bluuebunny/crossref_metadata_2025 huggingface dataset:
Data-Space Inversion With a Recurrent Autoencoder for Naturally Fractured Systems
Authors: Jiang Su , Hui Mun-Hong , Durlofsky Louis J.
Published: July 2021

Data-space inversion (DSI) is a data assimilation procedure that directly generates posterior flow predictions, for time series of interest, without calibrating model parameters. No forward flow simulation is performed in the data assimilation process. DSI instead uses the prior data generated by performingO(1000)simulations on prior geomodel realizations. Data parameterization is useful in the DSI framework as it enables representation of the correlated time-series data quantities in terms of low-dimensional latent-space variables. In this work, a recently developed parameterization based on a recurrent autoencoder (RAE) is applied with DSI for a real naturally fractured reservoir. The parameterization, involving the use of a recurrent neural network and an autoencoder, is able to capture important correlations in the time-series data. RAE training is accomplished using flow simulation results for 1,350 prior model realizations. An ensemble smoother with multiple data assimilation (ESMDA) is applied to provide posterior DSI data samples. The modeling in this work is much more complex than that considered in previous DSI studies as it includes multiple 3D discrete fracture realizations, three-phase flow, tracer injection and production, and complicated field-management logic leading to frequent well shut-in and reopening. Results for the reconstruction of new simulation data (not seen in training), using both the RAE-based parameterization and a simpler approach based on principal component analysis (PCA) with histogram transformation, are presented. The RAE-based procedure is shown to provide better accuracy for these data reconstructions. Detailed posterior DSI results are then presented for a particular “true” model (which is outside the prior ensemble), and summary results are provided for five additional “true” models that are consistent with the prior ensemble. These results again demonstrate the advantages of DSI with RAE-based parameterization for this challenging fractured reservoir case.
Differential Expression of Drosophila Transgelins Throughout Development
Authors: Vakaloglou Katerina M. , Mouratidou Maria , Keramidioti Athina , Zervas Christos G.
Published: July 2021

Transgelins are a conserved family of actin-binding proteins involved in cytoskeletal remodeling, cell contractility, and cell shape. In both mammals andDrosophila, three genes encode transgelin proteins. Transgelins exhibit a broad and overlapping expression pattern, which has obscured the precise identification of their role in development. Here, we report the first systematic developmental analysis of allDrosophilatransgelin proteins, namely, Mp20, CG5023, and Chd64 in the living organism.Drosophilatransgelins display overall higher sequence identity with mammalian TAGLN-3 and TAGLN-2 than with TAGLN. Detailed examination in different developmental stages revealed that Mp20 and CG5023 are predominantly expressed in mesodermal tissues with the onset of myogenesis and accumulate in the cytoplasm of all somatic muscles and heart in the late embryo. Notably, at postembryonic developmental stages, Mp20 and CG5023 are detected in the gut’s circumferential muscles with distinct subcellular localization: Z-lines for Mp20 and sarcomere and nucleus for CG5023. Only CG5023 is strongly detected in the adult fly in the abdominal, leg, and synchronous thoracic muscles. Chd64 protein is primarily expressed in endodermal and ectodermal tissues and has a dual subcellular localization in the cytoplasm and the nucleus. During the larval–pupae transition, Chd64 is expressed in the brain, eye, legs, halteres, and wings. In contrast, in the adult fly, Chd64 is expressed in epithelia, including the alimentary tract and genitalia. Based on the non-overlapping tissue expression, we predict that Mp20 and CG5023 mostly cooperate to modulate muscle function, whereas Chd64 has distinct roles in epithelial, neuronal, and endodermal tissues.
HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells
Authors: Dong Yu-Jie , Feng Wei , Li Yan
Published: July 2021

Ovarian cancer is a deadly gynecological malignancy with resistance to cisplatin a major clinical problem. We evaluated a role of long non-coding (lnc) RNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells, using paired cisplatin sensitive and resistant A2780 cells along with the SK-OV-3 cells. HOTTIP was significantly elevated in cisplatin resistant cells and its silencing reversed the cisplatin resistance of resistant cells. HOTTIP was found to sponge miR-205 and therefore HOTTIP silenced cells had higher levels of miR-205. Downregulation of miR-205 could attenuate HOTTIP-silencing effects whereas miR-205 upregulation in resistant cells was found to re-sensitize cells to cisplatin. HOTTIP silencing also led to reduced NF-κB activation, clonogenic potential and the reduced expression of stem cell markers SOX2, OCT4, and NANOG, an effect that could be attenuated by miR-205. Finally, ZEB2 was identified as the gene target of miR-205, thus completing the elucidation of HOTTIP-miR-205-ZEB2 as the novel axis which is functionally involved in the determination of cisplatin resistance in ovarian cancer cells.
Online Noise as Illustrated by Pitfalls and Biogeography Associated With Common Names for Puma concolor
Authors: Wood Emma , Ambrosini Angela , Wood Karen , Demetrio Christina , O'Malley W. Connor , Stratton Andrew , Elbroch L. Mark
Published: July 2021

Noise is the non-target search results that people encounter when searching for a particular topic of interest; it is also the cloud of distracting data that can obscure or deflect conservation communication. Online noise associated with large carnivores is particularly dense because their defining characteristics make them salient. Mountain lions (Puma concolor) exemplify noise associated with multiple vernaculars for a species in the crosshairs of conservation conundrums. We compared internet search results, Google Trends reflecting topic interest, use in science publications and sentiment in print and online media for P. concolor's most frequent vernacular names, “mountain lion,” “cougar,” “puma” and “Florida panther.” Puma and panther exhibited greater noise and salience than cougar or mountain lion, but, results for mountain lion, followed by cougar, yielded the highest biological relevance. Online sentiment negatively correlated with biological relevance, with positive sentiment highest for the noisiest vernaculars, puma and panther. As conservation practitioners, we must recognize that public outreach is part of our scientific agenda and be conscious of crafting communication that reaches and resonates with our intended audiences.
Adropin Alleviates Myocardial Fibrosis in Diabetic Cardiomyopathy Rats: A Preliminary Study
Authors: Liu Mao , Ai Jiao , Shuai Zhuang , Tang Kai , Li Zongyu , Huang Yin
Published: July 2021

Aim: Adropin (ADR) is a novel regulatory polypeptide and has important effects on energy metabolism in the heart. However, it is still unclear whether ADR can relieve ventricular remodeling in DCM. Therefore, this study was conducted to assess the effect of ADR on myocardial fibrosis in DCM rats.

Materials and Methods: Twenty Wistar rats were randomly assigned into four groups: healthy control group (CON), DCM model group (DCM), DCM model treated with ADR group (ADR) and DCM model treated with perindopril group (PER). Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were calculated. Diastolic function was assessed by echocardiography. The mitochondrial membrane potential assay was conducted by Rhodamine 123 staining. The protein expression levels of Col I, Col III, Mitofusin-1, Mitofusin-2 and Drp1 were evaluated using western blot.

Results: Compared to CON group, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 increased in DCM group. And the relative expression of Mitofusin-1 and Mitofusin-2 proteins decreased. During our investigations, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 decreased in ADR treated rats compared to DCM group. The diastolic function was elevated in ADR group. The fluorescence of Rhodamine 123 and the expression of Mitofusin-1 and Mitofusin-2 also increased in ADR group.

Conclusion: Our study demonstrated that ADR could alleviate myocardial fibrosis and improve diastolic function in DCM rats. ADR may be a putative candidate for the treatment of DCM.
Addressing the Ceiling Effect when Assessing STEM Out-Of-School Time Experiences
Authors: Staus Nancy L. , O'Connell Kari , Storksdieck Martin
Published: July 2021

The aim of this paper is to describe an analytical approach for addressing the ceiling effect, a measurement limitation that affects research and evaluation efforts in informal STEM learning projects. The ceiling effect occurs when a large proportion of subjects begin a study with very high scores on the measured variable(s), such that participation in an educational experience cannot yield significant gains among these learners. This effect is widespread in informal science learning due to the self-selective nature of participation in these experiences, such that participants are already interested in and knowledgeable about the content area. When the ceiling effect is present, no conclusions can be drawn regarding the influence of an intervention on participants’ learning outcomes which could lead evaluators and funders to underestimate the positive effects of STEM programs. We discuss how the use of person-centered analytic approaches that segment samples in theory driven ways could help address the ceiling effect and provide an illustrative example using data from a recent evaluation of a STEM afterschool program.
Risk Factors for Contralateral Occult Carcinoma in Patients With Unilateral Papillary Thyroid Carcinoma: A Retrospective Study and Meta-Analysis
Authors: Zhang Fan , Zheng Boyuan , Yu Xiaohui , Wang Xichang , Wang Shiwei , Teng Weiping
Published: July 2021

Background

Bilateral lesions are common in papillary thyroid carcinoma (PTC). For patients with unilateral PTC, occult carcinoma that is not detected preoperatively, but pathologically after surgery, might remain in the contralateral lobe. In this situation, inadequate surgical extent could cause relapse and even lead to re-operation. Here, we explore the frequency and investigate the risk factors of contralateral occult PTC in unilateral PTC through a retrospective study conducted by our team and published articles online, respectively.

Methods

We collected the patients’ clinical data in our hospital, whose cancer was determined to be confined to the unilateral lobe by preoperative image examination (N = 204). These patients underwent initially total or near-total thyroidectomy and included their clinical data in the meta-analysis. We searched related literature in the PubMed, Embase, MEDLINE, Cochrane, and Web of Science databases until December 7, 2020, in order to perform a meta-analysis. The relevant articles were examined and the eligible studies were included to assess the association between clinicopathologic factors and contralateral occult PTC.

Results

The meta-analysis included nine studies (involving 4347 patients). Of these, eight studies were from the databases, and one study was our retrospective data. The meta-analysis showed that the prevalence of contralateral occult PTC was 26.6% in all patients. A tumor size > 1 cm, ipsilateral multifocality, contralateral benign nodule, and central lymph node metastasis were significantly associated with contralateral occult PTC. In contrast, sex, age, ETE, capsular invasion, BRAF mutation, Hashimoto thyroiditis, and lateral lymph node metastasis were insignificantly associated with contralateral occult PTC.

Conclusion

The meta-analysis identified a tumor size > 1 cm, ipsilateral multifocality, contralateral benign nodule, and CLNM as being significant risk factors for contralateral occult PTC. These findings may guide the extent of surgery in unilateral PTC patients.
Population Genomics of the Commercially Important Gulf of Mexico Pink Shrimp Farfantepenaeus duorarum (Burkenroad, 1939) Support Models of Juvenile Transport Around the Florida Peninsula
Authors: Timm Laura E. , Jackson Thomas L. , Browder Joan A. , Bracken-Grissom Heather D.
Published: July 2021

The Gulf of Mexico pink shrimp, Farfantepenaeus duorarum, supports large fisheries in the United States and Mexico, with nearly 7,000 tons harvested from the region in 2016. Given the commercial importance of this species, management is critical: in 1997, the southern Gulf of Mexico pink shrimp fishery was declared collapsed and mitigation strategies went into effect, with recovery efforts lasting over a decade. Fisheries management can be informed and improved through a better understanding of how factors associated with early life history impact genetic diversity and population structure in the recruited population. Farfantepenaeus duorarum are short-lived, but highly fecund, and display high variability in recruitment patterns. To date, modeling the impacts of ecological, physical, and behavioral factors on juvenile settlement has focused on recruitment of larval individuals of F. duorarum to nursery grounds in Florida Bay. Here, we articulate testable hypotheses stemming from a recent model of larval transport and evaluate support for each with a population genomics approach, generating reduced representation library sequencing data for F. duorarum collected from seven regions around the Florida Peninsula. Our research represents the first and most molecular data-rich study of population structure in F. duorarum in the Gulf and reveals evidence of a differentiated population in the Dry Tortugas. Our approach largely validates a model of larval transport, allowing us to make management-informative inferences about the impacts of spawning location and recruitment patterns on intraspecific genetic diversity. Such inferences improve our understanding of the roles of non-genetic factors in generating and maintaining genetic diversity in a commercially important penaeid shrimp species.
Contrasting Resource Dynamics in Mast Years for European Beech and Oak—A Continental Scale Analysis
Authors: Nussbaumer Anita , Gessler Arthur , Benham Sue , de Cinti Bruno , Etzold Sophia , Ingerslev Morten , Jacob Frank , Lebourgeois François , Levanic Tom , Marjanović Hrvoje , Nicolas Manuel , Ostrogović Sever Maša Zorana , Priwitzer Tibor , Rautio Pasi , Roskams Peter , Sanders Tanja G. M. , Schmitt Maria , Šrámek Vít , Thimonier Anne , Ukonmaanaho Liisa , Verstraeten Arne , Vesterdal Lars , Wagner Markus , Waldner Peter , Rigling Andreas
Published: July 2021

Resource allocation to different plant tissues is likely to be affected by high investment into fruit production during mast years. However, there is a large knowledge gap concerning species-specific differences in resource dynamics. We investigated the influence of mast years on stem growth, leaf production, and leaf carbon (C), nitrogen (N), and phosphorus (P) concentrations and contents in Fagus sylvatica, Quercus petraea, and Q. robur at continental and climate region scales using long-term data from the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) and similar datasets. We discussed the results in the light of opposing resource dynamics hypotheses: (i) resource accumulation before mast years and exhaustion after mast years (resource storage hypothesis), (ii) shifting resources from vegetative to generative compartments (resource switching hypothesis), and (iii) investing resources concurrently in both vegetative and generative compartments (resource matching hypothesis). Linear mixed-effects modelling (LMM) showed that both stem growth and leaf production were negatively influenced by weather conditions which simultaneously lead to high fruit production. Thus, the impact of generative on vegetative growth is intermixed with effects of environmental factors. Superposed epoch analyses and LMM showed that for mast behaviour in F. sylvatica, there are indicators supporting the resource storage and the resource switching hypotheses. Before mast years, resources were accumulated, while during mast years resources switched from vegetative to generative tissues with reduced stem and leaf growth. For the Quercus species, stem growth was reduced after mast years, which supports the resource storage hypothesis. LMM showed that leaf C concentrations did not change with increasing fruit production in neither species. Leaf N and P concentrations increased in F. sylvatica, but not in Quercus species. Leaf N and P contents decreased with increasing fruit production in all species, as did leaf C content in F. sylvatica. Overall, our findings suggest different resource dynamics strategies in F. sylvatica and Quercus species, which might lead to differences in their adaptive capacity to a changing climate.
Stand-Level Variation Drives Canopy Water Storage by Non-vascular Epiphytes Across a Temperate-Boreal Ecotone
Authors: Hembre Kate , Meyer Abigail , Route Tana , Glauser Abby , Stanton Daniel E.
Published: July 2021

Epiphytes, including bryophytes and lichens, can significantly change the water interception and storage capacities of forest canopies. However, despite some understanding of this role, empirical evaluations of canopy and bole community water storage capacity by epiphytes are still quite limited. Epiphyte communities are shaped by both microclimate and host plant identity, and so the canopy and bole community storage capacity might also be expected to vary across similar spatial scales. We estimated canopy and bole community cover and biomass of bryophytes and lichens from ground-based surveys across a temperate-boreal ecotone in continental North America (Minnesota). Multiple forest types were studied at each site, to separate stand level and latitudinal effects. Biomass was converted into potential canopy and bole community storage on the basis of water-holding capacity measurements of dominant taxa. Bole biomass and potential water storage was a much larger contributor than outer canopy. Biomass and water storage capacity varied greatly, ranging from 9 to >900kg ha–1 and 0.003 to 0.38 mm, respectively. These values are lower than most reported results for temperate forests, which have emphasized coastal and old-growth forests. Variation was greatest within sites and appeared to reflect the strong effects of host tree identity on epiphyte communities, with conifer-dominated plots hosting more lichen-dominated epiphyte communities with lower potential water storage capacity. These results point to the challenges of estimating and incorporating epiphyte contributions to canopy hydrology from stand metrics. Further work is also needed to improve estimates of canopy epiphytes, including crustose lichens.
Comparative Repeat Profiling of Two Closely Related Conifers (Larix decidua and Larix kaempferi) Reveals High Genome Similarity With Only Few Fast-Evolving Satellite DNAs
Authors: Heitkam Tony , Schulte Luise , Weber Beatrice , Liedtke Susan , Breitenbach Sarah , Kögler Anja , Morgenstern Kristin , Brückner Marie , Tröber Ute , Wolf Heino , Krabel Doris , Schmidt Thomas
Published: July 2021

In eukaryotic genomes, cycles of repeat expansion and removal lead to large-scale genomic changes and propel organisms forward in evolution. However, in conifers, active repeat removal is thought to be limited, leading to expansions of their genomes, mostly exceeding 10 giga base pairs. As a result, conifer genomes are largely littered with fragmented and decayed repeats. Here, we aim to investigate how the repeat landscapes of two related conifers have diverged, given the conifers’ accumulative genome evolution mode. For this, we applied low-coverage sequencing and read clustering to the genomes of European and Japanese larch, Larix decidua (Lamb.) Carrière and Larix kaempferi (Mill.), that arose from a common ancestor, but are now geographically isolated. We found that both Larix species harbored largely similar repeat landscapes, especially regarding the transposable element content. To pin down possible genomic changes, we focused on the repeat class with the fastest sequence turnover: satellite DNAs (satDNAs). Using comparative bioinformatics, Southern, and fluorescent in situ hybridization, we reveal the satDNAs’ organizational patterns, their abundances, and chromosomal locations. Four out of the five identified satDNAs are widespread in the Larix genus, with two even present in the more distantly related Pseudotsuga and Abies genera. Unexpectedly, the EulaSat3 family was restricted to L. decidua and absent from L. kaempferi, indicating its evolutionarily young age. Taken together, our results exemplify how the accumulative genome evolution of conifers may limit the overall divergence of repeats after speciation, producing only few repeat-induced genomic novelties.
Camk2a-Cre and Tshz3 Expression in Mouse Striatal Cholinergic Interneurons: Implications for Autism Spectrum Disorder
Authors: Caubit Xavier , Arbeille Elise , Chabbert Dorian , Desprez Florence , Messak Imane , Fatmi Ahmed , Habermann Bianca , Gubellini Paolo , Fasano Laurent
Published: July 2021

Camk2a-Cre mice have been widely used to study the postnatal function of several genes in forebrain projection neurons, including cortical projection neurons (CPNs) and striatal medium-sized spiny neurons (MSNs). We linked heterozygous deletion of TSHZ3/Tshz3 gene to autism spectrum disorder (ASD) and used Camk2a-Cre mice to investigate the postnatal function of Tshz3, which is expressed by CPNs but not MSNs. Recently, single-cell transcriptomics of the adult mouse striatum revealed the expression of Camk2a in interneurons and showed Tshz3 expression in striatal cholinergic interneurons (SCINs), which are attracting increasing interest in the field of ASD. These data and the phenotypic similarity between the mice with Tshz3 haploinsufficiency and Camk2a-Cre-dependent conditional deletion of Tshz3 (Camk2a-cKO) prompted us to better characterize the expression of Tshz3 and the activity of Camk2a-Cre transgene in the striatum. Here, we show that the great majority of Tshz3-expressing cells are SCINs and that all SCINs express Tshz3. Using lineage tracing, we demonstrate that the Camk2a-Cre transgene is expressed in the SCIN lineage where it can efficiently elicit the deletion of the Tshz3-floxed allele. Moreover, transcriptomic and bioinformatic analysis in Camk2a-cKO mice showed dysregulated striatal expression of a number of genes, including genes whose human orthologues are associated with ASD and synaptic signaling. These findings identifying the expression of the Camk2a-Cre transgene in SCINs lineage lead to a reappraisal of the interpretation of experiments using Camk2a-Cre-dependent gene manipulations. They are also useful to decipher the cellular and molecular substrates of the ASD-related behavioral abnormalities observed in Tshz3 mouse models.
A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages
Authors: Zhang Jiawen , Jiang Peiyu , Sheng Lei , Liu Yunyi , Liu Yixuan , Li Min , Tao Meng , Hu Liang , Wang Xiaoyan , Yang Yanjing , Xu Yang , Liu Wentao
Published: July 2021

Background

Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration.

Objective

To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.

Methods

Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1β) evaluation. An in vivo murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase chain reaction and western blotting. Clinical facial images of patients were obtained using the VISIA skin analysis system before, 4, and 6 months following oral carvedilol administration.

Results

Rosacea skin lesions exhibited more pronounced inflammatory cell infiltration than peripheral areas, with profound macrophage infiltration and inflammatory cytokines (TLR2, kallikrein 5, cathelicidin, TNF-α, and IL-1β). In vivo, carvedilol alleviated inflammation in LL-37 mice, down-regulating TLR2, KLK5, and cathelicidin expression. In vitro, carvedilol decreased TLR2 expression in RAW 264.7 cells, further reducing KLK5 secretion and LL-37 expression and ultimately inhibiting rosacea-like inflammatory reactions. Clinical manifestations and facial redness obviously improved during 6-month follow-up with systemic carvedilol administration.

Conclusion

Carvedilol is effective against rosacea, with inhibition of macrophage TLR2 expression as a novel anti-inflammatory mechanism.
Case Report: Successful Management of a Refractory Plasmablastic Lymphoma Patient With Tislelizumab and Lenalidomide
Authors: Cheng Lili , Song Qi , Liu Mengke , Wang Yan , Yi Hongmei , Qian Ying , Xu Pengpeng , Cheng Shu , Wang Chaofu , Wang Li , Zhao Weili
Published: July 2021

Plasmablastic lymphoma (PBL) is a rare and aggressive hematological malignancy. PBL commonly occurs in immune incompetent patients, such as those with human immunodeficiency virus (HIV), post-transplant status, or immunosenescence. Given its rarity, there is no specific standard treatment for PBL. However, small case series have shown that intensive chemotherapies combined with anti-myeloma agents such as bortezomib and lenalidomide were effective in treating PBL. Unfortunately, some fragile patients could not tolerate intensive chemotherapeutic regimens, especially the elderly patients. Here we presented a 76-year-old female PBL patient refractory to miniCHOP regimen combined with bortezomib but achieved complete remission when treated with tislelizumab combined with lenalidomide, indicating that immune therapy may be a potential treatment for PBL. To our knowledge, this is the first chemoresistant PBL patient that has been successfully treated with checkpoint inhibitor plus lenalidomide, thus providing new insight towards PBL management.
Exploring the Nexus and Utilities Between Regional and Global Ocean Governance Architecture
Authors: Adewumi Ibukun Jacob
Published: July 2021

Regional and global ocean governance share complex, co-evolutionary histories in which both regimes – among others – interacted with and used the ocean and resources therein to consolidate, expand, and express power. Simultaneously, regional and global ocean governance relations have changed continuously, particularly when we are trying to understand their differences within the logic of regionalisation, regionalism, and globalisation. The paper is generally based on deductive reasoning and reflects scholarship in security studies, political science, international law, international relation, development studies, and African studies. It delves into the critical aspect of understanding the nexus/relationship between regional and global ocean governance in critical traditional and contemporary ocean policy domains, specifically from an African regional ocean governance standpoint. Ocean governance processes that are historically confronted by globalisation, multilateralism, and post-colonisation are confronted by the rise of regionalism, especially the need for nation-states and regions to respond to and manage traditional and emerging ocean challenges. Responses to these challenges by various actors, including states, economic blocks, private sector, financial institutions, and non-governmental organisations, development partners, etc., result in different forms of relationships that refocus regions’ activities toward globally defined ocean agendas. A review of different policy domains (including maritime security, environmental, economic, and socio-political governance) critical for regional ocean governance sets a robust background for understanding the contextual factors and concerns inherent in the regional-global ocean governance nexus. These outcomes, therefore, help us to arrive at a five-fold taxonomy of different types/degrees of linkages developed around the regional-global ocean governance relationship spectrum described as (1) discrete, (2) conflictual, (3) cooperative, (4) symmetric, and (5) ambiguous. Comparatively, experience and perspective from Africa are utilised to support raised arguments about these linkages. Furthermore, this spectrum allows for the diagnosis of the utilities and most prevalent arguments that regional governance’s effectiveness is directly related to the nature of the interaction between regional governance schemes and global governance; and vice-versa. This paper’s outcomes reveal how government, institutions, actors, and researchers address the relationship between regional and global ocean governance and generate a valuable way to think about current and future global and regional ocean governance direction while outlining some logical possibilities for an effective form of ocean governance.
Mass Drug Administration With Artemisinin-Piperaquine for the Elimination of Residual Foci of Malaria in São Tomé Island
Authors: Li Mingqiang , Tuo Fei , Tan Ruixiang , Zhang Hongying , Zheng Shaoqin , Wang Qi , Xu Qin , Yu Xinbing , Lu Fangli , Wu Zhibing , Huang Jun , Rampao Herodes Sacramento , D'almeida Carlos Alberto Bandeira , Yan Hong , Song Jianping , Guo Wenfeng , Deng Changsheng
Published: July 2021

Background: Mass drug administration with artemisinin-piperaquine (AP-MDA) is being considered for elimination of residual foci of malaria in Democratic Republic of São Tomé and Principe.

Methods: Three monthly rounds of AP-MDA were implemented from July to October 2019. Four zones were selected. A and B were selected as a study site and a control site, respectively. C and D were located within 1.5 and 1.5 km away from the study site, respectively. Parasite prevalence, malaria incidence, and the proportion of the Plasmodium falciparum malaria cases were evaluated.

Results: After 3 monthly rounds of AP-MDA, the parasite prevalence and the gametocyte carriage rate of P. falciparum in zone A decreased from 28.29(‰) to 0 and 4.99(‰) to 0, respectively. Compared to zone B, the relative risk for the population with Plasmodium falciparum malaria in zone A was lower (RR = 0.458, 95% CI: 0.146–1.437). Malaria incidence fell from 290.49(‰) (the same period of the previous year) to 15.27(‰) (from the 29th week in 2019 to the 14th week in 2020), a decrease of 94.74% in zone A, and from 31.74 to 5.46(‰), a decline of 82.80% in zone B. Compared to the data of the same period the previous year, the cumulative number of P. falciparum malaria cases were lower, decreasing from 165 to 10 in zone A and from 17 to 4 in zone B. The proportion of the P. falciparum malaria cases on the total malaria cases of the country decreased of 90.16% in zone A and 71.34% in zone C.

Conclusion: AP-MDA greatly curbed malaria transmission by reducing malaria incidence in the study site and simultaneously creating a knock-on effect of malaria control within 1.5 km of the study site and within the limited time interval of 38 weeks.
Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Disseminated Tuberculosis of an Immunocompetent Patient
Authors: Ye Yuanting , Yang Naibin , Zhou Jingying , Qian Guoqing , Chu Jinguo
Published: July 2021

Disseminated tuberculosis (TB) is a rare disease and mainly occurs in immunodeficient patients. It is marked by hematogenous or lymphatic dissemination of Mycobacterium tuberculosis, causing tuberculous infection involving any organ system. Here, we report a case of disseminated TB involving lung, liver, spine, mediastinum, and prostate in an immunocompetent man. The present patient found a hepatic mass without any symptom during health examination. In the next 2 years, further examinations revealed multiple lesions in the lung, mediastinum, spine, and prostate. Imaging examinations, such as contrast-enhanced abdominal CT, F-18 FDG-PET/CT, and radionuclide bone scan, suggested the diagnosis of malignancy or metastatic tumor. Furthermore, histopathological results of the biopsies of the hepatic mass, mediastinal mass, and prostatic mass demonstrated granulomatous inflammation. Therefore, metagenomic next-generation sequencing (mNGS) was utilized to confirm the diagnosis. Mycobacterium tuberculosis complex was simultaneously detected in the spinal surgical resection specimens and bronchoalveolar lavage fluid (BALF), indicating the diagnosis of disseminated TB. mNGS is an emerging molecular diagnostic technology, and its application in disseminated TB has been rarely reported. We highlight that disseminated TB should be considered even in an immunocompetent patient, and mNGS can be performed when the diagnosis is difficult.
The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality
Authors: Lahav Itay , Steinmetz Tali , Molcho Maya , Lev Neta , Agur Timna , Nesher Eviatar , Rozen-Zvi Benaya , Rahamimov Ruth
Published: July 2021

Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality.

Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model.

Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18–3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17–3.86, p = 0.013) in multivariate analysis.

Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.
Case Report: Indwelling Pleural Catheter Based Management of Refractory Hepatic Hydrothorax as a Bridge to Liver Transplantation
Authors: Selvan Mayurun , Collins Hannah , Griffiths William , Gelson William , Herre Jurgen
Published: July 2021

Introduction: Liver transplantation is the treatment of choice for decompensated liver disease, and by extension for hepatic hydrothorax. Persistent pleural effusions make it challenging for patients to maintain physiological fitness for transplantation. Indwelling pleural catheters (IPCs) provide controlled pleural fluid removal, including peri-operatively. The immune dysfunction of cirrhosis heightens susceptibility to bacterial infection and concerns exist regarding the sepsis potential from a tunnelled drain.

Method: Six patients were identified who underwent IPC insertion for hepatic hydrothorax before successful liver transplantation, between November 2016 and November 2017.

Results: All patients had recurrent transudative right sided pleural effusions. Mean age was 49 years (range 24–64) and mean United Kingdom Model for End-Stage Liver Disease score was 58. Four patients required correction of coagulopathy before insertion. There were no complications secondary to bleeding. Three patients were taught self-drainage at home of up to 1 litre (L) daily. A protocol was developed to ensure weekly review, pleural fluid culture and drainage of larger volumes in hospital. For every 2–3 L of pleural fluid drained, 100 mls of 20% Human Albumin Solution (HAS) was administered. On average an IPC was in situ for 58 days before surgery and drained 19 L of fluid in hospital. There was a small increase in average BMI (0.2) and serum albumin (2.1 g/L) at transplantation. There was one episode of stage one acute kidney injury secondary to high volume drainage. No further ascitic or pleural procedures were needed while an IPC was in situ. One thoracentesis was required after IPC removal. On average IPCs remained in situ for 7 days post transplantation and drained a further 2 L of fluid. Pleural fluid sampling was acquired on 92% of drainages in hospital. Of 44 fluid cultures, 2 cultured bacteria. Two patients had their IPCs and all other lines removed post transplantation due to suspected infection.

Conclusion: Our case series describes a novel protocol and successful use of IPCs in the management of refractory hepatic hydrothorax as a bridge to liver transplantation. The protocol includes albumin replacement during pleural drainage, regular clinical review and culture of pleural fluid, with the option of self-drainage at home.
Temporal and Spatial Changes in Phyllosphere Microbiome of Acacia Trees Growing in Arid Environments
Authors: Al Ashhab Ashraf , Meshner Shiri , Alexander-Shani Rivka , Dimerets Hana , Brandwein Michael , Bar-Lavan Yael , Winters Gidon
Published: July 2021

Background: The evolutionary relationships between plants and their microbiomes are of high importance to the survival of plants in general and even more in extreme conditions. Changes in the plant's microbiome can affect plant development, growth, fitness, and health. Along the arid Arava, southern Israel, acacia trees (Acacia raddiana and Acacia tortilis) are considered keystone species. In this study, we investigated the ecological effects of plant species, microclimate, phenology, and seasonality on the epiphytic and endophytic microbiome of acacia trees. One hundred thirty-nine leaf samples were collected throughout the sampling year and were assessed using 16S rDNA gene amplified with five different primers (targeting different gene regions) and sequenced (150 bp paired-end) on an Illumina MiSeq sequencing platform.

Results: Epiphytic bacterial diversity indices (Shannon–Wiener, Chao1, Simpson, and observed number of operational taxonomic units) were found to be nearly double compared to endophyte counterparts. Epiphyte and endophyte communities were significantly different from each other in terms of the composition of the microbial associations. Interestingly, the epiphytic bacterial diversity was similar in the two acacia species, but the canopy sides and sample months exhibited different diversity, whereas the endophytic bacterial communities were different in the two acacia species but similar throughout the year. Abiotic factors, such as air temperature and precipitation, were shown to significantly affect both epiphyte and endophytes communities. Bacterial community compositions showed that Firmicutes dominate A. raddiana, and Proteobacteria dominate A. tortilis; these bacterial communities consisted of only a small number of bacterial families, mainly Bacillaceae and Comamonadaceae in the endophyte for A. raddiana and A. tortilis, respectively, and Geodematophilaceae and Micrococcaceae for epiphyte bacterial communities, respectively. Interestingly, ~60% of the obtained bacterial classifications were unclassified below family level (i.e., “new”).

Conclusions: These results shed light on the unique desert phyllosphere microbiome highlighting the importance of multiple genotypic and abiotic factors in shaping the epiphytic and endophytic microbial communities. This study also shows that only a few bacterial families dominate both epiphyte and endophyte communities, highlighting the importance of climate change (precipitation, air temperature, and humidity) in affecting arid land ecosystems where acacia trees are considered keystone species.
Species-Specific Interferon-Gamma Release Assay for the Diagnosis of Mycobacterium abscessus Complex Infection
Authors: Steindor Mathis , Stehling Florian , Olivier Margarete , Kehrmann Jan , Diricks Margo , Maurer Florian P. , Horn Peter A. , Straßburg Svenja , Welsner Matthias , Sutharsan Sivagurunathan , Lindemann Monika
Published: July 2021

Mycobacterium abscessus complex (MABC) infection has a devastating impact on the course of cystic fibrosis (CF) and non-CF lung disease. Diagnosis of MABC pulmonary disease is challenging, and current diagnostic approaches lack accuracy, especially in CF. In this study, we aimed to establish an MABC-specific interferon-γ release assay to detect host immune responses to MABC and improve diagnostics of MABC infection by the detection of antigen-specific T cells. Four species-specific proteins of MABC were overexpressed in an Escherichia coli expression system. Purified proteins were used to stimulate peripheral blood mononuclear cells of study subjects in an ELISpot assay. Interferon-γ response of 12 subjects with established diagnosis of MABC infection (10 CF and two non-CF) was compared with 35 controls (22 CF and 13 non-CF) distributed to three control groups, 17 CF subjects without NTM infection, nine subjects with NTM infection other than MABC, and nine subjects with tuberculosis. Cellular in vitro responses in the MABC group were stronger than in the control groups, especially toward the protein MAB_0405c (39 vs. 4 spots per 300,000 PBMC, p = 0.004; data represent mean values) in all patients and also in the subgroup of CF subjects (39 spots vs. 1 spot, p = 0.003). Receiver operating characteristic curve analysis indicated that spot numbers of at least 20 were highly predictive of MABC infection (all patients: area under curve 0.773, sensitivity 58%, and specificity 94%; CF patients: area under curve 0.818, sensitivity 60%, and specificity 100%). In conclusion, we identified MAB_0405c as a protein that may stimulate MABC-specific interferon-γ secretion and may add to the diagnosis of MABC infection in affected patients.
A Graph Theory Approach to Clarifying Aging and Disease Related Changes in Cognitive Networks
Authors: Wright Laura M. , De Marco Matteo , Venneri Annalena
Published: July 2021

In accordance with the physiological networks that underlie it, human cognition is characterized by both the segregation and interdependence of a number of cognitive domains. Cognition itself, therefore, can be conceptualized as a network of functions. A network approach to cognition has previously revealed topological differences in cognitive profiles between healthy and disease populations. The present study, therefore, used graph theory to determine variation in cognitive profiles across healthy aging and cognitive impairment. A comprehensive neuropsychological test battery was administered to 415 participants. This included three groups of healthy adults aged 18–39 (n= 75), 40–64 (n= 75), and 65 and over (n= 70) and three patient groups with either amnestic (n= 75) or non-amnestic (n= 60) mild cognitive impairment or Alzheimer’s type dementia (n= 60). For each group, cognitive networks were created reflective of test-to-test covariance, in which nodes represented cognitive tests and edges reflected statistical inter-nodal significance (p< 0.05). Network metrics were derived using the Brain Connectivity Toolbox. Network-wide clustering, local efficiency and global efficiency of nodes showed linear differences across the stages of aging, being significantly higher among older adults when compared with younger groups. Among patients, these metrics were significantly higher again when compared with healthy older controls. Conversely, average betweenness centralities were highest in middle-aged participants and lower among older adults and patients. In particular, compared with controls, patients demonstrated a distinct lack of centrality in the domains of semantic processing and abstract reasoning. Network composition in the amnestic mild cognitive impairment group was similar to the network of Alzheimer’s dementia patients. Using graph theoretical methods, this study demonstrates that the composition of cognitive networks may be measurably altered by the aging process and differentially impacted by pathological cognitive impairment. Network alterations characteristic of Alzheimer’s disease in particular may occur early and be distinct from alterations associated with differing types of cognitive impairment. A shift in centrality between domains may be particularly relevant in identifying cognitive profiles indicative of underlying disease. Such techniques may contribute to the future development of more sophisticated diagnostic tools for neurodegenerative disease.
Progressive Brain Degeneration From Subjective Cognitive Decline to Amnestic Mild Cognitive Impairment: Evidence From Large-Scale Anatomical Connection Classification Analysis
Authors: Tao Wuhai , Li Hehui , Li Xin , Huang Rong , Shao Wen , Guan Qing , Zhang Zhanjun
Published: July 2021

People with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are both at high risk for Alzheimer’s disease (AD). Behaviorally, both SCD and aMCI have subjective reports of cognitive decline, but the latter suffers a more severe objective cognitive impairment than the former. However, it remains unclear how the brain develops from SCD to aMCI. In the current study, we aimed to investigate the topological characteristics of the white matter (WM) network that can successfully identify individuals with SCD or aMCI from healthy control (HC) and to describe the relationship of pathological changes between these two stages. To this end, three groups were recruited, including 22 SCD, 22 aMCI, and 22 healthy control (HC) subjects. We constructed WM network for each subject and compared large-scale topological organization between groups at both network and nodal levels. At the network level, the combined network indexes had the best performance in discriminating aMCI from HC. However, no indexes at the network level can significantly identify SCD from HC. These results suggested that aMCI but not SCD was associated with anatomical impairments at the network level. At the nodal level, we found that the short-path length can best differentiate between aMCI and HC subjects, whereas the global efficiency has the best performance in differentiating between SCD and HC subjects, suggesting that both SCD and aMCI had significant functional integration alteration compared to HC subjects. These results converged on the idea that the neural degeneration from SCD to aMCI follows a gradual process, from abnormalities at the nodal level to those at both nodal and network levels.