bluuebunny/crossref_metadata_2025 huggingface dataset:
Development, Validation, and Application of a Novel Method for the Analysis of Vitamin E Acetate and Other Tocopherols in Aerosol Emissions of E-Cigarettes, or Vaping Products Associated With Lung Injury
Authors: Puetz Andrew , Morel Espinosa Maria , Watson Clifford , Blount Benjamin C. , Valentín-Blasini Liza
Published: August 2021

E-cigarette, or vaping, product (EVP) use has increased dramatically in the United States over the last 4 years, particularly in youth and young adults. Little information is available on the chemical contents of these products. Typically, EVPs contain an active ingredient such as nicotine, CBD, or THC dissolved in a suitable solvent that facilitates aerosol generation. One EVP solvent, vitamin E acetate (VEA), has been measured in EVP liquids associated with lung injury. However, no validated analytical methods for measuring VEA in the aerosol from these devices was previously available. Therefore, we developed a high throughput isotope dilution LC-MS/MS method to simultaneously measure VEA and three other related tocopherols in aerosolized EVP samples. The assay was precise, with VEA repeatability ranging from 4.0 to 8.3% and intermediate precision ranging from 2.5 to 6.7%. Similar precision was obtained for the three other tocopherols measured. The LODs for the four analytes ranged from 8.85 × 10−6 to 2.28 × 10−5 μg analyte per mL of aerosol puff volume, and calibration curves were linear (R2 > 0.99). This method was used to analyze aerosol emissions of 147 EVPs associated with EVALI case patients. We detected VEA in 46% of the case-associated EVPs with a range of 1.87 × 10−4–74.1 µg per mL of aerosol puff volume and mean of 25.1 µg per mL of aerosol puff volume. Macro-levels of VEA (>0.1% w/w total aerosol particulate matter) were not detected in nicotine or cannabidiol (CBD) products; conversely 71% of the EVALI associated tetrahydrocannabinol (THC) products contained macro-levels of VEA. Trace levels of other tocopherol isoforms were detected at lower rates and concentrations (α-tocopherol: 41% detected, mean 0.095 µg analyte per mL of aerosol puff volume; γ-tocopherol: 5% detected, mean 0.0193 µg analyte per mL of aerosol puff volume; δ-tocopherol: not detected). Our results indicate that VEA can be efficiently transferred to aerosol by EVALI-associated EVPs vaped using a standardized protocol.
S-Propargyl-Cysteine Remodels the Gut Microbiota to Alleviate Rheumatoid Arthritis by Regulating Bile Acid Metabolism
Authors: Wang Zhou , Yu Yue , Liao Junyi , Hu Wei , Bian Xiqing , Wu Jianlin , Zhu Yi Zhun
Published: August 2021

Background

Rheumatoid arthritis (RA) is a long-term autoimmune disorder characterized by chronic inflammation that results in swollen and painful joints and even cartilage and bone damage. The gut microbiota, a novel anti-inflammatory target, is considered an important environmental factor in the development of RA. S-propargyl-cysteine (SPRC), an amino acid analogue, exerts anti-inflammatory, cardioprotective effects, and neuroprotective effects on various diseases. In recent studies, an SPRC treatment exerted anti-inflammatory effects on RA. Meanwhile, gut microbiome dysbiosis in individuals with RA has also been reported by many researchers. However, the relationship between SPRC and gut microbiota in individuals with RA remains unclear.

Methods

Thirty male Sprague-Dawley (SD) rats were randomly divided into three groups of 10 each, including the Control, Model, and SPRC groups. Adjuvant-induced arthritis (AIA) rats in SPRC group were treated with SPRC. Measurement of paw volume and serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were applied to evaluate the inflammatory status. Fecal samples were collected on the 14th day and 28th day. Gut microbiota were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Untargeted metabolomics on plasma samples was applied to investigate the metabolic changes induced by the altered gut microbiota by using derivatization-UHPLC-Q-TOF/MS.

Findings

Using 16S rRNA amplicon sequencing, we found that SPRC significantly altered the gut microbiota structure in AIA rats. In particular, Bifidobacterium, a genus of BSH (Bile Salt Hydrolase)-producing microbes, was overrepresented in SPRC-treated AIA rats. Additionally, a subsequent metabolomics analysis indicated that bile acid metabolism was also altered by SPRC treatment. Interestingly, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), which are formed with the participation of BSH-producing microbes in the intestine, were identified as crucial biomarkers responding to SPRC treatment with significantly lowered levels.

Interpretation

A mechanistic link between the gut microbiota and plasma metabolites was revealed in this study, which provides insights into the mechanism of SPRC treatment for RA from the perspective of the gut microbiota.
Readability Enhancement for PDF Documents
Authors: Yu Chen-Hsiang , Shelton Zachary , Abou Nassif Mourad Omar , Oulal Mohamed A.
Published: August 2021

Readability has been studied for decades, ranging from traditional paper reading to digital document reading, Web page reading, etc. Different audiences have different needs and the needs trigger the researchers to investigate innovative solutions. For example, in recent years, researchers have studied readability enhancement of English articles for non-native English readers, either on paper reading or hypertext document reading. Using a variety of methods, researchers were able to enhance the reading comprehension and the users’ satisfaction on hypertext document reading, such as changing content presentation with visual-syntactic text formatting (VSTF) format or Jenga format. In terms of dynamically changing content presentation for reading, one less explored format is Portable Document Format (PDF), which was traditionally viewed within a modern Web browser or Adobe Acrobat reader on the desktop. PDF format was standardized as an open format in 2008 and has been widely used to keep a fixed-layout content. However, a fixed layout document presents a challenge to apply existing transformation methods, not mention on mobile devices. In this paper, we not only present a system that uses a novel algorithm to decode PDF documents and apply content transformation to enhance its readability, but we also generalize it to a framework that allows the users to apply customizations and the developers to customize their needs. Although we used Jenga format as an example to enhance the readability of PDF documents, we envision the proposed framework can be used to adopt different customizations and transformation methods. The current result is promising, and we believe it is worth further investigation to make PDF documents readable and accessible for different populations, such as non-native English readers, people with dyslexia or special needs, etc.
Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment
Authors: Huang Chieh-Liang , Chiang Yao-Chang , Chang Wei-Chun , Su Yu-Ting , Yang Juan-Cheng , Cheng Wei-Chung , Lane Hsien-Yuan , Ho Ing-Kang , Ma Wen-Lung
Published: August 2021

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.
Accumulator, Transporter, Substrate, and Reactor: Multidimensional Perspectives and Approaches to the Study of Bark
Authors: Ponette-González Alexandra G.
Published: August 2021

Woody ecosystems have a relatively thin but aerially extensive and dynamic layer of bark that, like leaves, regulates material exchange at the interface of air, water, and biota. Through interception, retention, and leaching of materials and interactions with epiphytic communities, bark alters the chemistry and composition of water draining over its surface during precipitation. This mini-review explores different perspectives and approaches to the study of bark and what they reveal about the myriad ways bark surfaces influence the quality of sub-canopy precipitation. Observational studies conducted over the past five decades in the fields of environmental science, ecohydrology, epiphyte ecology, and microbiology demonstrate that bark is an accumulator, transporter, substrate, and reactor. Bark passively accumulates materials from the atmosphere, water, and canopies, and also serves as an active transport surface, exchanging materials laterally and longitudinally. In addition, bark substrates influence epiphyte diversity, composition, and distribution, which, in turn, affect material cycling. Bark surfaces are dynamic over time, changing in response to disturbances (e.g., insect outbreaks, aging, and tree death)—how such changes influence the chemical and elemental composition of throughfall and stemflow merits further study. Moving forward, integration of diverse perspectives and approaches is needed to elucidate the influence of bark surfaces on solute and particulate transport and cycling within woody ecosystems.
Identification of Root Rot Resistance QTLs in Pea Using Fusarium solani f. sp. pisi-Responsive Differentially Expressed Genes
Authors: Williamson-Benavides Bruce A. , Sharpe Richard M. , Nelson Grant , Bodah Eliane T. , Porter Lyndon D. , Dhingra Amit
Published: August 2021

Pisum sativum (pea) yields in the United States have declined significantly over the last decades, predominantly due to susceptibility to root rot diseases. One of the main causal agents of root rot is the fungus Fusarium solani f. sp. pisi (Fsp), leading to yield losses ranging from 15 to 60%. Determining and subsequently incorporating the genetic basis for resistance in new cultivars offers one of the best solutions to control this pathogen; however, no green-seeded pea cultivars with complete resistance to Fsp have been identified. To date, only partial levels of resistance to Fsp has been identified among pea genotypes. SNPs mined from Fsp-responsive differentially expressed genes (DEGs) identified in a preceding study were utilized to identify QTLs associated with Fsp resistance using composite interval mapping in two recombinant inbred line (RIL) populations segregating for partial root rot resistance. A total of 769 DEGs with single nucleotide polymorphisms (SNPs) were identified, and the putative SNPs were evaluated for being polymorphic across four partially resistant and four susceptible P. sativum genotypes. The SNPs with validated polymorphisms were used to screen two RIL populations using two phenotypic criteria: root disease severity and plant height. One QTL, WB.Fsp-Ps 5.1 that mapped to chromosome 5 explained 14.8% of the variance with a confidence interval of 10.4 cM. The other four QTLs located on chromosomes 2, 3, and 5, explained 5.3–8.1% of the variance. The use of SNPs derived from Fsp-responsive DEGs for QTL mapping proved to be an efficient way to identify molecular markers associated with Fsp resistance in pea. These QTLs are potential candidates for marker-assisted selection and gene pyramiding to obtain high levels of partial resistance in pea cultivars to combat root rot caused by Fsp.
Loop Interrupted: Dysfunctional Chromatin Relations in Neurological Diseases
Authors: Behrends Marthe , Engmann Olivia
Published: August 2021

The majority of genetic variants for psychiatric disorders have been found within non-coding genomic regions. Physical interactions of gene promoters with distant regulatory elements carrying risk alleles may explain how the latter affect gene expression. Recently, whole genome maps of long-range chromosomal contacts from human postmortem brains have been integrated with gene sequence and chromatin accessibility data to decipher disease-specific alterations in chromatin architecture. Cell culture and rodent models provide a causal link between chromatin conformation, long-range chromosomal contacts, gene expression, and disease phenotype. Here, we give an overview of the techniques used to study chromatin contacts and their limitations in brain research. We present evidence for three-dimensional genome changes in physiological brain function and assess how its disturbance contributes to psychiatric disorders. Lastly, we discuss remaining questions and future research directions with a focus on clinical applications.
Experiences, Preferences, and Needs of Adolescents and Urban Youth in Contraceptive Use in Conakry, 2019, Guinea
Authors: Bangoura Charlotte , Dioubaté Nafissatou , Manet Hawa , Camara Bienvenu Salim , Kouyaté Mariama , Douno Moussa , Tetui Moses , El Ayadi Alison M. , Delamou Alexandre
Published: August 2021

Introduction: The use of contraceptive methods is very low in Guinea, particularly among adolescents and young people. The purpose of this study is to analyze the experiences and expectations of adolescents and young people regarding the use of contraceptive methods in 2019 in Conakry, Guinea.

Methods: We conducted a 6-month qualitative and descriptive study. Data were collected through individual in-depth interviews and focus group discussions with adolescents and young people, health providers and health policy makers. Two approaches of deductive and inductive analysis were used to synthesize the main insights from the data.

Findings: Twenty-six participants were included in this study. Adolescents and young people have personal, family and community experiences that positively or negatively influence their contraceptive needs and preferences. Positive experiences include the relative cost of injectable forms, perceived absence of side effects of implants, proven efficacy and duration of action of the modern method used (implants and injectable form). Negative experiences included cost of implants remain high (15 Euros), perceived side effects including weight gain, pill compliance, method indiscretion, and low sensation of sexual pleasure for the condom. The preferences of the young participants were dominated by Implants and injectable forms that better meet their contraceptive needs. In terms of needs, the expectations expressed revolved around needs related to the health system, including sex education, reduction in the cost of some contraceptives (implants), availability of contraceptive methods, and equity in the provision of family planning services to adolescents and young people.

Conclusion: Exploring the contraceptive experiences, needs and preferences of adolescents and young people reveals decision-making dilemmas. Adolescents and young people expressed their experiences in terms of the cost of preferred contraceptives (implants), side effects, proven efficacy, and duration of action. However, their decisions are still influenced by availability, equity in service delivery, and the involvement of parents and religious leaders in sex education. Decision-makers should then place particular emphasis on improving health service delivery, adolescent sexual and reproductive health, availability of preferred contraceptive methods at affordable cost, and a program on sexuality education with the involvement of parents and religious leaders and the promotion of condom use.
Immunotherapy for Dogs: Still Running Behind Humans
Authors: Klingemann Hans
Published: August 2021

Despite all good intentions, dogs are still running behind humans in effective cancer immunotherapies. The more effective treatments in humans, like infusions of CAR-T and NK-cells are not broadly pursued for canines due to significant costs, the rather complicated logistics and the lack of targetable surface antigens. Monoclonal antibodies are challenging to develop considering the limited knowledge about canine target antigens and about their mode of action. Although immunogenic vaccines could be less costly, this approach is hampered by the fact that cancer by itself is immuno-suppressive and any preceding chemotherapy may suppress any clinically meaningful immune response. This review – rather than providing a comprehensive listing of all available immunotherapies for dogs, aims at pointing out the issues that are holding back this field but which hopefully can be addressed so that dogs can “catch up” with what is available to humans.
One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency
Authors: Körholz Julia , Gabrielyan Anastasia , Sowerby John M. , Boschann Felix , Chen Lan-Sun , Paul Diana , Brandt David , Kleymann Janina , Kolditz Martin , Toepfner Nicole , Knöfler Ralf , Jacobsen Eva-Maria , Wolf Christine , Conrad Karsten , Röber Nadja , Lee-Kirsch Min Ae , Smith Kenneth G. C. , Mundlos Stefan , Berner Reinhard , Dalpke Alexander H. , Schuetz Catharina , Rae William
Published: August 2021

Background

Inborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans.

Objective

We sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency.

Methods

We assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells.

Results

SOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients.

Conclusions

SOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.
Early Endothelial Activation in a Mouse Model of Graft vs Host Disease Following Chemotherapy
Authors: Pereira Melrine , Lee Natasha Ting , Noonan Jonathan , Willcox Abbey E. H. , Calvello Ilaria , Georgy Smitha Rose , Selan Carly , Chia Joanne S. , Hauw Wayne , Wang Xiaowei , Peter Karlheinz , Robson Simon C. , Nandurkar Harshal H. , Sashindranath Maithili
Published: August 2021

Allogenic hematopoietic stem cell transplant (allo-HSCT) can lead to sinusoidal obstruction syndrome (SOS) and graft-versus-host disease (GvHD) in some individuals. GvHD is characterised by an immune triggered response that arises due to donor T cells recognizing the recipient tissue as “foreign”. SOS results in impaired liver function due to microvascular thrombosis and consequent obstruction of liver sinusoids. Endothelial damage occurs following chemotherapy and allo-HSCT and is strongly associated with GvHD onset as well as hepatic SOS. Animal models of GvHD are rarely clinically relevant, and endothelial dysfunction remains uncharacterised. Here we established and characterised a clinically relevant model of GvHD wherein Balb/C mice were subjected to myeloablative chemotherapy followed by transplantation of bone marrow (BM) cells± splenic T-cells from C57Bl6 mice, resulting in a mismatch of major histocompatibility complexes (MHC). Onset of disease indicated by weight loss and apoptosis in the liver and intestine was discovered at day 6 post-transplant in mice receiving BM+T-cells, with established GvHD detectable by histology of the liver within 3 weeks. Together with significant increases in pro-inflammatory cytokine gene expression in the liver and intestine, histopathological signs of GvHD and a significant increase in CD4+ and CD8+ effector and memory T-cells were seen. Endothelial activation including upregulation of vascular cell adhesion molecule (VCAM)- 1 and downregulation of endothelial nitric oxide synthase (eNOS) as well as thrombosis in the liver indicated concomitant hepatic SOS. Our findings confirm that endothelial activation is an early sign of acute GvHD and SOS in a clinically relevant mouse model of GvHD based on myeloablative chemotherapy. Preventing endothelial activation may be a viable therapeutic strategy to prevent GvHD.
Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease
Authors: Deng Haobin , Liu Meijing , Yuan Ting , Zhang Huan , Cui Rui , Li Jingyi , Yuan Jijun , Wang Xiaofang , Wang Yafei , Deng Qi
Published: August 2021

In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies.

Clinical Trial Registration

http://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.
Multi-Parameter Quantitative Imaging of Tumor Microenvironments Reveals Perivascular Immune Niches Associated With Anti-Tumor Immunity
Authors: Stoltzfus Caleb R. , Sivakumar Ramya , Kunz Leo , Olin Pope Brandy E. , Menietti Elena , Speziale Dario , Adelfio Roberto , Bacac Marina , Colombetti Sara , Perro Mario , Gerner Michael Y.
Published: August 2021

Tumors are populated by a multitude of immune cell types with varied phenotypic and functional properties, which can either promote or inhibit anti-tumor responses. Appropriate localization and function of these cells within tumors is critical for protective immunity, with CD8 T cell infiltration being a biomarker of disease outcome and therapeutic efficacy. Recent multiplexed imaging approaches have revealed highly complex patterns of localization for these immune cell subsets and the generation of distinct tumor microenvironments (TMEs), which can vary among cancer types, individuals, and within individual tumors. While it is recognized that TMEs play a pivotal role in disease progression, a better understanding of their composition, organization, and heterogeneity, as well as how distinct TMEs are reshaped with immunotherapy, is necessary. Here, we performed spatial analysis using multi-parameter confocal imaging, histocytometry, and CytoMAP to study the microanatomical organization of immune cells in two widely used preclinical cancer models, the MC38 colorectal and KPC pancreatic murine tumors engineered to express human carcinoembryonic antigen (CEA). Immune responses were examined in either unperturbed tumors or after immunotherapy with a CEA T cell bispecific (CEA-TCB) surrogate antibody and anti-PD-L1 treatment. CEA-TCB mono and combination immunotherapy markedly enhanced intra-tumoral cellularity of CD8 T cells, dominantly driven by the expansion of TCF1-PD1+ effector T cells and with more minor increases in TCF1+PD1+ resource CD8 T cells. The majority of infiltrating T cells, particularly resource CD8 T cells, were colocalized with dendritic cells (DCs) or activated MHCII+ macrophages, but largely avoided the deeper tumor nest regions composed of cancer cells and non-activated macrophages. These myeloid cell – T cell aggregates were found in close proximity to tumor blood vessels, generating perivascular immune niches. This perivascular TME was present in untreated samples and markedly increased after CEA-TCB therapy, with its relative abundance positively associated with response to therapy. Together, these studies demonstrate the utility of advanced spatial analysis in cancer research by revealing that blood vessels are key organizational hubs of innate and adaptive immune cells within tumors, and suggesting the likely relevance of the perivascular immune TME in disease outcome.
Pooling of Samples for SARS-CoV-2 Detection Using a Rapid Antigen Test
Authors: Salcedo Nol , Harmon Alexander , Herrera Bobby Brooke
Published: August 2021

While molecular assays, such as reverse-transcription polymerase chain reaction (RT-PCR), have been widely used throughout the coronavirus disease 2019 (COVID-19) pandemic, the technique is costly and resource intensive. As a means to reduce costs and increase diagnostic efficiency, pooled testing using RT-PCR has been implemented. However, pooling samples for antigen testing has not been evaluated. Here, we propose a proof-of-concept pooling strategy for antigen testing that would significantly expand SARS-CoV-2 surveillance, especially for low-to-middle income countries, schools, and workplaces. Our laboratory-based testing demonstrates that combining of up to 20 nasal swab specimens per pool can expand surveillance with antigen tests, even if a pool contains only one positive sample.
The Institutional Dimension of Integration in Marine Spatial Planning: The Case of the Dutch North Sea Dialogues and Agreement
Authors: Spijkerboer Rozanne C.
Published: August 2021

Marine Spatial Planning (MSP) literature identifies various dimensions of integration to deal with fragmented, sectoral, and ad hoc approaches to managing various uses offshore. However, the spatial dimension of MSP has receded into the background, the dimensions of integration remain ill-defined, and there is a lack of appreciation for the institutional changes that these integration efforts induce and require. Moreover, in light of the urgency of energy transition, offshore wind farms (OWF) are often prioritized over other interests in MSP practice. This paper uses the case of the Dutch North Sea Dialogues (NSD) to explore to what extent actors during the NSD pursued formal and informal institutional change to progress the various dimensions of integration in line with the normative principles of MSP to improve spatial integration between OWF and other interests at sea. The NSD provided an, initially temporary, platform that proved key for stakeholders to pursue subsequent formal and informal institutional changes that progressed integration in MSP. While formal institutional changes were achieved during the NSD, informal institutional changes also proved fundamental in progressing various dimensions of integration. The NSD shows that incremental institutional change can be effective in progressing integration, but also shows the limits to this approach. The place-based and temporal dimensions of integration require additional attention because this is where stakeholders most notably rely on existing institutional frameworks and conflicts are most prominent.
Clinical Evaluation for Sublingual Immunotherapy With Dermatophagoides farinae in Polysensitized Allergic Asthma Patients
Authors: Zhang Ai-zhi , Liang Mei-e , Chen Xiao-xue , Wang Yan-fen , Ma Ke , Lin Zhi , Xue Kuan-kuan , Cao Li-ru , Yang Rong , Zhang Huan-ping
Published: August 2021

Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS).

Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT.

Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p < 0.05).

Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.
Case Report: Prolonged VV-ECMO (111 Days) Support in a Patient With Severe COVID-19
Authors: Xu Zhiheng , Xu Yonghao , Liu Dongdong , Liu Xuesong , Zhou Liang , Huang Yongbo , Li Yimin , Liu Xiaoqing
Published: August 2021

Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be a lifesaving rescue therapy for patients with severe coronavirus disease 2019 (COVID-19). However, little is known regarding the efficacy of prolonged ECMO (duration longer than 14 days) in patients with COVID-19. In this case report, we report the successful use of prolonged VV-ECMO (111 days) in a 61-year-old man with severe COVID-19. Given the high mortality rate of severe COVID-19, this case provided evidence for use of prolonged VV-ECMO as supportive care in patients with severe COVID-19.
Genomic Analysis of Antibiotic-Resistant Staphylococcus epidermidis Isolates From Clinical Sources in the Kwazulu-Natal Province, South Africa
Authors: Asante Jonathan , Hetsa Bakoena A. , Amoako Daniel G. , Abia Akebe L. K. , Bester Linda A. , Essack Sabiha Y.
Published: August 2021

Staphylococcus epidermidis has become an important nosocomial pathogen. Multidrug resistance makes S. epidermidis infections difficult to treat. The study aims to describe the genomic characteristics of methicillin-resistant S. epidermidis (MRSE) isolated from clinical sources, to comprehend the genetic basis of antibiotic resistance, virulence, and potential pathogenicity. Sixteen MRSE underwent whole-genome sequencing, and bioinformatics analyses were carried out to ascertain their resistome, virulome, mobilome, clonality, and phylogenomic relationships. In all, 75% of isolates displayed multidrug resistance and were associated with the carriage of multiple resistance genes including mecA, blaZ, tet(K), erm(A), erm(B), erm(C), dfrG, aac(6′)-aph(2′′), and cat(pC221) conferring resistance to β-lactams, tetracyclines, macrolide–lincosamide–streptogramin B, aminoglycosides, and phenicols, which were located on both plasmids and chromosomes. Their virulence profiles were evidenced by the presence of genes involved in adherence/biofilm formation (icaA, icaB, icaC, atl, ebh, and ebp), immune evasion (adsA, capC, and manA), and antiphagocytosis (rmlC, cdsA, and A). The community-acquired SCCmec type IV was the most common SCCmec type. The CoNS belonged to seven multilocus sequence types (MLSTs) and carried a diversity of mobile genetic elements such as phages, insertion sequences, and plasmids. The bacterial anti-phage defense systems clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) immunity phage system and restriction-modification system (R-M system) and the arginine catabolic mobile element (ACME) involved in immune evasion and transport of virulence genes were also found. The insertion sequence, IS256, linked with virulence, was found in 56.3% of isolates. Generally, the isolates clustered according to STs, with some similarity but also considerable variability within isolates. Whole-genome sequencing and bioinformatics analysis provide insights into the likely pathogenicity and antibiotic resistance of S. epidermidis, necessitating surveillance of this emerging pathogen.
Dual Transcriptomic Analyses Unveil Host–Pathogen Interactions Between Salmonella enterica Serovar Enteritidis and Laying Ducks (Anas platyrhynchos)
Authors: Zhang Yu , Song Lina , Hou Lie , Cao Zhengfeng , Vongsangnak Wanwipa , Zhu Guoqiang , Xu Qi , Chen Guohong
Published: August 2021

Salmonella enteritidis (SE) is a pathogen that can readily infect ovarian tissues and colonize the granulosa cell layer such that it can be transmitted via eggs from infected poultry to humans in whom it can cause food poisoning. Ducks are an important egg-laying species that are susceptible to SE infection, yet the host–pathogen interactions between SE and ducks have not been thoroughly studied to date. Herein, we performed dual RNA-sequencing analyses of these two organisms in a time-resolved infection model of duck granulosa cells (dGCs) by SE. In total, 10,510 genes were significantly differentially expressed in host dGCs, and 265 genes were differentially expressed in SE over the course of infection. These differentially expressed genes (DEGs) of dGCs were enriched in the cytokine–cytokine receptor interaction pathway via KEGG analyses, and the DEGs in SE were enriched in the two-component system, bacterial secretion system, and metabolism of pathogen factors pathways as determined. A subsequent weighted gene co-expression network analysis revealed that the cytokine–cytokine receptor interaction pathway is mostly enriched at 6 h post-infection (hpi). Moreover, a number of pathogenic factors identified in the pathogen–host interaction database (PHI-base) are upregulated in SE, including genes encoding the pathogenicity island/component, type III secretion, and regulators of systemic infection. Furthermore, an intracellular network associated with the regulation of SE infection in ducks was constructed, and 16 cytokine response-related dGCs DEGs (including IL15, CD40, and CCR7) and 17 pathogenesis-related factors (including sseL, ompR, and fliC) were identified, respectively. Overall, these results not only offer new insights into the mechanisms underlying host–pathogen interactions between SE and ducks, but they may also aid in the selection of potential targets for antimicrobial drug development.
Genetic Features of Plasmid- and Chromosome-Mediated mcr-1 in Escherichia coli Isolates From Animal Organs With Lesions
Authors: Liu Zengyuan , Liu Yingqiu , Xi Wei , Liu Shuangshi , Liu Jia , Mu Hailong , Chen Beibei , He Hao , Fan Yunpeng , Ma Wuren , Zhang Weimin , Fu Mingzhe , Wang Juan , Song Xiaoping
Published: August 2021

The genomic context of the mcr-1 gene in Escherichia coli from animal feces has been widely reported. However, less is known about the mcr-1-carrying plasmid characteristics and other functional regions of Escherichia coli isolates from animal organs with lesions. The present study investigated the antimicrobial resistance, population structure, and genetic features of mcr-1-positive Escherichia coli strains isolated from animal organs with lesions. The antimicrobial susceptibility testing indicated that 24 mcr-1-positive Escherichia coli isolates were resistant to at least three or all antimicrobial categories. MLST analysis suggested that the dominant clone complexes (CC) were mainly CC156, CC448, and CC10. In addition, ST10596, a newly discovered sequence type in swine, failed to be classified. Meanwhile, the mcr-1 gene located on the different plasmids was successfully transferred to the recipients, and whole-genome sequencing indicated the mcr-1 gene was embedded in mcr-1-pap2 cassette but not flanked by ISApl1. The mcr-1 gene is located on the chromosome and embedded in Tn6330. Furthermore, NDM-5 was found on the IncX3-type plasmid of J-8. The virB6 and traI gene of type IV secretion system (T4SS) were truncated by IS2 and IS100 and located on the IncX4- and the IncHI2/HI2A/N-type plasmids, respectively. The multidrug-resistant (MDR) region of IncHI2/HI2A/N-type plasmids contained two class 1 integrons (In0, In640) and four composite transposons (Tn4352, Tn6010, cn_4692_IS26, cn_6354_IS26). Overall, 24 mcr-1-positive Escherichia coli isolates in our study showed MDR, or even extensively drug resistant (XDR), and exhibited population diversity. The T4SS gene truncation by the insertion sequence may affect the efficiency of plasmid conjugative transfer. Furthermore, the class 1 integrons and composite transposons in the MDR region of IncHI2/HI2A/n-type plasmid contributed to the multireplicon plasmid formation, the acquisition, and transfer of antimicrobial resistance genes (ARGs).
MicroRNAs in Huntington’s Disease: Diagnostic Biomarkers or Therapeutic Agents?
Authors: Dong Xiaoyu , Cong Shuyan
Published: August 2021

MicroRNA (miRNA) is a non-coding single-stranded small molecule of approximately 21 nucleotides. It degrades or inhibits the translation of RNA by targeting the 3′-UTR. The miRNA plays an important role in the growth, development, differentiation, and functional execution of the nervous system. Dysregulated miRNA expression has been associated with several pathological processes of neurodegenerative disorders, including Huntington’s disease (HD). Recent studies have suggested promising roles of miRNAs as biomarkers and potential therapeutic targets for HD. Here, we review the emerging role of dysregulated miRNAs in HD and describe general biology of miRNAs, their pathophysiological implications, and their potential roles as biomarkers and therapeutic agents.
Not All Lesioned Tissue Is Equal: Identifying Pericavitational Areas in Chronic Stroke With Tissue Integrity Gradation via T2w T1w Ratio
Authors: Krishnamurthy Lisa C. , Krishnamurthy Venkatagiri , Rodriguez Amy D. , McGregor Keith M. , Glassman Clara N. , Champion Gabriell S. , Rocha Natalie , Harnish Stacy M. , Belagaje Samir R. , Kundu Suprateek , Crosson Bruce A.
Published: August 2021

Stroke-related tissue damage within lesioned brain areas is topologically non-uniform and has underlying tissue composition changes that may have important implications for rehabilitation. However, we know of no uniformly accepted, objective non-invasive methodology to identify pericavitational areas within the chronic stroke lesion. To fill this gap, we propose a novel magnetic resonance imaging (MRI) methodology to objectively quantify the lesion core and surrounding pericavitational perimeter, which we call tissue integrity gradation via T2w T1w ratio (TIGR). TIGR uses standard T1-weighted (T1w) and T2-weighted (T2w) anatomical images routinely collected in the clinical setting. TIGR maps are analyzed with relation to subject-specific gray matter and cerebrospinal fluid thresholds and binned to create a false colormap of tissue damage within the stroke lesion, and these are further categorized into low-, medium-, and high-damage areas. We validate TIGR by showing that the cerebral blood flow within the lesion reduces with greater tissue damage (p = 0.005). We further show that a significant task activity can be detected in pericavitational areas and that medium-damage areas contain a significantly lower magnitude of hemodynamic response function than the adjacent damaged areas (p < 0.0001). We also demonstrate the feasibility of using TIGR maps to extract multivariate brain–behavior relationships (p < 0.05) and show general agreement in location compared to binary lesion, T1w-only, and T2w-only maps but that the extent of brain behavior maps may depend on signal sensitivity as denoted by the sparseness coefficient (p < 0.0001). Finally, we show the feasibility of quantifying TIGR in early and late subacute stroke phases, where higher-damage areas were smaller in size (p = 0.002) and that lesioned voxels transition from lower to higher damage with increasing time post-stroke (p = 0.004). We conclude that TIGR is able to (1) identify tissue damage gradient within the stroke lesion across different post-stroke timepoints and (2) more objectively delineate lesion core from pericavitational areas wherein such areas demonstrate reasonable and expected physiological and functional impairments. Importantly, because T1w and T2w scans are routinely collected in the clinic, TIGR maps can be readily incorporated in clinical settings without additional imaging costs or patient burden to facilitate decision processes related to rehabilitation planning.
Accurate Decoding of Imagined and Heard Melodies
Authors: Di Liberto Giovanni M. , Marion Guilhem , Shamma Shihab A.
Published: August 2021

Music perception requires the human brain to process a variety of acoustic and music-related properties. Recent research used encoding models to tease apart and study the various cortical contributors to music perception. To do so, such approaches study temporal response functions that summarise the neural activity over several minutes of data. Here we tested the possibility of assessing the neural processing of individual musical units (bars) with electroencephalography (EEG). We devised a decoding methodology based on a maximum correlation metric across EEG segments (maxCorr) and used it to decode melodies from EEG based on an experiment where professional musicians listened and imagined four Bach melodies multiple times. We demonstrate here that accurate decoding of melodies in single-subjects and at the level of individual musical units is possible, both from EEG signals recorded during listening and imagination. Furthermore, we find that greater decoding accuracies are measured for the maxCorr method than for an envelope reconstruction approach based on backward temporal response functions (bTRFenv). These results indicate that low-frequency neural signals encode information beyond note timing, especially with respect to low-frequency cortical signals below 1 Hz, which are shown to encode pitch-related information. Along with the theoretical implications of these results, we discuss the potential applications of this decoding methodology in the context of novel brain-computer interface solutions.
The Clinical Application of Robot-Assisted Ventriculoperitoneal Shunting in the Treatment of Hydrocephalus
Authors: Liu De-feng , Liu Huan-guang , Zhang Kai , Meng Fan-gang , Yang An-chao , Zhang Jian-guo
Published: August 2021

Background

This work aims to assess the effectiveness and safety of robotic assistance in ventriculoperitoneal shunting and to compare the results with data from traditional surgery.

Methods

We retrospectively analyzed 60 patients who had undergone ventriculoperitoneal shunting, of which shunts were implanted using a robot in 20 patients and using traditional surgical methods in the other 40 patients. Data related to surgery were compared between the two groups, and the accuracy of the drainage tube in the robot-assisted group was assessed.

Results

In the robot-assisted surgery group, the operation duration was 29.75 ± 6.38 min, intraoperative blood loss was 10.0 ± 3.98 ml, the success rate of a single puncture was 100%, and the bone hole diameter was 4.0 ± 0.3 mm. On the other hand, the operation duration was 48.63 ± 6.60 min, intraoperative blood loss was 22.25 ± 4.52 ml, the success rate of a single puncture was 77.5%, and the bone hole diameter was 11.0 ± 0.2 mm in the traditional surgery group. The above are statistically different between the two groups (P < 0.05). Only one case of surgery-related complications occurred in the robot-assisted group, while 13 cases occurred in the traditional surgery group. There was no significant difference in the hospitalization time. In the robot-assisted surgery group, the average radial error was 2.4 ± 1.5 mm and the average axial error was 1.9 ± 2.1 mm.

Conclusion

In summary, robot-assisted implantation is accurate, simple to operate, and practical; the duration of surgery is short; trauma to the patient is reduced; and fewer postoperative complications related to surgery are reported.
Advances in Brain Imaging Techniques for Patients With Intractable Epilepsy
Authors: Algahtany Mubarak , Abdrabou Ahmed , Elhaddad Ahmed , Alghamdi Abdulrahman
Published: August 2021

Intractable epilepsy, also known as drug resistance or refractory epilepsy, is a major problem affecting nearly one-third of epilepsy patients. Surgical intervention could be an option to treat these patients. Correct identification and localization of epileptogenic foci is a crucial preoperative step. Some of these patients, however, have no abnormality on routine magnetic resonance imaging (MRI) of the brain. Advanced imaging techniques, therefore, can be helpful to identify the area of concern. Moreover, a clear delineation of certain anatomical brain structures and their relation to the surgical lesion or the surgical approach is essential to avoid postoperative complications, and advanced imaging techniques can be very helpful. In this review, we discuss and highlight the use of advanced imaging techniques, particularly positron emission tomography (PET)–MRI, single-photon emission computed tomography, functional MRI, and diffusion tensor imaging–tractography for the preoperative assessment of epileptic patients.