the Index Lesion in the Prostate Gland
Authors: Fumadó Lluís , Abascal Jose M. , Mestre-Fusco Antoni , Vidal-Sicart Sergi , Aguilar Guadalupe , Juanpere Nuria , Cecchini Lluís
Published: September 2022

Objectives

To determine the accuracy of nodal staging in patients with prostate cancer (PCa) when 99mTc-nanocolloid radiotracer is injected into an index lesion (IL).

Methods

This prospective study was conducted at our institution between June 2016 and October 2020. It included 64 patients with localized PCa with at least a 5% possibility for lymph node involvement in the Memorial Sloan Kettering Cancer Center nomogram, suitable for surgical treatment. All patients underwent magnetic resonance imaging (MRI) with IL and were pathologically confirmed. The day before surgery, transrectal ultrasound-guided injection (TRUS) of 99mTc-nanocolloid into the IL was performed. Surgical procedures included radical prostatectomy (RP), sentinel lymph node biopsy (SLNB), and extended pelvic lymphadenectomy (ePLND). Analysis was performed, including histopathological findings of RP, ePLND, and SLNB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative (FN), false positive (FP), diagnostic yield, and non-diagnostic rate were calculated.

Results

A total of 1,316 lymph nodes were excised, including 1,102 from the ePLND (83.7%) and 214 (16.3%) sentinel lymph nodes (SLN). 26 SLN were dissected outside the ePLND template. The final pathology demonstrated 46 (3.5%) lymph node metastasis, 31 (67.4%) in the SLNB and 15 (32.6%) in the non-SLN ePLND. At the patient level, 18 (28.1%) patients had pN1. With a mean follow-up of 33.1 months, 4/19 (21.1%) pN1 patients had undetectable PSA, and 3/19 (15.8%) had a PSA < 0.1 ng/mL. Lymph node dissection included 20.6 lymph nodes per patient (IQR 15–24.2), with 3.3 SLNB nodes per patient (IQR 2–4.2). PPV and NPV were 100 and 97.8%, respectively. Sensitivity and specificity were 94.4 and 100%, respectively. FN was 5.5% and FP was 4.3%. Diagnostic yields were 95.3% and the non-diagnostic rate was 4.7%.

Conclusion

Radiotracer injection into the prostate IL offers promising results for staging purposes in cases in which ePLND is considered. Negative SLNB is a predictor of negative ePLND. Patients with a limited burden of nodal metastasis have a significant chance of remaining free of biochemical recurrence at mid-term follow-up.
Moderate sedation by total intravenous remimazolam-alfentanil vs. propofol-alfentanil for third molar extraction: A prospective randomized controlled trial
Authors: Zhao Nan , Zeng Jie , Fan Lin , Wang Jing , Zhang Chao , Zou SiHai , Zhang Bi , Li Kai , Yu Cong
Published: September 2022

Background

Oral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction.

Methods

This single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 μg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 μg/kg and maintenance dosage of 5 μg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 μg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 μg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h.

Results

The incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049–0.377); P < 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025–0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA.

Conclusions

Remimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol.

Clinical trial registration

http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2200058106.
Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis
Authors: Caruso Cristiano , Cameli Paolo , Altieri Elena , Aliani Maria , Bracciale Pietro , Brussino Luisa , Caiaffa Maria Filomena , Canonica Giorgio Walter , Centanni Stefano , D’Amato Maria , Del Giacco Stefano , De Michele Fausto , Pastorello Elide Anna , Pelaia Girolamo , Rogliani Paola , Romagnoli Micaela , Schino Pietro , Caminati Marco , Vultaggio Alessandra , Zullo Alessandro , Rizzoli Sara , Boarino Silvia , Vitiello Gianfranco , Menzella Francesco , Di Marco Fabiano
Published: September 2022

Background

Severe asthma is a heterogeneous inflammatory disease driven by eosinophilic inflammation in the majority of cases. Despite biologic therapy patients may still be sub-optimally controlled, and the choice of the best biologic is a matter of debate. Indeed, switching between biologics is common, but no official guidelines are available and real-world data are limited.

Materials and methods

In this post hoc analysis of the Italian, multi-center, observational, retrospective study, ANANKE. Patients with severe eosinophilic asthma treated with benralizumab were divided in two groups based on history of previous biologic therapy (biologic-experienced [suboptimal response] vs naïve). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment. Change over time in blood eosinophils, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use following benralizumab initiation were collected in the two groups.

Results

A total of 147 biologic-naïve and 58 biologic-experienced (34 omalizumab, 19 mepolizumab, and 5 omalizumab-mepolizumab) patients were enrolled. Biologic-experienced patients were more likely to be atopic and have a higher AER despite more frequent OCS use. Similar reductions in AER (>90% in both groups), OCS use (≥49% reduction in dosage and ≥41% able to eliminate OCS), ACT improvement (≥7 points gained in 48 weeks) and lung function (≥300 mL of FEV1 improvement in 48 weeks) were observed after benralizumab introduction within the two groups. There were no registered discontinuations of benralizumab for safety reasons.

Conclusion

In this post hoc analysis, patients who were switched to benralizumab because of suboptimal control with a previous biologic therapy were more likely to be atopic and more often treated with omalizumab. Benralizumab is effective in both naïve patients and those previously treated with a biologic.
Authorship diversity in Gastroenterology-related Cochrane systematic reviews: Inequities in global representation
Authors: Dhali Arkadeep , D'Souza Christopher , Rathna Roger B. , Biswas Jyotirmoy , Dhali Gopal Krishna
Published: September 2022

The need for promoting diversity and equitable authorship representation in academics faces increasing recognition, with some articles pointing out the lack of diversity in specific fields. Currently, there are no such articles scrutinizing the author diversity in the field of Gastroenterology. Cochrane systematic reviews are perceived worldwide to be amongst the highest quality of evidence available, thereby its conclusions often impact policy and practice globally. However, little is known about the current state of authorship diversity in Gastroenterology-related Cochrane reviews.
Combined urine metabolomics and 16S rDNA sequencing analyses reveals physiological mechanism underlying decline in natural mating behavior of captive giant pandas
Authors: Zhang Ming-yue , Wang Xue-ying , Ayala James , Liu Yu-liang , An Jun-hui , Wang Dong-hui , Cai Zhi-gang , Hou Rong , Cai Kai-lai
Published: September 2022

The decline in natural mating behavior is the primary reason underlying in the poor population growth of captive giant pandas. However, the influencing factors and underlying mechanisms remain unclear to data. It is speculated that the decline in natural mating behavior could be related to the psychological stress caused by captivity, which restricts their free choice of mates. In order to test this hypothesis, we performed urinary metabolomics analysis using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC/-MS) combined with 16S rDNA sequencing for exploring the physiological mechanism underlying the decline in the natural mating behavior of captive giant panda. The results demonstrated that the decline in mating ability could be related to abnormalities in arginine biosynthesis and neurotransmitter synthesis. Additionally, the relative abundance of bacteria from the Firmicutes, Proteobacteria, and Actinobacteria phyla and the Acinetobacter, Weissella, and Pseudomonas genus was significantly reduced in the group with low natural mating behavior. These findings imply that the inhibition of arginine synthesis induced by environmental changes could be related to the poor libido and failure of mate selection in captive giant pandas during the breeding period. The results also demonstrate the relationship between the altered urinary microbes and metabolites related to arginine and neurotransmitter synthesis. These findings may aid in understanding the mechanism underlying environment-induced mate selection in captive giant pandas and propose a novel strategy for determining the sexual desire of giant pandas based on urinary microbes. The method would be of great significance in improving the natural reproductive success rate of captive giant pandas.
Microbial community structure and niche differentiation under different health statuses of Pinus bungeana in the Xiong'an New Area in China
Authors: Yang Jia , Masoudi Abolfazl , Li Hao , Gu Yifan , Wang Can , Wang Min , Yu Zhijun , Liu Jingze
Published: September 2022

Pinus bungeana is a native but endangered plant species in China, with high ornamental value and adaptability to drought and cold. The relationship between the soil community structure and endophytic microbes in the tissues of P. bungeana under different health statuses is poorly understood. In this study, the endophytic bacterial and fungal communities of P. bungeana under different health statuses were compared and analyzed in the Xiong'an New Area. Using high-throughput deep sequencing [16S and internal transcribed spacer (ITS) rRNA] techniques, the effect of the health status of P. bungeana on the microbial communities in bulk soil, rhizospheric soil, roots, stems, and leaves was determined in this study. We observed that the diversity of the bacterial and fungal communities of the aboveground parts (stems and leaves) of healthy P. bungeana plants was much higher than that of the unhealthy plants. However, the diversity of bacterial and fungal communities in the belowground parts (bulk soil, rhizospheric soil, and roots) showed almost no difference in microbial community richness, indicating that the possible cause of illness was transmitted in a “top-down” manner. Furthermore, there were significant differences in the microbial diversity and community structure in different ecological niches of P. bungeana (P < 0.01). Proteobacteria and Actinobacteria were the dominant bacterial phyla, while Ascomycota, Basidiomycota, and Mortierellomycota were the predominant fungal phyla. Redundancy analysis (RDA) revealed that soil organic matter (SOM), total phosphorous (TP), total potassium (TK), total nitrogen (TN), water content (WC), power of hydrogen (pH), total carbon (TC), and the ratio of carbon to nitrogen (C/N) were significantly correlated with the composition of the microbial communities. Altogether, these results provide a scientific basis for further studies on the mechanism underlying the “aboveground–underground” microbial interactions in plantation forests, which can aid in promoting the healthy and sustainable development of the Millennium Xiulin forest in the Xiong'an New Area.
Hepatitis B virus DNA integration as a novel biomarker of hepatitis B virus-mediated pathogenetic properties and a barrier to the current strategies for hepatitis B virus cure
Authors: Salpini Romina , D’Anna Stefano , Benedetti Livia , Piermatteo Lorenzo , Gill Upkar , Svicher Valentina , Kennedy Patrick T. F.
Published: September 2022

Chronic infection with Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality worldwide. HBV-DNA integration into the human genome is recognized as a frequent event occurring during the early phases of HBV infection and characterizing the entire course of HBV natural history. The development of refined molecular biology technologies sheds new light on the functional implications of HBV-DNA integration into the human genome, including its role in the progression of HBV-related pathogenesis and in triggering the establishment of pro-oncogenic mechanisms, promoting the development of hepatocellular carcinoma. The present review provides an updated and comprehensive overview of the current body of knowledge on HBV-DNA integration, focusing on the molecular mechanisms underlying HBV-DNA integration and its occurrence throughout the different phases characterizing the natural history of HBV infection. Furthermore, here we discuss the main clinical implications of HBV integration as a biomarker of HBV-related pathogenesis, particularly in reference to hepatocarcinogenesis, and how integration may act as a barrier to the achievement of HBV cure with current and novel antiviral therapies. Overall, a more refined insight into the mechanisms and functionality of HBV integration is paramount, since it can potentially inform the design of ad hoc diagnostic tools with the ability to reveal HBV integration events perturbating relevant intracellular pathways and for identifying novel therapeutic strategies targeting alterations directly related to HBV integration.